CA2471631A1 - Primary rat hepatocyte toxicity modeling - Google Patents

Abstract

The present invention is based on the elucidation of the global changes in gene expression and the identification of toxicity markers in tissues or cells exposed to a known toxin. The genes may be used as toxicity markers in drug screening and toxicity assays. The invention includes a database of genes characterized by toxin-induced differential expression that is designed for use with microarrays and other solid-phase probes.

Description

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PRIMARY RAT HEPATOCYTE TOXICITY MODELING
INVENTORS: Donna MENDRICK, Mark PORTER, Kory JOHNSON, Brandon HIGGS, Arthur CASTLE, Michael ORR and Michael ELASHOFF
RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. ~119(e) to U.S.
Provisional Applications 60/353,171, filed February 4, 2002; 60/363,534, filed March 13, 2002;
60/371,135, filed April 10, 2002; 60/371,134, filed April 10, 2002;
60/370,248, filed April 8, 2002; 60/371,150, filed April 10, 2002; 60/371,413, filed April 11, 2002;
60/373,601, filed April 19, 2002; 60/374,139, filed April 22, 2002; 60/394,253, filed July 9, 2002; 60/378,652, filed May 9, 2002; 60/373,602, filed April 19, 2002; 60/378,653, filed May 9, 2002;
60/378,665, filed May 9, 2002; 60/378,370, filed May 8, 2002; 60/394,230, filed July 9, 2002; and 60/407,688, filed September 4, 2002, all of wluch are herein incorporated by reference in their entirety.

[0002] This application is also related to pending U.S. Applications 09/917,800, filed July 31, 2001, 10/060,087, filed January 31, 2002, and PCT/LJS03/ , entitled "Molecular Hepatotoxicology Modeling," filed January 31, 2003, as well as to PCT
Application PCT/USOl/23872, filed July 31, 2001, all of which are herein incorporated by reference in their entirety.
SEQUENCE LISTING SUBMISSION ON COMPACT DISC

[0003] The Sequence Listing submitted concurrently herewith on compact disc under 37 C.F.R. ~ ~ 1.821 (c) and 1.821 (e) is herein incorporated by reference in its entirety. Four copies of the Sequence Listing, one on each of four compact discs are provided. Copy 1, Copy 2 and Copy 3 are identical. Copies 1, 2 and 3 are also identical to the CRF. Each electronic copy of the Sequence Listing was created on February 3, 2003 with a file size of 6321 I~B. The file names are as follows: Copy 1- g15113wo.txt; Copy 2-g15113wo.txt;
Copy 3- g15113wo.txt; CRF- g15113wo.txt.
BACKGROUND OF THE INVENTION

[0004] The need for methods of assessing the toxic impact of a compound, pharmaceutical agent or environmental pollutant on a cell or living organism has led to the development of procedures which utilize living organisms as biological monitors. The simplest and most convenient of these systems utilize unicellular microorganisms such as yeast and bacteria, since they are most easily maintained and manipulated. Unicellular screening systems also often use easily detectable changes in phenotype to monitor the effect of test compounds on the cell. Unicellular organisms, however, are inadequate models for estimating the potential effects of many compounds on complex multicellular animals, as they do not have the ability to carry out biotransformations to the extent or at levels found in higher organisms.

[0005] The biotransformation of chemical compounds by multicellular organisms is a significant factor in determining the overall toxicity of agents to which they are exposed.
Accordingly, multicellular screening systems or screening systems using isolated eukaryotic cells may be preferred or required to detect the toxic effects of compounds.
The use of multicellular organisms as toxicology screening tools has been significantly hampered, however, by the lack of convenient screening mechanisms or endpoints, such as those available in yeast or bacterial systems. In addition, previous attempts to produce toxicology prediction systems have failed to provide the necessary modeling data and statistical information to accurately predict toxic responses (e.g., WO 00/12760, WO
00/47761, WO
00/63435, WO 01/32928, WO 01/38579).
SUMMARY OF THE INVENTION

[0006] The present invention is based on the elucidation of the global changes in gene expression in primary hepatocytes exposed to known toxins in particular hepatotoxins, as compared to unexposed cells as well as the identification of individual genes that are differentially expressed upon toxin exposure.

[0007] In various aspects, the invention includes methods of predicting at least one toxic effect of a compound, predicting the progression of a toxic effect of a compound, and predicting the hepatoxicity of a compound. The invention also includes methods of identifying agents that modulate the onset or progression of a toxic response.
Also provided are methods of predicting the general pathology classes and cellular pathways that a compound modulates in a cell. The invention includes methods of identifying agents that modulate protein activities.

[0008] In a further aspect, the invention provides probes comprising sequences that specifically hybridize to genes in Tables 1-SXX. Also provided are solid supports comprising at least two of the previously mentioned probes. The invention also includes a computer system that has a database containing information identifying the expression level in a tissue or cell sample exposed to a hepatotoxin of a set of genes comprising at least two genes in Tables 1-SXX.

DETAILED DESCRIPTION

[0009] Many biological functions are accomplished by altering the expression of various genes through transcriptional (e.g. through control of initiation, provision of RNA precursors, RNA processing, etc.) and/or translational control. For example, fundamental biological processes such as cell cycle, cell differentiation and cell death are often characterized by the variations in the expression levels of groups of genes.

[0010] Changes in gene expression are also associated with the effects of various chemicals, drugs, toxins, pharmaceutical agents and pollutants on an organism or cells. For example, the lack of sufficient expression of functional tumor suppressor genes and/or the over expression of oncogene/protooncogenes after exposure to an agent could lead to tumorgenesis or hyperplastic growth of cells (Marshall, Cell, 64: 313-326 (1991); Weinberg, Science, 254:1138-1146 (1991)). Thus, changes in the expression levels of particular genes (e.g. oncogenes or tumor suppressors) may serve as signposts for the presence and progression of toxicity or other cellular responses to exposure to a particular compound.

[0011] Monitoring changes in gene expression may also provide certain advantages during drug screening and development. Often drugs are screened for the ability to interact with a major target without regard to other effects the drugs have on cells. These cellular effects may cause toxicity in the whole animal, which prevents the development and clinical use of the potential drug.

[0012] The present inventors have examined primary rat hepatocytes exposed to the known hepatotoxins which induce detrimental liver effects, to identify global and individual changes in gene expression induced by these compounds. These global changes in gene expression, which can be detected by the production of expression profiles, as well as the individual genes, provide useful toxicity markers that can be used to monitor toxicity and/or toxicity progression by a test compound. Expression profiles, as well as the individual markers, may also be used to monitor or detect various disease or physiological states, disease progression, drug efficacy and drug metabolism.
Identification of Toxicity Markers [0013] To evaluate and identify gene expression changes that are predictive of toxicity, studies using selected compounds with well characterized toxicity have been conducted by the present inventors to catalogue altered gene expression during exposure in vivo and ih vitro. In the present study, amiodarone, alpha-naphthylisothiocyante (ANIT), acetaminophen (APAP), AY-25329, carbamazepine, carbon tetrachloride, chlorpromazine, CI-1000, clofibrate, CPA, diclofenac, diflunisal, dimethylnitrosamine (DMl~, 17a-ethinylestradiol, gemfibrozil (Lopid~), hydrazine, imipramine (Janimine), indomethacin, lipopolysaccharide, lovastatin (Mevacor~), methotrexate, phenobarbital, tacrine, tamoxifen, tetracycline, valproate and Wy-14643 were selected as a known hepatotoxins.

[0014] Amiodarone (Cordarone~) is an anti-arrhythmic agent whose chemical structure contains a benzofuran ring (ring A) coupled to a p-OH-benzene structure substituted with 2 iodines and a diethyl-ethanolamine side chain (ring B). This drug is known to cause damage to the liver and has been shown to adversely effect the mitochondria by uncoupling oxidative phosphorylation and inhibiting beta-oxidation and respiration. Inhibition of respiration decreases ATP and increases production of reactive oxygen species, which in turn cause lipid peroxidation. The steatosis and hepatitis observed following treatment with amiodarone are believed to be due, at least in part, to lipid peroxidation products (Spaniol et al., JHepatol 35(5):628-636 (2001); Berson et al., GastYOenterology 114:764-774, (1998)).

[0015] Aromatic and aliphatic isothiocyanates are commonly used soil fumigants and pesticides (Shaaya et al., Pesticide Science 44(3):249-253 (1995); Cairns et al., JAssoc O~cial Analytical Chemists 71(3):547-550 (1988)). These compounds are also environmental hazards, because they remain as toxic residues in plants (Cerny et al., J
Ag~icultunal and Food Chemistry 44(12):3835-3839 (1996)) and because they are released from the soil into the surrounding air (Gar et al., JAgricutu~al and Food Chemistry 46(3):986-990 (1998)).

[0016] Exposure to a-naphthylisothiocyanate (ANIT) has been shown to increase serum levels of total bilirubin, alkaline phosphatase, serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase, while total bile flow was reduced, all of which are indications of severe biliary dysfunction. ANIT also induces j aundice and cholestatis (the condition caused by failure to secrete bile, resulting in plasma accumulation of bile substances, liver cell necrosis and bile duct obstruction) (Tanaka et al., Clinical and Expe~imeyatal Pharmacology and Physiology 20:543-547 (1993)). ANIT fails to produce extensive necrosis, but was found to produce inflammation and edema in the portal tract of the liver (Maziasa et al., Toxicol Appl Pha~macol 110:365-373 (1991)). AI~IIT-induced hepatotoxicity may also characterized by cholangiolitic hepatitis and bile duct damage.
Acute hepatotoxicity caused by Al~IT in rats is manifested as neutrophil-dependent necrosis of bile duct epithelial cells (BDECs) and hepatic parenchymal cells. These changes mirror the cholangiolitic hepatitis found in humans (Hill, Toxicol Sci 47:118-125 (1999)).

[0017] Histological changes include an infiltration of polymorphonuclear neutrophils and elevated number of apoptotic hepatocytes (Calvo et al., J Cell Biochem 80(4):461-470 (2001)). Other known hepatotoxic effects of exposure to ANIT include a damaged antioxidant defense system, decreased activities of superoxide dismutase and catalase (Ohta et al., Toxicology 139(3):265-275 (1999)), and the release of proteases from the infiltrated neutrophils, alanine aminotransferase, cathepsin G, elastase, which mediate hepatocyte killing (Hill et al., Toxicol Appl Pharmacol 148(1):169-175 (1998)).

[0018] Acetominophen (APAP) is a widely used analgesic and antipyretic agent that is an effective substitute for aspirin. Although acetaminophen does not have anti-inflammatory properties, it is preferably given to patients with ulcers or patients in whom prolonged clotting times would not be desirable. It also preferably taken by people who do not tolerate aspirin well.

[0019] Acetominophen is metabolized to N acetyl p-benzoquinoneimine (NAPQI) by N-hydroxylation in a cytochrome P450-mediated process. This highly reactive intermediate, which reacts with sulfhydryl ,groups in glutathione, and in other liver proteins following the depletion of glutathione, can cause centrilobular hepatic necrosis (particularly in zone 3), renal tubular necrosis, and hepatic and renal failure (Goodman and Gilinan's The Pharmacological Basis of Therapeutics, Ninth Ed., Hardman et al., eds., pp.
631-633, McGraw-Hill, New York, 1996; Chanda et al., Hepatology 21(2):477-486 (1995)).
Less serious side effects include skin rashes (erythemas and urticarias) and allergic reactions.

[0020] Upon treatment of rats with acetaminophen, hepatotoxicity can be observed 24 hours after dosing, as determined by statistically significant elevations of ALT and AST in the serum and by hepatocellular necrosis visualized at the light microscopic level (Hessel et al., B~az JMed Biol Res 29(6):793-796 (1996); Bruck et al., Dig Dis Sci 44(6):1228-(1999)). High, but non-lethal, doses of acetaminophen given to rats also produced elevated levels of genes involved in hepatic acute phase response and liver cell maintenance and repair: arginase, beta-fibrinogen, alpha 1-acid glycoprotein, alpha-tubulin, histone 3, TGF
beta and cyclin d. Expression levels of genes regulated by the cell cycle were decreased (Tygstrup et al., JHepatol 25(2):183-190 (1996); Tygstrup et al., JHepatol 27(1):156-162 (1997)). In mice, expression levels of genes that encode growth arrest and cell cycle regulatory proteins were increased, along with expression levels of stress-induced genes, transcription factor LRG-21, SOCS-2 (cytokine signaling repressor) and PAI-1 (plasminogen activator inhibitor-1) (Reilly et al., Biochem Biophys Res Comm 282(1):321-328 (2001)).

[0021] AY-25329 is a phenothiazine that has been shown to be toxic in liver and in kidney tissue, where it can cause nephrosis. Phenothiazines are a class of psychoactive drugs that are used to treat schizophrenia, paranoia, mania, hyperactivity in children, some forms of senility, and anxiety (http://www.encyclopedia.com/articlesnew/ 36591.html).
Side effects associated with prolonged use of these drugs are reduced blood pressure, Parkinsonism, reduction of motor activity, and visual impairment.

[0022] The present inventors have noted indications of liver and renal effects of AY-25329 by changes in serum chemistry. As early as 6 hours after the first dose, statistically significant increases in serum levels of creatinine, BUN, ALT, triglycerides and cholesterol were observed. Most of these markers of renal and liver dysfunction remained altered throughout the 14 day study period. Light microscopic analysis revealed effects in the liver as early as 6 and 24 hours, as evidenced by an increased number of hepatocytic mitotic figures and decreased glycogen content. Following 14 days of repeated dosing, nephrosis and alterations in the peripheral lobes of the liver and in the cytoplasm of hepatocytes were evident in rats dosed with 250 mg/kg/day of AY-25329.

[0023] Carbamazepine (Tegretol~) is an anti-epieleptic agent. In rats, it has been shown to induce a number of cytochrome P450 enzymes, in particular CYP2B, and the drug may also cause steatohepatitis in humans (Tateishi et al., Chem Biol Interact 117:257-268 (1999);
Grieco et al., Eur J Gastroenterol 13(8):973-975 (2001)).

[0024] The pathogenesis of acute carbon tetrachloride (CC14)-induced hepatotoxicity follows a well-characterized course in humans and experimental animals resulting in centrilobular necrosis and steatosis, followed by hepatic regeneration and tissue repair.
Severity of the hepatocellular injury is also dose-dependent and may be affected by species, age, gender and diet.

[0025] Differences in susceptibility to CC14 hepatotoxicity are primarily related to the ability of the animal.model to metabolize CC14 to reactive intermediates. CCl4 induced hepatotoxicity is dependent on CCl4 bioactivation to trichloromethyl free radicals by cytochrome P450 enzymes (CYP2E1), localized primarily in centrizonal hepatocytes.
Formation of the free radicals leads to membrane lipid peroxidation and protein denaturation resulting in hepatocellular damage or death.

[0026] The onset of hepatic injury is rapid following acute administration of CCl4 to male rats. Morphologic studies have shown cytoplasmic accumulation of lipids in hepatocytes within 1 to 3 hours of dosing, and by 5 to 6 hours, focal necrosis and hydropic swelling of _7_ hepatocytes are evident. Centrilobular necrosis and inflammatory infiltration peak by 24 to 48 hours post dose. The onset of recovery is also evident within this time frame by increased DNA synthesis and the appearance of mitotic figures. Removal of necrotic debris begins by 48 hours and is usually completed by one week, with full restoration of the liver by 14 days.

[0027] Increases in serum transaminase levels also parallel CCl4 induced hepatic histopathology. In male Sprague Dawley (SD) rats, alanine aminotrasferase (ALT) and aspartate aminotransferase (AST) levels increase within 3 hours of CC14 administration (0.1, 1,2, 3, 4 mL/kg, ip; 2.5 mL/kg, po) and reach peak levels (approximately 5-10 fold increases) within 48 hours post dose. Significant increases in serum -glutathione s-transferase (-GST) levels have also been detected as early as 2 hours after CC14 administration (25 L/kg, po) to male SD rats.

[0028] At the molecular level, induction of the growth-related proto-oncogenes, c-fos and c jun, is reportedly the earliest event detected in an acute model of CCl4 induced hepatotoxicity (Schiaffonato et al., Liver 17:183-191 (1997)). Expression of these early-immediate response genes has been detected within 30 minutes of a single dose of CC14 to mice (0.05 -1.5 mL/kg, ip) and by 1 to 2 hours post dose in rats (2 mL/kg, po;
5 mL/kg, po) (Schiaffonato et al., supra, and Hong et al., Yohsei Medical J 38:167-177 (1997)). Similarly, hepatic c-myc gene expression is increased by 1 hour following an acute dose of CC14 to male SD rats (5 mL/kg, po) (Hong et al., supra). Expression of these genes following exposure to CCl4 is rapid and transient. Peak hepatic mRNA levels for c-fos, c jun, and c-myc, after acute administration of CC14 have been reported at 1 to 2 hours, 3 hours, and 1 hour post dose, respectively.

[0029] The expression of tumor necrosis factor-cc (TNF-a).is also increased in the livers of rodents exposed to CC14, and TNF-a has been implicated in initiation of the hepatic repair process. Pre-treatment with anti-TNF-a antibodies has been shown to prevent mediated increases in c-jun and c-fos gene expression, whereas administration of TNF-a induced rapid expression of these genes (Bruccoleri et al., Hepatol 25:133-141 (1997)). Up-regulation of transforming growth factor-~i (TGF-Vii) and transforming growth factor receptors (TBRI-III) later in the repair process (24 and 48 hours after CCl4 administration) suggests that TGF-~i may play a role in limiting the regenerative response by induction of apoptosis (Grasl-Kraupp et al., Hepatol 28:717-7126 (1998)).

_g_ [0030] Chlorpromazine (Thorazine~) is a central nervous system depressant that is used as a sedative and also as an anti-nausea or anti-itching medication. The mechanism of action is not known. The drug induces canalicular cholestasis, a condition characterized by a decrease in the volume of bile formed and impaired secretion of solutes into bile, resulting in elevated serum levels of bile salts and bilirubin. Chlorpromazine has also been shown to inhibit bile acid uptake and canalicular contractility. Bile plugs can form in the bile ducts and canaliculi.
Drug-induced cholestasis is also associated with cell swelling, inflammation and cell death (Casarett and Doull's Toxicolo~~The Basic Science of Poisons, 6th Ed., Klaassen et al. eds., pp. 476-486, McGraw-Hill Medical Pub. Div., New York, 2001).

[0031] CI-1000 (4H-pyrrolo:3,2-d:pyrimidin-4-one, 2-amino-3,5-dihydro-7-(3-thienyhnethyl)-monohydrochloride monohydrate) is a compound with anti-inflammatory properties. After treatment with CI-1000, increased serum ALT levels, a standard marker of liver toxicity, were observed in dogs.

[0032] Clofibrate, a halogenated phenoxypropanoic acid derivative (ethyl ester of clofibric acid), is an antilipemic agent. The exact mechanism by which clofibrate lowers serum concentrations of triglycerides and low-density lipoprotein (LDL) cholesterol, as well as raising high-density lipoprotein (HDL) cholesterol is uncertain. The drug has several antilipidemic actions, including activating lipoprotein lipase, which enhances the clearance of triglycerides and very-low-density lipoprotein (VLDL) cholesterol, inhibition of cholesterol and triglyceride biosynthesis, mobilization of cholesterol from tissues, increasing fecal excretion of neutral steroids, decreasing hepatic lipoprotein synthesis and secretion, and decreasing free fatty acid release.

[0033] Clofibrate has a number of effects on the rat liver, including hepatocellular hypertrophy, cellular proliferation, hepatomegaly, induction of CYP450 isozymes, and induction of palmitoyl CoA oxidation. Long term administration of clofibrate causes increased incidence of hepatocellular carcinoma, benign testicular Leydig cell tumors, and pancreatic acinar adenomas in rats. Clofibrate induces proliferation of peroxisomes in rodents and this effect, rather than genotoxic damage, is believed to be the causative event in rodent carcinogenesis (AHFS Drub Information Handbook 2001, McEvoy, ed., pp.1735-1738; Electronic Physicians' Desk Reference- Atromid-S (clofibrate) at www.pdr.net; Brown and Goldstein, "Drugs used in the treatment of hyperliproteinemias," in Goodman and Gilman's The Pharmacological Basis of Therapeutics, Eighth ed., Goodman et al., eds., pp.
874-896, Pergamon Press, New York, 1990).

[0034] Clofibrate also increases hepatic lipid content and alters its normal composition by significantly increasing levels of phosphatidylcholine and phosphatidyl-ethanolamine (Adinehzadeh et al., Clzem Res Toxicol 11(5):428-440 (1998)). A rat study of liver hyperplasia and liver tumors induced by peroxisome proliferators revealed that administration of clofibrate increased levels of copper and altered copper-related gene expression in the neoplastic liver tissues. Down-regulation of the ceruloplasmin gene and of the Wilson's Disease gene (which encodes P-type ATPase), along with up-regulation of the metallothionein gene, were noted in these tissues (Eagon et al., Ca~cinogehesis 20(6):1091-1096 (1999)). Clofibrate-induced peroxisome proliferation and carcinogenicity are believed to be rodent-specific, and have not been demonstrated in humans.

[0035] Cyproterone acetate (CPA) is a potent androgen antagonist and has been used to treat acne, male pattern baldness, precocious puberty, and prostatic hyperplasia and carcinoma (Goodman ~z Gilinan's The Pharmacological Basis of Therapeutics 9th ed., p.
1453, J.G. Hardman et al., Eds., McGraw Hill, New York, 1996). Additionally, CPA has been used clinically in hormone replacement therapy to protect the endometrium and decrease menopausal symptoms and the risk of osteoporotic fracture (Schneider, "The role of antiandrogens in hormone replacement therapy," Climacteric 3 (Suppl. 2): 21-27 (2000)).

[0036] In experiments with rats, CPA was shown to induce unscheduled DNA
synthesis in vitro. After a single oral dose, continuous DNA repair activity was observed after 16 hours.
CPA also increased the occurrence of S phase cells, which corroborated the mitogenic potential of CPA in rat liver (I~asper et al., Caf~cinogefzesis 17(10): 2271-2274 (1996)). CPA
has also been shown to produce cirrhosis in humans (Gamy et al., EuY JPediat~
158(5): 367-370 (1999)).

[0037] Diclofenac, a non-steroidal anti-inflammatory drug, has been frequently administered to patients suffering from rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Following oral administration, diclofenac is rapidly absorbed and then metabolized in the liver by cytochrome P450 isozyme of the CYC2C subfamily (Goodman &
Gilinan's The Pharmacological Basis of Therapeutics 9th ed., p. 637, J.G.
Hardman et al., eds., McGraw Hill, New York, 1996). In addition, diclofenac has been applied topically to treat pain due to corneal damage (Jayamanne et al., Eye 11(Pt. 1): 79-83 (1997); Dornic et al., Am JOplathalrnol 125(5): 719-721 (1998)).

[0038] Although diclofenac has numerous clinical applications, adverse side-effects have been associated with the drug, such as corneal complications, including corneal melts, ulceration, and severe keratopathy (Guidera et al., Ophthalmology 108(5): 936-944 (2001)).
Another study investigated 180 cases of patients who had reported adverse reactions to diclofenac to the Food and Drug Administration (Banks et al., Hepatology 22(3): 820-827 (1995)). Of the 180 reported cases, the most common symptom was jaundice (75%
of the symptomatic patients). Liver sections were taken and analyzed, and hepatic injury was apparent one month after drug treatment. An additional report showed that a patient developed severe hepatitis five weeks after begimung diclofenac treatment for osteoarthritis (Bhogaraju et al., South Med J92(7): 711-713 (1999)).

[0039] In one study on diclofenac-treated Wistar rats (Ebong et al., Afi~ JMed Sci 27(3-4):
243-246 (1998)), diclofenac treatment induced an increase in serum chemistry levels of alanine aminotransferase, aspartate aminotransferase, methaemoglobin, and total and conjugated bilirubin. Additionally, diclofenac enhanced the activity of alkaline phosphatase and 5'nucleotidase. A study on humans revealed elevated levels of hepatic transaminases and serum creatine when compared to the control group (McI~enna et al., Scaud JRheumatol 30(1): 11-18 (2001)).

[0040] Diflunisal, a non-steroidal anti-inflammatory drug (NSAID), is a difluorophenyl derivative of salicylic acid (Goodman ~ Gilman's The Pharmacological Basis of Therapeutics 9th ed., p. 631, J.G. Hardman et al., Eds., McGraw Hill, New York, 1996). It is most frequently used in the treatment of osteoarthritis and musculoskeletal strains. NSAIDs have analgesic, antipyretic and anti-inflammatory actions, however, hepatotoxicity is known to be an adverse side effect of NSAID treatment (Masubuchi et al., JPharmacol Exp Then 287:208-213 (1998)). Diflunisal has been shown to be less toxic than other NSAIDs, but it can eventually have deleterious effects on platelet or kidney function (Bergamo et al., Am J
Neph~ol 9:460-463 (1989)). Other side effects that have been associated with diflunisal treatment are diarrhea, dizziness, drowsiness, gas or heartburn, headache, nausea, vomiting, and insomnia (http:/larthritisinsight.com/medical/ meds/dolobid.html).

[0041] In a comparative hepatotoxicity study of 18 acidic NSAIDs, diflunisal was shown to increase LDH leakage in rat hepatocytes, a marker for cell injury, when compared to control samples. Additionally, treatment with diflunisal led to decreased intracellular ATP
concentrations. In a study comparing the effects of diflunisal and ibuprofen, both drugs appeared to cause abdominal cramping, even during short-term usage. Because the toxic dosages were selected to be below the level at which gastric ulceration occurs, more severe gastrointestinal effects were not detected. But, increased serum levels of creatinine, a sign of renal injury, were also observed (Muncie et al., Clih Ther 11:539-544 (1989)).

[0042] Another model compound, dimethyhiitrosamine (DMN), is a known carcinogen and inducer of liver fibrosis and lipid peroxidation. DMN causes oxidative stress in liver cells, which may be the link between chronic liver damage and liver fibrosis. Rats treated with DMN showed diffuse fibronectin deposition, elevated hydroxyproline levels (an indicator of fibrosis), increased levels of collagens, fibrous septa, and impaired oxidative balance. Serum levels of ALT and malondialdehyde (MDA) were increased, while serum levels of SOD were decreased (Vendemiale et al., Toxicol Appl Pharfzaacol 175(2):130-139 (2001);
Liu et al., Zho~ghua Gah Zang Bing Za Zhi 9 Supp1:18-20 (2001)). Other studies in rats have noted severe centrilobular congestion and haemorrhagic necrosis several days after a three-day period of DMN administration. Following additional periods of DMN treatment, the rats developed centrilobular necrosis and intense neutrophilic infiltration, which progressed to severe centrilobular necrosis, fiber deposition, focal fatty deposits, bile duct proliferation, bridging necrosis and fibrosis around the central veins (cirrhosis-like symptoms). A decrease in total protein and increase in DNA were also observed (George et al. (2001) Toxicology 156(2-3):129-138).

[0043] 17a-ethinylestradiol, a synthetic estrogen, is a component of oral contraceptives, often combined with the progestational compound norethindrone. It is also used in post-menopausal estrogen replacement therapy (PDR 47th Ed., pp. 2415-2420, Medical Economics Co., Inc., Montvale, NJ, 1993; Goodmaiz & Gilman's The Pharmalo~ical Basis of Therapeutics 9th Ed., pp. 1419-1422, J.G. Hardman et al. Eds., McGraw Hill, New York, 1996).

[0044] The most frequent adverse effects of 17a-ethinylestradiol usage are increased risks of cardiovascular disease: myocardial infarction, thromboembolism, vascular disease and high blood pressure, and of changes in carbohydrate metabolism, in particular, glucose intolerance and impaired insulin secretion. There is also an increased risk of developing benign hepatic neoplasia. Because this drug decreases the rate of liver metabolism, it is cleared slowly from the liver, and carcinogenic effects, such as tumor growth, may result.

[0045] 17a-ethinylestradiol has been shown to cause a reversible intrahepatic cholestasis in male rats, mainly by reducing the bile-salt-independent fraction of bile flow (BSIF) (Koopen et al., Hepatology 27:537-545 (1998)). Plasma levels of bilirubin, bile salts, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in this study were not changed.

This study also showed that 17a-ethinylestradiol produced a decrease in plasma cholesterol and plasma triglyceride levels, but an increase in the weight of the liver after 3 days of drug administration, along with a decrease in bile flow. Further results from this study are as follows. The activities of the liver enzymes leucine aminopeptidase and alkaline phosphatase initially showed significant increases, but enzyme levels decreased after 3 days. Bilirubin output increased, although glutathione (GSH) output decreased. The increased secretion of bilirubin into the bile without affecting the plasma level suggests that the increased bilirubin production must be related to an increased degradation of heme from heme-containing proteins. Similar results were obtained in another experiment (Bouchard et al., Lives 13:193-202 (1993)) in which the livers were also examined by light and electron microscopy. Daily doses of 17a-ethinylestradiol have been shown to cause cholestasis as well, although, following drug treatment, bile flow rates gradually returned to normal (Hamada et al., Hepatology 21:1455-1464 (1995)). Liver hyperplasia, possibly in response to the effects of tumor promoters, has also been observed (Mayol, Carcihogeaesis 13:2381-2388 (1992)).

[0046] The lipid-lowering drug gemfibrozil (Lopid~) is a know peroxisome proliferator in liver tissue, causing both hyperplasia and enlargement of liver cells. Upon exposure to gemfibrozil, hepatocarcinogenesis has been observed in rats and mice, and a decrease in alpha-tocopherol and an increase in DT-diaphorase activity have been observed in rats and hamsters (impaired antioxidant capability). Peroxisome proliferators increase the activities of enzymes involved in peroxisomal beta-oxidation and omega-hydroxylation of fatty acids, which results in oxidative stress (O'Brien et al., Toxicol Sci 60(2):271-278 (2001); Carthew et al., JAppl Toxicol 17(1):47-51 (1997)).

[0047] Hydrazine (NHZ=NHa), is a component of many industrial chemicals, such as aerospace and airplane fuels, corrosion inhibitors, dyes and photographic chemicals. Its derivatives axe used in pharmaceuticals such as hydrazine sulphate, used to treat cachexia in cancer patients, isoniazid, an anti-tuberculosis drug, and hydralazine, an anti-hypertensive.
These drugs are metabolized in vivo to produce hydrazine, among other by-products.
Consequently, exposure to hydrazine is by direct contact, e.g., among military and airline personnel, or the result of its production in the body, e.g., in patients with cancer or high blood pressure.

[0048] Studies on rat hepatocytes have shown that hydrazine causes a dose-dependent loss of viability, leakage of LDH, depletion of GSH and ATP and a decreased rate of protein synthesis (Delaney et al., ~enobiotica 25(12):1399-1410 (1995)). When administered to rats, hepatotoxic changes, characterized by GSH and ATP depletion and induction of fatty liver (increases in liver weight and triglycerides, with the appearance of fatty droplets, swelling of mitochondria and appearance of microbodies) were also found to be dose-dependent (Jenner et al., Arch Toxicol 68(6):349-357 (1994); Scales et al., JToxicol Ehvi~oyz Health 10(6):941-953 (1982)). The hepatoxicity, as well as renal toxicity, associated with hydrazine exposure has been linked to free radical damage resulting from oxidative metabolism by cytochrome P4502E1 (CYP2E1), which catalyzes the conjugation of free radicals with reduced glutathione. Although exposure to hydrazine and several hydrazine derivatives increased enzyme levels in kidney tissue, increased enzyme levels were not detected in liver tissue (Range-Morns et al., Drug Metab Dispos 24(7):734-737 (1996)).

[0049] The mutagenic and hepatocarcinogenic effects of hydrazine were examined in hamster livers. Ih vivo, hydrazine reacts with formaldehyde to form formaldehyde hydrazone (CHZ N-NH2), an alkylating intermediate that methylates guanine in DNA. Upon treatment with hydrazine, liver DNA showed the presence of methylated guanine, DNA
adducts and the impairment of maintenance methylation (impaired methylation of deoxycytosine).
Hepatic adenomas and carcinomas also developed in a dose-dependent mamier and could be correlated with decreased maintenance methylation (FitzGerald et al., Carcinogeyiesis 17(12):2703-2709 (1996)).

[0050] Imipramine, a dibenzazepine derivative, is a tricyclic anti-depressant agent commonly used for the treatment of major depression. Experiments in rats have shown that the drug induces cytochrome P450-mediated formation of reactive metabolites, which cause acute cell injury. Decreased levels of glutathione and protein thiols, as well as lactate dehydrogenase leakage, all standard measures of liver toxicity, were also noted (Masubuchi et al., Arch Toxicol 73(3):147-151 (1999). On rare occasions, imipramine has induced cholestasis and hepatitis in humans (Moskovitz et al., J Clin Psychiatry 43(4):165-066 (1982);
Horst et al., Gastroenterology 79(3):550-544 (1980)).

[0051] Indomethacin is a non-steroidal antiinflamrnatory, antipyretic and analgesic drug commonly used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout and a type of severe, chronic cluster headache characterized by many daily occurrences and jabbing pain. This drug acts as a potent inhibitor of prostaglandin synthesis; it inhibits the cyclooxygenase enzyme necessary for the conversion of arachidonic acid to prostaglandins (PDR 47th Ed., Medical Economics Co., Inc., Montvale, NJ, 1993; Goodman &
Gilman's The Pharmalo~ical Basis of Therapeutics 9th Ed., J.G. Hardman et al. eds., pp.
1074-1075, 1089-1095, McGraw Hill, New York, 1996; Cecil Textbook of Medicine, 20th Ed., part XII, pp.
772-773, 805-808, J. C. Bennett and F. Plum Eds., W. B. Saunders Co., Philadelphia, 1996).

[0052] The most frequent adverse effects of indomethacin treatment are gastrointestinal disturbances, usually mild dyspepsia, although more severe conditions, such as bleeding, ulcers and perforations can occur. Hepatic involvement is uncommon, although some fatal cases of hepatitis and jaundice have been reported. Renal toxicity can also result, particularly after long-term administration. Renal papillary necrosis has been observed in rats, and interstitial nephritis with hematuria, proteinuria and nephrotic syndrome have been reported in humans. Patients suffering from renal dysfunction risk developing a reduction in renal blood flow, because renal prostaglandins play an important role in renal perfusion.

[0053] In rats, although indomethacin produces more adverse effects in the gastrointestinal tract than in the liver, it has been shown to induce changes in hepatocytic cytochrome P450.
In one study, no widespread changes in the liver were observed, but a mild, focal, centrilobular response was noted. Serum levels of albumin and total protein were significantly reduced, while the serum level of urea was increased. No changes in creatinine or aspartate aminotransferase (AST) levels were observed (Falzon et al., Br J
exp Path 66:527-534 (1985)). In another rat study, a single dose of indomethacin was shown to reduce liver and renal microsomal enzymes, including CYP450, and cause lesions in the GI tract (Fracasso et al., Agents Actions 31:313-316 (1990)).

[0054] LPS (lipopolysaccharide) is an endotoxin released by gram-negative bacteria upon breakage or rupture of the cells that induces an acute inflammatory response in mammals and that can cause septic shock. LPS is also a research tool used to initiate liver injury in rats through an inflammatory mechanism. Typically, the membrane components of LPS
are lipid-A, KDO (2-lceto-3-deoxy-octulosonic acid), core polysaccharides and O-antigen polysaccharides, the polysaccharide units differing from one bacterium to another (Zinsser Microbiolo~y 20th Ed., Joklik et al., eds., pp. 82-87, Appleton ~ Lange, Norwalk, CT, 1992).

[0055] Primary rat hepatocytes derived from liver parenchyma) cells and sinusoidal cells of rats that have been exposed to LPS in vivo can directly respond to LPS in cell culture.
Numerous effects of LPS-induced endotoxemia can be detected, including elevated levels of nitric oxide synthetase (NOS) with increased nitric oxide and nitrite production, cellular hypertrophy, vacuolization, chromosomal emargination, cytoplasmic DNA
fragmentation and necrosis (Pittner et al., Bioclaem Biophys Res Commun 185(1):430-435 (1992);
Laskin et al., Hepatology 22(1):223-234 (1995); Wang et al., Am JPhysiol 269(2 Pt 1):G297-304 (1995)).

Other studies have indicated that the presence of Kupffer cells with primary rat hepatocytes is essential for the induction of hepatocyte apoptosis by LPS (Hamada et al., JHepatol 30(5):807-818 (1999)).

[0056] Exposure of rats or primary hepatocytes to LPS induces the expression of a number of acute-phase proteins in the liver. Recent evidence has indicated that rat hepatocytes express soluble CD14 protein, and LPS is capable of markedly increasing levels of CD14 at both the gene expression and protein expression levels (Liu et al., Infect Immun 66(11):5089-5098 (1998)). Soluble CD14 is believed to be a critical LPS recognition protein required for the activation of a variety of cells to toxic levels of LPS, even in endothelial and epithelial cells (Pugin et al., P~oc Natl Acad Sci USA 90(7):2744-2748 (1993)). Another key component of the LPS recognition system is lipopolysaccharide-binding protein (LBP), which binds to LPS. The LPS-LBP complex interacts with the CD14 receptor, inducing LPS
sensitive genes. LBP can be induced in hepatocytes isolated from rats that have not been primed with LPS, indicating that this key regulatory pathway is intact in primary rat hepatocytes (Wan et al., Infect Immura 63(7):2435-2442 (1995)).

[0057] Lovastatin (Mevacor~) is a cholesterol-lowering agent belonging to a class of compounds, the statins, that are potent inhibitors of HMG-CoA reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, the rate-controlling enzyme in cholesterol biosynthesis. HMG-CoA reductase inhibitors block the production of cholesterol in the liver leading to a reduction of LDL particles in the plasma. Lovastatin has additional effects on lipid metabolism, including depletion of intracellular pools of sterols and increased synthesis of LDL receptors, leading to enhanced removal of LDL and LDL
precursors from plasma. Upon treatment with lovastatin, plasma levels of VLDL, IDL and triglycerides also decrease. Oral doses of lovastatin are extensively absorbed by the liver, and the drug is excreted primarily via the liver; less than 13% of its metabolites are excreted in the urine (Goodman and Gilman's The Pharmacological Basis of Therapeutics, Ninth Ed., Hardman et al., eds., pp. 884-888, McGraw-Hill, New York, 1996).

[0058] The most frequent side effects are liver damage, characterized by elevated levels of hepatic transaminases (e.g., AST and ALT), creatinine phosphokinase and alkaline phosphatase, and myopathy, characterized by muscle pain and destruction of skeletal muscle cells. Cases of drug-induced hepatitis, accompanied by j aundice and elevated levels of liver enzymes, have also been reported, although the symptoms were reversible following withdrawal of the drug (Huchzermeyer et al., Deutsch Med Wochenschr 120(8):252-(1995); Heuer et al., Med Kliyz 95(11):642-644 (2000)). Histologic examination of affected liver tissue showed centrilobular necrosis, centrilobular cholestasis, and infiltrates with mononuclear and polymorphonuclear cells, including eosinophils (Grimbert et al., Dig Dis Sci 39(9):2032-2033 (1994)).

[0059] Experiments by the present inventors have found that when rats were dosed with lovastatin, at 9 or 90 mg/kg twice a day, no effects were noted in liver tissue after 6 or after 24 hours. After 14 days of treatment at the higher dosage, however, liver cells showed abnormal vacuolization of the cytoplasm. Hepatoxicity data from other studies of laboratory animals treated with lovastatin have not been widely reported. Therefore, in order to establish a more sensitive model for examining the changes in liver tissue caused by lovastatin, as well as to have a means of examining changes in expression level of individual genes as a result of exposure to lovastatin, experiments in cultured hepatocytes were undertaken.

[0060] Methotrexate is a widely used antineoplastic drug that is also frequently prescribed for the treatment of psoriasis (a disease characterized by abnormal proliferation of epidermal cells), juvenile lymphoblastic leukemia, rheumatoid arthritis, and a number of other cancerous diseases, such as leukemic meningitis and choriocarcinoma. Although generally not metabolized, at high dosages, metabolites such as 7-hydroxy-methotrexate, a nephrotoxin, do accumulate. Methotrexate polyglutamates are retained in the kidneys for weeks and in the liver for months ((Goodman and Gilman's The Pharmacological Basis of Therapeutics, Ninth Ed., Hardman et al., eds., pp. 1243-1247, McGraw-Hill, New York, 1996).

[0061] Methotrexate acts to prevent DNA synthesis and cell replication by inhibiting the rate-limiting enzyme in purine and thymidine synthesis, dihydrofolate reductase (DHFR) (Goodman and Gilinan's, supra; Schwartz et al., P>"oc Nat Acad Sci USA
89(2):594-598 (1992)). It also acts as an suppressant of cell-mediated immune responses. The biochemical toxicology of methotrexate has been well characterized in man, where long-term administration produces hepatic fibrosis or cirrhosis, especially in heavy drinkers, which is linked to persistent, mild-to-moderate, increases in serum transaminases, alkaline phosphatases and bilirubin (Reynolds et al., South Med J 79(5):536-539 (1986);
Tolman et al., JRheumatol 12 (Suppl 12):29-34 (1985)). Methotrexate is a rather long-acting, rapidly reversible DHFR inhibitor, despite its high affinity for the target enzymes in many cell types, which may be due to the formation of methotrexate polyglutamates that reduce the ability of DHFR to pass through cell membranes. The toxic effects of methotrexate may be due to the depletion of tetrahydrofolate cofactors that are required for purine and thymidylate synthesis (methylation reactions in hepatic 1-carbon metabolism) and to the iuubition of folate-dependent enzymes involved in the metabolism of purines and thymidylate, the inhibition caused by the accumulation of methotrexate polyglutamates and dihydrofolate polyglutamates.

[0062] The mechanism of methotrexate-induced hepatotoxicity is not yet fully elucidated, partly because the pathological changes in humans are rather difficult to reproduce in animal models, although experiments in rats have shown that, in a dose-dependent fashion, methotrexate produces liver damage ranging from focal to confluent necrosis of zone 3 hepatocytes, with eaxly stage fibrosis (Hall et al., Hepatology 14(5):906-10 (1991)). Other studies in rats have demonstrated that treatment with methotrexate produces intrahepatocytic fat deposits, along with fatty accumulations in hepatocytes that range from fine droplets to large vacuoles. The areas of necrosis showed signs of the hypoxia associated with congestive failure, as well as anemic infarcts, fibrotic foci of the collapse type, atrophy of the hepatic cords, and hemosiderosis (Custer et al., ,I Natl Cancer Inst 58(4):1011-1015 (1977)).
Hepatotoxicity probably involves interference with triglyceride and other lipid biosynthetic pathways in the liver. For example, studies on rats have shown that methotrexate inhibits the biosynthesis of lipotropic substances such as methionine and choline through its interference with hepatic 1-carbon metabolism. The drug also inhibits the activity of vitamin B12, another lipotropic factor (Tuma et al., Biochem Pha~macol 24:1327-1331 (1975) and impairs RNA and protein synthesis, triglyceride secretion and total triglyceride esterification (Deboyser et al., Toxic ira Vitro 6(2):129-132 (1992).

[0063] Methotrexate does not appear to be cytotoxic to cultured primary hepatocytes following short-term exposures (up to 3.5 hr), but significant effects on HepG2 growth curves have been observed at low concentrations during the course of 7-day exposures (Wu et al., P~oc Natl Acad Sci USA 80(10):3078-3080 (1983)). Additionally, it has been demonstrated that methotrexate increases hepatic glycogenolysis, oxygen consumption and calcium efflux and decreases glutathione levels (Yamamoto et al., Biochem Pharmacol 44(4):761-767, (1992); de Oliveira et al., Res Commun Claem Pathol Pharmacol 53(2):173-181 (1986);
Lindenthal et al., EuY JPlaaYmacol 228(5-6):289-298 (1993)). Experiments on cultured rat hepatocytes have shown that methotrexate also inhibits the activity of hepatic N-acetyltransferase 2 (NAT2), although the drug has only a slight inhibitory effect on rat NAT1, enzymes that catalyze the acetylation of a variety of therapeutic arylamines (Zaher et al., Toxicol in hit~o 11:271-283 (1997)).

[0064] Phenobarbital, a barbiturate, is used as an anti-epileptic, sedative or hypnotic drug and can also be used to treat neuroses with related tension states, such as hypertension, coronary artery disease, gastrointestinal disturbances and preoperative apprehension.
Phenobarbital is also found in medications to treat insomnia and headaches (Remington: The Science and Practice of Pharmacy, 19th Ed., A. R. Gennaro ed., pp. 1164-1165, Mack Publishing Co., Easton, Pennsylvania, 1995).

[0065] Phenobarbital induces a variety of drug metabolizing enzymes such as cytochrome P450 oxidoreductase, aldehyde dehydrogenases, UDP-glucuronyltransferase, GSTs, epoxide hydrolase, and an assortment of cytochrome P450 monooxygenases (Waxman et al., Biochem J 1281(Pt 3):577-592 (1992); Kaplowitz et al., Biochem J 146(2):351-356 (1975); Tank et al., Biochem Pha~macol 35(24):4563-4569 (1986). The induction of liver enzymes is usually accompanied by liver enlargement, proliferation of smooth endoplasmic reticulum, and tumor promotion (Waxman et al., supra; Rice et al., Carcihogehesis 15(2):395-402 (1994); Nims et al., Ca~cihogenesis 8(1):67-71, (1987). Incidences of cholestasis and hepatocellular injury have also been found (Selim et al., Hepatology 29(5):1347-1351 (1999); Gut et al., Envi~of~
Health Perspect 104(Suppl 6):1211-1218 (1999)). Phenobarbital has been classified as nongenotoxic hepatocarcinogen as it induces liver tumors in rodents but lacks detectable signs of genotoxicity using short term iya vivo or ih vitro assays (Whysner et al., Pharmacol They 71(1-2):153-191 (1996)).

[0066] The effects of phenobarbital on phospholipid metabolism in rat liver have been studied. In one study, phenobarbital, administered intraperitonially (i.p.), was found to cause an increase in the microsomal phosphatidylcholine content. Additionally, levels of glycerophosphate acyltransferase (GAT), phosphatidate cytidylyltransferase (PCT), phosphatidate phosphohydrolase (PPH) and choline phosphotransferase (CPT) were significantly increased (Hoshi et al., Claem Phaf~m Bull 38:3446-3448 (1990)).

[0067] Tacrine (1,2,3,4-tetrahydro-9-aminoacridine-hydrochloride), a strong acetylcholinesterase (AChE) inhibitor, is used in the treatment of mild to moderate cases Alzheimer's dimentias. Alzheimer's patients have synaptic loss, neuronal atrophy and degeneration of cholinergic nuclei in the forebrain, which are associated with reduced oxidative metabolism of glucose and decreased levels of ATP and acetyl CoA.
Administration of AChE inhibitors, such as tacrine, is designed to increase cholinergic activity to combat this loss (Weinstock, Neurodegeneration 4(4):349-356 (1995)). The effect seen in the patients is a reversal of the cognitive and functional decline, but the drug does not appear to change the neurodegenerative process (Goodman & Gilinan's The Pharmacolo igLcal Basis of Therapeutics 9th Ed., Hardman et al. eds., p. 174, McGraw Hill, New York, 1996).

[0068] Hepatotoxicty caused by tacrine is typically reversible, although cases of severe hepatotoxicity have been seen (Blackard et al., J Clin Gastnoentenol 26:57-59 (1998)). The toxicity is characterized by decreased levels of protein synthesis and the release of lactate dehydrogenase, as well as by increased transaminase levels and decreased levels of ATP, glycogen and glutathione. The decrease in protein synthesis may represent a signal leading to cell death (Lagadic-Gossmann et al., Cell Biol Toxicol 14(5):361-373 (1998)).

[0069] Preclinical studies have failed to detect adverse hepatic events, although tacrine displayed cytotoxicity to human hepatoma cell lines and primary rat hepatocytes (Viau et al., Drug Clzem Toxicol 16:227-239 (1993)). While hepatotoxicity has been found in humans, in vivo rat studies have not shown a correlation between tacrine exposure and hepatotoxicity, and the mechanism of action is not completely understood. An in vitno study comparing the reaction of human and rat liver microsomal preparations to tacrine showed that the two species reacted differently to the drug, suggesting that the rat may not be the best model for monitoring tacrine-induced elevations in liver marker enzymes (Woolf et al., Dnug Metab Dispos 21:874-882 (1993)).

[0070] While tacrine does not reveal classic signs of hepatotoxicity in rats, gene expression changes due to tacrine administration can be used to predict that the drug will be a liver toxin in humans. This suggests that toxicogenomics might be able to detect drugs that prove to be toxic in the clinic even when classical but more crude measures in preclinical screening fail to detect toxicity.

[0071] Tamoxifen is a nonsteroidal anti-estrogen used for breast cancer in males and females. Tamoxifen has been associated with changes in liver enzyme levels, disruption of mitochondrial metabolism and, occasionally, with a spectrum of more severe liver abnormalities including fatty liver, cholestasis, hepatic necrosis and NASH
(nonalcoholic steatohepatitis) (Duthie et al., Xenobiotica 25(10):1151-1164 (1995); Cardoso et al., Toxicol Appl Phanrnacol 176(3):145-152 (2001); Pinol et al., Gastnoentenol Hepatol 23(2):57-61 (2000); and Farrell, Semin Liven Dis 22(2):185-194 (2002)). A few of these serious cases included fatalities. A few cases of liver cancer have also been reported.
Additionally, studies in mice and rats have shown that tamoxifen significantly alters the activities of liver enzymes and can induce hepatic carcinomas (Caballero et al., Irat JBioche~a Cell Biol 33(7):681-690 (2001); Guzelian, Semin Oncol 24(1 Suppl 1):S1-105-121 (1997)).

[0072] Tetracycline is a broad spectrum antibiotic whose main mechanism of action is the inhibition of bacterial protein synthesis. Hepatic toxicity, principally steatosis, has been observed in patients receiving high doses of tetracycline. In rats and dogs, exposure to tetracycline has been shown to increase levels of total lipids and triglycerides in liver cells due to inhibition of mitochondrial lipid metabolism and beta-oxidation (Lewis et al., Am J
Dig Dis 12:429-438, (1967); Amacher et al., Fundam Appl Toxicol 40(2):256-263 (1997).

[0073] Valproate (n-dipropylacetic acid, Depakene~) is routinely used to treat several types of epileptic seizures- absence seizures, myoclonic seizures and tonic-clonic seizures. Most other anti-epileptics are effective against only one type. Valproate acts on neurons to inhibit the sustained repetitive firing caused by depolarization of cortical or spinal cord neurons, and a prolonged recovery of inactivated voltage-activated Na channels follows. The drug also acts by reducing the low-threshold Caz+ current and its multiple mechanisms contribute to its use in multiple types of seizures. Although valproate does not affect neuronal responses to GABA, it does increase the activity of the GABA synthetic enzyme, glutamic acid decarboxylase, and it inhibits enzymes that degrade GABA, GABA transaminase and succinic semialdehyde dehydrogenase (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al., eds., pp. 462, 476 and 477, McGraw-Hill, New York, 1996).

[0074] The most common side effects are gastrointestinal symptoms, including anorexia, nausea and vomiting. Effects on the CNS include sedation, ataxia and tremor.
Rash, hair loss, increased appetite and teratogenic effects have also been observed (Briggs et al., A
Reference Guide to Fetal and Neonatal Risk. Drugs in Pre~y and Lactation, 4th ed., p.
869, Williams & Wilkins, Baltimore, 1994). With respect to liver toxicity, valproate produces elevated levels of hepatic enzymes in about 40% of patients, which may be an asymptomatic condition, and elevated levels of hepatic lipids. Fulininant hepatitis, microvesicular steatosis (fatty degeneration), hepatocyte necrosis and hepatic failure can also result. It is believed that hepatoxicity is caused by an accumulation of unsaturated metabolites of valproate, in particular 4-en-valproate, which is structurally similar to two known hepatotoxins, 4-en-pentanoate and methylenecyclopropylacetic acid (Eadie et al., Med Toxicol Adverse Drug Exp 3(2):85-106 (1988)).

[0075] In a study on rats, microvesicular steatosis caused by valproate was found to be accompanied by myeloid bodies, lipid vacuoles and mitochondria) abnormalities (Kesterson et al., Flepatology 4(6):1143-1152 (1984)). Experiments on cultured rat hepatocytes have shown that valproate produces a dose-dependent leakage of lactic acid dehydrogenase and increased amounts of acyl-CoA esters, compounds that interfere with the beta-oxidation of fatty acids (Vance et al., Epilepsia 35(5):1016-1022 (1994)). Administration of valproate to rats has also been shown to cause enhanced excretion of dicarboxylic acids, a sign of impaired mitochondria) beta-oxidation. Other metabolic effects include hypoglycemia, hyperammonemia, decreased levels of beta-hydroxybutyrate and carnitine and decreased activities of acyl-CoA dehydrogenases, enzymes involved in fatty acid oxidation. mRNA
levels of genes involved in fatty acid oxidation, however, such as the short-, medium- and long-chain acyl-CoA dehydrogenases, were found to have increased (Kibayashi et al., Pediaty~ Ifzt 41(1):52-60 (1999)).

[0076] Wy-14643, a tumor-inducing compound that acts in the liver, has been used to study the genetic profile of cells during the various stages of carcinogenic development, with a view toward developing strategies for detecting, diagnosing and treating cancers (Rockett et al., Toxicology 144(1-3):13-29 (2000)). In contrast to other carcinogens, Wy-14643 does not mutate DNA directly. Instead, it acts on the peroxisome proliferator activated receptor-alpha (PPARalpha), as well as on other signaling pathways that regulate growth (Johnson et al., J
Steroid Biochem Mol Biol 77(1):59-71 (2001)). The effect is elevated and sustained cell replication, accompanied by a decrease in apoptosis (Rusyn et al., Ca~ciraogehesis 21(12):2141-2145 (2000)). These authors (Rusyn et al.) noted an increase in the expression of enzymes that repair DNA by base excision, but no increased expression of enzymes that do not repair oxidative damage to DNA. In a study on rodents, Johnson et al.
noted that Wy-14643 inhibited liver-X-receptor-mediated transcription in a dose-dependent manner, as well as de novo sterol synthesis.

[0077] In experiments with mouse liver cells (Peters et al., CaYCinoge~esis 19(11):1989-1994 (1998)), exposure to Wy-14643 produced increased levels of acyl CoA
oxidase and proteins involved in cell proliferation: CDK-1, 2 and 4, PCNA and c-myc.
Elevated levels may be caused by accelerated transcription that is mediated directly or indirectly by PPARalpha. It is likely that the carcinogenic properties of peroxisome proliferators are due to the PPARalpha-dependent changes in levels of cell cycle regulatory proteins.

[0078] Another study on rodents (Keller et al., Bioclaim Biophys Acta 1102(2):237-244 (1992)) showed that Wy-14643 was capable of uncoupling oxidative phosphorylation in rat liver mitochondria. Rates of urea synthesis from ammonia and bile flow, two energy-dependent processes, were reduced, indicating that the energy supply for these processes was disrupted as a result of cellular exposure to the toxin. Wy-14643 has also been shown to activate nuclear factor kappaB, NADPH oxidase and superoxide production in Kupffer cells (Rusyn et al., Cancer Res 60(17):4798-4803 (2000)). NADPH oxidase is known to induce mitogens, which cause proliferation of liver cells.
Toxicity Identification, Prediction and Modeling [0079] The genes and gene expression information, as well as the portfolios and subsets of the genes provided in Tables 1-SXX may be used to predict or identify at least one toxic effect, including the hepatotoxicity of a test or unknown compound. As used, herein, at least one toxic effect includes, but is not limited to, a detrimental change in the physiological status of a cell or organism. The response may be, but is not required to be, associated with a particular pathology, such as tissue necrosis. Accordingly, the toxic effect includes effects at the molecular and cellular level. Hepatotoxicity is an effect as used herein and includes, but is not limited to, genotoxic and non-genotoxic carcinogenesis, cholestasis, hepatitis, liver enlargement, inflammation, necrosis, necrosis with steatosis, peroxisome proliferation, steatosis, and steatosis with hepatitis. In addition, hepatoxicity includes the effect of direct-acting agents (such as metformin, rosiglitazone and dexamethasone), which are pharmaceuticals that act in the liver, but are not considered toxic to the liver. Exposure to these agents results in altered gene expression profiles. As used herein, a gene expression profile comprises any quantitative representation of the expression of at least one mRNA
species in a cell sample or population and includes profiles made by various methods such as differential display, PCR, hybridization analysis, etc.

[0080] In general, assays to predict the toxicity or hepatotoxicity of a test agent (or compound or multi-component composition) comprise the steps of exposing a cell population to the test compound, assaying or measuring the level of relative or absolute gene expression of one or more of the genes in Tables SA-SXX and comparing the identified expression levels) to the expression levels disclosed in the Tables and databases) disclosed herein.
Assays may include the measurement of the expression levels of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 50, 75, 100, 200, 300, 400, 500, 1000 or more genes from Tables SA-SXX

to create multi-gene expression profiles. In some embodiments, all or substantially all of the genes of Tables SA-5XX may be used to predict toxicity, etc. In other embodiments, the genes or subsets of the genes for each individual toxin model, for instance, the genes of Table SA, may be used. An "adequate amount" of the data of Tables SA-SXX refers to an amount of information that allows toxicity identification or prediction (typically 2 or more genes).
"Substantially" or nearly all of the data in the tables refers to at least about 80% of the data for an individual model.

[0081] In the methods of the invention, the gene expression level for a gene or genes induced by the test agent, compound or compositions may be comparable to the levels found in the Tables or databases disclosed herein if the expression level varies within a factor of about 2, about 1.5 or about 1.0 fold. In some cases, the expression levels are comparable if the agent induces a change in the expression of a gene in the same direction (e.g., up or down) as a reference toxin. "Comparing" may comprise determinng the relationship of the database information to the sample gene expression profile with or without application of an algorithm to the results, differences or similarities between the two.

[0082] The cell population that is exposed to the test agent, compound or composition may be exposed iyz vitro or ih vivo. For instance, cultured or freshly isolated hepatocytes, in particular rat hepatocytes, may be exposed to the agent under standard laboratory and cell culture conditions. In another assay format, in vivo exposure may be accomplished by administration of the agent to a living animal, for instance a laboratory rat.

[0083] Procedures for designing and conducting toxicity tests in in vitro and ih vivo systems are well known, and are described in many texts on the subject, such as Loomis et al., Loomis's Esstentials of Toxicology, 4th Ed., Academic Press, New York, 1996;
Echobichon, The Basics of Toxici Testing, CRC Press, Boca Raton, 1992; Frazier, editor, Ih Yitro Toxici Testing, Marcel Dekker, New York, 1992; and the like.

[0084] In in vitro toxicity testing, two groups of test organisms are usually employed: One group serves as a control and the other group receives the test compound in a single dose (for acute toxicity tests) or a regimen of doses (for prolonged or chronic toxicity tests). Because, in some cases, the extraction of tissue as called for in the methods of the invention requires sacrificing the test animal, both the control group and the group receiving compound must be large enough to permit removal of animals for sampling tissues, if it is desired to observe the dynamics of gene expression through the duration of an experiment.

[0085] In setting up a toxicity study, extensive guidance is provided iil the literature for selecting the appropriate test organism for the compound being tested, route of administration. dose ranges, and the like. Water or physiological saline (0.9%
NaCl in water) is the solute of choice for the test compound since these solvents permit administration by a variety of routes. When this is not possible because of solubility limitations, vegetable oils such as corn oil or organic solvents such as propylene glycol may be used.

[0086] Regardless of the route of achninistration, the volume required to administer a given dose is limited by the size of the animal that is used. It is desirable to keep the volume of each dose uniform within and between groups of animals. When rats or mice are used, the volume administered by the oral route generally should not exceed about 0.005 ml per gram of animal. Even when aqueous or physiological saline solutions are used for parenteral inj ection the volumes that are tolerated are limited, although such solutions are ordinarily thought of as being innocuous. The intravenous LDso of distilled water in the mouse is approximately 0.044 ml per gram and that of isotonic saline is 0.068 ml per gram of mouse.
In some instances, the route of administration to the test animal should be the same as, or as similar as possible to, the route of administration of the compound to man for therapeutic purposes.

[0087] When a compound is to be administered by inhalation, special techniques for generating test atmospheres are necessary. The methods usually involve aerosolization or nebulization of fluids containing the compound. If the agent to be tested is a fluid that has an appreciable vapor pressure, it may be administered by passing air through the solution under controlled temperature conditions. Under these conditions, dose is estimated from the volume of air inhaled per unit time, the temperature of the solution, and the vapor pressure of the agent involved. Gases are metered from reservoirs. When particles of a solution are to be administered, unless the particle size is less than about 2 ~,m the particles will not reach the terminal alveolar sacs in the lungs. A variety of apparatuses and chambers are available to perform studies for detecting effects of irritant or other toxic endpoints when they are administered by inhalation. The preferred method of administering an agent to animals is via the oral route, either by intubation or by incorporating the agent in the feed.

[0088] When the agent is exposed to cells in vitYO or in cell culture, the cell population to be exposed to the agent may be divided into two or more subpopulations, for instance, by dividing the population into two or more identical aliquots. In some preferred embodiments of the methods of the invention, the cells to be exposed to the agent are derived from liver tissue. For instance, cultured or freshly isolated rat hepatocytes may be used.

[0089] The methods of the invention may be used generally to predict at least one toxic response, and, as described in the Examples, may be used to predict the likelihood that a compound or test agent will induce various specific liver pathologies, such as genotoxic and non-genotoxic carcinogenesis, cholestasis, direct action toxicity, hepatitis, liver enlargement, inflammation, necrosis, necrosis with steatosis, peroxisome proliferation, steatosis, steatosis with hepatitis, or other pathologies associated with at least one of the toxins herein described.
The methods of the invention may also be used to determine the similarity of a toxic response to one or more individual compounds. In addition, the methods of the invention may be used to predict or elucidate the potential cellular pathways influenced, induced or modulated by the compound or test agent due to the similarity of the expression profile compared to the profile induced by a known toxin (see Tables SA-SG, SJ, SK, SM-SS, SU-SY, SAA-SEE, SHH-SJJ, SMM, 500, SPP and SSS-SXX). Further, the link between a specific liver pathology that is the result of exposure to a toxin and a specific gene expression profile allows for distinction of the genes in Tables SA-SXX as markers of liver toxicity.
Diagnostic Uses for the Toxicity Markers [0090] As described above, the genes and gene expression information or portfolios of the genes with their expression information as provided in Tables SA-SXX may be used as diagnostic markers for the prediction or identification of the physiological state of tissue or cell sample that has been exposed to a compound or to identify or predict the toxic effects of a compound or agent. For instance, a tissue sample such as a sample of peripheral blood cells or some other easily obtainable tissue sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables SA-5XX may be compared to the expression levels found in tissues or cells exposed to the toxins described herein. These methods may result in the diagnosis of a physiological state in the cell or may be used to identify the potential toxicity of a compound, for instance a new or unknown compound or agent. The comparison of expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases as described below.

[0091] In another format, the levels of a genes) of Tables SA-SXX, its encoded protein(s), or any metabolite produced by the encoded protein may be monitored or detected in a sample, such as a bodily tissue or fluid sample to identify or diagnose a physiological state of an organism. Such samples may include any tissue or fluid sample, including urine, blood and easily obtainable cells such as peripheral lymphocytes.
Use of the Markers for Monitoring Toxicity Progression [0092] As described above, the genes and gene expression information provided in Tables SA-SXX may also be used as markers for the monitoring of toxicity progression, such as that found after initial exposure to a drug, drug candidate, toxin, pollutant, etc.
For instance, a tissue or cell sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables SA-SXX may be compared to the expression levels found in tissue or cells exposed to the hepatotoxins described herein. The comparison of the expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases.
Use of the Toxicity Markers for Drug Screening [0093] According to the present invention, the genes identified in Tables SA-SXX may be used as markers or drug targets to evaluate the effects of a candidate drug, chemical compound or other agent on a cell or tissue sample. The genes may also be used as drug targets to screen for agents that modulate their expression and/or activity.
In various formats, a candidate drug or agent can be screened for the ability to simulate the transcription or expression of a given marker or markers or to down-regulate or counteract the transcription or expression of a marker or markers. According to the present invention, one can also compare the specificity of a drug's effects by looking at the number of markers which the drug induces and comparing them. More specific drugs will have less transcriptional targets.
Similar sets of markers identified for two drugs may indicate a similarity of effects. As used herein, an agent is said to modulate the expression of a nucleic acid of the invention if it is capable of up- or down-regulating expression of the nucleic acid in a cell.

[0094] Assays to monitor the expression of a marker or markers as defined in Tables SA-SXX may utilize any available means of monitoring for changes in the expression level of the nucleic acids of the invention.

[0095] ~ In one assay format, microarrays containing probes to one, two or more genes from Tables SA-SXX may be used to directly monitor or detect changes in gene expression in the treated or exposed cell. Cell lines, tissues or other samples are first exposed to a test agent and in some instances, a known toxin, and the detected expression levels of one or more, or _27_ preferably 2 or more of the genes of Tables SA-SXX are compared to the expression levels of those same genes exposed to a known toxin alone. Compounds that modulate the expression patterns of the known toxins) would be expected to modulate potential toxic physiological effects ih vivo. The genes in Tables SA-SXX are particularly appropriate marks in these assays as they are differentially expressed in cells upon exposure to a known hepatotoxin.

[0096] In another format, cell lines that contain reporter gene fusions between the open reading frame and/or the transcriptional regulatory regions of a gene in Tables SA-SXX and any assayable fusion partner may be prepared. Numerous assayable fusion partners are known and readily available including the firefly luciferase gene and the gene encoding chloramphenicol acetyltransferase (Alam et al., Ahal Biochem 188:245-254 (1990)). Cell lines containing the reporter gene fusions are then exposed to the agent to be tested under appropriate conditions and time. Differential expression of the reporter gene between samples exposed to the agent and control samples identifies agents which modulate the expression of the nucleic acid.

[0097] Additional assay formats may be used to monitor the ability of the agent to modulate the expression of a gene identified in Tables SA-SXX. For instance, as described above, mRNA expression may be monitored directly by hybridization of probes to the nucleic acids of the invention. Cell lines are exposed to the agent to be tested under appropriate conditions and time and total RNA or mRNA is isolated by standard procedures such those disclosed in Sambrook et al. (Molecular Cloning: A Laboratory Manual, 3d Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2001).

[0098] In another assay format, cells or cell lines are first identified which express the gene products of the invention physiologically. Cell and/or cell lines so identified would be expected to comprise the necessary cellular machinery such that the fidelity of modulation of the transcriptional apparatus is maintained with regard to exogenous contact of agent with appropriate surface transduction mechanisms and/or the cytosolic cascades.
Further, such cells or cell lines may be transduced or transfected with an expression vehicle (e.g., a plasmid or viral vector) construct comprising an operable non-translated 5'-promoter containing end of the structural gene encoding the gene products of Tables SA-SXX fused to one or more antigenic fragments or other detectable markers, which are peculiar to the instant gene products, wherein said fragments are under the transcriptional control of said promoter and are expressed as polypeptides whose molecular weight can be distinguished from the naturally occurring polypeptides or may further comprise an immunologically distinct or other detectable tag. Such a process is well known in the art (see Sambrook et al., supra).

[0099] Cells or cell lines transduced or transfected as outlined above are then contacted with agents under appropriate conditions; for example, the agent comprises a pharmaceutically acceptable excipient and is contacted with cells comprised in an aqueous physiological buffer such as phosphate buffered saline (PBS) at physiological pH, Eagles balanced salt solution (BSS) at physiological pH, PBS or BSS comprising serum or conditioned media comprising PBS or BSS and/or serum incubated at 37°C.
Said conditions may be modulated as deemed necessary by one of skill in the art. Subsequent to contacting the cells with the agent, said cells are disrupted and the polypeptides of the lysate are fractionated such that a polypeptide fraction is pooled and contacted with an antibody to be further processed by immunological assay (e.g., ELISA, immunoprecipitation or Western blot). The pool of proteins isolated from the agent-contacted sample is then compared with the control samples (no exposure and exposure to a known toxin) where only the excipient is contacted with the cells and an increase or decrease in the immunologically generated signal from the agent-contacted sample compared to the control is used to distinguish the effectiveness and/or toxic effects of the agent.

[00100] Another embodiment of the present invention provides methods for identifying agents that modulate at least one activity of a proteins) encoded by the genes in Tables SA-SXX. Such methods or assays may utilize any means of monitoring or detecting the desired activity.

[00101] In one format, the relative amounts of a protein (Tables SA-SXX) between a cell population that has been exposed to the agent to be tested compared to an un-exposed control cell population and a cell population exposed to a known toxin may be assayed.
In this format, probes such as specific antibodies are used to monitor the differential expression of the protein in the different cell populations. Cell lines or populations are exposed to the agent to be tested under appropriate conditions and time. Cellular lysates may be prepared from the exposed cell line or population and a control, unexposed cell line or population. The cellular lysates are then analyzed with the probe, such as a specific antibody.

[00102] Agents that are assayed in the above methods can be randomly selected or rationally selected or designed. As used herein, an agent is said to be randomly selected when the agent is chosen randomly without considering the specific sequences involved in the association of the a protein of the invention alone or with its associated substrates, binding partners, etc. An example of randomly selected agents is the use a chemical library or a peptide combinatorial library, or a growth broth of an organism.

[00103] As used herein, an agent is said to be rationally selected or designed when the agent is chosen on a nonrandom basis which takes into account the sequence of the target site and/or its conformation in connection with the agent's action. Agents can be rationally selected or rationally designed by utilizing the peptide sequences that make up these sites.
For example, a rationally selected peptide agent can be a peptide whose amino acid sequence is identical to or a derivative of any functional consensus site.

(00104] The agents of the present invention can be, as examples, peptides, small molecules, vitamin derivatives, as well as carbohydrates. Dominant negative proteins, DNAs encoding these proteins, antibodies to these proteins, peptide fragments of these proteins or mimics of these proteins may be introduced into cells to affect function. "Mimic" used herein refers to the modification of a region or several regions of a peptide molecule to provide a structure chemically different from the parent peptide but topographically and functionally similar to the parent peptide (see G.A. Grant in: Molecular Biolo~;y and Biotechnolo~y, Meyers, ed., pp. 659-664, VCH Publishers, New York, 1995). A skilled artisan can readily recognize that there is no limit as to the structural nature of the agents of the present invention.
Nucleic Acid Assay Formats [00105] The genes identified as being differentially expressed upon exposure to a known hepatotoxin (Tables SA-SXX) may be used in a variety of nucleic acid detection assays to detect or quantititate the expression level of a gene or multiple genes in a given sample. The genes described in Tables SA-SXX may also be used in combination with one or more additional genes whose differential expression is associate with toxicity in a cell or tissue. In preferred embodiments, the genes in Tables SA-SXX may be combined with one or more of the genes described in prior and related applications 60/353,171; 60/363,534;
60/371,135;
60/371,134; 60/370,248; 60/371,150; 60/371,413; 60/373,601; 60/374,139;
60/394,253;
60/378,652; 60/373,602; 60/378,653; 60/378,665; 60/378,370; 60/394,230;
60/407,688;
09/917,800; 10/060,087; PCT/LJS03/ , entitled "Molecular Hepatotoxicology Modeling," filed January 31, 2003; and PCT/USO1/23872, all of which are incorporated by reference on page 1 of this application.

[00106] Any assay format to detect gene expression may be used. For example, traditional Northern blotting, dot or slot blot, nuclease protection, primer directed amplification, RT-PCR, semi- or quantitative PCR, branched-chain DNA and differential display methods may be used for detecting gene expression levels. Those methods are useful for some embodiments of the invention. In cases where smaller numbers of genes are detected, amplification based assays may be most efficient. Methods and assays of the invention, however, may be most efficiently designed with hybridization-based methods for detecting the expression of a large number of genes.

[00107] Any hybridization assay format may be used, including solution-based and solid support-based assay formats. Solid supports containing oligonucleotide probes for differentially expressed genes of the invention can be filters, polyvinyl chloride dishes, particles, beads, microparticles or silicon or glass based chips, etc. Such chips, wafers and hybridization methods are widely available, for example, those disclosed by Beattie (WO
95/11755).

[00108] Any solid surface to which oligonucleotides can be bound, either directly or indirectly, either covalently or non-covalently, can be used. A preferred solid support is a high density array or DNA chip. These contain a particular oligonucleotide probe in a predetermined location on the array. Each predetermined location may contain more than one molecule of the probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There may be, for example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 or more of such features on a single solid support. The solid support, or the area within which the probes are attached may be on the order of about a square centimeter. Probes corresponding to the genes of Tables SA-SXX or from the related applications described above may be attached to single or multiple solid support structures, e.g., the probes may be attached to a single chip or to multiple chips to comprise a chip set.

(00109] Oligonucleotide probe arrays for expression monitoring can be made and used according to any techniques known in the art (see for example, Lockhart et al., Nat Biotech~.ol 14:1675-1680 (1996); McGall et al., Proc Nat Acad Sci USA 93:13555-(1996)). Such probe arrays may contain at least two or more oligonucleotides that are complementary to or hybridize to two or more of the genes described in Tables SA-SXX. For instance, such arrays may contain oligonucleotides that are complementary or hybridize to at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 50, 70, 100 or more the genes described herein.
Preferred arrays contain all or nearly all of the genes listed in Tables SA-SXX, "or individually, the gene sets of Tables SA-SXX. In a preferred embodiment, arrays are constructed that contain oligonucleotides to detect all or nearly all of the genes in any one of or all of Tables SA-SXX on a single solid support substrate, such as a chip.

[00110] The sequences of the expression marker genes of Tables SA-SXX are in the public databases. Table 1 provides the GenBank Accession Number, SEQ m NO: and GLGC m No. (Gene Logic reference no.) for each of the sequences (see www.hcbi.hlm.~cih.gov~, while Table 2 provides identification information for the human homologues of the genes of Tables 1 and SA-SXX. Table 3 identifies the metabolic pathways in which the genes of Tables 1 and SA-SXX are believed to function. Table 4 defines the model codes used in Tables 1, 2, 3 and SA-SXX. The sequences of the genes in GenBank are expressly herein incorporated by reference in their entirety as of the filing date of this application, as are related sequences, for instance, sequences from the same gene of different lengths, variant sequences, polymorphic sequences, genomic sequences of the genes and related sequences from different species, including the human counterparts, where appropriate. These sequences may be used in the methods of the invention or may be used to produce the probes and arrays of the invention.
In some embodiments, the genes in Tables SA-SXX that correspond to the genes or fragments previously associated with a toxic response may be excluded from the Tables.

[00111] As described above, in addition to the sequences of the GenBank Accession Nos.
and GLGC m Nos. disclosed in the Tables SA-SXX, sequences such as naturally occurring variant or polymorphic sequences may be used in the methods and compositions of the invention. For instance, expression levels of various allelic or homologous forms of a gene disclosed in the Tables SA-SXX may be assayed. Any and all nucleotide variations that do not alter the functional activity of a gene listed in the Tables SA-SXX , including all naturally occurring allelic variants of the genes herein disclosed, may be used in the methods and to make the compositions (e.g., arrays) of the invention.

[00112] Probes based on the sequences of the genes described above may be prepared by any commonly available method. Oligonucleotide probes for screening or assaying a tissue or cell sample are preferably of sufficient length to specifically hybridize only to appropriate, complementary genes or transcripts. Typically the oligonucleotide probes will be at least about 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some cases, longer probes of at least 30, 40, or 50 nucleotides will be desirable.

[00113] As used herein, oligonucleotide sequences that are complementary to one or more of the genes described in Tables SA-SXX refer to oligonucleotides that are capable of hybridizing under stringent conditions to at least part of the nucleotide sequences of said genes. Such hybridizable oligonucleotides will typically exhibit at least about 75% sequence identity at the nucleotide level to said genes, preferably about 80% or 85%
sequence identity or more preferably about 90% or 95% or more sequence identity to said genes.

[00114] "Bind(s) substantially" refers to complementary hybridization between a probe nucleic acid and a target nucleic acid and embraces minor mismatches that can be accommodated by reducing the stringency of the hybridization media to achieve the desired detection of the target polynucleotide sequence.

[00115] The terms "background" or "background signal intensity" refer to hybridization signals resulting from non-specific binding, or other interactions, between the labeled target nucleic acids and components of the oligonucleotide array (e.g., the oligonucleotide probes, control probes, the array substrate, etc.). Baclcground signals may also be produced by intrinsic fluorescence of the array components themselves. A single background signal can be calculated for the entire array, or a different background signal may be calculated for each target nucleic acid. In a preferred embodiment, background is calculated as the average hybridization signal intensity for the lowest 5% to 10% of the probes in the array, or, where a different background signal is calculated for each target gene, for the lowest 5% to 10% of the probes for each gene. Of course, one of skill in the art will appreciate that where the probes to a particular gene hybridize well and thus appear to be specifically binding to a target sequence, they should not be used in a background signal calculation.
Alternatively, background may be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g.
probes directed to nucleic acids of the opposite sense or to genes not found in the sample such as bacterial genes where the sample is mammalian nucleic acids).
Background can also be calculated as the average signal intensity produced by regions of the array that lack any .
probes at all.

[00116] The phrase "hybridizing specifically to" refers to the binding, duplexing, or hybridizing of a molecule substantially to or only to a particular nucleotide sequence or sequences under stringent conditions when that sequence is present in a complex mixture (e.g., total cellular) DNA or RNA.

[00117] Assays and methods of the invention may utilize available formats to simultaneously screen at least about 100, preferably about 1000, more preferably about 10,000 and most preferably about 1,000,000 different nucleic acid hybridizations.

[00118] As used herein a "probe" is defined as a nucleic acid, capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i. e., A, G, U, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in probes may be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.

[00119] The term "perfect match probe" refers to a probe that has a sequence that is perfectly complementary to a particular target sequence. The test probe is typically perfectly complementary to a portion (subsequence) of the target sequence. The perfect match (PM) probe can be a "test probe", a "normalization~control" probe, an expression level control probe and the like. A perfect match control or perfect match probe is, however, distinguished from a "mismatch control" or "mismatch probe."

[00120] The terms "mismatch control" or "mismatch probe" refer to a probe whose sequence is deliberately selected not to be perfectly complementary to a particular target sequence. For each mismatch (MM) control in a high-density array there typically exists a corresponding perfect match (PM) probe that is perfectly complementary to the same particular target sequence. The mismatch may comprise one or more bases.

[00121] While the mismatch(s) may be located anywhere in the mismatch probe, terminal mismatches are less desirable as a terminal mismatch is less likely to prevent hybridization of the target sequence. In a particularly preferred embodiment, the mismatch is located at or near the center of the probe such that the mismatch is most likely to destabilize the duplex with the target sequence under the test hybridization conditions.

[00122] The term "stringent conditions" refers to conditions under which a probe will hybridize to its target subsequence, but with only insubstantial hybridization to other sequences or to other sequences such that the difference may be identified.
Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. Generally, stringent conditions are selected to be about 5°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH.

[00123] Typically, stringent conditions will be those in which the salt concentration is at least about 0.01 to 1.0 M Na~ ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°C for short probes (e.g., 10 to 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.

[00124] The "percentage of sequence identity" or "sequence identity" is determined by comparing two optimally aligned sequences or subsequences over a comparison window or span, wherein the portion of the polynucleotide sequence in the comparison window may optionally comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences.
The percentage is calculated by determining the number of positions at which the identical submit (e.g. nucleic acid base or amino acid residue) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Percentage sequence identity when calculated using the programs GAP or BESTFIT (see below) is calculated using default gap weights.
Probe design [00125] One of skill in the art will appreciate that an enormous number of array designs are suitable for the practice of this invention. The high density array will typically include a number of test probes that specifically hybridize to the sequences of interest. Probes may be produced from any region of the genes identified in the Tables and the attached representative sequence listing. In instances where the gene reference in the Tables is an EST, probes may be designed from that sequence or from other regions of the corresponding full-length transcript that may be available in any of the sequence databases, such as those herein described. See WO 99/32660 for methods of producing probes for a given gene or genes. In addition, any available software may be used to produce specific probe sequences, including, for instance, software available from Molecular Biology Insights, Olympus Optical Co. and Biosoft International. In a preferred embodiment, the array will also include one or more control probes.

[00126] High density array chips of the invention include "test probes." Test probes may be oligonucleotides that range from about 5 to about 500, or about 7 to about 50 nucleotides, more preferably from about 10 to about 40 nucleotides and most preferably from about 15 to about 35 nucleotides in length. In other particularly preferred embodiments, the probes are 20 or 25 nucleotides in length. In another preferred embodiment, test probes are double or single strand DNA sequences. DNA sequences are isolated or cloned from natural sources or amplified from natural sources using native nucleic acid as templates. These probes have sequences complementary to particular subsequences of the genes whose expression they are designed to detect. Thus, the test probes are capable of specifically hybridizing to the target nucleic acid they are to detect.

[00127] In addition to test probes that bind the target nucleic acids) of interest, the high density array can contain a number of control probes. The control probes may fall into three categories referred to herein as 1) normalization controls; 2) expression level controls; and 3) mismatch controls.

[00128] Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, "reading" efficiency and other factors that may cause the signal of a perfect hybridization to vary between arrays. In a preferred embodiment, signals (e.g., fluorescence intensity) read from all other probes in the array are divided by the signal (e.g., fluorescence intensity) from the control probes thereby normalizing the measurements.

[00129] Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length.
Preferred normalization probes are selected to reflect the average length of the other probes present in the axray, however, they can be selected to cover a range of lengths. The normalization controls) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few probes are used and they axe selected such that they hybridize well (i.e., no secondary structure) and do not match any target-specific probes.

[00130] Expression level controls axe probes that hybridize specifically with constitutively expressed genes in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typically expression level control probes have sequences complementary to subsequences of constitutively expressed "housekeeping genes" including, but not limited to the (3-actin gene, the glyceraldehyde-3-phosphate dehydrogenase (GADPH) gene, the transferrin receptor gene and the like.

[00131] Mismatch controls may also be provided for the probes to the target genes, for expression level controls or for normalization controls. Mismatch controls are oligonucleotide probes or other nucleic acid probes identical to their corresponding test or control probes except for the presence of one or more mismatched bases. A
mismatched base is a base selected so that it is not complementary to the corresponding base in the target sequence to which the probe would otherwise specifically hybridize. One or more mismatches are selected such that under appropriate hybridization conditions (e.g., stringent conditions) the test or control probe would be expected to hybridize with its target sequence, but the mismatch probe would not hybridize (or would hybridize to a significantly lesser extent) Preferred mismatch probes contain a central mismatch. Thus, for example, where a probe is a 20 mer, a corresponding mismatch probe will have the identical sequence except for a single base mismatch (e.g., substituting a G, a C or a T for an A) at any of positions 6 through 14 (the central mismatch).

[00132] Mismatch probes thus provide a control for non-specific binding or cross hybridization to a nucleic acid in the sample other than the target to which the probe is directed. For example, if the target is present the perfect match probes should be consistently brighter than the mismatch probes. In addition, if all central mismatches are present, the mismatch probes can be used to detect a mutation, for instance, a mutation of a gene in the accompanying Tables SA-SXX. The difference in intensity between the perfect match and the mismatch probe provides a good measure of the concentration of the hybridized material.
Nucleic Acid Samples [00133] Cell or tissue samples may be exposed to the test agent ih vitro or ih vivo. When cultured cells or tissues are used, appropriate mammalian liver extracts may also be added with the test agent to evaluate agents that may require biotransformation to exlubit toxicity.
In a preferred format, primary isolates of animal or human hepatocytes which already express the appropriate complement of drug-metabolizing enzymes may be exposed to the test agent without the addition of mammalian liver extracts.

[00134] The genes which are assayed according to the present invention are typically in the form of mRNA or reverse transcribed mRNA. The genes may be cloned or not. The genes may be amplified or not. The cloning and/or amplification do not appear to bias the representation of genes within a population. In some assays, it may be preferable, however, to use polyA+ RNA as a source, as it can be used with less processing steps.

[00135] As is apparent to one of ordinary skill in the art, nucleic acid samples used in the methods and assays of the invention may be prepared by any available method or process.
Methods of isolating total mRNA are well known to those of skill in the art.
For example, methods of isolation and purification of nucleic acids are described in detail in Chapter 3 of Laboratory Technicmes in Biochemistry and Molecular Biolo~y. Vol. 24, Hybridization With Nucleic Acid Probes: Theory and Nucleic Acid Probes, P. Tijssen, Ed., Elsevier Press, New York, 1993. Such samples include RNA samples, but also include cDNA
synthesized from a mRNA sample isolated from a cell or tissue of interest. Such samples also include DNA
amplified from the cDNA, and RNA transcribed from the amplified DNA. One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates before homogenates are used.

[00136] Biological samples may be of any biological tissue or fluid or cells from any organism as well as cells raised in vitro, such as cell lines and tissue culture cells. Frequently the sample will be a tissue or cell sample that has been exposed to a compound, agent, drug, pharmaceutical composition, potential environmental pollutant or other composition. In some formats, the sample will be a "clinical sample" which is a sample derived from a patient. Typical clinical samples include, but are not limited to, sputum, blood, blood-cells (e.g., white cells), tissue or fine needle biopsy samples, urine, peritoneal fluid, and pleural fluid, or cells therefrom.

[00137] Biological samples may also include sections of tissues, such as frozen sections or formalin fixed sections taken for histological purposes.
Forming High Density Arrays [00138] Methods of forming high density arrays of oligonucleotides with a minimal number of synthetic steps axe known. The oligonucleotide analogue array can be synthesized on a single or on multiple solid substrates by a variety of methods, including, but not limited to, light-directed chemical coupling, and mechanically directed coupling (see Pirrung, U.S.
Patent No. 5,143,854).

[00139] In brief, the light-directed combinatorial synthesis of oligonucleotide arrays on a glass surface proceeds using automated phosphoramidite chemistry and chip masking techniques. In one specific implementation, a glass surface is derivatized with a silane reagent containing a functional group, e.g., a hydroxyl or amine group blocked by a photolabile protecting group. Photolysis through a photolithogaphic mask is used selectively to expose functional groups which are then ready to react with incoming 5' photoprotected nucleoside phosphoramidites. The phosphoramidites react only with those sites which are illuminated (and thus exposed by removal of the photolabile blocking group).
Thus, the phosphoramidites only add to those areas selectively exposed from the preceding step. These steps are repeated until the desired array of sequences have been synthesized on the solid surface. Combinatorial synthesis of different oligonucleotide analogues at different locations on the array is determined by the pattern of illumination during synthesis and the order of addition of coupling reagents.

[00140] In addition to the foregoing, additional methods which can be used to generate an array of oligonucleotides on a single substrate are described in PCT
Publication Nos. WO
93/09668 and WO 01/23614. High density nucleic acid arrays can also be fabricated by depositing pre-made or natural nucleic acids in predetermined positions.
Synthesized or natural nucleic acids are deposited on specific locations of a substrate by light directed targeting and oligonucleotide directed targeting. Another embodiment uses a dispenser that moves from region to region to deposit nucleic acids in specific spots.
Hybridization [00141] Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing. See WO 99132660. The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids. Under low stringency conditions (e.g., low temperature andlor high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA, or RNA:DNA) will form even where the annealed sequences are not perfectly complementary.
Thus, specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization tolerates fewer mismatches. One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency.

[00142] In a preferred embodiment, hybridization is performed at low stringency, in this case in 6X SSPET at 37°C (0.005% Triton X-100), to ensure hybridization and then subsequent washes are performed at higher stringency (e.g., I X SSPET at 37°C) to eliminate mismatched hybrid duplexes. Successive washes may be performed at increasingly higher stringency (e.g., down to as low as 0.25 X SSPET at 37°C to 50°C) until a desired level of hybridization specificity is obtained. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level control, normalization control, mismatch controls, etc.).

[00143] In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in a preferred embodiment, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. Thus, in a preferred embodiment, the hybridized array may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.
Signal Detection [00144] The hybridized nucleic acids are typically detected by detecting one or more labels attached to the sample nucleic acids. The labels may be incorporated by any of a number of means well known to those of skill in the art. See WO 99/32660.
Databases [00145] The present invention includes relational databases containing sequence information, for instance, for the genes of Tables SA-SXX, as well as gene expression information from tissue or cells exposed to various standard toxins, such as those herein described (see Tables SA-SXX). Databases may also contain information associated with a given sequence or tissue sample such as descriptive information about the gene associated with the sequence information (see Tables 1, 2 and 3), or descriptive information concerning the clinical status of the tissue sample, or the animal from which the sample was derived.
The database may be designed to include different parts, for instance a sequence database and a gene expression database. Methods for the configuration and construction of such databases and computer-readable media to which such databases are saved are widely available, for instance, see U.S. Patent No. 5,953,727, which is herein incorporated by reference in its entirety.

[00146] The databases of the invention may be linked to an outside or external database such as GenBank (www.ncbi.nlna.nih.govlentYez.index.latml); I~EGG (www.genorne.ad jplkegg);
SPAD (www.grt.kyushu-u.ac jplspadlindex.latml); HUGO
(www.gene.ucl.ac.uklhugo); Swiss-Prot (www. expasy. ch.sprot); Prosite (www. expasy. chltoolslscyapsitl. html);
OMIM
(www.ncbi.nlnZ.nih.govlomina); LocusLink (www.ncbi.nlm.nih.govlLocusLink~;
RefSeq (www.ncbi.rZlm.nih.govlLocusLinklnefseq.html) and GDB (www.gdb.org). In apreferred embodiment, as described in Tables 1-3, the external database is GenBank and the associated databases maintained by the National Center for Biotechnology Information (NCBI) (www. ~ccbi. nlm. hih.gov).

[00147] Any appropriate computer platform, user interface, etc. may be used to perform the necessary comparisons between sequence information, gene expression information and any other information in the database or information provided as an input. For example, a large number of computer workstations are available from a variety of manufacturers, such has those available from Silicon Graphics. Client/server environments, database servers and networks are also widely available and appropriate platforms for the databases of the invention.

[00148] The databases of the invention may be used to produce, among other things, electronic Northerns that allow the user to determine the cell type or tissue in which a given gene is expressed and to allow determination of the abundance or expression level of a given gene in a particular tissue or cell.

[00149] The databases of the invention may also be used to present information identifying the expression level in a tissue or cell of a set of genes comprising one or more of the genes in Tables SA-5~, comprising the step of comparing the expression level of at least one gene in Tables SA-5~ in a cell or tissue exposed to a test agent to the level of expression of the gene in the database. Such methods may be used to predict the toxic potential of a given compound by comparing the level of expression of a gene or genes in Tables SA-SX~i from a tissue or cell sample exposed to the test agent to the expression levels found in a control tissue or cell samples exposed to a standard toxin or hepatotoxin such as those herein described. Such methods may also be used in the drug or agent screening assays as described herein.
Kits [00150] The invention further includes kits combining, in different combinations, high-density oligonucleotide arrays, reagents for use with the arrays, protein reagents encoded by the genes of the Tables, signal detection and array-processing instruments, gene expression databases and analysis and database management software described above. The kits may be used, for example, to predict or model the toxic response of a test compound, to monitor the progression of hepatic disease states, to identify genes that show promise as new drug targets and to screen known and newly designed drugs as discussed above.

[00151] The databases packaged with the kits are a compilation of expression patterns from human or laboratory animal genes and gene fragments (corresponding to the genes of Tables SA-SXX). In particular, the database software and packaged information that may contain the databases saved to a computer-readable medium include the expression results of Tables SA-SXX that can be used to predict toxicity of a test agent by comparing the expression levels of the genes of Tables SA-SXX induced by the test agent to the expression levels presented in Tables SA-SXX. In another format, database and software information may be provided in a remote electronic format, such as a website, the address of which may be packaged in the kit.

[00152] The kits may used in the pharmaceutical industry, where the need for early drug testing is strong due to the high costs associated with drug development, but where bioinformatics, in particular gene expression informatics, is still lacking.
These kits will reduce the costs, time and risks associated with traditional new drug screening using cell cultures and laboratory animals. The results of large-scale drug screening of pre-grouped patient populations, pharmacogenomics testing, can also be applied to select drugs with greater efficacy and fewer side-effects. The kits may also be used by smaller biotechnology companies and research institutes who do not have the facilities for performing such large-scale testing themselves.

[00153] Databases and software designed for use with use with microarrays is discussed in Balaban et al., U.S. Patent Nos. 6,229,911, a computer-implemented method for managing information, stored as indexed tables, collected from small or large numbers of microarrays, and 6,185,561, a computer-based method with data mining capability for collecting gene expression level data, adding additional attributes and reformatting the data to produce answers to various queries. Chee et al., U.S. Patent No. 5,974,164, discloses a software-based method for identifying mutations in a nucleic acid sequence based on differences in probe fluorescence intensities between wild type and mutant sequences that hybridize to reference sequences.

[00154] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.
EXAMPLES

Example 1: Identification of Toxicity Markers in Rat Hepatocytes [00155] To evaluate their toxicity, the hepatotoxins alpha-naphthylisothiocyante (ANIT), acetaminophen (APAP), AY-25329, carbon tetrachloride, clofibrate, diclofenac, 17a-ethinylestradiol, hydrazine, indomethacin, lipopolysaccharide, lovastatin, methotrexate, tacrine, valproate and control compositions were administered to cultures of primary rat hepatocytes from male Sprague-Dawley rats at various time points using administration diluents, protocols and dosing regimes as previously described in the art and in the prior applications discussed above, as well as in Table 6. Laboratory protocols for the administration of the hepatotoxins amiodarone, carbamazepine, chlorpromazine, CI-1000, CPA, diflunisal, DMN, gemfibrozil, imipramine, phenobarbital, tamoxifen, tetracycline and Wy-14643 also appear in Table 6. Identification of toxicity markers was performed by microarray analysis and by the AlamarBlue~ assay, a classical measure of cytotoxicity. The AlamarBlue~ assay was performed in triplicate.

[00156] The source of the primary rat hepatocytes was Sprague Dawley Outbred CD~ Rats (CRL:CD~[SD] IGS BR, Charles River Laboratories). Hepatocyte cultures were obtained in 24-well matrigel coated plates for the AlamarBlue~ assay (175,000 cells/cmz) or in T-75cm2 matrigel coated flasks for RNA isolation for microarray analysis (187,000 cells/cm2) .
Primary rat hepatocytes were received the day after the cells were removed from the animals.
After arrival, the cells, the cells were incubated overnight (~l5hrs) before the toxin was added to the cultures. The vehicle used in the toxicity experiments was HIM
culture medium (Hepatocyte Incubation Medium, In Vitro Technologies Cat. No. 290009) containing 0.2%
DMSO (Sigma Cat. No. D-5879). Toxin or vehicle was administered to hepatocyte cultures as follows. For each treatment, i.e., vehicle alone, vehicle + toxin at low dose, or vehicle +
toxin at high dose, cells were harvested after 3, 6 and 24-hour incubations with the toxin solution or with the vehicle.

[00157] The AlamarBlue~ assay was performed as follows, using only the 24-hour time point samples.
1. Primary rat hepatocyte cultures were prepared as described above in a matrigel-coated plates at 175,000 cells/cm2.
2. The culture medium (HIM) was removed from each well and replaced with 500 ~.1 of fresh HIM following arnval of the cells, and the cells were incubated overnight (approximately l5hrs) at 37°C, 5% C02.

3. The next day, the HIM was removed and 500 ~,1 of the medium containing either vehicle or a dose of toxin was added.
4. Lysis solution was used as a negative control. 450 ~,l medium + 50 X19%
Triton X100 were added to each of 3 wells containing cells, for a final Triton concentration of 1%.
5. The cells in all wells were incubated for 24 hours at 37°C, 5% COa.
6. HIM medium was removed, and a solution containing 500 ~,1 of fresh HIM
medium + 50 ~,1 AlamarBlue~ (BioSource International, Inc., Cat. No. DAL1100) was added to each well.
7. The cells were incubated at 37°C, 5% C02 for 2 hours.
8. 100 ~,1 medium was removed from each well of the 24-well plate and added to a well of a 96-well plate. The fluorescence was measured using 544 nm as the excitation and 590 nm as the emission on a Molecular Devices, SpectraMax Gemini, Softmax pro 2.6.1.
Alternatively, two absorbance readings can be measured for the oxidized (600nm) and the reduced (570nm) form of AlamarBlue~. After obtaining absorbance readings, results were calculated according to the manufacturer's protocol provided in the product description.
9. The data were evaluated to determine whether or not the toxin reduced cell viability. If so, the dose of the toxin that reduced cell viability by ~ 10-20% was determined.
Collection of RNA from Rat Hepatocytes [00158] More than 107 cells are typically prepared for each sample. RNA was collected at 3, 6~ and 24 hours following addition of the toxin according to the following procedure.

[00159] The medium from the flasks was discarded, and the cells were washed once with 20 ml of warm (37°C) RPMI-1640 + l OmM HEPES medium (Life Technologies, Cat. No.
22400-089). 12 ml of Trizol (Life Technologies, Cat. No. 15596-018) was placed immediately into each T-75 flask. Each flask contained ~10-20 million cells.
The contents of each flask were mixed vigorously for one minute with a vortex mixer and then aspirated up and down 5 times with a pipette. The contents of each flask (~12 ml each) was collected into a 50 ml conical polypropylene tissue culture tube (Falcon), snap frozen in liquid nitrogen and stored at < -86° C.

[00160] Microarray sample preparation was conducted with minor modifications, following the protocols set forth in the Affymetrix GeneChip~ Expression Analysis Manual. Frozen cells were ground to a powder using a Spex Certiprep 6800 Freezer Mill. Total RNA was extracted with Trizol (GibcoBRL) utilizing the manufacturer's protocol. The total RNA yield for each sample was 200-500 ~g per 300 mg cells. mRNA was isolated using the Oligotex mRNA Midi kit (Qiagen) followed by ethanol precipitation. Double stranded cDNA
was generated from mRNA using the Superscript Choice system (GibcoBRL). First strand cDNA synthesis was primed with a T7-(dT24) oligonucleotide. The cDNA was phenol-chloroform extracted and ethanol precipitated to a final concentration of 1 ~.g/ml. From 2 ~,g of cDNA, cRNA was synthesized using Ambion's T7 MegaScript in vitro Transcription Kit.

[00161] To biotin label the cRNA, nucleotides Bio-11-CTP and Bio-16-UTP (Enzo Diagnostics) were added to the reaction. Following a 37°C incubation for six hours, impurities were removed from the labeled cRNA following the RNeasy Mini kit protocol (Qiagen). cRNA was fragmented (fragmentation buffer consisting of 200 mM Tris-acetate, pH 8.1, 500 mM KOAc, 150 mM MgOAc) for thirty-five minutes at 94°C.
Following the Affymetrix protocol, 55 ~,g of fragmented cRNA was hybridized on the Affymetrix rat array set for twenty-four hours at 60 rpm in a 45°C hybridization oven. The chips were washed and stained with Streptavidin Phycoerythrin (SAPE) (Molecular Probes) in Affymetrix fluidics stations. To amplify staining, SAPE solution was added twice with an anti-streptavidin biotinylated antibody (Vector Laboratories) staining step in between.
Hybridization to the probe arrays was detected by fluorometric scanning (Hewlett Packard Gene Array Scanner). Data was analyzed using Affymetrix GeneChip~ version 3.0 and Expression Data Mining Tool (EDMT) software (version 1.0), S-Plus, and the GeneExpress~
software system.

[00162] Differential expression of genes between the toxin-exposed and control samples corresponding to patterns indicative of toxicity was determined using the following criteria.

[00163] Table 1 discloses those genes that are differentially expressed upon exposure to the named toxins with their corresponding SEQ ID NOS:, GenBank Accession or Refseq ID
Nos., GLGC ID Nos. (internal Gene Logic identification nos.), gene names and Unigene Sequence Cluster titles. The metabolic pathways in which the genes of Table 1 function are indicated in Table 3, and the corresponding human homologues are given in Table 2. The model codes, identified in Table 4, represent the various toxicity or liver pathology states associated with differential expression of each gene, as well as the individual toxin types associated with differential expression of each gene.

[00164] Tables SA-SXX disclose the summary statistics for each of the comparisons performed. Each of these tables contains a set of predictive genes and creates a model for predicting the hepatoxicity of an unknown, i.e., untested compound. Each gene is identified by its Gene Logic identification number and can be cross-referenced to a gene name and representative SEQ m NO. in Table 1. For each comparison of gene expression levels between samples in the toxicity group ("Tox" samples, i.e., samples affected by exposure to a specific toxin) and samples in the non-toxicity group ("Non-tox" samples, i.e., samples not affected by exposure to that same specific toxin), the group mean for Tox samples is the mean signal intensity, as normalized for the various chip parameters that are being assayed.
The Non-tox mean represents the mean signal intensity, as normalized for the various chip parameters that are being assayed, in samples other than those treated with the high dose of the specific toxin. These samples were treated with a low dose of the specific toxin, or with vehicle alone, or with a different toxin. Tox samples were obtained from treated cells processed at the timepoint(s) indicated in the tables, while Non-tox samples were obtained from control cells processed at all time points in the experiments. For individual genes, an increase in the Tox group mean compared to the Non-tox group mean indicates up-regulation upon exposure to a toxin. Conversely, a decrease in the Tox group mean compared to the Non-tox group mean indicates down-regulation.

[00165] The mean values are derived from Average Difference (AveDiff) values for a particular gene, averaged across the corresponding samples. Each individual Average Difference value is calculated by integrating the intensity information from multiple probe pairs that are tiled for a particular fragment. The normalization multiplies each expression intensity for a given experiment (chip) by a global scaling factor. The intent of this normalization is to make comparisons of individual genes between chips possible. The scaling factor is calculated as follows:
1. From all the unnormalized expression values in the experiment, delete the largest 2%
and smallest 2% of the values. That is, if the experiment yields 10,000 expression values, order the values and delete the smallest 200 and the largest 200.
2. Compute the trimmed mean, which is equal to the mean of the remaining values.
3. Compute the scale factor SF =100/(trimmed mean) [00166] The value of 100 used here is the standard target. value used. Some AveDiff values may be negative due to the general noise involved in nucleic acid hybridization experiments.
Although many conclusions can be made corresponding to a negative value on the GeneChip platform, it is difficult to assess the meaning behind the negative value for individual fragments. Our observations show that, although negative values are observed at times within the predictive gene set, these values reflect a real biological phenomenon that is highly reproducible across all the samples from which the measurement was taken. For this reason, those genes that exhibit a negative value are included in the predictive set.
It should be noted that other platforms of gene expression measurement may be able to resolve the negative numbers for the corresponding genes. The predictive ability of each of those genes should extend across platforms, however. Each mean value is accompanied by the standard deviation for the mean.

[00167] The linear discriminant analysis score (discriminant score), as disclosed in the tables, measures the ability of each gene to predict whether or not a sample is toxic. The discriminant score is calculated by the following steps:
Calculation of a discriminant score [00168] Let X; represent the AveDiff values for a given gene across the Group 1 samples, i=l...n.

[00169] Let Y; represent the AveDiff values for a given gene across the Group 2 samples, i=l...t.

[00170] The calculations proceed as follows:

[00171] Calculate mean and standard deviation for X;'s and Y;'s, and denote these by mx, mY, sx,sY.

[00172] For all X;'s and Y;'s, evaluate the function f(z) _ ((1/sy)*exp( -.5*( (z-mY)/sY)2)) /
(((1/sY)*exp( -.5*( (z-mY)/sY)2)) +((1/sx)*exp( -.5*( (z-mx)/sx)a))), [00173] The number of correct predictions, say P, is then the number of Yi's such that f(Y;)>.5 plus the number of X;'s such that f(X;)<.5.

[00174] The discriminant score is then P/(n+t).

[00175] Linear discriminant analysis uses both the individual measurements of each gene and the calculated measurements of all combinations of genes to classify samples. For each gene, a weight is derived from the mean and standard deviation of the Tox and Non-tox sample groups. Every gene is multiplied by a weight and the sum of these values results in a collective discriminate score. This discriminant score is then compared against collective centroids of the Tox and Non-tox groups. These centroids are the average of all tox and nontox samples respectively. Therefore, each gene contributes to the overall prediction. This contribution is dependent on weights that are large positive or negative numbers if the relative distances between the Tox and Non-tox samples for that gene are large and small numbers if the relative distances are small. The discriminant score for each unknown sample and centroid values can be used to calculate a probability between zero and one as to the group in which the unknown sample belongs.
Example 2: General Toxicity Modeling [00176] Samples were selected for grouping into Tox and Non-tox groups by examining each study individually with Principal Components Analysis (PCA) to determine which treatments had an observable response. Only sample groups where confidence of the tox-responding or non-tox-responding status (expression level affected by exposure to a specific toxin or expression level not affected by exposure to a specific toxin, respectively) was established were included in building a general toxicity prediction model.

[00177] Linear discriminant models were generated to describe Tox and Non-tox samples.
The top discriminant genes and/or EST's were used to determine toxicity by calculating each gene's contribution with homo and heteroscedastic treatment of variance and inclusion or exclusion of mutual information between genes. Prediction of samples within the database exceeded ~0% true positives with a false positive rate of less than 5%. It was determined that combinations of genes and/or EST's generally provided a better prediction than individual genes and that the more genes and/or EST used, the better the prediction.
Although the preferred embodiment includes fifty or more genes, many pairings or larger combinations of genes andlor EST can work better than individual genes. All combinations of two or more genes from the selected list could be used to predict toxicity. These combinations could be selected by pairing in an agglomerate, divisive, or random approach. Further, as yet undetermined genes and/or EST's could be combined with individual or a set of genes and/or EST's described here to increase predictive ability. However, the genes and/or EST's described here would contribute most of the predictive ability to any such undetermined combinations.

[00178] Other variations on the above method can provide adequate predictive ability.
These include selective inclusion of components via agglomerate, divisive, or random approaches or extraction of loading and combining them in agglomerate, divisive, or random approaches. Also the use of composite variables in logistic regression to determine classification of samples can also be accomplished with linear discriminate analysis, neural or Bayesian networks, or other forms of regression and classification based on categorical or continual dependent and independent variables.

Example 3: Modeling Methods [00179] The above modeling methods provide broad approaches of combining the expression of genes to predict sample toxicity. One could also provide no weight in a simple voting method or determine weights in a supervised or unsupervised method using agglomerate, divisive, or random approaches. All or selected combinations of genes may be combined in ordered, agglomerate, or divisive, supervised or unsupervised clustering algorithms with unknown samples for classification. Any form of correlation matrix may also be used to classify unknown samples. The spread of the group distribution and , discriminate score alone provide enough information to enable a skilled person to generate all of the above types of models with accuracy that can exceed the discriminate ability of individual genes. Some examples of methods that could be used individually or in combination after transformation of data types include but are not limited to:
Discriminant Analysis, Multiple Discriminant Analysis, logistic regression, multiple regression analysis, linear regression analysis, conjoint analysis, canonical correlation, hierarchical cluster analysis, k-means cluster analysis, self organizing maps, multidimensional scaling, structural equation modeling, support vector machine determined boundaries, factor analysis, neural networks, bayesian classifications, and resampling methods.
Example 4: Grouping of Individual compound and Pathology Classes [00180] Samples were grouped into individual pathology classes based on known toxicological responses and observed clinical chemical and pathology measurements or into observable toxicity produced by a compound (Tables SA-S~X). The top 10, 25, 50, 100 genes based on individual discriminate scores were used in a model to ensure that a combination of genes provided a better prediction than individual genes. As described above, all combinations of two or more genes from this list could potentially provide better prediction than individual genes when selected in any order or by ordered, agglomerate, divisive, or random approaches. In addition, combining these genes with other genes could provide better predictive ability, but most of this predictive ability would come from the genes listed herein.

[00181] A sample may be considered a Tox sample if it scores positive in any pathological or individual compound class represented here, or in any modeling method mentioned under general toxicology models, based on a combination of the sample's time point and dosage group in a study using an individual compound (with known or potentially toxic properties) by comparisons obtainable from the data. The pathological groupings and early and late phase models are preferred examples of all obtainable combinations of sample time and dose points. Most logical groupings with one or more genes and one or more sample dose and time points should produce better predictions of general toxicity, pathological specific toxicity, or similarity to a known toxin than individual genes.

[00182] Although the present invention has been described in detail with reference to examples above, it is understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims. All cited patents, patent applications and publications referred to in this application axe herein incorporated by reference in their entirety.

~n TABLE

Attorney Docket No.

Document No,19262713 SEQ GLGGGenBank Model Known Gene Name nigene Sequence Cluster ~ _ U Title .

ID D Acc.or _ I N0. C ode NQ~ RefSeq ID , No.

29 6901AA799479 HHs:NADH dehydrogenaseESTs, Highly similar 1 r to NUIM HUMAN

( ubiquinone) Fe-S NADH-ubiquinone oxidoreductase protein 8 23 kDa ( 23kD) (NADH-coenzymesubunit, mitochondria) Q precursor (Complex I-reductase) 23KD) (CI-23KD) (TYKY
subunit) f H.sapiensl 196 16756AA818089q, HHs:glycyl-tRNA ESTs, Highly similar z synthetase to SYG_HUMAN Glycyl-tRNA synthetase (Glycine--tRNA
ligase) (GIyRS) (H.sapiensl 231 5331AA818996i, HHs:glutaminyl-tRNAESTs, Moderately similar i rr to SYQ_HUMAN

synthetase Glutaminyl-tRNA synthetase (Glutamine--tRNA liqase) (GLNRS) (H.sapiens~

735 12031AA893860GeneralHHsahreonyl-tRNA ESTs, Moderately similar synthetase to SYTC_HUMAN

Threonyl-tRNA synthetase, cytoplasmic (Threonine--tRNA ligase) (ThrRS) fH.sapiensl 913 10569AA942681n, HHs:ATPase, H+ ESTs, Highly similar z, transporting, to VATH HUMAN

Generallysosomal 50I57kDVacuolar ATP synthase V1 subunit subunit H (V-H ATPase H subunit) (Vacuolar proton pump H

subunit) (V-ATPase 50157 kDa subunits) (Vacuolar proton pump subunit SFD) (CGI-11) fH.saoiensl 991 22283AA945172mm HHs:leucine aminopeptidaseESTs, Highly similar 3 to AMPL_HUMAN

Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolvl aminoaeotidasel fH.saoiensl 120216625AA998062j HHs:AlgS, S. cerevisiae,ESTs, Highly similar to T51776 dolichyl-homolog of phosphate beta-glucosyltransferase (EC

2.4.1.117) (imported) - human (H.sapiens~

130522056A1008066p, HHs:ubiquinol-cytochromeESTs, Moderately similar mm c to UCRH HUMAN

reductase hinge Ubiquinol-cytochrome protein C reductase complex 11 kDa protein, mitochondria) precursor (Mitochondria) hinge protein) (Cytochrome C1, nonheme 11 kDa protein) (Complex III

subunit VIII) [H.sapiensj 166710138A1059048m HHs:Sp3 transcriptionEST, Highly similar factor to SP3_HUMAN

TRANSCRIPTION FACTOR
SP3 (SPR-2) [H.sapiensl 175316058A1071490General,HHsaerine ESTs, Highly similar to JC5180 serine C-vv palmitoyltransferase,palmitoyltransferase long chain (EC 2.3.1.50) Lcb2 base subunit 2 chain - mouse [M.musculusl 195718278AI105080m HHs:3-oxoacid ESTs, Highly similar CoA transferase to SCOT_HUMAN

Succinyl-CoA:3-ketoacid-coenzyme A

transferase, mitochondria) precursor (Succinyl CoA:3-oxoacid CoA-transferase) H.sa iens TABLE

Attorney Docket No.

_ Documeht No.1926271.2 SE GLGCGenBank Model Known Gene Name Unigene Sequence-Cluster Q Title ID D Acc: Code I N0: or N0:- RefSeq ID

No.=:

214397027AI170679xx HHs:UDP-glucose ESTs, Highly similar to UDP-glucose pyrophosphorylasepyrophosphorylase 2;
2 UTP-glucose-1-phosphate uridyltransferase;
UDP-glucose diphosphorylase; UGPase 2 [Homo sapiens]

fH.saaiensl 24343376AI179755w HHs:Rho guanine ESTs, Highly similar nucleotide to Rho guanine exchange factor nucleotide exchange (GEF) 5 factor 5; oncogene TIM; transforming immortalized mammary oncogene; guanine nucleotide regulatory protein TIM (Homo sapiensl fH.saoiensl 28654714AI639518k, HHs:polymerase ESTs, Highly similar ww, (RNA) II (DNA to S55370 RNA
xx directed) polypeptidepolymerase II chain H hRPB17 - human (H.sapiensl 352423424NM 021680x, HHs:alanyl-tRNA ESTs, Highly similar z synthetase to SYA_HUMAN Alanyl-tRNA synthetase (Alanine--tRNA
ligase) (AIaRS) (H.sapiensl 4301242 NM_145683a HHs:protein tyrosineRattus norvegicus cytosolic protein tyrosine phosphatase, non-receptorphosphatase HePTPILC-PTP
type mRNA, 7 complete cds 885 16945AA925541c heterogeneous heterogeneous nuclear nuclear ribonucleoprotein L

ribonucleoprotein L

886 17513AA925554h, succinate dehydrogenasesuccinate dehydrogenase a complex, subunit complex, subunit A, flavoprotein (Fp) A, flavoprotein (Fp) 135422748A1009786g , ribosomal proteinribosomal protein L41 hh L41 287918456D00688 bb monoamine oxidaseESTs, Highly similar A to 1903159A

monoamine oxidase A
[Rattus norvegicus]

[R.norvepicusl 294324513J02705 v Oncomodulin Oncomodulin 307824504NM 012574k Glutamate receptor,Glutamate receptor, ionotropic, ionotropic, N-methyl D-N-meth I D-aspartateaspartate 2B

308424735NM 012596pp Leptin receptor Leptin receptor (fatty) (fatty) 32881561NM 016995d, Complement componentComplement component v, 4 4 binding protein, uu binding protein, beta beta 32966598NM 017020j, Interleukin 6 Interleukin 6 receptor n, receptor xx 3485235 NM 019347ii Urea transporter,Urea transporter solute carrier f amily 14, member 368022282NM_024394h, 5-Hydroxytryptamine5-Hydroxytryptamine m, (serotonin) (serotonin) receptor General,receptor 3A

uu 3728301 NM 031049jj 2,3-oxidosqualene:2,3-oxidosqualene: lanosterol lanosterol cyclase cyclase 3728302 NM 031049jj 2,3-oxidosqualene:2,3-oxidosqualene: lanosterol lanosterol cyclase cyclase 3728303 NM 031049k, 2,3-oxidosqualene:2,3-oxidosqualene: lanosterol jj lanosterol cyclase c clase 388013186NM 031755n carcinoembryonic carcinoembryonic antigen-related antigen- cell related cell adhesionadhesion molecule molecule TABLE

Aftocney Docket Ho.

' 271.2 Document No.1926 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster.Title lD D Acc. Code I NO. or NO~ RefSeq No.

414313424NM 080899ww nhibitor of kappanhibitor of kappa light i light i polypeptide enhancer polypeptide enhancern B-cells, kinase complex-associated in B-cells, i kinase complex-associatedprotein protein 414524604NM 080906r, HIF-1 responsiveHIF-1 responsive RTP801 pp RTP801 415317512NM_130428w succinate dehydrogenasesuccinate dehydrogenase complex, subunit complex, subunitA, flavoprotein (Fp) A, flavoprotein (Fp) 43961359U78977 mm ATPase, Class ATPase, Class II, type II, type 9A 9A

344518362NM 019187n, Coenzyme Q (ubiquinone)Coenzyme Q (ubiquinone) ff 370925476NM 031009xx angiotensin II angiotensin II type-1 type-1 receptor receptor 12 21815AA686423o ESTs, Highly similar to T46390 hypothetical protein DKFZp434C1920.1-human (fragment) fH.sapiensl 18 3636AA799336qq ESTs, Moderately similar to T00741 NADH

dehydrogenase (ubiquinone) (EC 1.6.5.3) acyl carrier chain, mitochondrial - human (fragment) fH.sapiensl 23 20957AA799440fP ESTs, Moderately similar to L13 protein [Homo sapiens] [H.sapiens]

28 19675AA799475s, ESTs, Weakly similar oo to T08700 hypothetical protein DKFZp564G013.1 - human (fragment) (H.sapiensl 42 16576AA799570c, ESTs, Highly similar a to hypothetical protein FLJ13725; KIAA1930 protein [Homo sapiensl (H.sapiensl 44 20973AA799581v, ESTs, Moderately similar General to Y218_HUMAN

Putative deoxyribonuclease [H.sapiensl 50 19472AA799616c, ESTs, Moderately similar f, to PTTG_HUMAN
p, -General, Pituitary tumor-transforming gene 1 protein-kk interacting protein (Pituitary tumor-transforming gene protein binding factor) (PTTG-binding factor) (PBF) [H.sapiens]

51 20980AA799633dd, ESTs, Moderately similar oo to hypothetical protein MGC13016 [Homo sapiens]

(H.sapiensl 69 16730AA799766I ESTs, Moderately similar to JTV1;

hypothetical protein PR00992 [Homo sapiensl fH.sapiensl 71 11531AA799773d ESTs, Weakly similar to A37098 gelation factor ABP-280, long form - human [H.sapiensl 91 20811AA799899ee ESTs, Highly similar to R5RT18 ribosomal protein L18a, cytosolic [validated] - rat R.norve icus TABLE

Attorney Docket No.
44921=5113W0 Document'No.19262712 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster Title ID D Acc. Code ' NQ. or I

NO." RefSeq ID

No. _ _ , 103 9202AA800053c ESTs, Highly similar to T08775 hypothetical protein DKFZp586C1620.1-human (fragment) fH.sapiensl 105 23329AA800126t ESTs, Highly similar t to 155595 splicing factor - human [H.sapiens]

115 22918AA8002430, ESTs, Highly similar p, to CIDA_MOUSE Cell w, ii, rr death activator CIDE-A
(Cell death-inducing DFFA-like effector A) [M.musculus]

120 17206AA800296a ESTs, Highly similar to PAP_HUMAN

Poly(A) polymerase alpha (PAP) (Polynucleotide adenylyltransferase alpha) [H.sapiensl 136 17997AA800671h, ESTs, Moderately similar p, to A54854 Ras w, General GTPase activating protein-related protein -human fH.sapiensl 149 21379AA800738II ESTs, Highly similar to TI60_HUMAN 60 kDa Tat interactive protein (HIV-1 Tat interactive protein) [H.sapiensl 155 19102AA800794ww ESTs, Highly similar to HT2A_HUMAN Zinc-finger protein HT2A
(72 kDa Tat-interacting protein) (Tripartite motif containing protein 32) IH.sapiensl 160 10320AA800855k ESTs, ESTs, Highly similar to MLF2_MOUSE Myeloid leukemia factor 2 (Myelodysplasia-myeloid leukemia factor 2) fM.musculusl 160 17775AA800855cc ESTs, Highly similar to MLF2_MOUSE

Myeloid leukemia factor 2 (Myelodysplasia-myeloid leukemia factor 2) [M.musculusl 164 19440AA800946II EST, Moderately similar to B Chain B, Crystal Structure Of The D1d2 Sub-Complex From The Human Snrnp Core Domain (H.sapiensl 170 21437AA801230z ESTs, Highly similar to hypothetical protein MGC19606 [Homo sapiens]
[H.sapiens]

208 6332AA818406a ESTs, Highly similar to LSM6_HUMAN U6 snRNA-associated Sm-like protein LSm6 (H.sapiensl 232 5527AA819027gg, ESTs, Highly similar hh to GLYC_MOUSE

Serine hydroxymethyltransferase, cytosolic (Serine methylase) (Glycine hydroxymethyltransferase) (SHMT) fM.musculusl 240 7208AA819337t, ESTs, Highly similar mm, to T47140 hypothetical qq protein DKFZp761 K1115.1-human fra ment H.sa lens .5d TABLE
1.
=
Attorney Docket No.
44921-51'I3WQ

Document No,19262T1.2 $EQ GLGCGenBank Model;Known Gene Name Upigene Sequence Cluster Title ID: I~NO.Acc.or Code N0 RefSeq ID

No.

241 17024AA819356 ESTs, Moderately similar j to hypothetical protein MGC15677 [Homo sapiens]

[H.sapiens]

287 19412AA849222j ESTs, Weakly similar j to T46904 hypothetical protein DKFZp761 D081.1-human [H.sapiens]

295 22933AA849763y ESTs, Moderately similar to Y188_HUMAN

Hypothetical protein KIAA0188 [H.sapiens]

299 18876AA849790a ESTs, Highly similar to hypothetical protein FLJ11773 [Homo sapiens]
[H.sapiens]

301 14608AA849805j, ESTs, Highly similar ss to HLA-B associated transcript-5; BAT5 protein [Homo sapiens]

[H.sapiens]

303 22071AA849843uu, ESTs, Highly similar ww to T08661 anti-silencing protein ASF1 homolog DKFZp547E2110.1 -human [H.sapiens]

331 14963AA851161ii ESTs, Highly similar to DYNC_HUMAN

Dynactin complex 50 kDa subunit (50 kDa dynein-associated polypeptide) (Dynamitin) (DCTN-50) iH.sapiens 333 12769AA851192a, ESTs, Highly similar cc, to T46254 hypothetical jj protein DKFZp761 H171.1-human [H.sapiens]

336 19187AA851230General, ESTs, Moderately similar to hypothetical pp protein MGC11102 [Homo sapiens]

[H.sapiens]

341 3833AA851255ss ESTs, Highly similar to T14743 hypothetical protein DKFZp586F1524.1-human (fragment) [H.sapiens]

347 11221AA851352II ESTs, Highly similar to A24050 ribonucleoside-diphosphate reductase (EC

1.17.4.1) chain M1 -mouse [M.musculusl 357 19269AA851785General ESTs, Highly similar to eukaryotic translation initiation factor 3, subunit 8 (110kD) [Homo Sapiens]
[H.sapiens]

363 16409AA852027pp ESTs, Weakly similar to DIA1 HUMAN

Diaphanous protein homolog 1 (Diaphanous-related formin 1) (DRF1) [H.sapiens]

368 10517AA858600nn ~ ESTs, Highly similar to 154388 LZTR-1 -human [H.sapiens]

392 15148AA859325w ESTs, Highly similar to hypothetical protein MGC14151 [Homo sapiens]
[H.sapiens]

403 23340AA859519jj ESTs, Highly similar to JC6127 RNA-binding protein type 1 - human [H.sapiens]

403 23341AA859519bb ESTs, Highly similar to JC6127 RNA-binding rotein t a 1 - human H.sa iens TABLE

Aftorney Docket No.

Document No.19262712 SEQ GLGCGenBank Model Known Gerie Name Unigene Sequence~ClusterTitle -~

ID D Acc. Code I N0. or :, NO: RefSeq ID

No. '' 423 19486AA859870, nn ESTs, Weakly similar I to Y063_HUMAN

Hypothetical protein KIAA0063 (HA1234) [ H.sapiensl 436 23346AA859983c ESTs, Weakly similar to T50607 hypothetical protein DKFZp43411016.1 - human (fragment) [H.sapiensl 440 23347AA860015c ESTs, Weakly similar to T50607 hypothetical protein DKFZp43411016.1-human (fragment) [H.sapiensl 462 16042AA874827cc ESTs, Weakly similar to Y008_HUMAN

Hypothetical protein KIAA0008 [H.sapiensl 463 15182AA874832ff ESTs, Moderately similar to anaphase-promoting complex subunit 5 [Homo sapiensl [H.sapiensl 469 15115AA874928r, ESTs, Highly similar v to SNX4_HUMAN

Sorting nexin 4 [H.sapiensl 474 16215AA874999j ESTs, Highly similar to protein translocation complex beta; protein transport protein SEC61 beta subunit [Homo sapiensj [H.sapiensl 493 7875AA875127x ESTs, Highly similar to cell division cycle like 5, isoform 1; cholinesterase-related cell division controller;
CDC2-related protein kinase 5 [Homo sapiensl fH.sapiensl 498 15371AA875205xx ESTs, Highly similar to IF39_HUMAN

Eukaryotic translation initiation factor 3 subunit 9 (eIF-3 eta) (eIF3 p116) (eIF3 p110) [H.sapiensl 498 15372AA875205y, ESTs, Highly similar General, to IF39_HUMAN

gg, Eukaryotic translation hh, initiation factor 3 II

subunit 9 (eIF-3 eta) (eIF3 p116) (eIF3 p110) [H.sapiensl 505 15410AA875268r ESTs, Highly similar to NUKM HUMAN
-NADH-ubiquinone oxidoreductase 20 kDa subunit, mitochondria) precursor (Complex I-20KD) (CI-20KD) (PSST
subunit) IH.saoiensl 513 17314AA875509r ESTs, Moderately similar to S15349 mdm2 rotein - mouse [M.musculusl 522 11889AA875641k ESTs, Highly similar to A Chain A, The Sh3 Domain Of Eps8 Exists As A Novel Intertwined Dimer [M.musculusl 523 18152AA875661x ESTs, Highly similar to S58284 BCL7B

protein - human [H.sapiensl 537 16037AA891441j ESTs, Moderately similar to MPL3_RAT

Microtubule-associated proteins 1A11B light chain 3 (MAP1AIMAP1B
LC3) R.norve icus .5F
TABLE

Attorney Docket No.

Document No.1=9262713 SEQ GLGGGenBank Model Known Gene Name Unigene Sequence ClusterT~tle ID D Acc: Code , NO. or I

NO.. RefSeq ID

No.

540 21952AA891537t ESTs, Weakly similar t to protein predicted by clone 23733 [Homo sapiens]
[H.sapiens]

561 17271AA891759a, ESTs, Moderately similar s to hypothetical protein MGC4308 [Homo sapiens]

[H.sapiensl 566 11966AA891800w ESTs, Weakly similar to F22G12.,5.p [Caenorhabditis elegans]
[C.elegans], ESTs, Weakly similar to IPYR_HUMAN
Inorganic pyrophosphatase (Pyrophosphate phospho-hydrolase) (PPase) [H.sapiens]

579 17779AA891914w ESTs, Moderately similar to A47488 aminoacylase (EC 3.5.1.14) - human [H.sapiensl 582 23862AA891933g ESTs, Moderately similar to A Chain A, Crystal Structure Of SmacDIABLO

[H.sapiensl 605 8317AA892234b, ESTs, Moderately similar s, to microsomal z, General glutathione S-transferase 3; microsomal glutathione S-transferase III [Homo sapiens]

fH.sapiensl 609 22903AA892250h, ESTs, Highly similar q, to SYK_HUMAN Lysyl-dd tRNA synthetase (Lysine--tRNA
ligase) (LysRS) [H.sapiensl 616 4373AA892310v ESTs, Highly similar to T08783 hypothetical protein DKFZp58600120.1 - human (fragment) [H.sapiensl 617 17405AA892313ii, ESTs, Moderately similar rr to beta-tubulin cofactor E [Homo sapiens]
[H.sapiens]

630 16469AA892462j, ESTs, Moderately similar mm to UCRY_HUMAN

Ubiquinol-cytochrome C reductase complex 6.4 kDa protein (Complex III subunit XI) fH.sapiensl 637 11994AA892507h ESTs, Moderately similar to S63540 protein DS 1, 24K - human [H.sapiens]

673 22872AA892859g, ESTs, Weakly similar rr to PL01 RAT

Procollagen-lysine,2-oxoglutarate dioxygenase 1 precursor (Lysyl hydroxylase 1) (LH1) [R.norveaicusl 686 3439AA893000o ESTs, Moderately similar to T00335 hypothetical protein KIAA0564 - human (fragment) [H.sapiensl 694 13856AA893183gg, ESTs, Weakly similar hh to S57447 HPBRII-7 protein - human [H.sapiens]

694 13857AA893183bb ESTs, Weakly similar to S57447 HPBRII-7 rotein - human H.sa lens ~7 TABLE

Attorney Docket No:

Document No.1926271:2 SEG1GLGCGenBank Model Known Gene Name Unigene Sequence Clusfer ' Title ID D Acc. Code I NO. or .

N0~ RefSeq ID ' No. - -699 3877AA893224d ESTs, Highly similar to UBPJ_HUMAN

Ubiquitin carboxyl-terminal hydrolase 19 (Ubiquitin thiolesterase 19) (Ubiquitin-specific processing protease 19) (Deubiauitinatina enzyme 191 IH.sapiensl 702 3879AA893237t, ESTs, Moderately similar cc, to hypothetical xx protein MBC3205 [Homo sapiens]

[H.sapiens]

728 19411AA893667r ESTs, Weakly similar to T46904 hypothetical protein DKFZp761 D081.1-human [H.sapiens]

731 24185AA893708y ESTs, Highly similar to T00333 hypothetical protein KIAA0560 - human [H.sapiens]

732 17858AA893741c, ESTs, Moderately similar d, to T46305 oo hypothetical protein DKFZp434D1411.1 -human (fra ment) [H.sapiens]

772 22490AA899289ii ESTs, Moderately similar to KIAA1049 protein [Homo sapiens]
[H.sapiens]

775 4636AA899491m ESTs, Highly similar to SYW_MOUSE

Tryptophanyl-tRNA synthetase (Tryptophan--tRNA ligase) (TrpRS) [M.musculus]

785 21213AA899991f, ESTs, ESTs, Highly similar General to T46254 hypothetical protein DKFZp761H171.1 -human [H.sapiens]

786 15373AA900018x ESTs, Highly similar to IF39_HUMAN

Eukaryotic translation initiation factor 3 subunit 9 (eIF-3 eta) (eIF3 p116) (eIF3 p110) fH.sapiensl 797 16754AA900474d ESTs, Moderately similar to T50619 hypothetical protein DKFZp762M136.1-human (fragment) [H.sapiensl 810 12335AA901065k, ESTs, Highly similar cc to T17225 hypothetical protein DKFZp564C246.1-human [H.sapiens]

816 17096AA901343g ESTs, Moderately similar to suppressor of G2 allele of SKP1 [Homo sapiens]

[H.sapiens]

823 12354AA923957a, ESTs, Weakly similar k, to UDP-N-cc, tt acteylglucosamine pyrophosphorylase 1;

AgX; sperm associated antigen 2; UDP-N-acteylglucosamine pyrophosphorylase 1;

Sperm associated antigen 2 [Homo sapiensJ

IH.saoiensl 830 4917AA924140p ESTs, Weakly similar to Y193_HUMAN

Hypothetical protein KIAA0193 [H.sapiens]

5ft TABLE

Attorney Docket No:
A~4921-51'13W0 Document'No.19262712 SEQ GLGCGenBank Modeh Known Genie NameUni~ene Sequence Cluster Title ID D Acc. Code I N0. or N0.- RefSeq ID _ No.

834 4931AA9242610o ESTs, Weakly similar to PRS4_MOUSE 26S

PROTEASE REGULATORY SUBUNIT

(P26S4) fR.norvegicusl 852 5009AA924737qq ESTs, Highly similar to T17237 hypothetical protein DKFZp434P106.1-human (fragment) [H.sapiensl 860 2462AA924913d ESTs, Moderately similar to T50619 hypothetical protein DKFZp762M136.1 -human (fragment) [H.sapiensl 906 16468AA926137p, ESTs, Moderately similar t, to UCRY_HUMAN
y, mm Ubiquinol-cytochrome C reductase complex 6.4 kDa protein (Complex III subunit XI) fH.sapiensl 915 9942AA942697y ESTs, Highly similar to hypothetical protein MGC3133 [Homo Sapiens]
[H.sapiens]

921 22102AA942845m ESTs, Weakly similar to Y218 HUMAN
-Putative deoxyribonuclease [H.sapiens]

931 21993AA943149t, ESTs, Weakly similar ff to T00084 hypothetical protein KIAA0512 - human [H.sapiens]

939 21911AA943610s ESTs, Highly similar to T08795 hypothetical protein DKFZp586J1822.1-human (fragment) [H.sapiensl 968 17948AA944581f ESTs, Moderately similar to A57088 nucleoporin-like protein Rab - human [H.sapiensl 969 22471AA944617bb ESTs, Highly similar to CU02_HUMAN

Protein C21orf2 (C21orf-HUMF09G8.5) (YF5/A2) [H.sapiensl 972 22492AA944741dd ESTs, Moderately similar to KIAA1049 protein [Homo sapiens]
[H.sapiens]

980 23423AA944912dd ESTs, Moderately similar to ERC6_HUMAN

Excision repair protein ERCC-6 (Cockayne syndrome protein CSB) [H.sapiens]

100722636AA945724v ESTs, Weakly similar to T12543 hypothetical protein DKFZp434M154.1-human (fragment) [H.sapiens]

10099657AA945739a ESTs, Moderately similar to Y391 HUMAN

Hypothetical protein KIAA0391 [H.sapiens]

101121334AA945753pp ESTs, Moderately similar to ANM2_HUMAN

Protein arginine N-methyltransferase [H.sapiens]

103421410AA946408c ESTs, Moderately similar to MCA3_HUMAN

Multisynthetase complex auxiliary com onent 18 H.sa iens TABLE

Attorney Docket No.-44921-5113W0 Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc: Code .
_ N0. or .

Nb: RefSeq ID
-' No.

103818383AA946421m ESTs, Highly similar to S59641 transcription f actor TFEB - mouse (fragment) [ M.musculusl 105417191AA955382c ESTs, Highly similar to T46457 hypothetical protein DKFZp434L032.1 - human (fragment) (H.sapiensl 106223278AA955553I ESTs, Moderately similar to hypothetical protein IMAGE3455200 [Homo sapiens]

~H.sapiensl 106423637AA955587pp ESTs, Highly similar to A45142 cleavage stimulation factor 50K
chain - human (H.sapiensl 108024046AA956185a ESTs, Moderately similar to COQ6_HUMAN

Putative ubiquinone biosynthesis monooxgenase COQ6 (CGI-10) [H.sapiens]

108518669AA956453w ESTs, Highly similar to OBRG_MOUSE

Leptin receptor gene-related protein (OB-R

gene related protein) (OB-RGRP) fM.musculusl 108723800AA956534j ESTs, Weakly similar to RNG1 HUMAN

Polycomb complex protein RING1 (RNF1) (H.sapiensl 108923852AA956746p ESTs, Highly similar to CHD4_HUMAN

Chromodomain helicase-DNA-binding protein 4 (CHD-4) (Mi-2 autoantigen 218 kDa protein) (Mi2-beta) fH.sapiensl 110418413AA957763ff ESTs, Highly similar to UBPJ_HUMAN

Ubiquitin carboxyl-terminal hydrolase 19 (Ubiquitin thiolesterase 19) (Ubiquitin-specific processing protease 19) (Deubiquitinatina enzyme 19) IH.saoiensl 111115183AA963036I ESTs, Moderately similar to anaphase-promoting complex subunit 5 [Homo sapiens fH.sapiensl 11125952 AA963102r amino acid transporteramino acid transporter system system A2 11252270 AA964116s ESTs, Moderately similar to tripartite motif-containing 37; RING-B-box-coiled-coil protein; MUL protein;
Mulibrey nanism (Homo sapiensl IH.sapiensl 113624166AA964630d, ESTs, Moderately similar n to T02345 hypothetical protein KIAA0324 - human (fragment) [H.sapiensl 11532583 AA965166u, ESTs, Moderately similar mm to IPYR_HUMAN

Inorganic pyrophosphatase (Pyrophosphate phospho-hydrolase) (PPase) [H.sapiens]

~n TABLE

Aftorney Docket No.

Document No.192627~:2 SEQ GLGGGenBank Mode) Known Gene Name- Unigene Sequence:Cluster = Title ID D Acc..or Code - N0.
:
I

NO: RefSeq ID

No.::

11612809AA996471p ESTs, Moderately similar to JM11 protein . Homo sapiens] [H.sapiens]

116711928AA996829gg, ESTs, Moderately similar hh to T46305 hypothetical protein DKFZp434D1411.1 -human (fragment) [H.sapiensl 12073367AA998110xx ESTs, Weakly similar to YCE3_HUMAN

Hypothetical protein CGI-143 [H.sapiens]

120812628AA998123General ESTs, Moderately similar to JC5707 HYA22 protein - human [H.sapiens]

121926118AA998471d ESTs, Highly similar to 149668 binding protein - mouse [M.musculus]

122323648AA998547mm ESTs, Highly similar to Y144_HUMAN

Hypothetical protein KIAA0144 [H.sapiens]

122526120AA998619s ESTs, Weakly similar to T51776 dolichyl-phosphate beta-glucosyltransferase (EC

2.4.1.117) [imported]
- human [H.sapiensl 12313660AA998833j ESTs, Weakly similar to T46908 hypothetical protein DKFZp76162423.1-human [H.sapiens]

12352526AA998979bb ESTs, Moderately similar to T00051 hypothetical protein KIAA0404 - human (fragment) [H.sapiens]

12383710AA999064s, ESTs, Highly similar t to T47142 hypothetical protein DKFZp761 P0724.1-human (fragment) [H.sapiens]

125423417AB022209I, ribonucleoproteinribonucleoprotein F
General,F

kk 127213464AF047707f, UDP-glucose:ceramideUDP-glucose:ceramide ss glycosyltransferase glycosyltransferase 130317359A1007981mm ESTs, Moderately similar to UCRX_HUMAN
-Ubiquinol-cytochrome C reductase complex 7.2 kDa protein (Cytochrome C1, nonheme 7 kDa protein) (Complex III subunit X) (7.2 kDa cytochrome c1-associated protein subunit) (HSPC119) [H.sapiens]

132522801A1009197a ESTs, Moderately similar to hypothetical protein IMAGE3455200 [Homo sapiens]

[H.sapiens]

133216956A1009390ee ESTs, Moderately similar to NIPM_HUMAN

NADH-ubiquinone oxidoreductase 15 kDa subunit (Complex I-15 kDa) (CI-15 kDa) [H.sapiensl 133711322A1009492j ESTs, Highly similar to hypothetical protein Homo sa iens H.sa iens TABLE

Attorney Docket No.

Document No.19262712 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster.Title ID D Acc: Code I N0. or ~

N0 RefSeq ID

No:

13638047A1010100a ESTs, Highly similar to vacuolar protein sorting 18 (yeast), isoform 1; vacuolar protein sorting protein 18 [Homo sapiens]

f H.sapiensl 140223768A1011709ii ESTs, Moderately similar to S21977 Pm5 protein - human [H.sapiens]

140618684A1011812pp ESTs, Highly similar to T12468 hypothetical protein DKFZp5640123.1 - human [H.sapiensl 14325528A1012631bb, Rattus norvegicus mRNA
qq for Vps54-like protein 143312475A1012632c ESTs, Weakly similar to hypothetical protein FLJ14775 [Homo sapiens]
[H.sapiens]

14399386A1012785c ESTs, Weakly similar to T47142 hypothetical protein DKFZp761 P0724.1-human (fragment) [H.sapiensl 14432937A1012951pp ESTs, Moderately similar to PEXD HUMAN

Peroxisomal membrane protein PEX13 (Peroxin-13) [H.sapiensl 145511969A1013273rr ESTs, Highly similar to B27496 proteinase inhibitor nexin 1 precursor - rat (fragment) [R.norvegicusl 146012794A1013442ee ESTs, Highly similar to T12539 hypothetical protein DKFZp434J154.1 - human [H.sapiensl 146123444A1013448rr ESTs, Highly similar to chromosome 20 open reading frame 30;
HSPC274 protein [Homo sapiensl fH.sapiensl 146312795A1013482y ESTs, Highly similar to T17303 hypothetical protein DKFZp566F2124.1-human (fragment) [H.sapiensl 14862909A1013946m ESTs, Weakly similar to A34581 oxysterol-binding protein - human [H.sapiens]

149415247A10141690, upregulated by upregulated by 1,25-dihydroxyvitamin ii, 1,25- D-3 II, pp, xx dihydroxyvitamin 15047420A1029291I ESTs, Highly similar to CLPX_MOUSE ATP-dependent CLP protease ATP-binding subunit CIpX-like, mitochondria) precursor fM.musculusl 15087451A1029450I, ESTs, Moderately similar z, to SYEP_HUMAN

General Bifunctional aminoacyl-tRNA
synthetase [Includes: Glutamyl-tRNA
synthetase (Glutamate--tRNA ligase);
Prolyl-tRNA

synthetase (Proline--tRNA
ligase)]

R~
TABLE

' Attorney Docket No.

Document No.1926271.2 SEQ GLGGGenBank Model Known Gene Name Unigene Sequence Cluster :; Title ID D=NO.Acc~ Code I or N0. RefSeq ID

No. .

15505346A1043601gg, ESTs, Weakly similar hh to T08680 hypothetical protein DKFZp564P0622.1-human (fragment) fH.sapiensl 15837136A1044604s ESTs, Weakly similar to T12528 hypothetical protein DKFZp434N093.1 - human (fragment) [H.sapiensl 15855556A1044638ii ESTs, Moderately similar to Y127_HUMAN

Hypothetical protein KIAA0127 [H.sapiens]

16035715A1045158v ESTs, Moderately similar to hypothetical protein MGC4675 [Homo sapiens]

[H.sapiensl 160511763A1045196tt ESTs, Weakly similar to A47328 natural killer cell tumor-recognition protein - human [H.sapiensl 16136609A1045458ii, ESTs, Highly similar tt to 155595 splicing factor - human [H.sapiens]

16236808A1045600a ESTs, Highly similar to S30034 translocating chain-associating membrane protein -human [H.sapiensl 16315866A1045751y ESTs, Moderately similar to SYN_HUMAN

Asparaginyl-tRNA synthetase, cytoplasmic (Asparagine--tRNA ligase) (AsnRS) [H.sapiensl 165010080A1058639General EST, Weakly similar to PRTZ_HUMAN

Vitamin K-dependent protein Z precursor [H.sapiensl 17008496A1059974tt ESTs, Moderately similar to T17285 hypothetical protein DKFZp434N0535.1 -human (fragment) [H.sapiensl 17038132A1060050p, ESTs, Highly similar bb to NGP1 HUMAN

Autoanti en NGP-1 [H.sapiens]

170610304A1060149b ESTs, Weakly similar to T48687 hypothetical protein DKFZp76161923.1 - human (fragment) fH.sapiensl 17104337A1060281II ESTs, Weakly similar to T50633 hypothetical protein DKFZp762F1811.1 - human (fragment) [H.sapiensl 174211596A1071194pp ESTs, Weakly similar to S16506 hypothetical protein - human [H.sapiens]

17499615A1071289I, ESTs, Highly similar z to Y779_HUMAN

Hypothetical protein KIAA0779 [H.sapiens]

17619259A1071606q ESTs, Highly similar to UBP1 HUMAN

Ubiquitin carboxyl-terminal hydrolase 1 (Ubiquitin thiolesterase 1) (Ubiquitin-specific processing protease 1) (Deubiquitinating enzyme 1) (hUBP) [H.sapiens]

TABLE

Attorney Docket No.

'Document No:1926271:2 SEQ GLGC GenBankModef Known Gene Name Unigene SequenceCluster ~ Title ID D Acc_or Code -- N0.
I

N0 RefSeq ID
--No.

177317673A1071895i EST, Moderately similar i to 138937 DNAIRNA

binding protein - human (fragment) fH.sapiensl 17758665 A1071965ee ESTs, Moderately similar to T17342 hypothetical protein DKFZp586K1924.1 -human (fragment) [H.sapiens], R.norvegicus hsp70.2 mRNA for heat shock protein 70 184016814AI101462jj ESTs, Highly similar to cisplatin resistance related protein CRR9p [Homo sapiens]

[H.sapiensl 18692972 AI102606ss ESTs, Moderately similar to NADH

dehydrogenase (ubiquinone) 1 alpha subcomplex, 10 (42kD) [Homo Sapiens]

IH.sapiensl 18717379 A1102643d, ESTs, Moderately similar dd, to 2105233A
rr transcription factor ISGF3gamma [Mus musculusl ~M.musculusl 19123940 AI103718qq ESTs, Highly similar to 139383 angio-associated migratory cell protein - human [H.sapiensl 193718395AI104388nn heat shock 27kD heat shook 27kD protein protein 1 1 195322957AI104897u, ESTs, Moderately similar w to MEA6_HUMAN

Meningioma-expressed antigen 6111 (MEA6) (MEA11) [H.sapiens]

195524375AI104979q, ESTs, Moderately similar z, to EBNA1 binding dd, ee protein 2; nucleolar protein p40; homolog of yeast EBNA1-binding protein;
nuclear FGF3 binding protein; EBNA1-binding protein 2 [Homo sapiens] [H.sapiens]

197518466AI1118280o ESTs, Highly similar to Y196_HUMAN

Hypothetical protein KIAA0196 [H.sapiens]

197611339AI111840jj ESTs, Moderately similar to PMVK_HUMAN

PHOSPHOMEVALONATE KINASE

(PMKASE) [H.sapiens]

200815196AI136610ee ESTs, Highly similar to RRP5 HUMAN
-RRP5 protein homolog (Fragment) [H.sapiensl 20176552 AI137062d ESTs, Highly similar to OM07_HUMAN

Probable mitochondria) import receptor subunit TOM7 homolog (Translocase of outer membrane 7 kDa subunit homology Protein AD-014 H.sa lens Fd TABLE

-Attorney Docket No.

Document No.192627~1:2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster 4 Title ID D Acc~.or Code - N0.
l N0. RefSeq ID

No.

20327414AI137586n, ESTs, Highly similar p, to IMB3_HUMAN
z, GeneralI mportin beta-3 subunit (Karyopherin beta-3 subunit) (Ran-binding protein 5) [H.sapiens]

203314396AI137689s Rattus norvegicus mRNA
for Vps54-like protein 20426898AI144623p ESTs, Moderately similar to TRI3_HUMAN

Thyroid receptor interacting protein 3 (TRIP-3) [H.sapiensl 205112482AI144965p ESTs, Highly similar to SN24_HUMAN

Possible global transcription activator SNF2L4 (SNF2-beta) (BRG-1 protein) (Mitotic growth and transcription activator) (Brahma protein homoloa 1) fH.saoiensl 206115399AI14545100 ' ESTs, Highly similar to RR41 HUMAN

Exosome complex exonuclease (Ribosomal RNA processing protein 41) fH.sapiensl 210016727AI169287z, ESTs, Highly similar General, to T47146 hypothetical kk protein DKFZp761 C169.1-human (fragment) fH.sapiensl 210711550AI169591a ESTs, Highly similar to S57447 HPBRII-7 protein - human [H.sapiens]

213624048AI170570qq ESTs, Moderately similar to COQ6_HUMAN

Putative ubiquinone biosynthesis monooxgenase COQ6 (CGI-10) [H.sapiens]

21422750AI170666n, ESTs, Highly similar q, to ARGR_HUMAN
dd Arginine-rich protein [H.sapiens]

21461923AI170754r, ESTs, Highly similar z, to T50836 Yippee ee protein [imported] -human (fragment) [H.sapiensl 215914941AI171196pp ESTs, Highly similar to MAN1 HUMAN Inner nuclear membrane protein Man1 [H.sapiens]

21625953AI171231r, amino acid transporteramino acid transporter y, system system A2 z, tt 216611518A1171272a ESTs, Highly similar to similar to S.

cerevisiae RER1 [Homo sapiens]

[H.sapiensl 217817746AI171615ss ESTs, Moderately similar to 139166 cellular apoptosis susceptibility protein CAS - human [H.sapiensl 21926085AI171990ww ESTs, Highly similar to T50620 hypothetical protein DKFZp762M186.1 - human (fragment) [H.sapiensl 219422876AI172041r, ESTs, Moderately similar w, to CGD7_HUMAN
z, ee Protein CGI-137 (Protein AD-004) H.sa lens TABLE

-Attorney Docket No.

Document No.1926271~2 SEQ GLGCGenBank Model Kriown Gene NameUnigene Sequence Cluster Title ID D Acc.or Code I N0.

NO. RefSeq ID

No.

21996057AI172102dd ESTs, Highly similar to STXH_HUMAN

Syntaxin 18 [H.sapiensl 220511416AI172185t, ESTs, Highly similar ff to mitochondria) ribosomal protein L49;
chromosome 11 open reading frame 4 [Homo sapiensj [H.sapiens]

221311525AI172286p ESTs, Moderately similar to LPRC_HUMAN

130 kDa leucine-rich protein (LRP 130) (GP130) (Leucine-rich PPR-motif containing protein) fH.sapiensl 22297740AI175011vv ESTs, Moderately similar to COF1 RAT

COFILIN, NON-MUSCLE ISOFORM

[R.norveaicusl 22366454AI175342p, ESTs, Weakly similar kk to T31067 BIR repeat containing ubiquitin-conjugating enzyme BRUCE - mouse [M.musculusl 224218562AI175515s ESTs, Moderately similar to PRTP_MOUSE

Lysosomal protective protein precursor (Cathepsin A) (Carboxypeptidase C) (M054) [M.musculusj 22571587AI176063ii Rat general mitochondria) matrix processing protease (MPP) mRNA, 3' end 22617711AI176125a ESTs, Moderately similar to T14773 hypothetical protein DKFZp564B0482.1 -human [H.sapiensl 226812999AI176276General ESTs, Highly similar to UAP1 HUMAN UDP-N-acetylhexosamine pyrophosphorylase (Antigen X) (AGX) (Sperm-associated antigen 2) [Includes:
UDP-N-acetylgalactosamine pyrophosphorylase (AGX-1); UDP-N-acetylglucosamine pyrophosphorylase (AGX-2)]
[H.sapiens]

227717920AI176422n, ESTs, Highly similar kk, to S41115 probable pp flavoprotein-ubiquinone oxidoreductase (EC

1.6.5.-) - human [H.sapiensl 227717921AI176422p, ESTs, Highly similar kk to S41115 probable flavoprotein-ubiquinone oxidoreductase (EC

1.6.5.-) - human [H.sapiensl 228213678AI176490a ~ ESTs, Weakly similar to T00065 hypothetical protein KIAA0442 - human (fragment) [H.sapiensl 22903619AI176588vv ESTs, Weakly similar to tumor protein p53-binding protein; topoisomerase I binding protein [Homo sapiensl [H.sapiensl 23144190AI177016z, ESTs, Highly similar ee to LSMB_HUMAN U6 snRNA-associated Sm-like protein LSm8 H.sa iens FR
TABLE

_ Attorney Docket No.

Document'No.1926271.2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence.ClusterTitle ~

ID D Acc: Code ' N0. or I

N0 RefSeq ID

No:

232823162AI177353a, ESTs, Highly similar q, to A47220 x, dd dermatopontin precursor - human [H.sapiens]

23386315AI177645bb ESTs, Weakly similar to S69890 mitogen i nducible gene mig-2 - human [H.sapiens]

235716739AI178151cc ESTs, Highly similar to T46366 hypothetical protein DKFZp434C0118.1-human (fragment) fH.sapiens]

236023248AI178267b, ESTs, Weakly similar f, to JC7185 p, q, General, chromosome 1 C1orf9 protein - human dd [H.sapiensl 23718418AI178566a ESTs, Highly similar to T00260 hypothetical protein KIAA0605 - human [H.sapiens]

237423456AI178665p ESTs, Moderately similar to T08719 hypothetical protein DKFZp566B183.1 -human [H.sapiens 237511374AI178672k ESTs, Weakly similar to 601614 zinc finger protein 127 - human [H.sapiens]

23911924AI178902r, ESTs, Highly similar z to T50836 Yippee protein [imported] -human (fragment) [H.sapiensl 24004587AI179092ff ESTs, Moderately similar to RL22_RAT 60S
-[R.norvegicus]

240213055AI179100General, ESTs, Highly similar jj to CN01 HUMAN
-Protein C14orf1 (HSPC288) (Protein AD-011) (x0006) [H.sapiens]

240421631AI179125s ESTs, Highly similar to eukaryotic translation initiation factor 3, subunit 3 (gamma, 40kD) [Homo sapiens] [H.sapiens]

240617358AI179147b, ESTs, Highly similar ii, to B Chain B, Three-pp Dimensional Structure Of Human Electron Transfer Flavoprotein To 2.1 A Resolution fH.sapiens 241013606AI179289j ESTs, Weakly similar to S65464 pregnancy-associated plasma protein A precursor-human [H.sapiens]

243823989AI179953ii, ESTs, Highly similar ss to 1604368A gap junction protein Cx26 [Rattus norvegicus]

(R.norvegicusl 244617365AI180249m ESTs, Highly similar to colon cancer-associated protein Mic1 [Homo sapiens]

[H.sapiens]

24537460AI180413r ESTs, Highly similar to NBRT apolipoprotein H precursor - rat [R.norvegicus]

248921822AI2286420o ESTs, Highly similar to hypothetical protein MGC1936 Homo sa iens H.sa iens TABLE

Attorney Docket No.
44921'-5113W0 Document No.1926271.2 SEQ GLGCGenBa~k Model Known Gene Name Uriigene Sequence ClusterTitle -ID D Acc. Code I N0. or ~

N0. RefSeq tD

No.

250223955AI229178a ESTs, Highly similar to S51635 fibroblast growth factor receptor 2b, keratinocyte growth factor receptor - rat [R.norvegicusl 250811527AI229307rr, ESTs, Highly similar uu to S27958 transcription factor BTF2 62K chain - human [H.sapiens]

251119138AI229413s ESTs, Moderately similar to T00054 hypothetical protein KIAA0415 - human (fragment) [H.sapiensl 251323563AI229421pp ESTs, Moderately similar to S78100 MAPK-activated protein kinase (EC 2.7.1.-) 2 -mouse (fragment) [M.musculus]

25232688AI229793k, ESTs, Weakly similar s to hypothetical protein FLJ20010 [Homo sapiens]
[H.sapiens]

252713879AI2300040o ESTs, Moderately similar to T00374 hypothetical protein KIAA0648 - human (fragment) f H.sa lens]

25284722AI230038c, ESTs, Moderately similar II to T08811 hypothetical protein DKFZp586M1523.1 -human (fragment) [H.sapiensl 25354662AI230215II ESTs, Moderately similar to hypothetical protein FLJ10468 [Homo sapiens]

[H.sapiensl 253615862AI230228m, ESTs, Weakly similar n, to SERC_HUMAN
a -Phosphoserine aminotransferase (PSAT) [H.sapiens]

255524270AI230758rr ESTs, Moderately similar to cargo selection protein (mannose 6 phosphate receptor binding pr; cargo selection protein (mannose 6 phosphate receptor binding protein) [Homo sapiensl fH.saaiensl 25578036AI230884c, ESTs, Highly similar tt to HMBA-inducible [Homo sapiens] [H.sapiens]

256514303AI231159y ESTs, Highly similar to KIAA1049 protein [Homo sapiens] [H.sapiens]

257619271AI231566f, ESTs, Highly similar q, to MAX_RAT MAX
pp, ww protein [R.norvegicus]

258824501AI232006m translation elongationtranslation elongation factor 1- factor 1-delta subunit delta subunit 260615122AI232303g, ESTs, Weakly similar General, to JC5393 zinc finger dd proteinKF-1 precursor-mouse [M.musculusl 261914051AI232489w, ESTs, Weakly similar z, to dual specificity dd, ee phosphatase 11; RNAIRNP
complex-interacting phosphatase;
serinelthreonine specific protein phosphatase [Homo sapiens]

H.sa i ns RR
TABLE~1.
-Attorney Docket No.

Document No.1926271.2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster Title ID D Acc. Code I NO. or NO: RefSeq . ID

No.

26203662AI232506o ESTs, Weakly similar to T46908 hypothetical protein DKFZp76162423.1-human [H.sapiensl 262813645AI232694tt ESTs, Weakly similar to S24C_HUMAN

Protein transport protein Sec24C (SEC24-related protein C) [H.sapiensl 263817240AI233054mm ESTs, Weakly similar to UCRC~HUMAN

Ubiquinol-cytochrome C reductase complex ubiquinone-binding protein QP-C (Ubiquinol-cytochrome C reductase complex 9.5 kDa protein) (Complex III
subunit VII) [H.sapiens]

264611507AI233222ee ESTs, Highly similar to hypothetical protein MGC2803 [Homo sapiens]
[H.sapiens]

266118900AI233570ee ESTs, Highly similar to PSD8 HUMAN 26S
-proteasome non-ATPase regulatory subunit 8 (26S proteasome regulatory subunit S14) (p31)[H.sapiensl 26637888A1233583n, ESTs, Highly similar kk to SYR_HUMAN

ARGINYL-TRNA SYNTHETASE
(ARGININE

-TRNA LIGASE) (ARGRS) [H.sapiens], ESTs, Moderately similar to JC4365 arginine -tRNA ligase (EC 6.1.1.19) - human IH.saoiensl 26697243AI233717z, ESTs, Moderately similar ee to ERHUAH

coatomer complex alpha chain homolog -human [H.sapiens]

267017210AI233746pp ESTs, Weakly similar to SC14_HUMAN

SEC14-like protein 1 [H.sapiens]

269514745AI234919bb, ESTs, Moderately similar mm to SYHUQT

multifunctional aminoacyl-tRNA
ligase -human [H.sapiens]

26983875AI235047q ESTs, Highly similar to S50082 nuclear cap bindin protein - human [H.sapiens]

271720140AI235566g ESTs, Moderately similar to SYEP_HUMAN

Bifunctional aminoacyl-tRNA
synthetase [Includes: Glutamyl-tRNA
synthetase (Glutamate--tRNA ligase);
Prolyl-tRNA

synthetase (Proline--tRNA
ligase)]

IH.saoiensl 272224373AI235748I, ESTs, Moderately similar y, to Y110_HUMAN
ee, rr Hypothetical protein KIAA0110 (HA0666) [H.sapiens]

272514768AI235912f ESTs, Weakly similar to highly charged protein [Homo sapiens]
[H.sapiens]

27326976AI236072qq , ESTs, Weakly similar to T08680 hypothetical protein DKFZp564P0622.1 - human fra ment H.sa lens RA
TABLE

.:
Attorney Docket No.

Document No.19262'T1.2 SEQ GLGCGeriBankModel.:Known Gene Name Unigene=Sequenae Cluster . Title ID D Accor Code = N0.
I

N0 RefSeq ID

No;

273814879AI236200ee ESTs, Moderately similar to M1A1 MOUSE

Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (Processing alpha-1,2-mannosidase IA) (Alpha-1,2-mannosidase I A) (Mannosidase alpha class 1A member 1) (Man(9)-alpha-mannosidase) [M.musculus]

274615398AI236566s ESTs, Moderately similar to T12473 hypothetical protein DKFZp564G1762.1 -human (fragment) [H.sapiensl 274823249AI236597p, ESTs, Weakly similar ff to JC7185 chromosome 1 C1 orf9 protein - human f H.sapiensl 278121653AI237535I, LPS-induced TNF-alphaLPS-induced TNF-alpha qq factor factor 278915248AI237654nn, upregulated by upregulated by 1,25-dihydroxyvitamin xx 1,25- D-3 dihydroxyvitamin 283218533AI639231g ESTs, Highly similar to T46480 hypothetical protein DKFZp434L1850.1-human (fragment) [H.sapiensl 283925942AI639291cc ESTs, Weakly similar to S38783 integrin alpha chain - rat (fragment) [R.norvegicus]

284314606AI639342d ESTs, Highly similar to YS64 HUMAN
_ Hypothetical protein S164 [H.sapiens]

286120468AI639494m ESTs, Weakly similar to 601614 zinc finger protein 127 - human [H.sapiensl 290721864H31144 pp ESTs, Moderately similar to 1914275A non-receptor Tyr kinase [Homo sapiens]

[H.sapiensl 290720456H31144 II, ESTs, Moderately similar pp to 1914275A non-receptor Tyr kinase [Homo sapiens]

[H.sapiensl 291717913H31707 I, ESTs, Moderately similar x, to T50621 General, hypothetical protein DKFZp7620076.1 -dd, human fragment) [H.sapiensl uu 29184360H31813 z, ESTs, Moderately similar General to T14781 hypothetical protein DKFZp586B1621.1 -human (fragment) [H.sapiensl 30104224M31322 ff, sperm membrane sperm membrane protein mm protein (YWK- (YWK-II) II) 30104225M31322 nn, sperm membrane sperm membrane protein uu protein (YWK- (YWK-II) II) 30201586M57728 00, Rat general mitochondria) pp matrix processing protease (MPP) mRNA, 3' end 313515174NM_012756j, Insulin-like growthInsulin-like growth ss factor 2 factor 2 receptor rece for 7(1 TABLE

Attorney Docket No.
44921'-5113W0 Document No.=1926271.2 SEQ GLGC GenBankModel;Known Gene Name Unigene Sequetlce Cluster Title ID D Acc.-orCode I N0. _ N0~ RefSeq ID

No.

340320583NM 017306k, ESTs, Highly similar nn to D3D2_RAT 3,2-TRANS-ENOYL-COA ISOMERASE, MITOCHONDRIAL PRECURSOR

(DODECENOYL-COA DELTA-ISOMERASE) IR.norveaicusl 35791867 NM 022510ee ribosomal proteinribosomal protein L4 37131024 NM 031016k muscarinic receptormuscarinic receptor m2 m2 37251336 NM 031042k general transcriptiongeneral transcription factor IIF, factor IIF, polypeptide polypeptide 2 (30kD subunit) (30kD subunit) 38831105 NM_031758nn somatostatin receptor-likesomatostatin receptor-like protein protein 399822919NM 053556uu, maternal G10 transcriptmaternal G10 transcript ww 407420939NM 053884I, ATPase, vacuolar,14ATPase, vacuolar, 14 m, kD kD
s, General, bb, qq, uu 414918027NM_130407a UDP glycosyltransferaseUDP glycosyltransferase 1 1 family, family, polypeptidepolypeptide A7 414918028NM_130407a UDP glycosyltransferaseUDP glycosyltransferase 1 1 family, family, polype polypeptide A7 tide A7 418321703NM 1335250o putative c-Myc-responsiveputative c-Myc-responsive 420515655NM_133621nn global ischemia global ischemia induced induced protein protein GIIG15B

421212719NM 134373I, Esau Esau uu 422114697NM_134419dd protein associatingprotein associating with small with small stress protein stress protein PASS1 423413563NM 138530m, MAWD binding proteinMAWD binding protein fP

42581049 NM_138901g phosphatidylinositolphosphatidylinositol glycan, glycan, class L

class L

426616176NM_139087a cell growth regulatorycell growth regulatory with EF- with EF-hand domain hand domain 428022595NM_139253d stem cell derivedstem cell derived neuronal neuronal survival protein survival protein precursor precursor 42847859 NM_139328kk liver regeneration-relatedliver regeneration-related protein protein 429417277NM_145082g Rattus norvegicus glycine-, glutamate-, thienylcyclohexylpiperidine-binding protein mRNA, complete cds 42976731 NM_145096c Rattus norvegicus small rec (srec) mRNA, complete cds 43106824 NM_147138II, Rattus norvegicus SNAP25 ss interacting protein 30 (Sip30) mRNA, complete cds 434024351S74257 ii, ESTs, Weakly similar kk, to ABD4_MOUSE ATP
II, ww binding cassette, sub-family D, member 4 (Peroxisomal membrane protein 69) (PMP69) (Peroxisomal membrane protein 1-like) (PXMP1-L) (P70R) [M.muscqlus]

TABLE

Attorney Docket No:

Document No.1926271:2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster Title lD D Acc:: Code I N0. or NO'. RefSeq ID . a:

No.

438221654U53184 f, LPS-induced TNF-alphaLPS-induced TNF-alpha I, factor factor y, General, ee 439923282U90725 q, ipoprotein-bindinipoprotein-binding protein ff, protein l tt l 441520810X14181 I ESTs, Highly similar to R5RT18 ribosomal protein L18a, cytosolic [validated] - rat [R.norveqicusl 44207459X15551 a, ESTs, Highly similar j, to NBRT apolipoprotein n, r H precursor- rat [R.norvegicus]

442323987X51615 w, ESTs, Highly similar gg, to 1604368A gap hh j unction protein Cx26 [Rattus norvegicus]

[R.norvegicusl 44634223X77934 mm sperm membrane sperm membrane protein protein (YWK- (YWK-II) II) 73 13683AA799788s HHs:cell divisionESTs, Moderately similar cycle 34 to 154552 hypothetical serine proteinase - rat [R.norveqicusl 82 16346AA799824a, HHs:ATPase, H+ ESTs, Highly similar e, transporting, to VATC_MOUSE
f, s, General,lysosomal 42kD, Vacuolar ATP synthase V1 subunit C, subunit C (V-kk, isoform 1 ATPase C subunit) (Vacuolar oo proton pump C

subunit) IM.musculusl 107 4832AA8001900o HHs:phosphorylase,ESTs, Highly similar glycogen; to S37300 glycogen brain phosphorylase (EC 2.4.1.1 ), brain - rat [R.norvegicusl 12063364AA998097GeneralHHsaelenium donorESTs, Moderately similar protein to SPS2_MOUSE
_ Selenide,water dikinase 2 (Selenophosphate synthetase 2) (Selenium donor protein 2) (M.musculusl 171517506A1070068n, HHs:growth arrestESTs, Weakly similar kk and DNA- to 2104282A Gadd45 damage-inducible,gene [Rattus norvegicus]
beta [R.norvegicus]

191323829AI103754h HHs:UDP-Gal:betaGIcNAcESTs, Weakly similar beta to glycoprotein 1,4- galactosyltransferase,galactosyltransferase beta 1, 4; beta-1,4-polypeptide 2 GaIT; galactosyltransferase 2 beta 1, 4; B-1,4-GaIT1; beta-1,4-GaIT1 [Mus musculus]

IM.musculusl 191915050AI103911r HHs:ubiquinol-cytochromeESTs, Highly similar c to A32296 ubiquinol--reductase, Rieskecytochrome-c reductase iron-sulfur (EC 1.10.2.2) polypeptide 1 Rieske iron-sulfur protein precursor - rat (fragment) [R.norveaicusl 196723596AI105435uu, HHs:glutaryl-CoenzymeESTs, Highly similar vv A to GCDH_MOUSE

dehydrogenase Glutaryl-CoA dehydrogenase, mitochondrial precursor (GCD) [M.musculus]

209023152AI169170xx HHs:eukaryotic ESTs, Highly similar translation to S00985 translation initiation factorinitiation factor eIF-4A
4A, isoform 2 II - mouse M.musculus 7?
TABLE

Attorney-Docket No.

Document No.19262712 SEQ GLGCGenBank Model Known Gene-Name Unigene Sequence Cluster Title ID D Acc. Code I N0. or ' NO: RefSeq ID

No.

297913682L38482 p HHs:cell divisionESTs, Moderately similar cycle 34 to 154552 hypothetical serine proteinase - rat fR.norveaicus~

13 1599AA686470GeneralDNA-damage inducibleDNA-damage inducible transcript 3 transcript 3 13 1600AA686470pp DNA-damage inducibleDNA-damage inducible transcript 3 transcript 3 65 14250AA799729qq, PhosphodiesteraseESTs, Phosphodiesterase vv 4B, cAMP- 4B, cAMP-specific specific (dunce (dunce (Drosophila)-homolog (Drosophila)-homolog phosphodiesterasephosphodiesterase E4) E4) 66 18060AA799735c, RuvB-like proteinRuvB-like protein 1 j, 1 q, x 66 18061AA799735dd, RuvB-like proteinRuvB-like protein 1 oo 1 74 1680AA799792, hh Carboxyl ester Carboxyl ester lipase lipase 163 15852AA800942g, Complement componentComplement component hh 4 4 166 11901AA801058I, aldehyde dehydrogenasealdehyde dehydrogenase nn family family 9, subfamily 9, subfamily A1 A1 216 6054AA818658ww Diphtheria toxin Diphtheria toxin receptor receptor (heparin binding (heparin binding epidermal growth factor epidermal - like growth factor) growth factor - like growth factor) 217 4230AA818669I, RAB7, member RAS RAB7, member RAS oncogene ss oncogene family family ' 234 576 AA819118vv S - adenosylmethionineS - adenosylmethionine synthetase synthetase 236 6018AA819140x carbonic anhydrasecarbonic anhydrase 3 252 6288AA819554ww brain-specific brain-specific angiogenesis angiogenesis inhibitor 1-inhibitor 1-associatedassociated protein 2 protein 2 449 17742AA866302ss 4-hydroxyphenylpyruvic4-hydroxyphenylpyruvic acid acid dioxygenase dioxy enase 455 16333AA866414k Solute carrier Solute carrier family family 4, member 4, member 1, anion 1, anion exchangeexchange protein 1 (kidney protein 1 band 3) (kidney band 3) 484 1190AA875089II Calpastatin Calpastatin 549 19321AA891666t melanoma antigen,melanoma antigen, family family D,1 D,1 572 21674AA891828jj procolla en, typeprocollagen, type I, I, alpha 2 alpha 2 624 820 AA892395a, Aldolase B, fructose-Aldolase B, fructose-biphosphate s, ss, uu biphosphate 778 4661AA899709a receptor activityreceptor activity modifying modifying protein 3 protein 3 805 23038AA900881t, branched chain branched chain aminotransferase mm 1, aminotransferase cytosolic 1, cytosolic 835 20711AA924267o Cytochrome P450, Cytochrome P450, subfamily subfamily IVB, IVB, polypeptide polypeptide 1 869 23451AA925243j restin (Reed-Steinbergrestin (Reed-Steinberg cell- cell-espressed espressed intermediate- intermediate filament-associated filament protein) associated rotein TABLE

Attorney Docket No.

Document No.1v926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster _, _ Title ID D Acc~ Code I N0. or NO. Ref$eq ID

No.

108323700AA956382f Acetyl-CoA acyltransferase,Acetyl-CoA acyltransferase, f 3- 3-oxo acyl-CoA

oxo acyl-CoA thiolasehiolase A 1, peroxisomal A 1, t peroxisomal 119420712AA997806b, Cytochrome P450, Cytochrome P450, subfamily uu subfamily IVB, IVB, polypeptide polypeptide 1 12413081 AA999171GeneralSignal transducerSignal transducer and and activator activator of of transcription transcription 1 125222567AB017544u, peroxisomal membraneperoxisomal membrane kk anchor anchor protein protein 125619702AF008587p hemochromatosis hemochromatosis 127122602AF044574o putative peroxisomalputative peroxisomal 2,4-dienoyl~ 2,4-dienoyl-CoA

CoA reductase reductase 127122603AF0445740, putative peroxisomalputative peroxisomal kk 2,4-dienoyl~ 2,4-dienoyl-CoA

CoA reductase reductase 129910108A1007857b, HGF-regulated HGF-regulated tyrosine General,tyrosine kinase kinase substrate dd substrate 137617524A1010568ss Growth hormone Growth hormone receptor receptor 142824411A1012577h, Insulin-like growthInsulin-like growth z factor II factor II (somatomedin A) (somatomedin A) 14541332 A1013222mm Platelet-derived ESTs, Platelet-derived growth factor growth factor A chain A

chain 149617957A1028975d Adaptor protein Adaptor protein complex complex AP-1, AP-1, beta 1 beta 1 subunit subunit 15665648 A1044035ss protein phosphataseprotein phosphatase 4, 4, regulatory subunit re ulatory subunit 162624336A1045621r Myristoylated Myristoylated alanine-rich alanine-rich protein kinase C

protein kinase substrate C substrate 166619835A1058964II transporter protein;transporter protein;
system N1 system N1 Na+ and H+-Na+ and H+-coupledcoupled glutamine transporter glutamine transporter 190218679AI103496bb GDP-dissociation GDP-dissociation inhibitor inhibitor 1 1 21054091 AI169417I, Phosphoglycerate Phosphoglycerate mutase rr, mutase 1 1 tt 216423465AI171243ww erythrocyte proteinerythrocyte protein band 4.1-like band 4.1-like 3 216814960AI171319gg, guanine nucleotideESTs, Highly similar hh binding to SWI/SNF related, protein (G protein),matrix associated, actin beta dependent regulator polypeptide 2-likeof chromatin, subfamily 1 b, member 1;

integrase interactor 1 [Mus musculus]

[M.musculus], guanine nucleotide binding protein (G protein), beta polypeptide 2-like 22197579 AI172453v proteasome (prosome,proteasome (prosome, macropain) 26S

macropain) 26S subunit, non-ATPase, subunit, non- 10 ATPase, 10 226410182AI176185tt FBJ murine osteosarcomaFBJ murine osteosarcoma viral viral (v-fos) (v-fos) oncogene oncogene homolo homolog 229916477AI176701jj Fatty acid bindingFatty acid binding protein protein 3, 3, muscle and muscle and heart heart TABLE

Attorney Docket Ho.'44921-5113WQ

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluste~
. Title...::

ID D Acc. Code I N0. or NO: RefSeq ID

No.

230617235AI176815n Tissue inhibitor Tissue inhibitor of of metalloproteinase 3 metalloproteinase 233014989AI177366b Integrin, beta ntegrin, beta 1 234713558AI177901k Adrener is receptorAdrener is receptor beta 1 beta 1 234815315AI177911x cal actin I heavycalpactin I heavy chain chain 242716081AI179610s, Heme oxygenase Heme oxygenase rr 25374280 AI230247c, selenoprotein selenoprotein P, plasma,1 v, P, plasma,1 General 25461378 AI230602m Retinoblastoma-relatedRetinoblastoma-related gene gene 256118778AI230982ww Eph receptor B2 Eph receptor B2 (ELK-related (ELK-related protein protein tyrosine tyrosine kinase) kinase) 257024326AI231292a, Cystatin C (cysteineCystatin C (cysteine I, proteinase proteinase inhibitor) General,inhibitor) cc, qq 257024327AI231292h, Cystatin C (cysteineCystatin C (cysteine I, proteinase proteinase inhibitor) rr inhibitor) 257119288AI231305a Platelet-derived Platelet-derived growth growth factor factor receptor alpha receptor alpha 264717907AI233224t Epidermal growth Epidermal growth factor factor receptor, formerly receptor, formerlyavian erythroblastic avian leukemia viral (v-erbB) erythroblastic oncogene homolog (Erbb1) leukemia viral (v-erbB) oncogene homolog (Erbb1) 270619995A1235320p, mitochondrial mitochondrial aconitase t aconitase (nuclear(nuclear aco2 gene) aco2 gene) 27122241 A1235500ss cofilin 1, non-musclecofilin 1, non-muscle 288018686D00729 0, dodecenoyl-CoenzymeRat mRNA for delta3, ff, A delta delta2-enoyl-CoA
jj isomerase (3,2 isomerase, dodecenoyl-Coenzyme trans-enoyl- A delta Coenyme A isomerase)isomerase (3,2 trans-enoyl-Coenyme A

isomerase) 2889536 D25290 Cadherin 6 (K-cadherin)Cadherin 6 (K-cadherin) 289016610D28557 n, cold shock domaincold shock domain protein General,protein A A

oo, rr 2897935 D49434 bb, Arylsulfatase Arylsulfatase B (MPS
ww B (MPS VI) VI) 294620429J05035 t, Steroid-5-alpha-reductase,Steroid-5-alpha-reductase, xx alpha alpha polypeptidepolypeptide 1 (3-oxo-5 1 (3-oxo-5 alpha-steroid delta alpha-steroid dehydrogenase alpha delta 4- 1 ) dehydroaenase alpha 1) 294620430J05035 bb, Steroid-5-alpha-reductase,Steroid-5-alpha-reductase, qq alpha alpha polypeptidepolypeptide 1 (3-oxo-5 1 (3-oxo-5 alpha-steroid delta alpha-steroid dehydrogenase alpha delta 4- 1) dehvdroaenase alpha 1) 29471247 J05181 vv Glutamylcysteine Glutamylcysteine gamma gamma synthetase light s nthetase light chain chain 294920549K01701 y OxytocinlneurophysinOxytacin/neurophysin 295620865L00117 g, Elastase 1 Elastase 1 w, rr 29575616 L00191 j Fibronectin 1 Fibronectin 1 295924425L08812 k transcri tion transcri tion factor factor EC EC

TABLE~1 Attorney Docket No.

Documenfi No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence,ClusterTitle ID D Acc~ Code I N0. or ' NQ-. RefSeq ID

No.

297415073L22761 ww GATA-binding proteinGATA-binding protein 297512058L25387 phosphofructokinase,ESTs, Highly similar t platelet to A53047 6-phosphofructokinase (EC
2.7.1.11) - rat fR.norveqicusl 29806406 L38615 v Glutathione synthetaseGlutathione synthetase ene ene 298521097M12112 s Angiotensinogen Angiotensinogen 299120714M14972 0, Cytochrome P450, Cytochrome P450, subfamily r subfamily IVB, IVB, polypeptide polypeptide 1 299524407M17960 v Insulin-like growthInsulin-like growth factor factor II II (somatomedin A) (somatomedin A) 30046626 M24353 I, mannosidase 2, ESTs, Highly similar k, alpha 1 to M2A1 RAT Alpha-General, mannosidase II (Mannosyl-oligosaccharide II

1,3-1,6-alpha-mannosidase) (MAN II) (Golgi alpha-mannosidase II) (Mannosidase alpha class 2A member 1) [R.norvegicus]

3005668 M25823 jj Protein tyrosine Protein tyrosine phosphatase, phosphatase, receptor-type, receptor-type, c polypeptide (antigen c polypeptide Cd45, leukocyte-(antigen Cd45, common antigenlT200 glycoprotein) leukocyte- also common antigenlT200RT7 qlvcooroteinl also RT7 300716930M27440 h, Apolipoprotein Apolipoprotein B
o, B
ss, vv 301123610M32754 I Inhibin, alpha Inhibin, alpha 301920713M57718 0, Cytochrome P450, Cytochrome P450, subfamily r, subfamily IVB, xx IVB, polypeptide polypeptide 1 30222465 M59814 ee, Eph receptor B2 Eph receptor B2 (ELK-related ww (ELK-related protein protein tyrosine tyrosine kinase) kinase) 3023457 M60666 c, Tropomyosin 1 Tropomyosin 1 (alpha) nn (alpha) 302424253M61142 s Thimet oli opeptidaseThimet oli opeptidase 304317991M96626 g ATPase, Ca++ transporting,ATPase, Ca++ transporting, plasma plasma membrane membrane 3 30441678 M96674 I, glucagon receptorglucagon receptor General, nn, pp 304623698NM 0124890, Acetyl-CoA acyltransferase,Acetyl-CoA acyltransferase, xx 3- 3-oxo acyl-CoA

oxo acyl-CoA thiolasethiolase A 1, peroxisomal A 1, peroxisomal 304623699NM 0124890, Acetyl-CoA acyltransferase,Acetyl-CoA acyltransferase, u, 3- 3-oxo acyl-CoA
v, ss oxo acyl-CoA thiolasethiolase A 1, peroxisomal A 1, peroxisomal 3047265 NM 012494, hh, Angiotensin receptorAn iotensin receptor jj 2 2 30487062 NM 012495t, Aldolase A, fructose-Aldolase A, fructose-bisphosphate bb, mm bisphosphate 30487064 NM 012495s Aldolase A, fructose-Aldolase A, fructose-bisphosphate bisphosphate 30491655 NM 012497n Aldolase C, fructose-Aldolase C, fructose-biphosphate bi hos hate TABLE

Aftorney Docket No44921-5113W0 Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster '' Title ID D Acc. Code I N0. or.
' NO RefSeq ID .

N o. '' 30501421 NM 012500 N-acylaminoacyl-peptideN-acylaminoacyl-peptide f hydrolase hydrolase 305117787NM 012501ee Apolipoprotein Apolipoprotein C-III
C-III

305315675NM 012504GeneralATPase, Na+K+ ATPase, Na+K+ transporting, transporting, alpha 1 alpha 1 polypeptidepolypeptide 305315677NM_012504General,ATPase, Na+K+ ATPase, Na+K+ transporting, transporting, alpha 1 mm alpha 1 polypeptidepolypeptide 3054855 NM 012507II ATPase, Na+K+ ATPase, Na+K+ transporting, transporting, beta beta polypeptide polypeptide 2 30567427 NM 012515II Benzodiazepin Benzodiazepin receptor receptor (peripheral) (peripheral) 305820518NM 012518e, CalmOdulin III Calmodulin III
nn 305915740NM 012520p Catalase Catalase 305915741NM 0125200, Catalase Catalase General, bb 306024865NM 012521ss Calcium-binding Calcium-binding protein, protein, intestinal, vitamin D

intestinal, vitamindependent (9-kDa CaBP) D-dependent (9-kDa CaBP) 306111115NM 012531I, Catecholamine-0- Catecholamine-0-methyltransferase nn methyltransferase 306111116NM 012531nn Catecholamine-0- Catecholamine-0-methyltransferase methyltransferase 306320357NM 012534p, Crystallin, alphaCrystallin, alpha polypeptide bb polypeptide A A

3064488 NM 012540j, Cytochrome P450, Cytochrome P450, subfamily w subfamily I I (aromatic (aromatic compound-inducible),compound-inducible), member A1 (C6, form member A1 (C6, c) form c) 3064489 NM 012540e, Cytochrome P450, Cytochrome P450, subfamily tt subfamily I I (aromatic (aromatic compound-inducible),compound-inducible), member A1 (C6, form member A1 (C6, c) form c) 306420705NM 012540j Cytochrome P450, Cytochrome P450, subfamily subfamily I I (aromatic (aromatic compound-inducible),compound-inducible), member A2 (Q42, member A2 (Q42, form d) form d) 306520703NM 012541xx Cytochrome P450, Cytochrome P450, subfamily subfamily I I (aromatic (aromatic compound-inducible),compound-inducible), member A2 (Q42, member A2 (Q42, form d) form d) 3066225 NM 012544j Angiotensin I-convertingAngiotensin I-converting enzyme (Dipeptidyl enzyme (Dipeptidylcarboxypeptidase 1) carboxypeptidase 1) 306723868NM 012551dd, Early rowth responseEarly rowth response oo, 1 1 tt 306723869NM 01255100, Early growth responseEarly growth response tt 1 1 306723871NM 012551tt, Early growth responseEarly growth response vv 1 1 306723872NM 012551dd, Early growth responseEarly growth response tt 1 1 306917676NM 012556g, Fatty acid bindingFatty acid binding protein j protein 1, liver 1, liver TABLE

Afto~ney Docket Ho~

Document No.-1926271:2 SEQ GLGC GenBank'Model Known Gene Name Jnigene'Sequence Cluster l Title ID D Acc: Code ' NO. or I

N0. Ref$eq ID

No.f.

30721732 NM 012561p Follistatin Follistatin 307420717NM 012569c Glutaminase Glutaminase 30754573 NM 012570, GeneralGlutamate dehydroGlutamate dehydrogenase I enase 30754574 NM 012570h, Glutamate dehydrogenaseGlutamate dehydrogenase I, p, General, dd, ii, uu 307785 NM 012572c Glutamate receptor,Glutamate receptor, ionotropic, ionotropic, kainate kainate 4 307916024NM 012578m Histone H1-0 Histone H1-0 307916025NM 012578m, Histone H1-0 Histone H1-0 ww 307916026NM 012578m, Histone H1-0 Histone H1-0 ww 308120313NM 012585k 5-Hydroxytryptamine5-Hydroxytryptamine (serotonin) (serotonin) receptor rece for 1A

308221162NM 012591d, Interferon re Interferon regulatory a ulatory factor factor 1 30834449 NM 012592z, Isovaleryl CoenzymeIsovaleryl Coenzyme GeneralA A dehydrogenase dehydro enase 30834450 NM 012592p Isovaleryl CoenzymeIsovaleryl Coenzyme A A dehydrogenase dehydrogenase 30852505 NM 012597w Lipase, hepatic Lipase, hepatic 30882628 NM_012603f, Avian myelocytomatosisAvian myelocytomatosis I, viral (v- viral (v-myc) y, z, Generalmyc) oncogene onco ene homolo homolog 30882629 NM 012603f, Avian myelocytomatosisAvian myelocytomatosis I, viral (v- viral (v-myc) I, z, General,myc) oncogene oncogene homolog homolog nn 308916850NM_012608k Membrane metallo-Membrane metallo-endopeptidase (neutral endopeptidase endopeptidase/enkephalinase) (neutral endopeptidase/enkephalinase) 309124506NM 012614d, Neuropeptide Y Neuropeptide Y
v 309223522NM 012615c, Ornitine decarboxylaseOrnitine decarboxylase g, I, m, n, w, General, kk 309223523NM 012615I, Ornitine decarboxylaseOrnitine decarboxylase v 30936055 NM 012619b, Phenylalanine Phenylalanine hydroxylase I, hydroxylase General, uu 309524568NM 012630g Prolactin receptorProlactin receptor 309618553NM 012631b, Prion protein, Prion protein, structural c, structural qq, vv 309820798NM 012639II Murine leukemia Murine leukemia viral viral (v-raf-1) (v-raf-1) oncogene oncogene homolog homolog 1 (3611-MSV) 1 (3611-MSV) 309820799NM 012639p Murine leukemia Murine leukemia viral viral (v-raf-1) (v-raf-1) oncogene oncogene homolog homolog 1 (3611-MSV) 1 (3611-MSV) 310016220NM 012656c, Secreted acidic Secreted acidic cystein-rich cc cystein-rich glycoprotein glycoprotein (osteonectin)(osteonectin) 310324825NM 012668x, T rosine aminotransferaseT rosine aminotransferase ee, ss TABLE

Attorney,Docket No.
44921~51131NQ

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name nigene Sequence Cluster U Title ID- ID Acc: Code N0. or NO. RefSeq w ID'' No 310424427NM 012669pp Transcription Transcription factor factor 1, hepatic;1, hepatic; LF-B1, LF-B1, hepatic hepatic nuclear factor nuclear factor (HNF1): albumin (HNF1): albumin proximal factor, also proximal TCF1 factor, also TCF1 310617117NM 012673w Thymus cell surfaceThymus cell surface anti en antigen 31104185 NM_012681ee, Transthyretin Transthyretin (prealbumin, gg, (prealbumin, amyloidosis type hh amyloidosis type I) I) 31104186 NM 012681n, Transthyretin Transthyretin (prealbumin, ee (prealbumin, myloidosis type a am loidosis type I) I) 31115850 NM 012687g ThromboxA ane ThromboxA ane s nthase synthase 1 1 311224453NM 012690a, ATP-binding cassette,ATP-binding cassette, s sub- sub-family B

family B (MDRITAP),(MDRITAP), member 4 member 4 (P-glycoprotein 3I

(P-glycoprotein multidrug resistance 3/ multidrug 2 resistance 2 31161850 NM 012696a T-kininogen, see T-kininogen, see also also D11EIh1 D11EIh1 and D11Mit8 and D11Mit8 31161854 NM 012696a T-kininogen, see T-kininogen, see also also D11EIh1 11EIh1 and D11Mit8 D

and D11Mit8 31204002 NM 012708p, Low molecular Low molecular mass polypeptide General,mass 2 nn polypeptide 2 31204003 NM 012708p Low molecular Low molecular mass polypeptide mass 2 polypeptide 2 31204004 NM 012708nn Low molecular Low molecular mass polypeptide mass 2 polypeptide 2 31204005 NM 012708GeneralLow molecular Low molecular mass mass olypeptide 2 p polypeptide 2 3122322 NM 012715p, Adrenomedullin Adrenomedullin t, ff, ii, pp, xx 31231632 NM 012717d, Calcitonin receptor-likeCalcitonin receptor-like y receptor receptor 31271372 NM 012734xx Hexokinase 1 Hexokinase 1 31371348 NM 012776m adrenergic receptoradrenergic receptor kinase, beta inase, beta 1 k 31371349 NM 012776i, adrenergic receptoradrenergic receptor i rr kinase, beta kinase, beta 1 313911938NM 012783x Basigin (0x47 Basigin (0x47 antigen antigen or CE-9) or C E-9) (EMMPRIN

( EMMPRIN in human)n human) (neurothelin, i HT7 or 5A11 in ( neurothelin, HT7 avian) or 5A11 in avian) 314216947NM 012793a, Guanidinoacetate Guanidinoacetate methyltransferase b, e, m, s, methyltransferase z, General, aa, uu, vv 314216948NM 012793qq, Guanidinoacetate Guanidinoacetate uu m ethyltransferase methyltransferase 3143961 NM 012796p g lutathione S-transferase,lutathione S-theta g ransferase, theta 2 t TABLE

..
Attorney:Docket No.

Document No.1926271 ~2 SEQ GLGC GenBankModel'Known Gene Name Unigene SequencevCluster Title ID D Acc: Code ' N0. or I

N0: RefSeq ID

No.
.

314715032NM_012816 alpha-methylacyl-CoAalpha-methylacyl-CoA
t racemase racemase 3148326 NM_012818ss Arylalkylamine Arylalkylamine N - acetyltransferase N -acetyltransferase(Serotonin N - acetyltransferase) (Serotonin N
-acetyltransferase) 31496780 NM 012819n Acyl Coenzyme Acyl Coenzyme A dehydrogenase, A long dehydrogenase, chain long chain 315120586NM 012826a, Zn - alpha2 - Zn - alpha2 - glycoprotein m, lycoprotein vv 315120587NM 012826v, Zn - alpha2 - Zn - alpha2 - glycoprotein vv lycoprotein 315215035NM 012836nn Carboxypeptidase Carboxypeptidase D precursor D precursor 31532853 NM 012838j, Cystatin beta Cystatin beta I, qq 31532854 NM 012838j, Cystatin beta Cystatin beta I, General, cc, rr 31532855 NM 012838I, Cystatin beta Cystatin beta cc 3155338 NM 012843t, Epithelial membraneEpithelial membrane ff, protein 1 protein 1 mm 315617541NM_012844I, Epoxide hydrolaseEpoxide hydrolase 1 s, 1 (microsomal xenobiotic General,(microsomal xenobiotichydrolase) ff, II, hydrolase) ww 3157644 NM 012846kk Fibroblast growthFibroblast growth factor factor 1 1 (heparin binding) ( heparin binding) 315820819NM 012847vv Farnesyltransferase,Farnesyltransferase, subunit subunit alpha alpha 316515872NM 012879bb Solute carrier Solute carrier family family 2 A2 2 A2 (gkucose ( kucose transporter,transporter, type 2) ty a 2) 316616301NM 012883g, Estrogen sulfotransferaseEstro en sulfotransferase w, rr 31664282 NM 012883rr Estrogen sulfotransferase,Estrogen sulfotransferase, selenoprotein P, selenoprotein plasma, 1 P, plasma, 1 316716870NM 012887v Thymopoietin (laminaThymopoietin (lamina associated associated polypeptidepolypeptide 2) 2) 316716871NM 012887r, Thymopoietin (laminaThymopoietin (lamina z, associated ee, oo associated polypeptidepolypeptide 2) 2) 316716872NM 012887pp Thymopoietin (laminaThymopoietin (lamina associated associated polypeptidepolypeptide 2) 2) 316916708NM 012895a, Adenosin kinase Adenosin kinase b, h, w 317116273NM 012898k alpha-2-HS-glycoproteinalpha-2-HS-glycoprotein 317116274NM 012898r alpha-2-HS-glycoproteinalpha-2-HS-glycoprotein 317116275NM 012898r, alpha-2-HS-glycoproteinalpha-2-HS-glycoprotein ee 317218564NM 012899k, aminolevulinate,delta-aminolevulinate,delta-,dehydratase w ,dehydratase 31737897 NM 012901a Alpha-1 micro Alpha-1 microglobulinlbikunin lobulinlbikunin 31737898 NM 012901e, Alpha-1 microglobulinlbikuninAlpha-1 microglobulinlbikunin r 31737899 NM 012901a Alpha-1 micro Alpha-1 micro lobulinlbikunin lobulinlbikunin 317620590NM 012913n, ATPase, Na+K+ ATPase, Na+K+ transporting, kk transporting, beta beta polypeptide polypeptide 3 317724783NM 012914p ATPase, Ca++ transporting,ATPase, Ca++ transporting, ubiquitous ubi uitous TABLE

.
Attorney DockefNo.

Document No.1926271.2 SEQGL.GCGenBankModel Known Gene Name IJnlgene Sequence Cluster _ Title ID ID Acc. Code N0. or N0. RefSeq ID

No:

3179776 NM 012922a Caspase 3, apoptosisCaspase 3, apoptosis related related cysteine cysteine proteaseprotease (ICE-like cysteine (ICE-like protease) cysteine protease) 3179777 NM 012922z Caspase 3, apoptosisCaspase 3, apoptosis related related cysteine cysteine proteaseprotease (ICE-like cysteine (ICE-like protease) cysteine protease) 31821977 NM 0129300, Carnitine palmitoyltransferaseCarnitine palmitoyltransferase p, 2 2 y, ff, xx 3186190 NM 012940a Cytochrome P4501b1Cytochrome P4501b1 3186191 NM 012940a Cytochrome P4501 Cytochrome P4501 b1 b1 3186192 NM 012940a Cytochrome P4501b1Cytochrome P4501b1 3186193 NM 012940e, Cytochrome P4501b1Cytochrome P4501b1 v 318720928NM 012941ee Cytochrom P450 Cytochrom P450 Lanosterol Lanosterol 14 14 alpha-alpha-demethylasedemethylase 318720929NM 012941jj Cytochrom P450 Cytochrom P450 Lanosterol Lanosterol 14 14 alpha-alpha-demethylasedemethylase 318720931NM 012941uu Cytochrom P450 Cytochrom P450 Lanosterol Lanosterol 14 14 alpha-alpha-demethylasedemethylase 31891285 NM 012948r, Emerin Emerin x 31901813 NM_012953I, Fos-like antigen Fos-like antigen 1 p, 1 y, z, ee 31925034 NM 012966v Heat shock 10 Heat shock 10 kD protein kD protein 1 1 (chaperonin 10) (chaperonin 10) 31932554 NM_012967vv Intercellular Intercellular adhesion adhesion moleculemolecule 1 31932555 NM_012967vv Intercellular Intercellular adhesion adhesion moleculemolecule 1 319524528NM 012973g Potassium (K+) Potassium (K+) channel channel protein, protein, slowly slowly activatin activating (Isk) (Isk) 320024492NM 012987jj Nestin Nestin 3201764 NM 012988c, Nuclear Factor Nuclear Factor IA
p, IA
r, z, General 3201765 NM_012988h, Nuclear Factor Nuclear Factor IA
q, IA
z, General 320216417NM 012991I, Nucleoprotein Nucleoprotein 50kD
x, 50kD

General, VV

320317393NM 012992b, Nucleoplasmin-relatedNucleoplasmin-related I, protein protein (Nuclear j, General,(Nuclear protein protein B23 aq 320317394NM 012992GeneralNucleoplasmin-relatedNucleoplasmin-related protein protein (Nuclear (Nuclear protein protein B23 32061640 NM 013000pp Peptidylglycine Peptidylglycine alpha-amidating alpha-amidating monooxygenase monooxygenase 32061649 NM 013000n Peptidylglycine Peptidylglycine alpha-amidating alpha-amidating monoox enase monoox enase TABLE

Attorney Docket No.

Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title fD D Act: Code:
= N'0. or I

N0. Ref$eq ID

No:

320825279NM 013011bb Tyrosine 3- Tyrosine 3-monooxygenase/tryptophan monooxygenase/tryptophanmonooxygenase activation 5- protein, zeta monooxygenase polypeptide activation protein, zeta polVpeptide 32083405 NM_013011ss Tyrosine 3- Tyrosine 3-monooxygenaseltryptophan monooxygenase/tryptophanmonooxygenase activation 5- protein, zeta monooxygenase polypeptide activation protein, zeta polVpeptide 321011905NM 013016s, Protein tyrosine Protein tyrosine phosphatase, x phosphatase, non-receptor non-receptor typetype substrate 1 (SHP
substrate 1 substrate 1 ) (SHP substrate 1) 32121588 NM_013026j, Syndecan 1 Syndecan 1 t, mm, ww 32121589 NM 013026mm Syndecan 1 Syndecan 1 321317894NM 013027v Selenoprotein Selenoprotein W muscle W muscle 1 1 32141734 NM 0130280o Short stature Short stature homeobox homeobox 2 2 3216313 NM 013033g Solute carrier Solute carrier family family 5, member 5, member alpha 1 alpha 1 (Na+Iglucose(Na+/glucose cotransporter) cotransporter) 321724809NM 013036g Somatostatin receptorSomatostatin receptor subtype 4 subtype 4 Rattus R attus norvegicus norvegicus Sprague-Dawley Sprague- major Dawley major hippocampalhippocampal somatostatin receptor (SSTR4) somatostatin receptormRNA
(SSTR4) mRNA

3218115 NM 013037a Interleukin 1 Interleukin 1 receptor-like receptor-like 1 (Fos-responsive 1 (Fos~

responsive ene gene 1) 1) 322112013NM 013050I, Ubiquitin conjugatingUbiquitin conjugating nn enzyme enzyme E21 322112014NM_013050I, Ubiquitin conjugatingUbiquitin conjugating j, enzyme enzyme E21 y 322216683NM 013052r Tyrosine 3- Tyrosine 3-monooxygenaseltryptophan monooxygenaseltryptophanmonooxygenase activation 5- protein, eta monooxygenase polypeptide activation protein, eta polypeptide 322216684NM 013052pp Tyrosine 3- Tyrosine 3-monooxygenase/tryptophan monooxygenaseltryptophanmonooxygenase activation 5- protein, eta monooxygenase polypeptide activation protein, eta polVpeptide 322412370NM 013055a Mitogen activatedMitogen activated protein protein kinase kinase 12 (Zipper 12 (Zipper (leucine)(leucine) protein kinase) protein kinase) 323213282NM 013078n, Ornithine carbamoyltransferaseOrnithine carbamoyltransferase jj 323213283NM 013078h, Ornithine carbamoyltransferaseOrnithine carbamoyltransferase I, m, s, General, cc, uu 323915296NM 013102k FK506 binding FK506-binding protein protein 2 (13 1 (12kD) kDa), FK508-binding protein 1 12kD

TABLE
1;
_ Aftorney DocketNo.
44921=5113W0 Document No.1.926271:2 SEQGLGC GertBankModel Knowrt:Gene Name Unigene'Sequence ClusterTitle ID ID_N0.Acc, Code or NO. RefSeq ID

No.

32401885 NM 013103I, Transcription Transcription factor u, factor 2, hepatic;2, hepatic; LF-B3;
z LF-B3; variant variant hepatic nuclear hepatic nuclear factor factor 324224195NM 013111f, Solute carrier Solute carrier family q family 7 member 7 member A1 (amino A1 (amino acid acid transporter cationic transporter 1) cationic 1) 324224196NM 013111f, S0lute carrier Solute carrier family I, family 7 member 7 member A1 (amino q, z, General,A1 (amino acid acid transporter cationic transporter 1) dd cationic 1) 324614300NM 013129pp Interleukin 15 Interleukin 15 3248650 NM_013134vv 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-Coenzyme A

Coenzyme A reductasereductase 3248651 NM_013134t 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-Coenzyme A

Coenz me A reductasereductase 3248652 NM_013134n, 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-Coenzyme t A

Coenzyme A reductasereductase 32501712 NM_013138nn Inositol 1, 4, Inositol 1, 4, 5-triphosphate 5-triphosphate receptor 3 receptor 3 32515837 NM 013143s Meprin 1 alpha Meprin 1 alpha 325421683NM 013154d, CCAAT/enhancerbinding,CCAAT/enhancerbinding, g protein (C/EBP) protein (CIEBP) delta delta 32563430 NM 013156g, Cathepsin L Cathepsin L
General, oo, pp, uu 32563431 NM 013156z, Cathepsin L Cathepsin L
cc 3260447 NM 013165tt Cholecystokinin Cholecystokinin B receptor B receptor 326124750NM 013167cc Uncoupling proteinUncoupling protein 3, 3, mitochondria) mitochondria) 327320854NM 013200j, Carnitine palmitoyltransferaseCarnitine palmitoyltransferase nn 1 1 beta, beta, muscle isoformmuscle isoform 327320856NM_0132000, Carnitine palmitoyltransferaseCarnitine palmitoyltransferase jj 1 1 beta, beta, muscle isoformmuscle isoform 327523361NM 013216r Ras homolog enrichedRas homolo enriched in brain in brain 328221078NM_016986I, Acyl-Coenzyme Acyl-Coenzyme A dehydrogenase, o, A C-4 to C-ss dehydrogenase, 12 straight-chain C-4 to C-12 straight-chain 328315612NM 016987ee ATP citrate lyaseATP citrate lyase 328315613NM 016987ii, ATP citrate lyaseATP citrate lyase II, ww 328524868NM 016992nn Arginine vasopressinArginine vasopressin (Diabetes (Diabetes insipidus) insipidus) 328524869NM 016992g Arginine vasopressinArginine vasopressin (Diabetes (Diabetes insipidus) insipidus) 329015620NM 017005p Fumarate hydrataseFumarate hydratase 32918417 NM 017008I Glyceraldehyde-3-phosphateGlyceraldehyde-3-phosphate dehydrogenase dehydrogenase 329417815NM 017015p, Glucuronidase, Glucuronidase, beta r, beta w, z 3295649 NM 017017cc Hepatocyte growthHepatocyte growth factor factor (scatter factor) scatter factor TABLE

-Attorney Docket No~'44921-5113W0 Document No.1926271.2 SEQ GLGC GenBankMode Known Gene Name Unigene'Sequence Cluster I Title 1D ID Ace. _ NO. or Code N0. RefSeq ID

No.

329811836NM 017023g Potassium inwardly-rectifyingPotassium inwardly-rectifying channel, channel, subfamilysubfamily J
J

3299670 NM 017024a, Lecithin-cholesterolLecithin-cholesterol m, acyltransferase v, cc, uu, acyltransferase vv 33014500 NM 017037m, Peripheral myelinPeripheral myelin protein protein General, ii, qq, uu, vv 33023202 NM 017039 Protein phosphataseProtein phosphatase t 2 (formerly 2 (formerly 2A), 2A), catalytic catalytic subunit, alpha subunit, alpha isoform isoform 33023203 NM 0170390o Protein phosphataseProtein phosphatase 2 (formerly 2 (formerly 2A), 2A), catalytic catalytic subunit, alpha subunit, alpha isoform isoform 330324697NM 017048rr S0lute carrier Solute carrier family family 4, member 4, member 2, anion 2, anion exchangeexchange protein 2 protein 2 330420876NM 017050k, Superoxide dismutaseSuperoxide dismutase tt 1, 1, soluble soluble 33051877 NM 017052w Sorbitol dehydrogenaseSorbitol dehydrogenase 33096653 NM 017068tt Lysosomal-associatedLysosomal-associated membrane protein 2 membrane protein .

331020649NM 017072b, Carboamyl-phosphateCarboamyl-phosphate General, synthetase 1 kk, synthetase 1 vv 331020650NM 017072b, Carboamyl-phosphateCarboamyl-phosphate c, synthetase 1 General,synthetase 1 cc, kk, uu, vv 331218957NM 0170750, Acetyl-CO A acetyltransferaseAcetyl-Co A
acetyltransferase xx 1, 1, mitochondria) mitochondria) 331218958NM 0170750, Acetyl-CO A acetyltransferaseAcetyl-Co A
acetyltransferase jj 1, 1, mitochondria) mitochondria) 33171550 NM 017084uu Glycine methyltransferaseGlycine methyltransferase 33171551 NM 017084uu Glycine methyltransferaseGlycine methyltransferase 33171552 NM 017084g, Glycine methyltransferaseGlycine methyltransferase uu 33181383 NM 017088GeneralGDP-dissociation GDP-dissociation inhibitor inhibitor 1 1 33206013 NM 017096e, C-reactive proteinC-reactive protein w, rr, vv 332420745NM 017113a, granulin granulin k, I, cc, tt, uu 332420746NM 017113a, granulin granulin j, I, cc, ss, uu, vv 332521538NM 017116, hh calpain 2 calpain 2 332721663NM 017126I, ferredoxin 1 ferredoxin 1 p 33281305 NM 0171270o Choline kinase Choline kinase 33281306 NM 017127f, Choline kinase Choline kinase I, General, kk vv TABLE

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Document No:1926271-.2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster-Title ID ID r- Code a N0.NO. Acc.
or RefSeq ID
No.

333024693NM 017134a, arginase 1, liverarginase 1, liver b, I, General, cc 333116681NM 017136r, squalene epoxidasesqualene epoxidase w, jj 333116682NM 017136t, squalene epoxidasesqualene epoxidase mm 333224885NM 017138q, laminin receptor laminin receptor 1 333224886NM 017138I, laminin receptor laminin receptor 1 3333492 NM 017140I dopamine receptordopamine receptor 3 333424105NM 017141a DNA polymerase DNA polymerase beta beta 333424107NM 017141d, DNA polymerase DNA polymerase beta g beta 333715364NM 017147j cofilin 1, non-musclecofilin 1, non-muscle 333916953NM 017151h, ribosomal proteinribosomal protein S15 333916954NM 017151bb, ribosomal proteinribosomal protein S15 gg, S15 hh 333916955NM 017151a ribosomal proteinribosomal protein S15 334021643NM_017152u, ribosomal proteinribosomal protein S17 General,S17 ee, II

33411694 NM 017153h, ribosomal proteinribosomal protein S3a z, S3a General, ee 334470 NM 017159b, histidine ammoniahistidine ammonia lyase c, lyase y 334517105NM 017160ee ribosomal proteinribosomal protein S6 3346595 NM 017161bb, Adenosine A2b Adenosine A2b receptor mm receptor 335624670NM 017189a, asialoglycoproteinasialo lycoprotein receptor n receptor 2 2 335920779NM_017201a S-adenosylhomocysteineS-adenosylhomocysteine hydrolase hydrolase 336014694NM 017202ff cytochrome c oxidase,cytochrome c oxidase, subunit subunit IVa IVa 33631703 NM 017210mm deiodinase, iodothyroninedeiodinase, iodothyronine type type III
III

33631704 NM 017210mm, deiodinase, iodothyroninedeiodinase, iodothyronine xx type type III
III

3365317 NM 017218h, avian erythroblastosisavian erythroblastosis General,oncogene oncogene B 3 bb, B 3 pp 336818147NM_017226cc peptidyl argininepeptidyl arginine deiminase, deiminase, type II
type II

3369442 NM_017229y phosphodiesterasephosphodiesterase 3B, 3B, cGMP- cGMP-inhibited inhibited 337020192NM 017232s prostaglandin-endoperoxideprostaglandin-endoperoxide synthase 2 synthase 2 337020193NM 017232qq, prostaglandin-endoperoxideprostaglandin-endoperoxide vv synthase 2 synthase 2 337117740NM 017233ss 4-hydroxyphenylpyruvic4-hydroxyphenylpyruvic acid acid dioxygenase dioxygenase 337315598NM 017236rr phosphatidylethanolaminephosphatidylethanolamine binding protein binding protein 337624582NM_017243kk, phosphoribosyl phosphoribosyl pyrophosphate pp pyrophosphate synthetase 1 s nthetase 1 TABLE

Aftorney Docket No:
44921'-5113W0 Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc. Code N0. or NO'. RefSeq ID

No,.

33781418 NM 017246u, mitogen activatedmitogen activated protein cc protein kinase kinase kinase 5 kinase 5 3380614 NM 017251General,gap junction membranegap junction membrane channel channel protein beta rr, protein beta 1 1 uu 338123037NM_017253, mm branched chain branched chain aminotransferase t 1, aminotransferase cytosolic 1, cytosolic 33821496 NM 017255qq, purinergic receptorpurinergic receptor vv P2Y, G- P2Y, G-protein coupled protein coupled 338415300NM 017259n, Early induced Early induced gene, p, gene, B-cell B-cell translocation rr t ranslocation genegene 2 338415301NM 017259n, Early induced Early induced gene, p, gene, B-cell B-cell translocation ss, tt t ranslocation ene ene 2 338415299NM_017259p Early induced Early induced gene, gene, B-cell B-cell translocation translocation gene 2 gene 2 338515224NM_017264f protease (prosome,protease (prosome, macropain) macropain) 28 subunit, 28 subunit, alphaalpha 338620600NM 017268q, 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-Coenzyme w, A
jj Coenzyme A synthasesynthase 1 338620601NM_017268q, 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-Coenzyme w, A
jj Coenzyme A synthasesynthase 1 3387570 NM 017271a, nuclear distributionnuclear distribution I, gene C gene C homolog v, General,homolog (Aspergillus)(Aspergillus) dd, 339017959NM 017277w Adaptor protein Adaptor protein complex complex AP-1, AP-1, beta 1 beta 1 subunit subunit 339115141NM 017278gg, proteasome (prosome,proteasome (prosome, hh macropain) subunit, macropain) subunit,alpha type 1 alpha type 33925747 NM 017279p proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,alpha type 2 alpha type 33925748 NM 017279xx proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,alpha type 2 alpha type 33931447 NM_017281t proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,alpha type 4 alpha type 33943254 NM 017282e, proteasome (prosome,proteasome (prosome, kk, macropain) subunit, mm, nn macropain) subunit,alpha type 5 alpha type 33943256 NM 017282I, proteasome (prosome,proteasome (prosome, j, macropain) subunit, xx macropain) subunit,alpha type 5 alpha type 340015819NM_017298a calcium channel, calcium channel, voltage-dependent, voltage- L type, dependent, L type,alpha 1 D sutiunit alpha 1 D

subunit 34011531 NM 017300General,bile acid-Coenzymebile acid-Coenzyme A
ff, A dehydrogenase:

rr, dehydrogenase: amino acid n-acyltransferase uu amino acid n-ac Itransferase TABLE

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Document No.:1926271.2 SEQGLGC GenBankModel Known-Gene Name Unigene Sequence Cluster Title ID ID Acc. Code N0. or N~.. RefSeq ID

No.

340214002NM 017305qq glutamate-cysteineglutamate-cysteine ligase ligase , , modifier subunit modifier subunit 340214003NM 017305qq, glutamate-cysteineglutamate-cysteine ligase vv ligase , , modifier subunit modifier subunit 340318685NM 017306o dodecenoyl-Coenzymedodecenoyl-Coenzyme A delta A delta isomerase isomerase (3,2 (3,2 trans-enoyl-Coenyme trans-enoyl- A isomerase) Coenyme A isomerase) 340318687NM 0173060, dodecenoyl-CoenzymeRat mRNA for delta3, ff, A delta delta2-enoyl-CoA
rr isomerase (3,2 isomerase, dodecenoyl-Coenzyme traps-enoyl- A delta Coenyme A isomerase)isomerase (3,2 traps-enoyl-Coenyme A

isomerase) 340519671NM_017309k, protein phospataseprotein phospatase 3, mm 3, regulatory regulatory subunit B, subunit B, alpha alpha isoform (calcineurin isoform B, type I) (calcineurin B, type p 340616844NM 017311r ATP synthase, ATP synthase; H+ transporting, N+ transporting, mitochondria) mitochondria) FO complex, FO complex, subunit c (subunit subunit c (subunit9), isoform 1 9), isoform 1 342021846NM 017355gg, ras-related GTP-bindingras-related GTP-binding hh protein protein 4b 4b 342220417NM 017359Generalras-related proteinras-related protein rab10 rab10 3427455 NM_019131k, Tropomyosin 1 Tropomyosin 1 (alpha) bb, (alpha) II, mm, nn 342916227NM 019137gg, Zinc-finger transcriptionZinc-finger transcription hh factor factor NGFI-C (early NGFI-C (early response gene) response gene) 343013715NM 019139gg, Glial cell line ESTs, Glial cell line hh derived neutrophicderived neutrophic factor factor 343114971NM 019140n, Protein tyrosine Protein tyrosine phosphatase, bb phosphatase, receptor type, receptor type, D
D

343114975NM 019140dd Protein tyrosine Protein tyrosine phosphatase, phosphatase, receptor type, receptor type, D
D

34335617 NM 019143k Fibronectin 1 Fibronectin 1 34335618 NM 019143k Fibronectin 1 Fibronectin 1 34335619 NM 019143GeneralFibronectin 1 Fibronectin 1 34335622 NM 019143I, Fibronectin 1 Fibronectin 1 ii 343520863NM 019152g calpain 1 calpain 1 343721090NM 019158General,aquaporin 8 aquaporin 8 dd, fP, nn 343820256NM 019163ii presenilin 1 presenilin 1 34407489 NM 019169 synuclein, alpha synuclein, alpha 344424019NM 019186ss, ADP-ribosylation-likeADP-ribosylation-like tt 4 4 344615242NM 019191f, MAD homolog 2 MAD homolog 2 (Drosophila) General,(Drosophila) 344722065NM 019195bb, integrin-associatedintegrin-associated nn protein protein 344818572NM 019201pp, C-terminal bindingC-terminal binding protein tt protein 1 1 345019241NM 019206I, Serinelthreonine Serine/threonine kinase y, kinase 10 10 General, TABLE

Attorney Docket No.

Document No.1926271.2 SE GLGC GenBankModel Known Gene Name Unigene Sequerice-Cluster ': Q Title lD D Ace. Code I N0. or NO RefSeq .

No.

34522078 NM 019220p, amino-terminal amino-terminal enhancer s, enhancer of splitof split pp 34522079 NM_019220z amino-terminal amino-terminal enhancer enhancer of splitof split 345420938NM 019223t NADH dehydrogenaseNADH dehydrogenase Fe-S
Fe-S protein 6 protein 6 345816449NM 019238j farnesyl diphosphatefarnesyl diphosphate j farnesyl farnesyl transferase transferase 1 345816450NM 019238j, farnesyl diphosphatefarnesyl diphosphate j oo, farnesyl farnesyl transferase ss 1 transferase 1 345816451NM 019238bb, farnesyl diphosphatefarnesyl diphosphate jj farnesyl farnesyl transferase transferase 1 345816452NM_019238jj farnesyl diphosphatefarnesyl diphosphate farnesyl farnesyl transferase transferase 1 346121109NM_019243r prostaglandin prostaglandin F2 receptor F2 receptor negative regulator ne ative regulator 3462888 NM_019246n proprotein convertaseproprotein convertase subtilisinlkexin type subtilisinlkexin type 7 346324849NM_019248e, neurotrophic tyrosineneurotrophic tyrosine a kinase, kinase, receptor, type receptor, type 3 34651450 NM 019251x blocked early blocked early in transport in transport 1 homolog homolog (S.cerevisiae)(S.cerevisiae) 346610340NM 019252d, dolichol-phosphatedolichol-phosphate (beta-D) j, (beta-D) tt mannosyltransferasemannosyltransferase 34687693 NM 019258g cystatin 8 (cystatin-relatedcystatin 8 (cystatin-related epididymal epididymal spermatogenic)spermato enic) 346915259NM 019259rr complement componentcomplement component 1, q 1, q subcomponent subcomponent bindingbinding protein protein 347115763NM 019265k sodium channel, sodium channel, voltage-gated, voltage-gated, type XI, type XI, alpha alpha polypeptide polypeptide 347223625NM 0192690 solute carrier solute carrier family family 22 (organic22 (organic cation cation transporter),transporter), member member 5 5 34731412 NM 019271ww stress 70 proteinstress 70 protein chaperone, chaperone, microsome-microsome-associated,associated, 60kD human 60kD homolog human homolog 34741129 NM_019274nn collagen-like collagen-like tail subunit tail subunit (single strand of (single strand of homotrimer)homotrimer) of asymmetric of asymmetric acetylcholinesterase acetvlcholinesterase 347620734NM_019283q, solute carrier solute carrier family z, family 3 (activators3 (activators of dibasic General,of dibasic and and neutral amino acid jj neutral amino transport), member acid transport), member 2 347620735NM 019283I, solute carrier solute carrier family I, family 3 (activators3 (activators of dibasic q, z, Generalof dibasic and and neutral amino acid neutral amino transport), member acid transport), member 2 TABLE

Attorney Docket No.
44921=5113W0 Documerit No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence;Clustee ~ Title ID ID Acc. Code' NO. or N0 RefSeq-ID

No.

347722219NM 019286c, Alcohol dehydrogenaseAlcohol dehydrogenase vv (class (class I), alpha I ), alpha polypeptidepolypeptide 34871389 NM 019350g synaptotagmin synaptotagmin 5 348923491NM 019359k, calponin 3, acidiccalponin 3, acidic v 349118819NM 019367gg, palmitoyl-proteinpalmitoyl-protein thioesterase hh, thioesterase 2 ii 2 349820443NM_019379n, vesicle docking vesicle docking protein,115 q, protein,115 kDa kDa dd, 350024626NM 019381h, Testis enhanced Testis enhanced gene x, gene transcript transcript General 350918714NM 020075y eukaryotic initiationeukaryotic initiation factor 5 (eIF- factor 5 (eIF-5) 5) 350918715NM 020075I eukaryotic initiationeukaryotic initiation factor 5 (eIF- factor 5 (eIF-5) 5) 350918716NM_020075p, eukaryotic initiationeukaryotic initiation gg, factor 5 (eIF- factor 5 (eIF-5) hh 351020493NM 020076b, 3-hydroxyanthranilate3-hydroxyanthranilate k, 3,4- 3,4-dioxygenase I, General,dioxygenase bb, ff, qq, tt, uu 351020494NM 020076cc, 3-hydroxyanthranilate3-hydroxyanthranilate ii, 3,4- 3,4-dioxygenase ss dioxy enase 352622916NM 021740ff prothymosin alphaprothymosin alpha 352719709NM 021742d nuclear receptor nuclear receptor subfamily subfamily 5, 5, group A, group A, member member 2 352919712NM 021745t, nuclear receptor nuclear receptor subfamily General,subfamily 1, 1, group H, ff, group H, member member 4 kk, 4 oo 353220090NM 021757v, pleiotropic regulatorpleiotropic regulator ww 1 1 353417936NM_021766qq progesterone receptorprogesterone receptor membrane membrane componentcomponent 1 353520162NM 021835u, Avian sarcoma Avian sarcoma virus tt virus 17 (v-jun) 17 (v-jun) oncogene oncogene homolog homolog 353522350NM 021835tt Avian sarcoma Avian sarcoma virus virus 17 (v-jun) 17 (v-jun) oncogene onco ene homolo homolog 353522351NM 021835kk, Avian sarcoma Avian sarcoma virus tt virus 17 (v-jun) 17 (v-jun) oncogene oncogene homolog homolog 353522352NM_021835y, Avian sarcoma Avian sarcoma virus kk, virus 17 (v-jun) 17 (v-jun) oncogene ss, tt oncogene homolog homolog 3539243 NM 021989ii, tissue inhibitor ESTs, tissue inhibitor rr of of metalloproteinase metalloproteinase 354325699NM 022180General,Hepatic nuclear Hepatic nuclear factor tt factor 4 (alpha 4 (alpha transcription transcription factor 4) factor 4) 354320257NM 022180GeneralHepatic nuclear Hepatic nuclear factor factor 4 (alpha 4 (alpha transcription transcription factor 4) factor 4) 355020312NM 022224bb phosphotriesterasephosphotriesterase related related 355310509NM 022268p, liver glycogen liver glycogen phosphorylase Generalphosphorylase 355325814NM 022268I liver I co en liver I co en hos ho hos ho lase lase TABLE

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Document No.19262712 SEQ GLGC GenBankModel'Known Gene Name Unigene Sequence.Cluster = w Title ID D Acc:-orCode I N0.

NO. RefSeq ID
':

No.

35581914 NM 022380g signal transducersignal transducer and and activator activator of of transcription transcription 5b 5b 355911454NM_022381c, Proliferating Proliferating cell nuclear f, cell nuclear antigen kk, antigen tt 355911455NM 022381c, Proliferating Proliferating cell nuclear f, cell nuclear antigen jj, antigen kk, nn 3569402 NM 022403c, tryptophan-2,3-dioxygenasetryptophan-2,3-dioxygenase I, vv, xx 357020915NM_022407b, Aldehyde dehydrogenaseAldehyde dehydrogenase ff 1, 1, subfamily A1 subfamily A1 35714647 NM_022498h, Protein phosphataseProtein phosphatase r, 1, catalytic 1, catalytic subunit, w, rr subunit, gamma gamma isoform 1 isoform 1 35729183 NM 022499s, Parvalbumin (calciumParvalbumin (calcium nn binding binding protein) protein) 35742515 NM 022501ww cysteine-rich cysteine-rich protein protein 2 2 35761347 NM 022506h, ribosomal proteinribosomal protein L31 35813027 NM 022514h, ribosomal proteinribosomal protein L27 w, L27 ee, II, as 35822696 NM 022515z, ribosomal proteinribosomal protein L24 General,L24 ee 35822697 NM 022515ee, ribosomal proteinribosomal protein L24 35938984 NM 022539ww methionine aminopeptidasemethionine aminopeptidase 359621062NM 022585c, ornithine decarboxylaseornithine decarboxylase kk, antizyme inhibitor tt, ww antizyme inhibitor 359621063NM_022585ff ornithine decarboxylaseornithine decarboxylase antizyme inhibitor antizyme inhibitor 361117567NM 022672h, ribosomal proteinribosomal protein S14 gg, S14 hh 361324564NM 022676bb protein phosphataseprotein phosphatase 1, 1, regulatory (inhibitor) regulatory (inhibitor)subunit 1A
subunit 1A

361717729NM 022697h, ribosomal proteinribosomal protein L28 v, L28 x 362124344NM 022701pp flotillin 1 flotillin 1 363024838NM 022924tt coagulation factorcoagulation factor II
II

363519669NM 022944x SH2-containing SH2-containing inositol inositol phosphatase 2 phosphatase 2 364115727NM 022953g SIit1 SIit1 36474228 NM 023950a RAB7, member RAS RAB7, member RAS oncogene oncogene family family 364921238NM 024125t, Liver activating Liver activating protein ff protein (LAP, (LAP, also NF-IL6, also NF-IL6, nuclearnuclear factor-IL6, factor-IL6, previously designated previously designatedTCFS) TCFS) 364921239NM 024125d, Liver activating Liver activating protein I, protein (LAP, (LAP, also NF-IL6, z also NF-IL6, nuclearnuclear factor-IL6, factor-IL6, previously designated previously designatedTCFS) TCFS) TABLE

Attorney Docket No._44921-51137N0 Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc: Code Nb. or N0. RefSeq ID

No. _ : .

3650352 NM_024127s, DNA-damage-inducibleDNA-damage-inducible General transcript 1 transcript 1 3650353 NM 024127n, DNA-damage-inducibleDNA-damage-inducible z, transcript 1 General,transcript 1 ee, kk, qq, ww 3650354 NM 024127n, DNA-damage-inducibleDNA-damage-inducible r, transcript 1 General,transcript 1 qq, vv 365217226NM 024131b, D-dopachrome tautomeraseD-dopachrome tautomerase ff, vv 365217227NM 024131b, D-dopachrome tautomeraseD-dopachrome tautomerase f, ff, vv 3653851 NM 024132c, fatty acid amide fatty acid amide hydrolase kk hydrolase 36541598 NM 024134f, DNA-damage inducibleDNA-damage inducible I, transcript 3 o, p, q, General,transcript 3 cc, dd, kk, II, qq 36561878 NM 024138cc guanine nucleotideguanine nucleotide binding binding protein (G

protein (G protein),protein), gamma 7 subunit gamma 7 subunit 365720801NM 024148m, apuriniclapyrimidinicapuriniclapyrimidinic cc, endonuclease 1 oo, uu, endonuclease 1 ww 3661561 NM 024156nn annexin VI annexin VI

366222079NM 024157a, complement factorcomplement factor I
General,I

uu, vv 36644655 NM 024346a Scgn101ike-proteinSc n101ike-protein 366517764NM 024351h, heat shock 70kD heat shock 70kD protein I, protein 8 8 w, uu 366517765NM 024351I heat shock 70kD heat shock 70kD protein protein 8 8 366715350NM 024356p GTP cyclohydrolaseGTP cyclohydrolase 1 36681146 NM 024359a, hypoxia induciblehypoxia inducible factor m factor 1, alpha 1, alpha subunit subunit 36681148 NM 024359a hypoxia induciblehypoxia inducible factor factor 1, alpha 1, alpha subunit subunit 367020772NM_024363c, heterogeneous heterogeneous nuclear v, nuclear ribonucleoproteins oo ribonucleoproteinsmethyltransferase-like 2 (S. cerevisiae) methyltransferase-like 2 (S.

cerevisiae) 367320380NM 024381o Glycerol kinase Glycerol kinase 368119993NM 0243980, mitochondria) mitochondria) aconitase xx aconitase (nuclear(nuclear aco2 gene) aco2 ene) 36851835 NM 024483a adrenergic receptor,adrenergic receptor, alpha 1d alpha 1d 368621039NM 024484ii aminolevulinic aminolevulinic acid acid synthase synthase 1 36971928 NM 030872z, pyruvate dehydrogenasepyruvate dehydrogenase General,kinase kinase 2 subunit ee, 2 subunit p45 p45 (PDK2) kk (PDK2) 369917377NM 030989jj Tumor protein Tumor protein p53 (Li-Fraumeni p53 (Li-Fraumeni syndrome) s ndrome TABLE

-Attorney Docket No.

Document No.
X926271.:2 SE4 GLGCGenBank Model Known Gene Name Unigene $equenee Cluster Title ID ID Acc. Code N0. or N0. RefSeq ID

No.

370691 NM 031006II adenosine deaminaseadenosine deaminase RNA-specific RNA-specific 371015682NM 031011a S-AdenosylmethionineS-Adenosylmethionine decarboxylase 1 decarboxylase 371015683NM 031011kk, S-AdenosylmethionineS-Adenosylmethionine oo decarboxylase 1 decarboxylase 371215700NM 031013k l iver multidrug liver multidrug resistance-associated resistance- protein associated protein6 3721626 NM_031032b, glia maturation glia maturation factor h, factor beta beta m, s, x, General, dd, 37337351NM 031059g homeo box, msh-likehomeo box, msh-like 1 3734400 NM 031062jj, mevalonate pyrophosphatemevalonate pyrophosphate ww decarboxylase decarboxylase 373521701NM 031063jj mevalonate kinasemevalonate kinase 373611849NM 031065j, ribosomal proteinribosomal protein L10a z, L10a General, II

37441376NM 031094a Retinoblastoma-relatedRetinoblastoma-related gene gene 374920462NM 031102h, ribosomal proteinribosomal protein L18 m L18 375119268NM 031104gg, ribosomal proteinribosomal protein L22 hh L22 375724615NM 031112Generalribosomal proteinribosomal protein S24 37591579NM_031117c, SNRPN upstream small nuclear ribonucleoparticle-associated oo, reading ww frame, small protein (snRNP) mRNA, nuclear clone Sm51 ribonucleoparticle-associated protein (snRNP) mRNA, clone Sm51 377516157NM 0312350o three-PDZ containingthree-PDZ containing protein protein similar to C.

similar to C. elegans PAR3 (partitioning elegans PAR3 defect) (partitioning defect) 37791857NM 0313150, acyl-C0A thioesteraseacyl-CoA thioesterase xx 1, 1, cytosolic cytosolic 378015661NM 031318a, t-complex testist-complex testis expressed b, expressed 1 1 m, uu, vv 378015662NM 031318m, t-complex testist-complex testis expressed Generalexpressed 1 1 378015663NM 031318m t-complex testist-complex testis expressed expressed 1 1 37834234NM_031330m, argininosuccinateheterogeneous nuclear ff lyase, ribonucleoprotein heterogeneous AIB
nuclear ribonucleoprotein AIB

379315608NM 031355n mitochondria) mitochondria) voltage voltage dependent anion dependent anion channel 3 channel 3 379524645NM 031502a, Amylase 1 Amylase 1 d, k, I, dd, uu 379824410NM 031511g Insulin-like Insulin-like growth factor growth factor II (somatomedin A) II

(somatomedin Aj 38011783NM 0315210o Cell adhesion Cell adhesion molecule, molecule, neuralneural (CD56) TABLE

Attorney Docket No.

Document No.19262712 SEQGLGC GenBankModel Knowri: Gene NameJnigene Sequence Cluster Title ID ID Acc. Code NO. or N0. RefSeq ID

No.

380616047NM 031541j, CD36 antigen (collagenCD36 antigen (collagen General,type I type I receptor, II receptor, thrombospondinthrombospondin receptor)-like 1 (scavanger receptor)-like receptor class B type 1 (scavanger 1 ) receptor class B tvpe 1) 38081504 NM 031544a, Adenosine monophosphateAdenosine I, m onophosphate deaminase General,deaminase 3 uu 380918389NM 031545gg, Brain natriureticBrain natriuretic factor hh factor 381028 NM 031546v, Regucalcin Regucalcin rr 381315411NM 0315590, Carnitine palmitoyltransferaseCarnitine y, 1 almitoyltransferase 1 ff p alpha, liver alpha, liver isoformisoform 381418315NM 031561o CD36 antigen (collagenCD36 antigen (collagen type I type I receptor, receptor, thrombospondinthrombospondin receptor) receptor) 381418316NM_031561o CD36 antigen (collagenCD36 antigen (collagen type I type I receptor, receptor, thrombospondinthrombospondin receptor) receptor) 381418317NM_031561o CD36 antigen (collagenCD36 antigen (collagen type I type I receptor, receptor, thrombospondinthrombosp0ndin receptor) receptor) 381418318NM_031561j CD36 antigen (collagenCD36 antigen (collagen type I type I receptor, receptor, thrombospondinhrombospondin receptor) t receptor) 381418319NM 031561o CD36 antigen (collagenCD36 antigen (collagen type I type I receptor, receptor, thrombospondinhrombospondin receptor) t receptor) 381425139NM 031561o CD36 antigen (collagenCD36 antigen (collagen type I type I receptor, receptor, thrombospondinhrombospondin receptor) t receptor) 381516164NM 031563h, nuclease sensitivenuclease sensitive element m, element binding protein 1 n, Generalbindin protein 382024219NM 031579n, protein tyrosine protein tyrosine phosphatase Generalphosphatase 4a1 4a1 38211444 NM 031583ww chondroitin sulfatechondroitin sulfate proteoglycan proteoglycan 6 3822405 NM_031587f, peroxisomal membraneperoxisomal membrane k, protein protein 2, 22 kDa w, cc 2, 22 kDa 38245496 NM 031589e, glucose-6-phosphatase,glucose-6-phosphatase, k, transport protein 1 I, m, General,transport protein dd, qq, ss 38245497 NM 031589a, glucose-6-phosphatase,lucose-6-phosphatase, k, g transport protein 1 I, qq transport protein 382621843NM_031594e, purinergic receptorpurinergic receptor P2X, ee, P2X, ligand- ligand-gated ion tt, ww gated ion channelhannel 4 4 c 382919344NM 031603ee tyrosine 3- t yrosine 3-monooxygenase/tryptophan monooxygenaseltryptophanmonooxygenase activatioprotein, 5- epsilon monooxygenase olypeptide p activatioprotein, epsilon of a tide AR
TABLE

Attorney Docket No.=44921-5113W0 Document No.1926271.2 SE GLGC GenBankModel-Known Gene Name Un(gene Sequence Cluster=Title - Q

ID D _ Code I N0. Acc~
or N0. RefSeq ID

No.

383211296NM_031606b, phosphatase and phosphatase and tensin m, tensin homolog (mutated General,homolog (mutated n multiple advanced cancers in multiple i 1) oo, advanced cancers ww, 1) xx 383211297NM 031606ss phosphatase and phosphatase and tensin tensin homolog (mutated homolog (mutated n multiple advanced cancers in multiple i 1) advanced cancers 1) 383319023NM 031609cc Neuroblastoma, Neuroblastoma, suppression suppression of of tumorigenicity tumorigenicity 1 (DNA
1 (DNA segment segment human human D1S1733E) D1S1733E) 383412132NM 031612ss apelin apelin 383524235NM 031614uu thioredoxin reductasethioredoxin reductase 38361925 NM 031616a, zinc fin er proteinzinc fin er protein 265 384015767NM 031623n, growth factor growth factor receptor y, receptor bound bound protein 14 z, General,protein 14 dd 384220940NM 031629y, proteasome (prosome,proteasome (prosome, nn macropain) subunit, macropain) subunit,beta type, 4 , beta type, 4 384220941NM 031629bb proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,beta type, 4 beta type, 4 384220942NM 031629mm proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,beta type, 4 beta type, 4 38446554 NM 031640f plasma glutamate plasma glutamate carboxypeptidase carboxypeptidase 384718368NM 031648k FXYD domain-containingFXYD domain-containing ion ion transport transport regulatorregulator 1 384718369NM 031648s FXYD domain-containingFXYD domain-containing ion ion transport transport re ulatorregulator 1 3849866 NM_031657gg, G protein-coupledG protein-coupled receptor hh, receptor kinase 6 pp kinase 6 385124881NM_031663pp solute carrier solute carrier family family 18 18 (vesicular (vesicular monoamine),monoamine), member 3 member 38535358 NM 031675t, Actinin, alpha Actinin, alpha 4 ee, 4 mm 385515823NM 031680g pyrimidinergic pyrimidinergic receptor receptor P2Y, P2Y, G-protein G-protein coupled, coupled, 4 38581004 NM 031685m, golgi SNAP receptorgolgi SNAP receptor complex x, complex member 2 dd member 2 386121575NM 031698xx ribophorin II ribophorin II

386320404NM 031700Generalclaudin 3 claudin 3 386320405NM 031700a, claudin 3 claudin 3 I, General, cc, ss 3865811 NM 031705c, dihydropyrimidinasedihydropyrimidinase s, General, II

3865812 NM 031705s, dih dro rimidinasedih dro rimidinase oo TABLE

Attorney Docket No44921-5113W0 Document No.1926271.2 SEQGLGC CenBankMode) Known Gene Name UntgeneSequence Cluster Title -ID ID Ace. Code N0. or ~

N0. RefSeq No.

386616204NM 031706, x, ibosomal proteinribosomal protein S8 I r S8 General 386718055NM 031707nn RuvB-like proteinRuvB-like protein 1 386718056NM 031707c RuvB-like proteinRuvB-like protein 1 386921693NM 031714p, tt heat-responsive heat-responsive protein protein 12 12 38701339 NM 031715e, bb phosphofructokinase,phosphofructokinase, muscle muscle 387119049NM_031719a chloride channel,chloride channel, nucleotide-sensitive, nucleotide- 1A

sensitive,1A

387119050NM 031719e, p chloride channel,chloride channel, nucleotide-sensitive,1A
nucleotide-sensitive,1A

387323883NM_031731n, General,alcohol dehydrogenasealcohol dehydrogenase family 3, family 3, subfamily ee subfamily A2 A2 387323884NM 031731ii alcohol dehydrogenasealcohol dehydrogenase family 3, family 3, subfamily subfamily A2 A2 38761214 NM 031741z, jj nuclear receptorsolute carrier family subfamily 1, 2 (facilitated glucose group H, member transporter), member 4, solute 5 carrier family 2 (facilitated glucose transporter), member 5, synaptojanin 2 binding protein 388111611NM 031756w gamma-glutamyl gamma- lutamyl carboxylase carboxylase 388716115NM 031775bb caspase 6 caspase 6 389515864NM_031797x Kangai 1 (suppressionESTs, Kangai 1 (suppression of of tumorigenicity tumorigenicity 6, prostate;
6, prostate; CD82 antigen (R2 antigen (R2 leukocyteleukocyte antigen, antigen antigen, detected by antigen detectedmonoclonal and antibody by monoclonal IA4)) and antibody IA4)) 390322321NM 031832f, j, lectin, galactoselectin, galactose binding, binding, solublesoluble 3 General,3 ss 391316726NM 031855General,Ketohexokinase Ketohexokinase dd 391519190NM 031969s Calmodulin 1 Calmodulin 1 (phosphorylase (phosphorylase kinase, delta) kinase, delta) 391519193NM_031969I, dd Calmodulin 1 Calmodulin 1 (phosphorylase (phosphorylase kinase, delta) kinase, delta) 391519195NM 031969c Calmodulin 1 Calmodulin 1 (phosphorylase (phosphorylase kinase, delta) kinase, delta) i 391519196NM_031969rr Calmodulin 1 Calmodulin 1 (phosphorylase (phosphorylase kinase, delta) kinase, delta) 391525802NM 031969c, x Calmodulin 1 Calmodulin 1 (phosphorylase (phosphorylase kinase, delta) kinase, delta) 391716865NM 031973a, cc, dipeptidyl peptidasedipeptidyl peptidase uu 7 7 391817075NM 031974I, General,clathrin light clathrin light chain chain kk, II, ss 392017601NM_031976ww 5'-AMP-activated5'-AMP-activated protein protein kinase, kinase, beta beta subunit subunit TABLE

Attorney Docket No.?44921-5113W0 Document No.1926271:2 SEQ GL:GCGenBank Model Known Gene Name:Unigene Sequence Cluster . Title ID D Acc..or Code -. NO. ' I

N0. RefSeq - ID

No.

39215470NM 031978u, 26S proteasome, 26S proteasome, subunit 1 mm subunit p112 p112 392418501NM 031984s, cerebellar Ca-bindingcerebellar Ca-binding v, protein, protein, spot 35 mm, xx spot 35 protein protein 392720554NM 031987o carnitine 0-octanoyltransferasecarnitine 0-octanoyltransferase 392720555NM 031987o carnitine 0-octanoyltransferasecarnitine 0-octanoyltransferase 392818640NM 032057p, Inositol (myo)-1Inositol (myo)-1 (or ee (or 4)- 4)-monophosphatase 1 monophosphatase 3932590 NM 032080b, glycogen synthaseglycogen synthase kinase c, kinase 3 3 beta m, kk b eta 3932591 NM 032080b, glycogen synthaseglycogen synthase kinase c, kinase 3 3 beta I, z, General,beta tt, vv 393517474NM 032614a thioredoxin-likethioredoxin-like 2 393720490NM_032617II RAB11 B, member RAB11 B, member RAS oncogene RAS family oncogene family 39431409NM 033349t, Hydroxyacyl glutathioneHydroxyacyl glutathione jj hydrolase hydrolase 394412363NM 0333510o Fc fragment immunoglobulinFc fragment immunoglobulin G G receptor receptor 394412364NM_033351o Fc fragment immunoglobulinFc fragment immunoglobulin G G receptor receptor 394623895NM 033485tt Prostate apoptosisProstate apoptosis response response protein 4 protein 4 39481423NM 052801mm von Hippel-Lindauvon Hippel-Lindau syndrome syndrome 39481424NM 052801ww von Hippel-Lindauvon Hippel-Lindau syndrome syndrome 395025024NM 052809b, cytosolic cysteinecytosolic cysteine dioxygenase o, dioxygenase 1 vv 1 395015028NM 052809b, cytosolic cysteinecytosolic cysteine dioxygenase qq, dioxygenase 1 vv 1 3951412 NM 053288y Orosomucoid 1 Orosomucoid 1 39531524NM 053293GeneralGlutathione S-transferaseGlutathione S-transferase 1 1 (theta) (theta) ' 39541187NM 053295t Calpastatin Calpastatin 395615749NM_053309cc homer, neuronal homer, neuronal immediate immediate early gene, 2 early ene, 2 395615750NM 053309a homer, neuronal homer, neuronal immediate immediate early gene, 2 early gene, 2 395615751NM 053309x homer, neuronal homer, neuronal immediate immediate early gene, 2 early ene, 2 395717473NM_053319pp, dynein, cytoplasmic,dynein, cytoplasmic, tt light chain light chain 1 395925480NM 053329x insulin-like insulin-like growth factor growth factor binding protein, binding protein, acid acid labile subunit labile subunit 396214934NM 053337m, Msx-interacting-zincMsx-interacting-zinc x, finger finger II, ww 396418949NM 053345f general transcriptiongeneral transcription factor Ila, factor Ila, 2 (12kD

(12kD subunit) subunit) 3968623 NM 053369' transcri tion transcri tion factor factor 4 4 TABLE

Attorney Docket No.

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster ' Title ; '~

ID;:fD' Acc, Code:
NO. or NO _ RefSeq ID

No.

39703844 NM 053371j fractured callus fractured callus expressed expressed transcript 1 transcript 1 398222586NM 053469a, hepcidin antimicrobialhepcidin antimicrobial n, peptide peptide y 398321866NM 053472s cytochrome c oxidase,cytochrome c oxidase, subunit subunit IVb IVb 39902016 NM 053527d CDC5 (cell divisionCDC5 (cell division cycle 5, S. cycle 5, S. pombe, pombe, homology-likehomology-like 400110986NM 053571c, regucalcin gene regucalcin gene promotor I, promotor region region related m, Generalrelated protein protein 400219252NM 053576x peroxiredoxin peroxiredoxin 5 400421154NM 053584m, golgi SNAP receptorgolgi SNAP receptor z, complex complex member 1 dd, ee member 1 401615925NM_053607m long-chain fatty long-chain fatty acid acid coenzyme coenzyme A ligase 5 A ligase 5 401720243NM 053615ff casein kinase casein kinase 1, alpha 1, alpha 1 1 40183062 NM 053617a, carboxypeptidase carboxypeptidase B2 cc B2 (plasma) (plasma) 4019926 NM 053619g complement componentcomplement component 5, 5, receptor 1 receptor 1 4021659 NM 053622q nuclear pore membranenuclear pore membrane glycoprotein 121 kD

glycoprotein 121 kD

402523305NM 053638jj isocitrate dehydrogenaseisocitrate dehydrogenase 3 3 (NAD+) alpha (NAD+) alpha 40291120 NM 053655g, dynamin 1-like dynamin 1-like n 403813369NM 053742v phosphotidylinositolphosphotidylinositol transfer transfer protein, beta protein, beta 403910512NM 053743k, CDC37 (cell divisionCDC37 (cell division mm cycle 37, S. cycle 37, S. cerevisiae, cerevisiae, homologyhomology 404115376NM 053747x, ubiquilin 1 ubiquilin 1 General, kk 40447927 NM 053765e, UDP-N-acetylglucosamine-2-UDP-N-acetylglucosamine-2-epimerase/N-t epimerase/N- acetylmannosamine kinase acetylmannosamine kinase 404615995NM_053769r, protein tyrosine protein tyrosine phosphatase, ff phosphatase, non-receptor non-receptor typetype 16 404615996NM 053769n, protein tyrosine protein tyrosine phosphatase, ff, phosphatase, non-receptor kk non-receptor typetype 16 404615997NM 053769d, protein tyrosine protein tyrosine phosphatase, n, phosphatase, non-receptor r, w, y non-receptor typetype 16 4080794 NM 053902I kynureninase(L-kynureninekynureninase (L-kynurenine hydrolase) hydrolase) 408217937NM 053911ss, pleckstrin homology,pleckstrin homology, uu Sec7 and Sec7 and coiledlcoil coiledlcoil domainsdomains 2 408515857NM 053948b, polymerase (RNA) polymerase (RNA) II
e, II (DNA (DNA
bb, oo, directed)polypeptidedirected)polypeptide ww G G

409019991NM 053961cc mitochondria) mitochondria) aconitase aconitase (nuclear(nuclear aco2 gene) aco2 ene TABLE

Attorney Docket No.

Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigepe Sequence Cluster : Title ' lD ID Acc. Code N0. or NO: RefSeq ID

No.

410822849NM 057099c proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,beta type 6 beta type 6 41119527 NM 057104c, ectonucleotide ectonucleotide q, General,jjpyrophosphataselphosphodiestpyrophosphataselphosphodiesterase erase 2 41125492 NM 057105a UDP glycosyltransferaseESTs, UDP glycosyltransferase 1 1 family, family, polypeptidepolypeptide A6 41125493 NM 057105a UDP glycosyltransferaseESTs, UDP glycosyltransferase 1 1 family, family, polypeptidepolypeptide A6 411215124NM_057105jj UDP glycosyltransferaseUDP glycosyltransferase 1 1 family, family, polypeptidepolypeptide A6, UDP
A6, UDP glycosyltransferase glycosyltransferasefamily, polypeptide 1 family, A7, UDP-polypeptide A7, glucuronosyltransferase UDP- 1 family, member 1 glucuronosyltransferase family. member 411215126NM_057105t, UDP glycosyltransferaseUDP glycosyltransferase jj 1 1 family, family, polypeptidepolypeptide A6, UDP
A6, UDP glycosyltransferase glycosyltransferasefamily, polypeptide 1 family, A7, UDP-polypeptide A7, glucuronosyltransferase UDP- 1 family, member 1 glucuronosyltransferase family. member 411215127NM 057105k, UDP glycosyltransferaseUDP glycosyltransferase t, 1 1 family, General,family, polypeptidepolypeptide A6, UDP
A6, UDP glycosyltransferase mm glycosyltransferasefamily, polypeptide 1 family, A7, UDP-polypeptide A7, glucuronosyltransferase UDP- 1 family, member 1 glucuronosyltransferase family. member 41133743 NM 057107nn fatty acid Coenzymefatty acid Coenzyme A ligase, A ligase, long chain long chain 3 412119834NM_057139v transporter protein;transporter protein;
system N1 system N1 Na+ and H+-Na+ and H+-coupledcoupled glutamine transporter glutamine transporter 412615408NM 057197rr 2,4-dienoyl CoA 2,4-dienoyl CoA reductase reductase 1, 1, mitochondria) mitochondria) 412615409NM 057197ff, 2,4-dienoyl CoA 2,4-dienoyl CoA reductase ii, reductase 1, 1, mitochondria) jj mitochondria) 413224653NM 080580a RAB3D, member RAB3D, member RAS oncogene RAS family oncogene family 413317956NM_080583m, adaptor-related adaptor-related protein vv protein complex complex 2, beta 1 2, beta 1 subunitsubunit 413317958NM 080583ff, adaptor-related adaptor-related protein xx protein complex complex 2, beta 1 2, beta 1 subunitsubunit 413416108NM 080585d, N-ethylmaleimide N-ethylmaleimide sensitive q, sensitive fusion protein gg, hh fusion protein attachment protein alpha attachment protein alpha 413416109NM 080585e, N-ethylmaleimide N-ethylmaleimide sensitive q sensitive fusion protein fusion protein attachment protein alpha attachment rotein al ha QR
TABLE

Attorney Docket No.
44921=5113W0 "Document No.1926271.2 SEQ GLGCGenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc. Code N0. or N0. RefSeq ~ ID

No ~

4136 19831NM_080781b, coatomer protein coatomer protein complex, q, complex, subunit beta 1 x, dd subunit beta 1 4138 25693NM 080783jj, alactose-4-epimerase,galactose-4-epimerase, xx UDP UDP

4139 25799NM 080886a, sterol-C4-methyl sterol-C4-methyl oxidase-like f, oxidase-like n, x, cc, ff, jj, uu 4139 21842NM 080886a, sterol-C4-methyl~oxidase-likesterol-C4-methyl oxidase-like f, jj, pp 4148 8167NM 130406q, Fas-associated Fas-associated factor II factor 1 1 4154 13515NM_130430y proteasome (prosome,proteasome (prosome, macropain) 26S

macropain) 26S subunit, non-ATPase, subunit, non- 9 ATPase, 9 4156 14959NM_130734h, guanine nucleotideguanine nucleotide binding x, binding protein (G

General,protein (G protein),protein), beta polypeptide beta 2-like 1 dd, polypeptide 2-like ee 1 4159 22220NM_130780vv Alcohol dehydrogenaseAlcohol dehydrogenase (class (class I), alpha I), alpha polypeptidepolypeptide 4165 25730NM 133290r, zinc finger proteinzinc finger protein t 36 36 4166 20879NM 133295j carboxylesterase carboxylesterase 3 4167 19456NM_133298I, glycoprotein (transmembrane)glycoprotein (transmembrane) cc, nmb qq, uu nmb 4167 4048NM_133298I, glycoprotein (transmembrane)glycoprotein (transmembrane) cc, nmb qq, uu nmb 4167 4049NM 133298, cc, glycoprotein (transmembrane)lycoprotein (transmembrane) I tt, g nmb uu nmb 4184 2788NM 133528z, preimplantation preimplantation protein ee protein 3 3 4222 21098NM 134432qq Angiotensinogen An iotensino en 4226 12215NM 138502o monoglyceride monoglyceride lipase lipase 4228 16179NM 138508xx Sterol carrier Sterol carrier protein protein 2, liver 2, liver 4228 16180NM_138508h, Sterol carrier Sterol carrier protein I, protein 2, liver 2, liver General, dd, jj, 4238 4822NM_138708m, Rab geranylgeranylRab geranylgeranyl transferase 1 s transferase c omponenet, subunitcomponenet, subunit beta beta 4240 6248NM_138827, mm Solute carrier Solute carrier family 1 t family 2 a 1 2 a 1 (facilitated glucose ( facilitated glucosetransporter) brain transporter) b rain 4240 6249NM 138827p, Solute carrier Solute carrier family 1 ff family 2 a 1 2 a 1 (facilitated glucose ( facilitated glucosetransporter) brain transporter) b rain 4240 6250M 138827mm olute carrier Solute carrier family 1 N S family 2 a 1 2 a 1 (facilitated glucose ( facilitated glucosetransporter) brain transporter) b rain 4240 6251M 138827mm olute carrier Solute carrier family 1 N S family 2 a 1 2 a 1 (facilitated glucose ( facilitated glucoseransporter) brain transporter) t b rain 4241 6400M 138828m, polipoprotein Apolipoprotein E, 1 N x E, A

4271 7203M_139099p A TP synthase, H+ ATP synthase, H+ transporting, 1 N p transporting, mitochondrial mitochondrial F1 complex, F1 complex, epsilon subunit a silon subunit AA
TABLE

Attorney Docket No.

Document:
No.1926271.2 SEQ GLGCGeriBankModel Known Gene Name Unigene Sequence Cluster Title ID D:NO.Accor Code I

NO. RefSeq ID

No.

427117204NM_139099p, ATP synthase, ATP synthase, H+ transporting, x, H+ transporting, mm mitochondria) mitochondria) F1 complex, F1 complex, epsilon subunit epsilon subunit 427217549NM_139100m, solute carrier solute carrier family ee family 25 25 (mitochondria) (mitochondria) carrier; adenine nucleotide carrier; adenine translocator), nucleotide translocator),member 3 member 3 43111382NM 147177c, RuvB-like proteinRuvB-like protein 1 e, 1 dd 43265624847122 bb, Fibronectin 1 Fibronectin 1 cc 43351471S68809 a S100 calcium bindingESTs, Highly similar protein A1 to S10A RAT S-100 -protein, alpha chain [R.norvegicus]

435120431S81448 qq, Steroid-5-alpha-reductase,Steroid-5-alpha-reductase, xx alpha alpha polypeptidepolypeptide 1 (3-oxo-5 1 (3-oxo-5 alpha-steroid delta alpha-steroid dehydrogenase alpha delta 4- 1) dehvdroaenase alpha 1) 436316675017565 ww mini chromosome mini chromosome maintenance maintenance deficient 6 deficient 6 (S. (S. cerevisiae) cerevisiae) 437715851042719 vv Complement componentComplement component 437819543044948 ww cysteine-rich cysteine-rich protein protein 2 2 43901715072660 0, Ninjurin Ninjurin mm 4404818 X02291 a, Aldolase B, fructose-Aldolase B, fructose-biphosphate s, ff, qq, tt, biphosphate uu 440820715X07259 0, Cytochrome P450, Cytochrome P450, subfamily xx subfamily IVB, IVB, polypeptide polypeptide 1 441220597X12459 b, Ar inosuccinate Arginosuccinate synthetase ff synthetase 1 1 4421575 X15734 a, S - adenosylmethionineS - adenosylmethionine I synthetase synthetase 442920427X53378 General,ribosomal proteinribosomal protein S13 443925702X58465 I Ribosomal proteinRibosomal protein S5 443910109X58465 h, Ribosomal proteinRibosomal protein S5 I, S5 ee, II

448319694248444 ee A disintegrin A disintegrin and metalloprotease and domain metalloprotease (ADAM) 10 domain (ADAM) 10 448415569278279 bb procollagen, typeprocollagen, type I, I, alpha 1 alpha 1 63 20995AA799724GeneralHMm:RNA polymeraseESTs, Highly similar 1-3 (16 to RPA9_MOUSE DNA-kDa subunit) directed RNA polymerase I 16 kDa polypeptide (RPA16) [M.musculus]

63 20996AA799724b, HMm:RNA polymeraseESTs, Highly similar f, 1-3 (16 to RPA9_MOUSE DNA-General,kDa subunit) directed RNA polymerase I 16 kDa kk, polypeptide (RPA16) nn, [M.musculus]
qq 416 14138AA859700p, HMm:protoporphyrinogenESTs, Highly similar General to PPOX_MOUSE

oxidase PROTOPORPHYRINOGEN OXIDASE

PPO M.musculus 1 (1(1 TABLE

Aftorraey Docket No.

Document No.19262712 SE GLGCGenl3ankModel Known Gene Name Unigerie Sequence Cluster _ Title Q

ID D Accaor Code = N0. ' I

NO. RefSeq ID

No.

464 16074AA874874t HMm:alcohol dehydrogenaseESTs, Highly similar 5 to ADHX_RAT

ALCOHOL DEHYDROGENASE
CLASS III

(ALCOHOL DEHYDROGENASE
2) (GLUTATHIONE-DEPENDENT

FORMALDEHYDE DEHYDROGENASE) (FDH) (FALDH) (ALCOHOL

DEHYDROG NASE-B21 fR.norveai sl 480 20389AA87504500 HMm:phosphodiesteraseESTs, Highly similar 6D, to CNRD_MOUSE

cGMP-specific, Retinal rod rhodopsin-sensitive rod, delta cGMP 3',5'-cyclic phosphodiesterase delta-subunit (GMP-PDE delta) fM.musculusl 483 21589AA875084y, HMmaransducin-likeESTs, Highly similar nn enhancer to TLE4_RAT

of split 1, homologTransducin-like enhancer of Drosophila protein 4 (ESP2 E(spp protein) fR.norveqicusl 552 9090AA891690h, HMmaumor necrosisESTs, Highly similar s factor to tumor necrosis (ligand) superfamily,factor (ligand) superfamily, member 13 member 13 [Mus musculusl f M.musculusl 668 11997AA892828II HMm:pyruvate dehydrogenaseESTs, Highly similar to S15892 pyruvate (lipoamide) beta dehydrogenase (lipoamide) (EC 1.2.4.1) beta chain - rat [R.norveqicusl 705 17754AA893246a, HMm:ATPase, H+ ESTs, Highly similar w transporting, to VATD_MOUSE

lysosomal 34kD, Vacuolar ATP synthase V1 subunit D subunit D (V-ATPase D subunit) (Vacuolar proton pump D

subunit) (V-ATPase 28 kDa accessory protein) fM.musculusl 107624289AA955986t HMm:galactokinaseESTs, Highly similar to GAL1 MOUSE
-Galactokinase (Galactose kinase) [M.musculusl 109812000AA957319bb HMm:pyruvate dehydrogenaseESTs, Highly similar to S15892 pyruvate (lipoamide) beta dehydrogenase (lipoamide) (EC 1.2.4.1) beta chain - rat (R.norveqicusl 11262308AA964227I, HMm:methylenetetrahydrofolateESTs, Highly similar General to A33267 dehydrogenase methylenetetrahydrofolate (NAD+ dehydrogenase dependent), (NAD+) (EC 1.5.1.15) /

methenyltetrahydrofolatemethenyltetrahydrofolate cyclohydrolase (EC

cyclohydrolase 3.5.4.9) precursor-mouse [M.musculus]

128420214AF091567xx olfactory receptorolfactory receptor 41 128520236AF091570cc olfactory receptorolfactory receptor 41 128625222AF091574g olfactory receptorolfactory receptor 41 133615452A1009484s HMm:gelsolin ESTs, Highly similar to GELS_MOUSE

Gelsolin (Actin-depolymerizing factor) (ADF) (Brevin) [M.musculusl 145621302A1013297o HMm:NADH dehydrogenaseESTs, Moderately similar to NADH

(ubiquinone) Fe-Sdehydrogenase (ubiquinone) protein 4 Fe-S protein 4;

NADH dehydrogenase (ubiquinone) Fe-S

protein 4 (18 kDa) [Mus musculus]

M.mu ulu 1f11 TABLE

' Attorriey Docket No.

Document No.1926271,2 SEQ GLGC GenBankModel Known Gene Name- Unigene Sequence Cluster Title ID D Acc. Code I NO, or- -' N0. RefSeq == ID

No.

15657935 A1043945GeneralHMm:ferrochelataseESTs, Highly similar to A37972 ferrochelatase (EC 4.99.1.1) precursor-mouse fM.musculusl 18099421 A1072885pp HMm:inositol polyphosphate-1-ESTs, Moderately similar to INPP_MOUSE

phosphatase Inositol polyphosphate 1-phosphatase (IPPase) (IPP) [M.musculusl 202023788AI137176ss HMm:alpha-N- ESTs, Moderately similar to alpha-N-acetylglucosaminidaseacetylglucosaminidase (Sanfilippo disease (Sanfilippo diseaseIIIB); alpha-N-acetylglucosaminidase, IIIB) Ivsosomal [Mus musculusl fM.musculusl 22595876 AI1761170o HMm:pyruvate dehydrogenaseESTs, ESTs, Highly similar to S15892 (lipoamide) beta pyruvate dehydrogenase (lipoamide) (EC

1.2.4.1) beta chain -rat R.norvegicusl 23874279 AI178808k HMm:interleukin ESTs, Highly similar 2 receptor, to 149280 interleukin-2 gamma chain receptor gamma chain precursor - mouse [M.musculusl 268916781AI234527II, HMm:glutathione ESTs, Highly similar qq S-transferase, to S23433 glutathione alpha 4 transferase (EC 2.5.1.18) 8 - rat [R.norvegicusl 286020082AI639488h, HMmaransformed ESTs, Highly similar r, mouse 3T3 to A42772 mdm2 General,cell double minuteprotein - rat (fragments) ii 2 [R.norvegicus]

287814882D00362 w, Esterase 2 Esterase 2 II, rr 29284378 H32966 y HMm:Tnf receptor-associatedESTs, Highly similar to 161512 TNF receptor factor 2 associated factor 2 -mouse [M.musculus]

299714881M20629 j, Esterase 2 Esterase 2 dd, II

30341379 M83676 qq, RAB12, member RAB12, member RAS oncogene vv RAS oncogene family family 318318694NM_012931mm v-crk-associated v-crk-associated tyrosine tyrosine kinase kinase substrate substrate 3194709 NM 012968h Interleukin 1 Interleukin 1 receptor receptor accessoryaccessory protein protein 32049917 NM 012993qq N-arginine dibasicN-arginine dibasic convertase convertase 1 1 32049918 NM 012993II N-arginine dibasicN-arginine dibasic convertase convertase 1 1 320724718NM_013003tt PhosphatidylethanolaminePhosphatidylethanolamine N- N-methyltransferasemethyltransferase 322314421NM 013053o Tyrosine 3- Tyrosine 3-monooxygenase/tryptophan monooxygenaseltryptophanmonooxygenase activation 5- protein, theta monooxygenase polypeptide activation protein, theta polvpeptide 3313923 NM 017076f, Tumor-associated Tumor-associated glycoprotein I, glycoprotein pE4 n, p, kk, pE4 xx 336118050NM 017204nn microtubule-associatedmicrotubule-associated protein protein 6 3399707 NM 017293b kinase interacting- kinase interacting with leukemia with leukemia-associated associated ene ene stathmin stathmin Ana TABLE

Attorney Docket No:

Document:No.1926271.2 SEQ GLGGGenBank Model Kriowri Gene Namenigene Sequence Cluster U Title ID D. Acc: Code > N0. or =
I

N0.- RefSeq ID

No. __ 34752439NM 019277m, SEC15 homolog SEC15 homolog (S. cerevisiae) ss (S. cerevisiae) 3562695 NM 022388y corticosteroid-inducedcorticosteroid-induced protein protein 36698879NM_024360a hairy and enhancerhairy and enhancer of of split 1, split 1, (Drosophila) ( Drosophila) 383167 NM 031605cc cytochrome P450, cytochrome P450, 4a10 4a10 386016664NM 031695v sialyltransferasesialyltransferase 5 386816918NM 031709x, ribosomal proteinribosomal protein S12 z, S12 ee, gg, hh, II

395520235NM_053302bb adrenomedullin ESTs, Weakly similar receptor to dual-specificity phosphatase [Mus musculus]
[M.musculus]

41171888NM 057130n, BH3 interacting BH3 interacting (with bb (with BCL2 BCL2 family) domain, f amily) domain, apoptosis agonist apoptosis agonist 41851394NM_133536I, RAB3C, member RAB3C, member RAS oncogene v, RAS family xx oncogene family 43051448NM_1457830o HMm:cytochrome Rat CoxVa mRNA for mitochondria) c oxidase, subunit Va cytochrome c oxidase subunit Va 435313520S87522 c HMm:leukotriene ESTs, Highly similar A4 hydrolase to S20444 leukotriene-A4 hydrolase (EC 3.3.2.6) - rat [R.norvegicus]

444916780X62660 b, HMm:glutathione ESTs, Highly similar m, S-transferase, to S23433 glutathione qq, vv alpha 4 transferase (EC 2.5.1.18) 8 - rat [R.norvegicus]

6 6049AA685178a, ESTs, Highly similar General, to T30827 nascent cc, polypeptide-associated rr complex alpha chain, non-muscle splice form - mouse f M.musculusl 16 22646AA799301r ESTs, Highly similar to LIGA_MOUSE

Ligatin [M.musculus]

22 6581AA799412v ESTs, Weakly similar to 167424 hERR-2 homolo - rat (fra ment) (R.norvegicus]

32 6505AA799499p ESTs, Moderately similar to RIKEN cDNA

2700033116 [Mus musculus]
[M.musculus]

34 16942AA799520ee ESTs, Highly similar to ITMB_MOUSE

Integral membrane protein 2B (E25B

protein) [M.musculus]

35 21120AA799526pp ~ ESTs, Highly similar to RIKEN cDNA

1700043E15 Mus musculus]
[M.musculus]

40 16959AA799550a ESTs, Moderately similar to RIKEN cDNA

9130413122 [Mus musculus]
[M.musculus]

52 20093AA799637a ESTs, Weakly similar to A55071 hydrogen peroxide-inducible protein hic-5 - mouse (M.musculus]

53 18226AA799641u, ESTs, Moderately similar rr, to 153063 testicular ss tumor overexpressed protein - mouse M.musculus ~n~
TABLE

Attorney Docket No.

Document-No.1926271.2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence: Cluster Title ID D Acc. Code I N0. or NO. RefSeq ID

_ No. .

76 18880AA799801bb, ESTs, Moderately similar ii to predicted gene I CRFP703B1614Q5.6;

I CRFP703N2430Q5.6; C11orf17 [Mus musculusl ~M.musculusl 87 18378AA799888bb ESTs, Highly similar to nuclear localization signal protein absent in veto-cardio-facial patients [Mus musculus]
[M.musculusl 90 15011AA799893I, ESTs, Highly similar s, to DDRT helix-z, kk, nn destabilizin protein - rat [R.norve icus]

95 18881AA799992a, ESTs, Moderately similar d to predicted gene ICRFP703B1614Q5.6;

ICRFP703N2430Q5.6; C11orf17 [Mus musculusl [M.musculusl 95 18883AA799992a ESTs, ESTs, Moderately similar to predicted gene ICRFP703B1614Q5.6;

ICRFP703N2430Q5.6; C11orf17 [Mus musculusl [M.musculusl 96 2098AA799995I ribosomal proteinribosomal protein L14 106 21064AA800175m, ESTs, Highly similar ww to JC7136 peptidylprolyl isomerase (EC 5.2.1.8) - mouse [M.musculus]

110 15659AA800199ss ESTs, Weakly similar to 839066 proline-rich protein 15 - rat [R.norve icus]

116 18442AA800258f, ESTs, Moderately similar pp, to low density ww lipoprotein B [Mus musculus]
[M.musculus]

133 16463AA800663k ESTs, Highly similar to RAN binding protein 16 [Mus musculus] [M.musculus]

158 22025AA800849ss ESTs, Moderately similar to 0806162L

protein URF5 [Mus musculus]
[M.musculus]

168 23115AA801165d Testis-specific Testis-specific histone histone 2a 2a 175 1397AA817787s, ESTs, Highly similar General to potassium channel modulatory factor DEBT-91;
clone DEBT-91 [Mus musculus [M.musculus]

188 2431AA817945ff ESTs, Highly similar to TBCA_MOUSE

TUBULIN-SPECIFIC CHAPERONE
A

(TUBULIN-FOLDING COFACTOR
A) (CFA) (TCP1-CHAPERONIN COFACTOR
A) IM.musculusl 193 2845AA818026h ESTs, Weakly similar to PSD7_MOUSE 26S

proteasome non-ATPase regulatory subunit 7 (26S proteasome regulatory subunit S12) (Proteasome subunit p40) (Mov34 protein) IM.musculusl 198 3275AA818112f, ESTs, Weakly similar uu to neugrin; neurite outgrowth associated protein [Mus musculusl [M.musculus]

213 14123AA818554g R.norvegicus mRNA for tropomyosin isoform TX~BLE

Attorriey Docket No.
4492~Ir5113WQ

Document No:1926271:2 SEQGLGC GenBankModel Known Gene Name tJnigene Sequence Cluster Title ID ID Acc. Code N0. or N0. RefSeq ID

No. .

2254491 AA818798xx Rattus norvegicus mRNA
for cathepsin Y, partial cds 23511978AA819129b ESTs, Moderately similar to S27161 glutathione transferase (EC 2.5.1.18) 5 - rat fR.norvegicusl 2376329 AA819259j, ESTs, Moderately similar p to S31799 apolipoprotein C2 precursor-mouse [M.musculusl 2399000 AA819318r ESTs, Highly similar to JC4141 YL-1 protein mouse [M.musculus]

2485169 AA819488I, ESTs, Weakly similar General to 834488 calpain (EC

3.4.22.17) large chain 3 - rat [R.norvegicus]

26019451AA819788II ESTs, Weakly similar to 28kD interferon alpha responsive protein [Mus musculusJ

M.musculusl 264230 AA819870uu Rattus norvegicus complement C8 beta (C8b) mRNA, partial cds 26519566AA819879c ESTs, Weakly similar to phosducin-like protein 2; protein B
[Mus musculusJ

[M.musculusl 266320 AA819905ee stearoyl-Coenzymestearoyl-Coenzyme A desaturase desaturase 1 27123759AA848402a ESTs, Weakly similar to A57284 spermatid perinuclear RNA-binding protein Spnr-mouse [M.musculusl 2827749 AA848804jj ESTs, Highly similar to BTF3_MOUSE

Transcription factor BTF3 (RNA polymerase B transcription factor 3) [M.musculus]

30618696AA849965q, ESTs, Highly similar nn, to M025_MOUSE
qq, xx M025 protein [M.musculus]

31519042AA850378t ESTs, Moderately similar to methyl-CpG

binding domain protein 2 [Mus musculusJ

[M.musculusl 31713975AA850450xx Rattus norvegicus mRNA
for class I beta-tubulin, complete cds 32316132AA850885ee unknown Glu-Pro unknown Glu-Pro dipeptide dipeptide repeat protein repeat protein 3272847 AA850919cc ESTs, Weakly similar to FAS_RAT FATTY

ACID SYNTHASE [INCLUDES:
EC 2.3.1.38;

EC 2.3.1.39; EC 2.3.1.41;
EC 1.1.1.100; EC

4.2.1.61; EC 1.3.1.10;
EC 3.1.2.14]

IR.norveoicusl 3283924 AA851017ff ESTs, Highly similar to molybdenum cofactor synthesis 2 [Mus musculusJ

[M.musculusl 3324490 AA851184ii Rattus norvegicus mRNA
for cathepsin Y, artial cds ~n5 TABLE
1;
Attorney Docket No.

Documerit No.1926271 ~2 SEQ GLGC GenBankMode[ Known Gene Name Unigene Sequence Cluster _ Title ID_ D Acc. Code-I N0. or NO. RefSeq ID

No:

335 17823AA851214y ESTs, Highly similar to hypothetical protein MGC7474 [Mus musculus]
[M.musculus]

338 19189AA851237dd ESTs, Highly similar to UBPI MOUSE
_ Ubiquitin carboxyl-terminal hydrolase 18 (Ubiquitin thiolesterase 18) (Ubiquitin-specific processing protease 18) (Deubiquitinating enzyme 18) (43 kDa ubiauitin-specific protease) fM.musculusl 346 883 AA851347t ESTs, Highly similar to SNXS_MOUSE

Sortin nexin 5 M.musculus]

349 21489AA851443a ESTs, Weakly similar to 149523 tumor necrosis factor alpha-induced protein 2 -mouse [M.musculus]

355 6687 AA851739General ESTs, Highly similar to tousled-like kinase (Arabidopsis); protein kinase U-alpha;

Tousled-like kinase (Arabidopsis) [Mus musculusl IM.musculusl 356 18697AA851776j ESTs, Highly similar to M025 MOUSE
_ M025 protein [M.musculus]

358 14292AA851791c ESTs, Weakly similar to CBP_MOUSE

CREB-binding protein [M.musculus]

365 18001AA858573x, spp-24 precursor spp-24 precursor bb, gg, hh 375 6380 AA858758o ESTs, Weakly similar to RIKEN cDNA

1500031019 [Mus musculus]
[M.musculus]

379 6403 AA858879y ESTs, Highly similar to proteasome (prosome, macropain) 26S subunit, non-ATPase,13; 26S proteasome subunit p40.5 fMus musculusl IM.musculusl 381 14589AA858982p, ESTs, Highly similar y to LIM only 4 [Mus musculus] [M.musculus]

382 16985AA858990rr ESTs, Highly similar to EF1 G_MOUSE

Elongation factor 1-gamma (EF-1-gamma) (eEF-1 B gamma) [M.musculus]

383 17559AA858994II parathymosin parathymosin 388 6440 AA859130w, ESTs, Weakly similar pp to JC2524 phosphoprotein phosphatase (EC 3.1.3.16) 1A-beta - rat [R.norvegicus]

396 15172AA859362p ESTs, Highly similar to BAG3_MOUSE BAG-family molecular chaperone regulator-3 (BCL

2 binding athanogene-3) (BAG-3) (Bcl-2-bindinq protein Bis) [M.musculusl 408 17142AA859612gg, EST, Moderately similar hh to 0806162) protein URF4 [Mus musculus]
[M.musculus]

434 22593AA859977tt ESTs, Highly similar to HS9B_RAT Heat _ shock protein HSP 90-beta (HSP 84) R.norve icus TABLE

Attorney Docket Nor Document No.19262712 _ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster SEQ Title ~

ID ID Acc: Code ~ N0. or NO:. RefSeq ID.

No.

441 4222 AA860024I, ESTs, Highly similar I rr to EF1 G_MOUSE

Elongation factor 1-gamma (EF-1-gamma) ( eEF-1B gamma) [M.musculus]

442 13974AA860030n, Rattus norvegicus mRNA
qq, for class I beta-ss t ubulin, complete cds 460 16013AA866482r, ESTs, Highly similar x to FGD1 MOUSE

Putative Rho/Rac guanine nucleotide exchange factor (Rho/Rac GEF) (Faciogenital dysplasia protein homology IM.musculusl 461 16029AA874803ss ESTs, Moderately similar to 0806162L

protein URF5 [Mus musculus]
[M.musculus]

470 16146AA874934y ESTs, Moderately similar to A Chain A, The C2b-Domain Of Rabphilin:
Structural Variations In A Janus-Faced Domain fR.norveaicusl 471 17303AA874990a ESTs, Weakly similar to RIKEN cDNA

6330407611 [Mus musculus]
[M.musculus]

481 16319AA875047tt ESTs, Highly similar to TCPZ_MOUSE T-complex protein 1, zeta subunit (TCP-1-zeta) (CCT-zeta) (CCT-zeta-1) [M.musculus]

504 15205AA875263m ESTs, Highly similar to microspherule protein 1; nucleolar protein [Mus musculus]

[M.musculusl 514 24470AA875523jj ESTs, Highly similar to MLES_RAT Myosin light chain alkali, smooth-muscle isoform (MLC3SM) [R.norvegicus]

514 24471AA875523y ESTs, Highly similar to MLES_RAT Myosin light chain alkali, smooth-muscle isoform (MLC3SM) [R.norvegicus]

518 18911AA875615s, ESTs, Highly similar qq to PMC1 MOUSE

Polymyositis/scleroderma autoantigen 1 (Autoantigen PM/Scl 1) (Polymyositislscleroderma autoantigen 75 kDa) (PMIScI-75) (P75 polymyositis-scleroderma overlap syndrome associated a t antiaenl fM.musculusl 521 2846 AA875639bb, ESTs, Weakly similar ll, to FAS RAT FATTY
rr _ ACID SYNTHASE [INCLUDES:
EC 2.3.1.38;

EC 2.3.1.39; EC 2.3.1.41;
EC 1.1.1.100; EC

4.2.1.61; EC 1.3.1.10;
EC 3.1.2.14]

fR.norveaicusl 525 5384 AA891041vv jun B proto-onco jun B proto-onco ene ene 539 21951AA891535f, ESTs, Highly similar s, to hippocampus pp abundant gene transcript 1 [Mus musculus]

M.musculus TABLE

Attorney Docket No.

Document No.1926271.2 SEQ GLGCGeriBankModel Known Gene Name Unigene Sequence Gluster'Title ID D Accor Code _ N0.--I

NO RefSeq ID

No:

542 17225AA891553I, ESTs, Moderately similar nn to IF37_MOUSE

Eukaryotic translation initiation factor 3 subunit 7 (eIF-3 zeta) (eIF3 p66) f M.musculusl 548 22858AA891591w programmed cell programmed cell death death 8 8 (apoptosis-(apoptosis-inducingnducin factor) factor) i 559 6535AA891746r ESTs, Highly similar to endothelial differentiation-related factor 1; hypothetical rotein 1-9 [Mus musculusl [M.musculusl 567 6967AA891810pp ESTs, Moderately similar to g1-related zinc finger protein [Mus musculus] [M.musculus]

567 6968AA891810q, ESTs, Moderately similar x, to g1-related zinc ss fin er protein [Mus musculus] [M.musculus]

575 16023AA891872w ESTs, Highly similar to NNTM_MOUSE

NAD(P) transhydrogenase, mitochondrial precursor (Pyridine nucleotide transhydrogenase) (Nicotinamide nucleotide transhydrogenase) [M.musculus]

588 17088AA891998General, ESTs, Highly similar to JC4978 oxidative cc, stress protein A170 oo, - mouse [M.musculus]
uu 589 16836AA892005r ESTs, Weakly similar to PGC1 RAT

Membrane associated progesterone receptor component 1 (Acidic 25 kDa protein) (25-DX) fR.norveaicusl 599 19469AA892112r ESTs, Weakly similar to PROD MOUSE
_ PROLINE OXIDASE, MITOCHONDRIAL

PRECURSOR (PROLINE

DEHYDROGENASE) (M.musculusl 607 3427AA892246nn ESTs, Weakly similar to serine/threonine kinase 25 (yeast); Ste20-like kinase;

serinelthreonine kinase 25 (Ste20, yeast homology; Yeast Sps1/Ste20-related kinase 1 fMus musculusl fM.musculusl 618 18208AA892318gg, ESTs, Highly similar hh to JC7219 nuclear protein SR-25 - mouse [M.musculus]

618 18209AA892318r, ESTs, Highly similar bb to JC7219 nuclear protein SR-25 - mouse [M.musculus]

627 23194AA892417c ephrin A1 ephrin A1 639 _ AA892531f, ESTs, Weakly similar 13160 pp to 839066 proline-rich protein 15 - rat [R.norvegicus]

640 15154AA892532q, R.norvegicus (Wistar) x, CaBP1 mRNA
dd, tt 641 _ AA892545General ESTs, Moderately similar 17468 to organic cationic transporter-like 2 [Mus musculus]

fM.musculusl 655 20065AA892647c germinal histone erminal histone H4 ene H4 gene 660 4524AA892759f, synaptosomal-associatedsynaptosomal-associated s, protein, 23 kD
ff, pp, vv rotein 23 kD

TABLE~1 Attorney Docket No:44921-5113W0 Document No.1926271.2 S~Q GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID._-D Acc. Code' I NO. or N0. RefSeq ID

No.' 670 17581AA892835f ESTs, Moderately similar to BTF3_MOUSE

Transcription factor BTF3 (RNA polymerase B transcription factor 3) [M.musculus]

685 3381 AA892993j ESTs, Moderately similar j to high mobility group protein 20 B;
BRCA2-associated factor 35 [Mus musculus [M.musculusl 689 3865 AA893065k, ESTs, Weakly similar p to THDE_RAT
_ Thyrotropin-releasing hormone degrading ectoenzyme (TRH-degrading ectoenzyme) (TRH-DE) (TRH-specific aminopeptidase) (Thyroliberinase) (Pyroglutamyl-peptidase II) (PAP-Ill iR.norveaicusl 693 14859AA893173a ESTs, Highly similar to vacuolar protein sorting 29 (S. pombe);
vacuolar protein sorting 29 (yeast);
vacuolar sorting protein 29 fMus musculusl fM.musculusl 706 16168AA893280z, ESTs, Moderately similar nn to ADFP_MOUSE

ADIPOPHILIN (ADIPOSE

DIFFERENTIATION-RELATED
PROTEIN) (ADRP) fM.musculusl 708 17900AA893353gg, ESTs, Highly similar hh, to DNPE_MOUSE
rr _ Aspartyl aminopeptidase [M.musculus]

710 4678 AA893384v ESTs, Moderately similar to IRF3_MOUSE

Interferon regulatory factor 3 (IRF-3) [M.musculusl 715 13088AA893495x ESTs, Highly similar to A40066 corticosteroid-binding globulin precursor - rat [R.norveaicusl 750 24473AA894200y ESTs, Highly similar to MLES_RAT Myosin light chain alkali, smooth-muscle isoform (MLC3SM) [R.norvegicusl 751 22783AA894207cc ESTs, Weakly similar to dual-specificity phosphatase [Mus musculus]
[M.musculus]

766 15009AA899106pp cyclin D2 cyclin D2 792 21649AA900351I, ESTs, Weakly similar uu to RIKEN cDNA

3930402F23 [Mus musculus]
[M.musculus]

803 3944 AA900688ww ESTs, Weakly similar to A45988 dentin matrix acidic phosphoprotein AG1 - rat [R.norvegicus]

808 18379AA900993a ESTs, Highly similar to nuclear localization signal protein absent in velo-cardio-facial patients [Mus musculus]
[M.musculus]

813 4857 AA901237mm ESTs, Weakly similar to CYCK_MOUSE

Cyclin K [M.musculus]

839 4944 AA924405h ESTs, Weakly similar to NFH_MOUSE

Neurofilament triplet H protein (200 kDa neurofilament protein) (Neurofilament heavy of a tide NF-H M.musculus TABLE

Attorney Docket No44921-5113W0 Document No:1926271-.2 SEQ-GLGC'GenBankModel Knowri Gene Name Upigene Sequence Clusfer : Title a ID:ID=N0._Acc. Code or N0.. RefSeq ID

No.

84616806AA924591r, Rat Cyp4a locus, encoding nn cytochrome P450 (IVA3) mRNA, complete cds 8514994 AA924658k ESTs, Moderately similar to PIN21TRF1-interacting protein [Mus musculus]

[M.musculus]

87423159AA925318I, I-kappa-B-beta I-kap a-B-beta q, x, dd 88222125AA925503ss ribosomal proteinribosomal protein S27 90811691AA926193t, sulfotransferase sulfotransferase family, mm family, cytosolic,1 C, cytosolic,1 C, member 2 member 2 91114223AA926352h ESTs, Highly similar to Trk-fused gene;
TFG

[Mus musculus] [M.musculus]

91420910AA942693x ESTs, Highly similar to RIKEN cDNA

5730406115 [Mus musculus]
[M.musculus]

91922677AA942718t, B cell lymphoma B cell lymphoma 2 like ff, 2 like pp 94421600AA943997r ESTs, Highly similar to C184L-22 [Mus musculus] [M.musculus]

9462762 AA944165c ESTs, Highly similar to C10_MOUSE

Putative C10 protein (B-cell receptor-associated protein 37) M.musculus]

94922017AA944209d ESTs, Moderately similar to PIM1 RAT

Proto-oncogene serinelthreonine-protein kinase pim-1 [R.norveqicusl 96219480AA9444420o ESTs, Weakly similar to SLI3_RAT

SKELETAL MUSCLE LIM-PROTEIN

(SLIM 3) (LIM-DOMAIN
PROTEIN DRAL) (FOUR AND A HALF LIM
DOMAINS

PROTEIN 2) (FHL-21 fR.norveaicusl 9652175 AA944528ii ESTs, Weakly similar to T9S2_MOUSE

Transmembrane 9 superfamily protein member 2 precursor [M.musculus]

98823813AA945149b, ESTs, Moderately similar vv to S27161 glutathione transferase (EC 2.5.1.18) 5 - rat [R.norveqicus]

99016635AA945171k ESTs, Highly similar to APC4_RAT

APOLIPOPROTEIN C-IV
PRECURSOR

(APO-CIV) (APOLIPOPROTEIN
E-LINKED) (ECL) [R.norveaicusl 99522029AA945284dd ESTs, Moderately similar to 0806162L

protein URF5 [Mus musculus]
[M.musculus]

9967683 AA945320a ESTs, Highly similar to IMA3_MOUSE

Importin alpha-3 subunit (Karyopherin alpha-3 subunit) (Importin alpha Q2) [M.musculus]

100513751AA945699kk synaptosomal-associatedsynaptosomal-associated protein, 23 kD

protein, 23 kD

101022639AA945746t ESTs, Highly similar to SPT4_HUMAN

Transcription initiation protein SPT4 homolo 1 M.musculus ~~n TABLE

.
Attorney Docket No.

Document No.19262T1.3 SEQ GLGC GenBankModel Known Gene Name. Unigene Sequence = C lusterTitle ID_ ID Acc, Code NO: or N0. RefSeq ID
-No:

102018110AA945932a Annexin A3 Annexin A3, ESTs, ESTs, Weakly similar to LURT3 annexin III -rat [R.norve icus]

102821157AA946189I ESTs, Moderately similar to RGP1 MOUSE

Ran-GTPase activating protein 1 [M.musculus]

103218280AA946361c ESTs, Weakly similar to CBP_MOUSE

CREB-bindin protein [M.musculus]

107217540AA955914f EST, EST, Moderately PP similar to FBRL_MOUSE Fibrillarin (Nucleolar protein 1 ) [M.musculus], ESTs, Highly similar to S38342 fibrillarin -mouse [M.musculus]

107522576AA955983m, ESTs, Weakly similar dd to FLAP RAT 5-lipoxygenase activating protein (FLAP) (MK-886-binding protein) [R.norveqicus]

109316578AA957143d ESTs, Highly similar to DP30 MOUSE Dpy-30-like protein [M.musculus]

109316579AA957143bb ESTs, Highly similar to DP30_MOUSE Dpy-30-like protein [M.musculus]

109522357AA957264k Rattus norvegicus hypothetical RNA binding protein RDA288 mRNA, complete cds 110624156AA957803k ESTs, Moderately similar to RNP_RAT

Ribonuclease pancreatic precursor (RNase 1) (RNaseA) (RL1) [R.norvegicus]

11202205 AA963808t ESTs, Highly similar to zinc finger RNA

binding protein [Mus musculus]

f M.musculus]

11228430 AA964033t Rattus norvegicus NonOlp54nrb homolog mRNA, partial cds 113312563AA964533m ESTs, Highly similar to RIKEN cDNA

1 500003K04 [Mus musculus]
[M.musculus]

11452326 AA964892ii E STs, Highly similar to CA14 MOUSE

C OLLAGEN ALPHA 1(IV) CHAIN

P RECURSOR [M.musculusl 11692939 AA996885II E STs, Moderately similar to SY19_MOUSE

S mall inducible cytokine A19 precursor ( CCL19) (Epstein-Barr virus induced m olecule 1 ligand chemokine) (EB11-ligand c hemokine) IELC) fM.musculusl 11703054 AA996899, hh spermato enesis permatogenesis associated associated 2 2 s 11732958 AA996944ee E STs, Weakly similar to ring finger protein 2 3; RING-B box-coiled coil-830.2 [Mus m usculus] [M.musculus]

118516883AA997345dd E STs, Highly similar to RIKEN cDNA

1 190017819 [Mus musculus]
[M.musculus]

11913250 AA997765n f ibrillin-1 fi brillin-1 TABLE

Attorney Docket No.

Document No.1926271.2 SE GLGC GenBankModel':Known Gene Name Jnigene SequencevCluster Q t Title lD' D Accor Code I N0.

NO: RefSeq ID

No.

121014149AA998172y platelet-activatingplatelet-activating factor factor acetylhydrolase acetylhydrolase alpha 2 subunit (PAF-AH
alpha 2 subunit alpha 2) (PAF-AH alpha 2) 12183558 AA9984610o ESTs, Moderately similar to gene trap ROSA 26 antisense, Philippe Soriano; gene trap ROSA 26 antisense [Mus musculus]

[M.musculusl 12216965 AA998523h ESTs, Moderately similar to C54354 calnexin precursor -rat [R.norvegicus]

122822210AA998690p ESTs, Highly similar to IF6_MOUSE

Eukaryotic translation initiation factor 6 (eIF-6) (B4 integrin interactor) (CAB) (p27(BBP)) fM.musculusl 122920271AA998747cc, procollagen-lysine,procollagen-lysine, mm 2- 2-oxoglutarate 5-oxoglutarate 5-dioxygenasedioxygenase (lysine hydroxylase, Ehlers-(lysine hydroxylase,Danlos syndrome type Ehlers- VI) Danlos syndrome type VI) 124516304ABOO8424e, Rat cytochrome P-450 j IID3 mRNA, complete cds 124813973AB011679y, Rattus norvegicus mRNA
ee for class I beta-tubulin, complete cds 12664292 AF034896e, Rattus norvegicus olfactory h receptor-like protein (SCR D-8) mRNA, complete cds 12698426 AF036335pp Rattus norvegicus Non01p54nrb homolog mRNA, partial cds 12698427 AF036335pp Rattus norvegicus NonO/p54nrb homolog mRNA, partial cds 127317597AF0519430o nucleoside diphosphatenucleoside diphosphate kinase kinase type 6 type 6 127317598AF0519430o nucleoside diphosphatenucleoside diphosphate kinase kinase type 6 type 6 127615801AF061443p Rattus norvegicus G
protein-coupled receptor LGR4 (LGR4) mRNA, complete cds 13104233 A1008409h unknown Glu-Pro unknown Glu-Pro dipeptide dipeptide repeat protein repeat protein 131524151A1008793a ESTs, Highly similar to T2D5_RAT

Transcription initiation factor TFIID 70 kDa subunit (TAFII-70) (TAFII-80) (TAF1180) (p80) iR.norveaicusl 131616701A1008838ff ESTs, Highly similar to RIKEN cDNA

1300002A08 [Mus musculus]
[M.musculus]

13269150 A1009198h ESTs, Highly similar to UNRI_MOUSE UNR-interacting protein (Serine-threonine kinase receptor-associated protein) [M.musculus]

133819092A1009501h, ESTs, Highly similar w to SU11 MOUSE

Protein translation factor SU11 homolog M.musculus TABLE

Attorney:Docket No:

Document No.
t192627~~.2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster ' Title ID D Acc~ Code - IVO.or I

N0 RefSeq ID ' No.

13413926A1009592e, ESTs, Highly similar o to molybdenum cofactor synthesis 2 [Mus musculus]

[ M.musculus]

13528431A1009761y Rattus norvegicus Non01p54nrb homolog mRNA, partial cds 136815644A1010256a, H3 histone, familyH3 histone, family 3B
d, 3B
n, kk 137515624A1010449qq follistatin-relatedfollistatin-related protein protein precursor precursor 13874203A1011082j ESTs, Highly similar to IMA3_MOUSE

Importin alpha-3 subunit (Karyopherin alpha-3 subunit) (Importin alpha Q2) [M.musculus]

138822030A1011177n ESTs, Moderately similar to 0806162L

protein URF5 [Mus musculus]
[M.musculus]

139316702A1011436ss ESTs, Highly similar to RIKEN cDNA

1300002A08 [Mus musculus [M.musculus]

13983941A1011598xx ESTs, Moderately similar to LMA5 MOUSE
_ Laminin alpha-5 chain precursor f M.musculus]

14003995A1011678I,'j RyudocanlsyndecanRyudocan/syndecan 2 140414267A1011738d, ESTs, Highly similar o to P044_RAT 0-44 protein [R.norvegicus]

14137104A10121030o ESTs, Moderately similar to low density lipoprotein B [Mus musculus]
[M.musculus]

142612766A1012505ee ESTs, Highly similar to diacylglycerol 0-acyltransferase 2; diacylglycerol acyltransferase 2 [Mus musculus]

iM.musculusl 14644251A1013494a ATP-binding cassette,ATP-binding cassette, sub- sub-family F

family F (GCN20),(GCN20), member 1 member 1 14747310A1013816ff ESTs, Moderately similar to RIKEN cDNA

0610006108 [Mus musculus]
[M.musculus]

147621950A1013861h 3-hydroxyisobutyrate3-hydroxyisobutyrate dehydrogenase dehydrogenase 14807316A1013883s ESTs, Highly similar to MKR1 MOUSE

Makorin 1 [M.musculus]

149323530A1014148t, ESTs, Highly similar w to A4B1 MOUSE

Adapter-related protein complex 4 beta 1 subunit (Beta subunit of AP-4) (AP-4 adapter complex beta subunit) [M.musculus]

15052699A1029306ii ESTs, Highly similar to 158376 hypothetical protein unp - mouse [M.musculus]

15154679A1029847General ESTs, Moderately similar to IRF3_MOUSE

Interferon regulatory factor 3 (IRF-3) M.musculus TABLE

:
Attorney Docket No..44921=5113W0 Document No:1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene.Sequence-.Cluster Title ID D-N0.Accor Code .
I

NO.. RefSeq ID
-No.

154616169A1030932nn, ESTs, Moderately similar rr to ADFP_MOUSE

ADIPOPHILIN (ADIPOSE

DIFFERENTIATION-RELATED
PROTEIN) ( ADRP) fM.musculusl 155318002A1043655g, spp-24 precursor spp-24 precursor x, dd 15607913 A1043849ff ESTs, Weakly similar to ELL MOUSE RNA
_ POLYMERASE II ELONGATION
FACTOR

ELL (ELEVEN-NINETEEN
LYSINE-RICH

LEUKEMIA PROTEIN) iM.musculusl 157115240A1044241General ESTs, Highly similar to CIDB_MOUSE Cell death activator CIDE-B
(Cell death-inducing DFFA-like effector B) [M.musculus]

159018422A1044827a ESTs, Highly similar to nitrilase 1 [Mus musculus] [M.musculus]

16025712 A1045154n ESTs, Moderately similar to ORCS_MOUSE

Origin recognition complex subunit 5 [M.musculusl 16086241 A1045321bb ESTs, Weakly similar to IGEB MOUSE IGE-_ BINDING PROTEIN [M.musculus]

163321490A1045764jj ESTs, Weakly similar to 149523 tumor necrosis factor alpha-induced protein 2 -mouse fM.musculus]

164415241A1058382General ESTs, Highly similar to CIDB_MOUSE Cell death activator CIDE-B
(Cell death-inducing DFFA-like effector B) [M.musculus]

1677965 A1059340I huntingtin-associatedhuntingtin-associated protein protein interacting interacting proteinprotein (duo) (duo) 16848347 A1059519dd ESTs, Weakly similar to EGRT epidermal growth factor precursor - rat [R.norve icus]

1698900 A1059963ii, vacuolar protein vacuolar protein sorting jj sorting homolog r-vps33b homolog r-vps33b 17098590 A1060207nn ESTs, Highly similar to splicing factor 3b, subunit 1,155 kDa [Mus musculus]

[M.musculus]

17189054 A1070138dd ESTs, Moderately similar to RIKEN cDNA

1110028N05 [Mus musculus]
[M.musculus]

172917871A1070601ii ESTs, Weakly similar to NOE1 RAT Noelin precursor (Neuronal olfactomedin-related ER

localized protein) (Olfactomedin 1) (Pancortin) (1B426B) fR.norveQicusl 17898856 A1072402b, ESTs, Weakly similar h, to S42077 finger a protein 30 - mouse [M.musculus]

179512863A1072467nn ESTs, Highly similar to 2207230A

transcription factor ATBF1 [Mus musculus]

[M.musculusl 18069399 A1072812a ESTs, Highly similar to glioma-amplified se uence-41 Mus musculus M.musculus TABLE

~
Attorney Docket No.:44929~5113W0 Document No.19262T1.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence-Cluster Title ID ID Acc. Code ' NO. or =

N0: RefSeq ID

No 181115308A1072896nn ESTs, Weakly similar to catenin delta 2;

neural plakophilin-related arm-repeat protein; catenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein);
neurojungin [Mus musculusl iM.musculusl 181720834A1073056cc kinesin li ht kinesin light chain chain 1 1 185415080AI102045I ESTs, Moderately similar to NIF1 MOUSE
_ Nuclear LIM interactor-interacting factor 1 (NLI-interacting factor 1) (NIF-like protein) [M.musculusl 186413892AI102438gg, ESTs, Highly similar hh to CNIH_MOUSE

CORNICHON HOMOLOG (M.musculus]

186615218AI102495cc ESTs, Moderately similar to PNPH_MOUSE

Purine nucleoside phosphorylase (Inosine phosphorylase) (PNP) [M.musculus]

18735910 AI102689k ESTs, Highly similar to RPP20 protein [Mus musculus] [M.musculus]

188618607AI103105z ESTs, Highly similar to RL12_RAT 60S

[R.norvegicus]

19072297 AI103602General ESTs, Highly similar to SAP3_MOUSE

Ganglioside GM2 activator precursor (GM2-AP) (Cerebroside sulfate activator protein) (Shingolipid activator protein 3) (SAP-3) fM.musculusl 190913317AI103637ee ESTs, Moderately similar to RIKEN cDNA

2810411623 [Mus musculus]
[M.musculus]

19184402 AI103874kk ESTs, Weakly similar to FKB1 RAT FK506-BINDING PROTEIN (FKBP-12) (PEPTIDYL-PROLYL CIS-TRANS ISOMERASE) (PPIASE) (ROTAMASE) (IMMUNOPHILIN

FKBP121 fR.norveaicusl 192220833AI104035mm ESTs, Highly similar to COXG_MOUSE

Cytochrome c oxidase polypeptide Vlb (AED) (M.musculusl 19288372 AI104256pp ESTs, Highly similar to MUS81 endonuclease [Mus musculus]
[M.musculus]

193122211AI104279tt ESTs, Highly similar to IF6_MOUSE

Eukaryotic translation initiation factor 6 (eIF-6) (B4 integrin interactor) (CAB) (p27(BBP)) fM.musculusl 194622822AI104679p, ESTs, Moderately similar z to RIKEN cDNA

2310016K22; RIKEN cDNA

gene [Mus musculusl (M.musculusl 19586225 AI105105ss ESTs, Highly similar to tangerin [Mus musculus M.musculus 11.5 TABLE

:
Attorney Docket No:

Document No.19262712 SEQ GLGCGenBank.Model Known Gene Name Unigene Sequence;Cluster Title ID D Acc: Code I N0. or NO:: RefSeq ID

No.

195921253AI105110i, ESTs, Highly similar i ww to S58180 suit protein -mouse (fra ment) [M.musculus]

196018742AI105131bb, ESTs, Highly similar qq to lung alphalbeta hydrolase 1; alphalbeta hydrolase-1 [Mus musculus] [M.musculus]

19867266AI112237d, ESTs, Moderately similar kk, to RIKEN cDNA
nn 1810011001 [Mus musculus]
[M.musculus]

19879575AI112250General,protein tyrosine protein tyrosine phosphatase phosphatase type IVA, kk, type IVA, member member 2 nn 2 19892501AI112343f, ubiquitin fusion ubiquitin fusion degradation nn, degradation 1- 1-like ww like 199023099AI112365y, ESTs, Highly similar nn, to MGN HUMAN Mago ww nashi protein homolo [M.musculus]

19952296AI112979q, ESTs, Highly similar x, to SAP3_MOUSE

General Ganglioside GM2 activator precursor (GM2-AP) (Cerebroside sulfate activator protein) (Shingolipid activator protein 3) (SAP-3) fM.musculusl 200423653AI136396bb farnesyltransferasefarnesyltransferase beta subunit beta subunit 201324212AI136747c ESTs, Highly similar to H33_HUMAN

Histone H3.3 (H3.A) (H3.B) (H3,3Q) [M.musculus]

201613090AI136977m, ESTs, Highly similar II to S14538 transition protein - mouse [M.musculus]

201613091AI136977v ESTs, Highly similar to S14538 transition protein - mouse [M.musculus]

202811270AI137480nn ESTs, Weakly similar to A39066 proline-rich protein 4 - rat [R.norve icus]

203018943AI137495d, ESTs, Highly similar II to H2A1 RAT Histone H2A.1 [R.norvegicus]

206519034AI145768a ESTs, Weakly similar to A55817 cyclin-dependent kinase p130-PITSLRE
- mouse [M.musculusl 207123224AI146033h, translocase of translocase of inner z, inner mitochondria) II

mitochondria) membrane 9 homolog (yeast) membrane 9 homolog (yeast) 207711693AI168953mm sulfotransferase sulfotransferase family, family, cytosolic, 1 C, cytosolic,1 C, member 2 member 2 208016580AI1689890o ESTs, Highly similar to DP30_MOUSE Dpy-30-like protein [M.musculus]

20976732AI169269kk ESTs, Highly similar to dim1 (S. pombe) [Mus musculus] [M.musculus]

209916879AI169284ww ESTs, Highly similar to AR61 MOUSE ARL-6 interacting protein-1 (Aip-1) (TBX2 protein) [M.musculusl 210124213AI169289c ESTs, Highly similar to H33_HUMAN

Histone H3.3 (H3.A) (H3.B) (H3.3Q) M.musculus a~~
TABLE
~
~.
Attorney Docket No:
44921:5113W0 Document No.1926271.2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence-Cluster . Title ID= ID Acc. Code N0. or N0. RefSeq ID ' .
T:F

No ~ , 211421660AI169751b, Rattus norvegicus interferon-inducible dd protein variant 10 mRNA, complete cds 21163909AI169903I ESTs, Moderately similar to lymphocyte antigen 96 [Mus musculus]
[M.musculus]

212218367AI170064j ESTs, Moderately similar to JC7279 Down syndrome critical region gene-2 (DSCR2) protein - mouse [M.musculus]

213423966AI170442t, ESTs, Highly similar mm to JE0223 destrin -rat R.norvegicus]

215416170AI170894ii ESTs, Moderately similar to ADFP_MOUSE

ADIPOPHILIN (ADIPOSE

DIFFERENTIATION-RELATED
PROTEIN) (ADRP) fM.musculusl 216720905AI171273t, ESTs, Moderately similar mm to C54819 actin-capping protein beta chain, splice form mouse M.musculus 217117529AI171460a ESTs, Weakly similar to HCD2_RAT 3-hydroxyacyl-CoA dehydrogenase type II

(Type II HADH) (Endoplasmic reticulum-associated amyloid beta-peptide binding protein) IR.norveqicusl 217515684AI171535n, ESTs, Weakly similar General to PAB1 MOUSE

Polyadenylate-binding protein 1 (Poly(A)-binding protein 1) (PABP
1) (PABP1) fM.musculusl 21836582AI171726bb ESTs, Weakly similar to 167424 hERR-2 homolog - rat (fragment) [R.norvegicus]

21967733AI172086z ESTs, Highly similar to SH3 domain binding glutamic acid-rich protein-like 3 [Mus musculus] [M.musculus]

2197537 AI172097y heat shock transcriptionheat shock transcription 9 factor 1 factor 1 2200398 AI172105kk ESTs, Highly similar 1 to potassium channel modulatory factor DEBT-91;
clone DEBT-91 [Mus musculus] [M.musculusl 2207147 AI172236a ESTs, Highly similar 6 to RIKEN cDNA

1110063805 [Mus musculus]
[M.musculus]

2210140 AI172272g, ESTs, Weakly similar 2 g hh to A53004 transcription elongation factor S-II - rat [R.norvegicus]

2211193 AI172274d ESTs, Weakly similar 4 d to A Chain A, 2-Enoyl-Coa Hydratase, Data Collected At 100 K, Ph 6.5 [R.norvegicus]

22253098AI172610, ii ESTs, Moderately similar 1 c to STT3_MOUSE

OLIGOSACCHARYL TRANSFERASE

SUBUNIT HOMOLOG (B5) (INTEGRAL

MEMBRANE PROTEIN 1) [M.musculusj 2231926 AI175034 ESTs, Highly similar 4 II to RIKEN cDNA

2410002022 Mus musculus M.musculus TABLE:1 Attorney Docket No.
44921=5113W0 Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene SequenceCluster-Title ID D Acc. Code I NO. or NOs RefSeq ID

No.T-224318507AI175551z ESTs, Highly similar to EF1 B_MOUSE

Elongation factor 1-beta (EF-1-beta) [M.musculusl 225124214AI175794s ESTs, Highly similar to H33_HUMAN

Histone H3.3 (H3.A) (H3.B) (H3.3Q) [M.musculusl 225219004AI175875i Rattus norvegicus Sprague-Dawley i lipid-binding protein mRNA, complete cds 22537647 AI175991d ESTs, Moderately similar to minichromosome maintenance deficient (S.

cerevisiae) 3-associate;
nuclear protein GANP [Mus musculusl iM.musculusl 225824745AI176101d, ESTs, Highly similar j to MTRP_MOUSE

Lysosomal-associated transmembrane protein 4A (Golgi 4-transmembrane spanning transporter) (Mouse transporter protein) (MTP) fM.musculusl 227619006AI176393f Rattus norvegicus Sprague-Dawley lipid-bindin protein mRNA, complete cds 227815191AI176456t, ESTs, Highly similar w to SMRT2 metallothionein II -rat [R.norvegicus]

228121661AI176479y, Rattus norvegicus interferon-inducible nn protein variant 10 mRNA, complete cds 22832993 AI176492j, ESTs, Highly similar II to eukaryotic translation initiation factor 3, subunit 2 (beta, 36kD); TGF-beta receptor binding protein;

DNA segment, Chr 4, ERATO Doi 632, expressed fMus musculusl fM.musculusl 22943034 AI176613b ESTs, Moderately similar to PEX7 MOUSE

PEROXISOMAL TARGETING

RECEPTOR (PTS2 RECEPTOR) (PEROXIN

7)iM.musculusl 230023403A1176714bb ESTs, Highly similar to CHD1 MOUSE

CHROMODOMAIN-HELICASE-DNA-BINDING PROTEIN 1 (CHD-1) [M.musculus]

23173862 AI177052nn, Nuclear pore complexNuclear pore complex tt protein protein 232514083AI177181n ESTs, Weakly similar to FYV1 MOUSE

FYVE finger-containing phosphoinositide kinase (1-phosphatidylinositol-4-phosphate kinase) (PIPSK) (Ptdlns(4)P-5-kinase) (0235) fM.musculusl 233714910AI177631z ESTs, Moderately similar to MYPS_RAT

MYOSIN-BINDING PROTEIN
C, SLOW-TYPE (SLOW MYBP-C) (C-PROTEIN, SKELETAL MUSCLE SLOW-ISOFORM) fR.norveaicusl 23491131 AI177919nn, Rat cytochrome P450CMF1 pp, b mRNA, ww corn lete cds TABLE

_ ~
Attorney Docket No:

Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc: Code ~ NQ. or N0: RefSeq ID

No.:

235119184AI178025d ESTs, Highly similar to TGIF_MOUSE 5'-TG-3' INTERACTING FACTOR
(HOMEOBOX

PROTEIN TGIF) [M.musculus]

235413389AI178104d ESTs, Highly similar to RIKEN cDNA

2400009811 [Mus musculus]
[M.musculus]

238115091AI178740 ESTs, Highly similar f to A56418 transcription f actor delta - mouse [M.musculus]

23832825 AI178752, nn ESTs, Highly similar I to CLN3_MOUSE CLN3 PROTEIN (BATTENIN) [M.musculus]

239719041AI1790490o ESTs, Weakly similar to RN12_MOUSE

RING finger protein 12 (LIM domain i nteracting RING finger protein) (RING finger LIM domain-binding protein) (R-LIM) [M.musculusl 24015887 AI179099, o ESTs, Moderately similar j to VNN1 MOUSE

Pantetheinase precursor (Pantetheine hydrolase) (Vascular non-inflammatory molecule 1) (Vanin 1) [M.musculus]

241116703AI179300ff ESTs, Highly similar to RIKEN cDNA

1300002A08 [Mus musculus]
[M.musculus]

243614803AI179906r ESTs, Highly similar to transformed mouse 3T3 cell double minute 4 [Mus musculus]

[M.musculusl 24412099 AI180015w, ribosomal proteinribosomal protein L14 tt L14 24439821 AI180114ss ESTs, Highly similar to NIP2_MOUSE

PROTEIN-INTERACTING

fM.musculusl 246222366AI227743tt ESTs, Highly similar to Fas-activated serine/threonine kinase [Mus musculus]

[M.musculusl 247014230AI228064y ESTs, Weakly similar to A47179 homeotic protein LH-2 - rat [R.norvegicus]

247216970AI228112tt protein phosphataseprotein phosphatase 2 (formerly 2 (formerly 2A), 2A), regulatory regulatory subunit B
subunit B (PR (PR 52), alpha isoform 52), alpha isoform 247922915AI228299m, ESTs, Highly similar II to craniofacial development protein 1 [Mus musculus]

[M.musculusl 248322455AI228524s ESTs, Moderately similar to RIKEN cDNA

1700021 F05 [Mus musculus]
[M.musculus]

249515078AI228830s stearoyl-CoenzymeRat DNA polymerase alpha A mRNA, 3' end, desaturase 2 stearo I-Coenz me A
desaturase 2 TABLE

-Attorney Docket No.

Document No.1926271;2 SEQ GLGC GenBankModel Known Gene Name Jnigene Sequence Cluster t Title :.

ID D Acc. Code ' NO. or I .

N0. _ RefSeq ID

No.' 252113977AI229707, bb, Rattus norvegicus mRNA
j nn for class I beta-t ubulin, complete cds 254513555AI230547d ESTs, Moderately similar to 1920362A tumor suppressor gene mgl1 [Mus musculus]

[M.musculus]

255422387AI230753a, ESTs, Highly similar tt to BI3_MOUSE Brain protein 13 [M.musculus]

256014224AI230956rr ESTs, Highly similar to Trk-fused gene;
TFG

[Mus musculus] [M.musculus]

25632299 AI231094w ~ ESTs, Highly similar to SAP3_MOUSE

Ganglioside GM2 activator precursor (GM2-AP) (Cerebroside sulfate activator protein) (Shingolipid activator protein 3) (SAP-3) fM.musculusl 257513092AI2315470o ESTs, Highly similar to S14538 transition protein - mouse [M.musculus]

25784703 AI231606k, ESTs, Moderately similar r to RIKEN cDNA

6330579817 [Mus musculus]
[M.musculus]

258317297AI231785ii, ESTs, Moderately similar rr to Niemann Pick type C2 [Mus musculus]
[M.musculus]

259514102AI232131rr ESTs, Highly similar to 148253 beta-N-acetylhexosaminidase (EC 3.2.1.52) alpha chain precursor- mouse [M.musculus]

259619274AI232135ii ESTs, Highly similar to COG2_MOUSE

Coatomer gamma-2 subunit (Gamma-2 coat protein) (Gamma-2 COP) [M.musculus]

2602409 AI232268p, low density lipoproteinlow density lipoprotein r receptor- receptor-related related protein protein associated protein associated 1 protein 1 260815582AI232320k, Rat mitochondrial 3-hydroxy-3-methylglutaryl o, oo CoA synthase mRNA, complete cds 261814547AI232431z, ESTs, Highly similar ww to TLP1 MOUSE TATA

BOX BINDING PROTEIN-LIKE

(TBP-LIKE PROTEIN 1) (21-KDATBP-LIKE

PROTEIN) iM.musculusl 26228709 AI232534ii ESTs, Weakly similar to DnaJ (Hsp40) homolog, subfamily B, member 3; heat shock protein, DNAJ-like 3 [Mus musculus]

iM.musculusl 264014098AI233114j ESTs, Moderately similar to S29510 ubiquinol--cytochrome-c reductase (EC

1.10.2.2) core protein II precursor- rat iR.norveqicusl 265210378AI233300I ESTs, Moderately similar to C05 MOUSE
_ Complement C5 precursor (Hemolytic complement) [Contains:
C5A anaphylatoxin]

M.musculus TABLE

Attorney Docket No44921-5113W0 Document No:19262T1:2 SEQ GLGC GenBankModel Known Gene Name Uniger~e Sequence Cluster Title ,-ID ID Acc. Code N 0. or N0. RefSeq ID

No:

267615685AI233870m ESTs, Weakly similar to PAB1 MOUSE

Polyadenylate-binding protein 1 (Poly(A)-binding protein 1) (PABP
1) (PABP1) fM.musculusl 270015034AI235054s ESTs, Weakly similar to RIKEN cDNA

0610008N23 [Mus musculus]
[M.musculus]

270315004AI235224k tissue inhibitor tissue inhibitor of of metalloproteinase 1 metalloproteinase 271115858AI235455rr ESTs, Moderately similar to 854745 beta-N-acetylhexosaminidase (EC 3.2.1.52) beta chain - mouse [M.musculusl 27283617 AI236021d ESTs, Highly similar to JC4857 hepatocarcinogenesis-related transcription factor- rat fR.norveqicusl 273120788AI236053qq acyl-coenzyme acyl-coenzyme A:cholesterol A:cholesterol acyltransferase acyltransferase 273311465AI236084q ESTs, Moderately similar to TNR9_MOUSE

Tumor necrosis factor receptor superfamily member 9 precursor (4-1 BB ligand receptor) (T-cell antigen 4-1 BB) (CD137 antigen) iM.musculusl 27369543 AI236164k ESTs, Moderately similar to A41641 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase (EC 3.2.1.114) - mouse fM.musculusl 274719035AI236576pp, ESTs, Highly similar rr to S06147 GTP-binding protein rab1 B - rat [R.norvegicus]

27527691 AI236611v, isopentenyl-diphosphateisopentenyl-diphosphate x, delta delta isomerase bb isomerase 276415850AI236795b, ESTs, ESTs, Highly similar tt to HS9B_RAT

Heat shock protein HSP
90-beta (HSP 84) [R.norveqicusl 276911404AI237002v, spermidine synthasespermidine synthase w, bb 277714841AI237372v ESTs, Highly similar to RTC1 MOUSE RNA

3'-terminal phosphate cyclase (RNA-3'-phosphate cyclase) (RNA
cyclase) iM.musculusl 27853489 AI237620n ESTs, Highly similar to IF36_HUMAN

Eukaryotic translation initiation factor 3 subunit 6 (eIF-3 p48) (Mammary tumor-associated protein INT-6) (Viral integration site protein INT-6 fM.musculusl 278618854AI237636I ESTs, Weakly similar to CNE6_MOUSE

Copine VI (Neuronal-copine) (N-copine) [M.musculusl 278714837AI237638k, EST, Highly similar mm to VAT1 MOUSE

Synaptic vesicle membrane protein VAT-1 homolo M.musculus TABLE

Attor=ney Docket No44921-5113W0 Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc. Code NO. or N0. RefSeq ID

No:_ 280717108AI639017bb ESTs, Weakly similar to T17453 ERG-associated protein ESET
- mouse [ M.musculus~

281318504AI639044cc ESTs, Moderately similar to T4S9_MOUSE

TRANSMEMBRANE 4 SUPERFAMILY, MEMBER 8 (TETRASPANIN
5) (TSPAN-5) [M.musculusl 284819152AI639387c ESTs, Highly similar to RT06_MOUSE

Mitochondria) 28S ribosomal protein S6 (MRP-S6) [M.musculus) 286823220AJ000347pp 3'(2'),5'-bisphosphate3'(2'),5'-bisphosphate nucleotidase nucleotidase 287014332AJ001044q, tumor-associated tumor-associated calcium ff calcium signal signal transducer transducer 1 1 28739866 AJ005424ss mitogen-activatedmitogen-activated protein protein kinase kinase 7 28739867 AJ005424tt mitogen-activatedmitogen-activated protein protein kinase kinase 7 288319053D12770 j, solute carrier solute carrier family o family 25 25 (mitochondria) (mitochondria) adenine nucleotide translocator) adenine member 4 nucleotide transl0cator) member 293016986H33020 bb ESTs, Highly similar to EF1 G MOUSE

Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) [M.musculus~

295323485K02816 ww pR-ET2 encoded pR-ET2 encoded oncodevelopmental protein oncodevelopmental protein 295323486K02816 kk, pR-ET2 encoded pR-ET2 encoded oncodevelopmental ww protein oncodevelopmental protein 297613499L26267 s nuclear factor nuclear factor kappa kappa B p105 B p105 subunit subunit 299419256M15562 xx Rat (diabetic BB) MHC
class II alpha chain RT1.D alpha (u) 300811956M28255 ff cytochrome c oxidase,cytochrome c oxidase, subunit subunit Vllla Vllla 300917123M29295 nn, small nuclear small nuclear ribonucleoprotein tt ribonucleoprotein,polypeptides polypeptides B B and B1 and B1 301315579M33648 d, Rat mitochondria) 3-hydroxy-3-methylglutaryl k, I, o, ff, oo, CoA synthase mRNA, complete ss cds 301315580M33648 k, Rat mitochondria) 3-hydroxy-3-methylglutaryl I, o, ff CoA synthase mRNA, complete cds 301416807M33936 k, Rat Cyp4a locus, encoding o, cytochrome v, ss, uu, P450 (IVA3) mRNA, complete xx cds 301817145M38566 b, Serine protease Serine protease inhibitor qq inhibitor 302920836M75148 I, kinesin light kinesin light chain General,chain 1 1 qq TABLE

' Attorney Docket No.:44921-5113W0 Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence.Cluster - Title I17 ID Acc, Code N0. or NO.. RefSeq ID

No.

30301138 M76740 cc Mucin3 Mucin3 303524651M83678 u, RAB13 RAB13 y, nn 304125467M93297 t ornithine aminotransferaseornithine aminotransferase 30423424 M94557 o Single-stranded ESTs, Highly similar DNA-binding to SSB RAT SINGLE-protein STRANDED DNA-BINDING
PROTEIN, MITOCHONDRIAL PRECURSOR
(MT-SSB) (MTSSB) (P16) fR.norveaicusl 308017292NM 012584General,Hydroxy-delta-5-steroidHydroxy-delta-5-steroid dehydrogenase, 3 cc dehydrogenase, beta- and steroid delta-isomerase 3 beta- and steroid delta-isomerase 3086382 NM 012599a, Mannose binding Mannose binding protein d, protein A, A, serum gg, hh serum 310117147NM 012657e, Serine protease Serine protease inhibitor n, inhibitor r, ii 310117148NM 012657r, Serine protease Serine protease inhibitor ii inhibitor 31081514 NM 012678b, Tropomyosin 4 Tropomyosin 4 t 31171602 NM 012697dd, Or anic ration Organic ration transporter mm transporter 312418730NM_012730a, Cytochrome P450, Cytochrome P450, subfamily j subfamily IID2 313413731NM 012755bb Fyn proto-oncogeneFyn proto-oncogene 313617257NM 012766x, Cyclin D3 Cyclin D3 II, rr, ww 313617258NM 012766I, Cyclin D3 Cyclin Ic, D 3 nn, ww 321517174NM_013030gg, R.norvegicus ASl mRNA
hh for mammalian equivalent of bacterial large ribosomal subunit protein L22 32271859 NM 013063p, ADP-ribosyltransferaseADP-_ y, (NAD+; ribosyltransferase (NAD+;
nn poly (ADP-poly (ADP-ribose)ibose) polymerase) polymerase) r 3228675 NM 013066g Microtubule-associatedMicrotubule-associated protein protein 2 32299335 NM 013067x, Ribophorin I Ribophorin I
1 dd 3234529 NM 013082b, Ryudocan/syndecanyudocan/syndecan 2 1 e, 2 R
h, I, General 3241793 NM 013105j Cytochrome P450, Cytochrome 1 j subfamily 450, subfamily IIIA, P

I IIA, pol peptide olypeptide 3 3 p 3241794 NM 013105j Cytochrome P450, Cytochrome 1 j subfamily 450, subfamily IIIA, P

I IIA, polypeptide ol peptide 3 3 p 3241795 NM 013105j Cytochrome P450, Cytochrome 1 j subfamily 450, subfamily IIIA, P

I IIA, polypeptide olypeptide 3 3 p 3241796 M 013105C ytochrome P450, Cytochrome P450, subfamily 1 N v subfamily IIIA, I IIA, polypeptide olypeptide 3 3 p 3241797 M 013105, r, ytochrome P450, ytochrome 1 N j jj subfamily C 450, subfamily IIIA, C P

I IIA, polypeptide olypeptide 3, Rattus 3 p norvegicus Sprague D awley testosterone 6-beta-hydroxylase, c ytochrome P450/6-beta-A, (CYP3A2) mRNA. complete cds 324328 M 013112A oli o rotein A-IIoli o rotein A-II
4 N x A

1~R
TABLE

Attorney Docket No.

Document No.1926271.2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster ID D Accor Code Title I N0. RefSeq ~ Y , N0. ID - - ~:_ No.
~

324423709NM_013113, w, ATPase Na+IK+ ATPase Na+IK+ transporting I z transporting beta 1 beta 1 polypeptidepolypeptide 324423710NM 013113ww ATPase Na+IK+ ATPase Na+IK+ transporting transporting beta 1 beta 1 polypeptidepolypeptide 324522582NM 013120b, Glucokinase re Glucokinase re ulatory kk ulatory protein protein 324716650NM 013132a Annexin V Annexin V

324920150NM 0131350o RAS p21 protein RAS p21 protein activator activator 325216982NM 013144f, Insulin-like growthInsulin-like growth r, factor binding factor binding protein z, protein 1 1 ee, ff, rr 325346 NM 013151I, Plasminogen activator,Plasminogen activator, vv tissue tissue 32571309NM 013159e, Insulin degradingInsulin degrading enzyme bb, enzyme oo 32621451NM 013168tt HydroxymethylbilaneHydroxymethylbilane synthase synthase 32621452NM 013168ii Hydroxymeth IbilaneHydroxymethylbilane synthase synthase 326424774NM 013176uu Transcription Transcription factor factor 12 12 32671258NM_013185o Hemopoietic cell Hemopoietic cell tyrosine tyrosine kinase kinase 32681255NM 013189ff, Guanine nucleotideGuanine nucleotide binding xx binding protein, alpha protein, alpha 32691300NM_013190t Phosphofructokinase,Phosphofructokinase, liver, B- liver, B-type type 327121396NM 013198k, Monoamine oxidaseMonoamine oxidase B
jj B

327620826NM 013218gg, adenylate kinase adenylate kinase 3 hh 3 327718313NM 013220x cardiac ankyrin cardiac ankyrin repeat repeat protein protein 32791567NM 013223p, hemin-sensitive hemin-sensitive initiation s initiation factorfactor 2a kinase 2a kinase 3280815 NM 013224h, ribosomal proteinribosomal protein S26 I, S26 II, oo 329780 NM 017021cc Interleukin 9 Interleukin 9 receptor receptor 33151523NM 017079GeneralCD1D anti en CD1D antigen 33191968NM 017091g Proprotein convertaseProprotein convertase subtilisinlkexin subtilisinlkexin type type 2 2 332220653NM_017104s Colony stimulatingColony stimulating factor factor 3 3 (granulocyte) (granulocyte) 33432968NM 017158n cytochrome P450, cytochrome P450, 2c39 2c39 33432970NM 017158f, cytochrome P450, cytochrome P450, 2c39 rr, 2c39 ss 334820702NM_017166General,Leukemia-associatedLeukemia-associated dd, cytosolic cytosolic oo, phosphoprotein phosphoprotein stathmin pp stathmin 336618445NM 017220y growth and transformation-growth and transformation-dependent dependent proteinprotein 340718142NM 017314r ubiquitin C ubiquitin C

34091894NM 017320ii, cathepsin S cathepsin S
nn, pp 341017516NM 0173210, iron-responsive iron-responsive element-binding ii, element-binding protein jj, protein tt 341124766NM 017322k stress activated stress activated protein protein kinase kinase alpha II
alpha II

341124767NM 017322a stress activated stress activated protein protein kinase kinase alpha II
alpha II

341324247NM 017332n, fatty acid synthasefatty acid synthase rr 34142000NM 017333g endothelin receptorendothelin receptor 341525515NM 017339 isl-1=homeobox isl-1=homeobox TABLE

Attorney Dockef No:'44921-5113W0 Document No.1926271':2 SEQ GLGC GenBankModef Known Gene Name Unigene Sequence.ClusterTitle ID D Acc: Code - N0. or I

NO.'_ RefSeq ID

No.

341716381NM_017343, y, myosin regulatorymyosin regulatory light I z, light chain chain General, ee 341716382NM 017343z myosin regulatorymyosin regulatory light light chain chain 3418520 NM 017345n neural cell adhesionneural cell adhesion molecule molecule L1 342420778NM 019124a, rabaptin 5 rabaptin 5 ww 343417304NM 019144d, Acid phosphatase Acid phosphatase 5, p, 5, tartrate tartrate resistant gg, hh resistant 34551386 NM 019226d dynein, cytoplasmic,dynein, cytoplasmic, heavy heavy chain 1 chain 1 347810016NM 019289v, Actin-related Actin-related protein x protein complex complex 1b 1b 347923678NM 019290I, B-cell translocationB-cell translocation u, gene 3 gene 3 General 347923679NM_019290General,B-cell translocationB-cell translocation gene 3 gene 3 ss 348117507NM_019299w clathrin, heavy clathrin, heavy polypeptide polypeptide (Nc) (Hc) 348451 NM 019335a Protein kinase, Protein kinase, interferon-inducible interferon- double inducible double stranded RNA dependent stranded RNA

dependent 348452 NM_019335a Protein kinase, Protein kinase, interferon-inducible interferon- double inducible double stranded RNA dependent stranded RNA

dependent 34884592 NM 019356h eukaryotic translationeukaryotic translation initiation initiation factor 2, factor 2, subunitsubunit 1 (alpha ) 1 (alpha ) 349420057NM 019370General,alkaline phosphodiesterasealkaline phosphodiesterase nn 349615066NM 019373cc, apolipoprotein apolipoprotein M
rr M

350224066NM 019384d, CTD-binding SR-likeCTD-binding SR-like kk rA1 rA1 350316 NM 019386b, tissue-type transglutaminasetissue-type transglutaminase I, q, General, dd, kk 350520716NM 019623b, cytochrome P450 cytochrome P450 4F1 I, 4F1 General, gg, hh, II, uu 351118702NM 0200800o nuclear protein nuclear protein E3-3 E3-3 orf1 orf1 351413485NM_020306d, a disintegrin a disintegrin and metalloproteinase bb and domain metalloproteinase17 domain 17 351413486NM 020306s a disintegrin a disintegrin and metalloproteinase and domain metalloproteinase17 domain 17 351718727NM 021577g, ar ininosuccinateargininosuccinate lyase m lyase 352018544NM 021592a eHand protein eNand protein 352519696NM 021699I, serinelthreonine serinelthreonine kinase nn kinase 352819710NM 021744bb CD14 anti en CD14 anti en TABLE

' Attorney Docket No.

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Urrigene SequenceiGluter ID' D Arc. Code: Title I N0: or.
N0. RefSeq ID
=.
No:' 353019824NM 021750c, cysteine-sulfinatecysteine-sulfinate decarboxylase General,decarboxylase kk 353019825NM 021750, General,cysteine-sulfinatecysteine-sulfinate decarboxylase I dd, decarboxylase ii, qq, vv 353120035NM 021754qq Nopp140 associatedNopp140 associated protein protein 353120036NM 021754r Nopp140 associatedNopp140 associated protein protein 353317884NM 021765q beta prime COP beta prime COP

353317885NM 021765q beta prime COP beta prime COP

353620161NM 0218360o jun B proto-oncogenejun B proto-oncogene 353718839NM 021840g histone 2a histone 2a 353820129NM 021850gg, Bcl-w protein Bcl-w protein hh 354217100NM 022179d, Hexokinase 3 Hexokinase 3 h, I, ee 354217101NM 022179b, Hexokinase 3 Hexokinase 3 General, ii, kk, ss 354520194NM_022192v putative protein putative protein kinase kinase C C inhibitor inhibitor 354620204NM 022196f leukemia inhibitoryleukemia inhibitory factor factor 354820269NM 022214bb CXC chemokine CXC chemokine LIX
LIX

354920299NM 022220j L-gulono-gamma-lactoneL-gulono-gamma-lactone oxidase oxidase 3551762 NM 022245t, cytochrome b5 cytochrome b5 mm 35526585 NM 022266y connective tissueconnective tissue rowth rowth factor factor 355717158NM 022298c, alpha-tubulin alpha-tubulin f, vv, xx 355717160NM 022298nn alpha-tubulin alpha-tubulin 355717161NM 022298y, alpha-tubulin alpha-tubulin nn, tt 356023980NM 022383w cyclase-associatedcyclase-associated protein protein homologue homologue 356312082NM 022389jj 7-dehydrocholesterol7-dehydrocholesterol reductase reductase 356312083NM 022389jj 7-dehydrocholesterol7-dehydrocholesterol reductase reductase 356413479NM 022390e, quinoid dihydropteridinequinoid dihydropteridine y, reductase reductase xx 356413480NM 022390r, quinoid dihydropteridinequinoid dihydropteridine ss reductase reductase 356623060NM 022394a scaffold attachmentscaffold attachment factor B factor B

35781610 NM 022509ee, survival motor survival motor neuron gg, neuron hh 35781611 NM 022509h, survival motor survival motor neuron I neuron 35802384 NM 022513b, dopaltyrosine dopaltyrosine sulfotransferase k, sulfotransferase I, qq, uu, vv 35844145 NM 022518j, ADP-ribosylation ADP-ribosylation factor ii factor 1 1 35844153 NM 022518bb ADP-ribosylation ADP-ribosylation factor factor 1 1 35864242 NM 022521xx ornithine aminotransferaseornithine aminotransferase 35874256 NM 02252200, cas ase 2 cas ase 2 uu 1~~, TABLE

Aftorney Docket No.

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence-Cluster ID D Acc: Code Title I NO. or NO. ' RefSeq ID
No.

35874257 NM 022522k, caspase 2 caspase 2 mm 35884412 NM 022523, x CD151 antigen CD151 anti en j 359720803NM 022592d, transketolase transketolase q 360020944NM 022597m, cathepsin B cathepsin B
ff, ii 360120960NM_022598a cellular nucleic cellular nucleic acid acid binding binding protein protein 360421115NM 022602r, serine threonine serine threonine kinase z, kinase pima pima ss 360621211NM 022607t, MIPP65 protein MIPP65 protein nn 361420506NM 022686ii germinal histone erminal histone H4 ene H4 gene 361520509NM 022689f, synaptosomal-associatedsynaptosomal-associated cc, protein, 23 kD protein, 23 kD
dd, ff 361617586NM 022694u, p105 coactivator p105 coactivator ff 361617587NM 022694u, p105 coactivator p105 coactivator w 361817757NM 022698y bcl-2 associated bcl-2 associated death death agonist a onist 361917808NM 022699h, ribosomal proteinribosomal protein L30 II L30 , 362424540NM 022707a phospholamban phospholamban 362553 NM_022714v, corticotropin-releasingcorticotropin-releasing jj factor factor receptor receptor subtype subtype 2 3628194 NM 022861s Munc13-1 Munc13-1 36322006 NM 0229360, cytosolic epoxidecytosolic epoxide hydrolase xx hydrolase 36322007 NM 0229360, cytosolic epoxidecytosolic epoxide hydrolase s hydrolase 36322008 NM 0229360, cytosolic epoxidecytosolic epoxide hydrolase s, hydrolase xx 36322009 NM 022936n, cytosolic epoxidecytosolic epoxide hydrolase o hydrolase 363415696NM 022939a syntaxin 12 syntaxin 12 363718100NM 022948y tricarboxylate tricarboxylate carrier-like carrier-like protein protein 363818107NM 022949b, ribosomal proteinribosomal protein L14 I, L14 General, ee 363921491NM 022951tt putative protein putative protein phosphatase phosphatase 1 1 nuclear nuclear targetin targeting subunit subunit 36431053 NM 022962pp CL1BA protein CL1BA protein 36458266 NM 023103a, alpha(1)-inhibitoralpha(1)-inhibitor 3, j, 3, variant I variant I
r, cc 36458267 NM 023103r alpha(1)-inhibitoralpha(1)-inhibitor 3, 3, variant I variant I

36458268 NM 023103r, alpha(1)-inhibitoralpha(1)-inhibitor 3, mm, 3, variant I variant I
xx 36458269 NM 023103r, alpha(1)-inhibitoralpha(1)-inhibitor 3, jj, 3, variant I variant I
xx 364623976NM 023104jj acetoacetyl-CoA acetoacetyl-CoA synthetase synthetase 365917517NM 024151q, ADP-ribosylation ADP-ribosylation factor u, factor 4 4 dd 3663220 NM 024161c, cysteine string cysteine strin protein m protein 3671771 NM 024368a, src related tyrosinesrc related t rosine qq kinase kinase 367223489NM 024375xx prepro bone inducinprepro bone inducin protein protein 3674768 NM 024382u, leuserpin-2 leuserpin-2 rr 36762733 NM 024385bb, hematopoieticallyhematopoietically expressed jj expressed homeobox homeobox 3678713 NM 024391pp 17-beta hydroxysteroid17-beta hydroxysteroid dehydro enase dehydrogenase type type 2 2 367925070NM 0243920, peroxisomal multifunctionalperoxisomal multifunctional Generalenz me t a II enzyme type II

1?7 TABLE

Attorney Docket No.~:44921-5113W0 Document No.1926271:2 SEQ GLGC GenBankModeh Known Gene Name Unigene:Sequence Cluster Title ID D Acc: Code I N0. or N0: RefSeq ID

No.
s 36799929 NM 024392p, peroxisomal multifunctionalperoxisomal multifunctional w, enzyme type II
ss enzyme type II

36799931 NM 0243920, peroxisomal multifunctionalperoxisomal multifunctional xx enzyme type II

enzyme type II

368213633NM 024403w activating transcriptionactivating transcription factor factor ATF-4 368213634NM 024403r, activating transcriptionactivating transcription w, factor factor ATF-4 z, General,ATF-4 ee, rr 368817916NM 024488g, CDK5 activator-bindingCDK5 activator-binding q protein protein C53 369010305NM_030835ee, ribosome associatedribosome associated ff membrane membrane protein 4 protein 4 369010306NM 030835b, ribosome associatedribosome associated q, membrane membrane protein 4 x, General,protein 4 dd 369010308NM_030835I, ribosome associatedribosome associated q membrane membrane protein 4 protein 4 369218728NM 030846b, growth factor growth factor receptor ww receptor bound bound protein 2 protein 2 369218023NM 030846k growth factor growth factor receptor receptor bound bound protein 2 protein 2 369321509NM 030847f epithelial membraneepithelial membrane protein 3 protein 3 36951035 NM 030851y Bradykinin receptorBrad kinin receptor 37018815 NM 030991ff ESTs, Highly similar to LAS1 MOUSE LIM

1 CLASP-1) (MLN 50) (M.musculusl 370125130NM 030991k Synaptosomal-associatedSynaptosomal-associated protein, 25 kDa protein, 25 kDa 37021991 NM 030995xx Microtubule-associatedMicrotubule-associated protein protein 1a 1a 3704135 NM 031003I, 4-aminobutyrate 4-aminobutyrate aminotransferase General aminotransferase 371524658NM 031018ff RATF2 RATF2 37171480 NM 031021 casein kinase casein kinase II beta II beta subunit subunit 37181624 NM 031023q, di-N-acetylchitobiasedi-N-acetylchitobiase z, General 372315886NM 031035k, GTP-binding proteinGTP-binding protein nn (G-alpha- (G-alpha-i2) i2) 372421095NM 031039a glutamic-pyruvateglutamic-pyruvate transaminase transaminase (alanine (alanine aminotransferase)aminotransferase) 372617726NM 031043jj lycogenin lyco enin 372617727NM 031043pp, glycogenin lycogenin uu 372625328NM 031043e, glycogenin glycogenin bb 37271731 NM 031047tt unction plako unction plakoglobin lobin 37319516 NM 031053g mismatch repair mismatch repair protein protein 373724508NM 031073nn neurotrophin-3 neurotrophin-3 (HDNFINT-3) (HDNF/NT-3) 37404683 NM 031083d, hos hatid linositolhos hatid linositol f 4-kinase 4-kinase TABLE

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Attorney Docket No.
44921=5113W0 Document No.1926271:2 ~

SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster . Title ID ID Acc. Code N0. or N0. Ref$eq ID

No:

37404684 NM 031083k phosphatidylinositol4-kinasephosphatidylinositol4-kinase 374315201NM 031093gg, #NAME? #NAME?
hh 374315203NM 031093I, #NAME? #NAME?
m, s, w, General, tt 37451515 NM 031095uu renin-binding renin-binding protein protein 37451516 NM 031095x renin-binding renin-binding protein protein 37451517 NM 031095ss renin-binding renin-binding protein protein 374612639NM_031099I, ribosomal proteinribosomal protein L5 General,L5 ee, II

375316929NM 031108h, mRNA for ribosomalmRNA for ribosomal protein I, protein S9 S9 w, z, General, ee, ii, II

375416847NM 031109h, ribosomal proteinribosomal protein S10 xx S10 37591580 NM 03111700, small nuclear small nuclear ribonucleoparticle-associated ww ribonucleoparticle-associated proteinprotein (snRNP) mRNA, (snRNP) clone Sm51 mRNA, clone Sm51 376114970NM 031127I, sulfite oxidase sulfite oxidase p, x, z, General, kk, nn 376313358NM_031135xx TGFB inducible TGFB inducible early early growth growth response response 376415052NM 031136s thymosin beta-4 thymosin beta-4 376715185NM 031140s, vimentin vimentin ii 37701291 NM 031149w for proteasomal for proteasomal ATPase ATPase (SUG1) (SUG1 ) 37711201 NM 031150v zona pellucida zona pellucida 2 glycoprotein 2 glycoprotein 37761963 NM 031236xx Alpha1,2-fucosyltransferaseAlpha1,2-fucosyltransferase a a 37811422 NM 031324ss prolyl endopeptidaseprolyl endopeptidase 378218597NM 031325y, UDP- lucose dehydrogeanseUDP-glucose dehydrogeanse uu 378418373NM 031331ii, proteasome (prosome,proteasome (prosome, ww macropain) 26S

macropain) 26S subunit, non-ATPase,4 subunit, non-ATPase,4 378418375NM 031331h proteasome (prosome,proteasome (prosome, macropain) 26S

macropain) 26S subunit, non-ATPase,4 subunit, non-ATPase,4 37856671 NM 031333t, cadherin 2, type cadherin 2, type 1, General,1, N-cadherin N-cadherin (neuronal) mm (neuronal) 37856672 NM 031333g cadherin 2, type cadherin 2, type 1, 1, N-cadherin N-cadherin (neuronal) (neuronal) 37856673 NM_031333j cadherin 2, type cadherin 2, type 1, 1, N-cadherin N-cadherin (neuronal) (neuronal) 378811962NM 031337rr sialyltransferasesialyltransferase 9 9 (CMP- (CMP-NeuAc:lactosylceramideNeuAc:lactosylceramide alpha- alpha-2,3-2,3-sialyltransferase;sialyltransferase; GM3 GM3 synthase) s nthase TABLE

Attorney Docket Nor Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigerte Sequence Cluster Title ID D-.NO.Acc.. Code-- or I

N0. Ref$eq ID .

No. s _ , ' . s 378811963NM 031337xx sialyltransferasesialyltransferase 9 (CMP-9 (CMP-NeuAc:lactosylceramideeuAc:lactosylceramide alpha- N alpha-2,3-2,3-sialyltransferase;sialyltransferase; GM3 GM3 synthase) svnthase) 37904346 NM 031343k solute carrier solute carrier family family 6 6 (neurotransmitter (neurotransmittertransporter,noradrenalin), member 2 transporter,noradrenalin), member 2 37915821 NM 031351I attractin attractin I

379218538NM 031353t, voltage-dependentvoltage-dependent anion y, anion channel 1 mm channel 1 379218539NM 031353t, voltage-dependentvoltage-dependent anion mm anion channel 1 channel 1 38033292 NM 031531dd Serine protease Serine protease inhibitor inhibitor 380414633NM 031533b, Androsterone UDP-Androsterone UDP-glucuronosyltransferase I, s, General,glucuronosyltransferase vv 3805444 NM 031535t, B cell lymphoma B cell lymphoma 2 like mm 2 like 3805445 NM 031535t, B cell lymphoma B cell lymphoma 2 like, mm 2 like ESTs, Moderately similar to ilvB (bacterial acetolactate synthase)-like; acetolactate synthase homoloq fHomo sapiensl fH.sapiensl 3805446 NM 031535t, B cell lymphoma B cell lymphoma 2 like, w, 2 like ESTs, Moderately ii, II, mm similar to ilvB (bacterial acetolactate synthase)-like; acetolactate synthase homoloa fHomo sapiensl fH.sapiensl 381715024NM 031572General,Cytochrom P45015-betaCytochrom P45015-beta II, gene gene qq 381715025NM 031572bb, Cytochrom P45015-betaCytochrom P45015-beta qq ene gene 382318005NM 031588j neuregulin 1 neuregulin 1 382318011NM 031588dd neuregulin 1 neuregulin 1 384620766NM 031643nn mitogen-activatedmitogen-activated protein protein kinase kinase kinase 1 kinase 1 384620767NM 031643s mitogen-activatedmitogen-activated protein protein kinase kinase kinase 1 kinase 1 387713543NM 031749q, glucosidase 1 glucosidase 1 oo 387713544NM 031749c lucosidase 1 glucosidase 1 387713545NM 031749a glucosidase 1 glucosidase 1 387725209NM 031749v, glucosidase 1 glucosidase 1 w, bb, rr 387816624NM 031751k Shank1 Shank1 387920724NM 031753w activated leukocyteactivated leukocyte cell cell adhesion molecule adhesion molecule 388216003NM 031757j matrix metalloproteinasematrix metalloproteinase 24 24 (membrane-(membrane-inserted)inserted) 38844314 NM_031760b, ATP-binding cassette,ATP-binding cassette, m, sub- sub-family B
dd, uu, family B (MDRITAP),(MDRITAP), member 11 vv member 388814184NM 031776' uanine deaminase uanine deaminase TABLE

' Attorney packet No:
44921=5113W0 Document No:.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster ' . Title ID= ID Acc. Code' N0. or N0. l2efSeq Ho:

388814185NM 031776j, guanine deaminaseguanine deaminase r, y 38891184 NM 031778cc Shab-related delayed-rectifierShab-related delayed-rectifier K+ channel K+ channel (Kv9.3)(Kv9.3) 38914325 NM 031784u, potassium channelpotassium channel regulatory v, regulatory protein tt protein KChAP KChAP

38971000 NM 031809j cyclic nucleotide-gatedcyclic nucleotide-gated channel channel beta subunit beta subunit 1 1 389816155NM 031810bb, defensin beta defensin beta 1 ff 1 389916039NM 031811b, transaldolase transaldolase 1 c, 1 ee, xx 390710176NM 031837w E-septin E-septin 39111302 NM 031841pp stearoyl-Coenzymestearoyl-Coenzyme A
A desaturase 1 desaturase 1, stearoyl-Coenzyme A desaturase 39161475 NM 031971ee Heat shock proteinESTs, Highly similar 70-1 to S10A_RAT S-100 protein, alpha chain [R.norvegicus], Heat shock protein 70-1 391916257NM 031975I, parathymosin parathymosin s, General, II, rr 392217805NM 031980b, UDP-glucuronosyltransferaseUDP-glucuronosyltransferase General, gg, hh, vv 392217806NM_031980General,UDP-glucuronosyltransferaseUDP-glucuronosyltransferase ii, II

392315265NM 031981p, p47 protein 47 protein w, ff 392518898NM 031985pp S6 kinase S6 kinase 3929964 NM 032062v huntingtin-associatedhuntingtin-associated protein protein interacting interactin proteinprotein (duo) (duo) 393919148NM 0330960o Protein phosphataseProtein phosphatase type 1 B type 1 B (formely 2C), (formely 2C), Mg-dependent, beta isoform Mg-dependent, beta isoform 39414723 NM 033235j, Malate dehydrogenase-likeMalate dehydrogenase-like II, enzyme qq enzyme 39414724 NM 033235j Malate dehydrogenase-likeMalate dehydrogenase-like enzyme enzyme 39422577 NM 033236u, Proteasome (prosome,Proteasome (prosome, bb macropain) 26S

macropain) 26S subunit, ATPase subunit, ATPase 394924484NM 052806k Acetylcholine Acetylcholine receptor receptor beta beta 4 396123211NM 053334f, calcium modulatingcalcium modulating ligand nn li and 396315790NM 053341a regulator of G-proteinregulator of G-protein signaling signaling 19 39662548 NM 053359rr ATX1 (antioxidantATX1 (antioxidant protein protein 1) 1) homolog 1 homolog 1 (yeast)(yeast) 396719512NM 053365xx adipocyte lipid-bindingadipocyte lipid-binding protein protein 396912223NM 053370nn, translocase of translocase of inner qq inner mitochondria) mitochondria) membrane 8 (yeast) homolog membrane 8 A

east homolo A

TABLE

' Aftorney Docket No:

Document No.1926271:2 SEQ.GLGC GengankModel:Known Gene Name Jpigene Sequence-ClusterTitle t lD D Accor Code I N0.

N0 RefSeq ID

No.

397113492NM 053400ss ransducin-like ransducin-like enhancer t enhancer of splitof split 3, homolog t 3, homolog of of Drosophila Drosophila 397216017NM 053401a brain expressed brain expressed X-linked X-linked 3 3 397216018NM 053401a, brain expressed brain expressed X-linked j X-linked 3 3 39736773 NM 053410rr acyl- acyl-CoA:dihydroxyacetonephosphate CoA:dihydroxyacetonephosphatacyltransferase a acyltransferase 397413903NM 053412Generalnterleukin enhancernterleukin enhancer i binding i binding factor 3 factor 3 39766186 NM 053430i Flap structure-specificFlap structure-specific i endonuclease 1 endonuclease 1 39772242 NM_053433 flavin-containingflavin-containing monooxygenase monooxygenase 398123274NM_053467b, integral membraneintegral membrane protein j, protein Tmp21-I (p23) q, ee Tmp21-I (p23) 398123276NM 053467n integral membraneintegral membrane protein protein Tmp21-I (p23) Tmp21-I (p23 39843860 NM 053477, o, malonyl-CoA decarboxylasemalonyl-CoA decarboxylase ff, ii 39854290 NM 0534870, peroxisomal membraneperoxisomal membrane y, protein protein Pmp26p xx Pmp26p (Peroxin-11)(Peroxin-11) 398623558NM 053507Generalexpressed in non-metastaticexpressed in non-metastatic cells 3, protein cells 3, protein (nucleoside diphosphate (nucleoside kinase) diphosphate kinase) 398716133NM 053516dd, unknown Glu-Pro unknown Glu-Pro dipeptide jj dipeptide repeat protein repeat protein 398819199NM 053522a ras-like protein ras-like protein 398819200NM 053522k, ras-like protein ras-like protein I, s, cc 398819205NM 053522cc, ras-like protein ras-like protein pp 398819206NM 053522a, ras-like protein ras-like protein cc 398918826NM 053523x, homocysteine-inducible,homocysteine-inducible, ff, endoplasmic nn, ss endoplasmic reticulumreticulum stress-inducible, stress- ubiquitin-like inducible, ubiquitin-likedomain member 1 domain member 1 399231 NM 053537j solute carrier solute carrier family family 22 (organic22 (organic anion anion transporter),transporter), member member 7 7 399232 NM 053537h, solute carrier solute carrier family k, family 22 (organic22 (organic anion I, uu anion transporter),transporter), member member 7 7 39931058 NM 053539d, isopentenyl-diphosphateisopentenyl-diphosphate o, delta delta isomerase q, v, jj, isomerase pp 399412496NM 053541kk low density lipoproteinlow density lipoprotein receptor- receptor-related related protein protein 3 399515829NM 053551y, pyruvate dehydrogenasepyruvate dehydrogenase nn, kinase, isoenzyme xx kinase, isoenzyme4 39961198 NM 053554t, phosphatidylinositolphosphatidylinositol mm binding binding clathrin clathrin assemblyassembly protein protein 399711843NM_053555Generalvesicle-associatedvesicle-associated membrane membrane protein 5 rotein 5 TABLE

Attorney Docket No:

Document No.-1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title fD ID Acc. Codev ' NO. or , N0. RefSeq ID
__ No:

399711844NM 053555v vesicle-associatedvesicle-associated membrane membrane protein 5 protein 5 39994327 NM 053563w, nuclear RNA helicase,nuclear RNA helicase, tt DECD DECD variant of variant of DEAD DEAD box family box famil 400021940NM 053568Generalphosphate cytidylyltransferasephosphate cytidylyltransferase 2, 2, ethanolamine ethanolamine 400021941NM_053568f phosphate cytidylyltransferasephosphate cytidylyltransferase f 2, 2, ethanolamine ethanolamine 400322617NM 053578d vacuolar proton-ATPasevacuolar proton-ATPase subunit subunit M9.2 M9.2 400521423NM_053586r cytochrome c oxidasecytochrome c oxidase subunit subunit Vb Vb 400521424NM 053586e, cytochrome c oxidasecytochrome c oxidase Generalsubunit subunit Vb Vb 400820842NM 053590mm proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,beta type 1 beta type 1 400920896NM 053592w, DeoxyuridinetriphosphataseDeoxyuridinetriphosphatase x, (dUTPase) bb (dUTPase) 401121709NM 053596kk, Endothelin-convertingEndothelin-converting ss enzyme 1 enzyme 1 401211830NM_053598Generaldiphosphoinositoldiphosphoinositol polyphosphate polyphosphate phosphohydolase type II

phosphohydolase type II

401218795NM 053598bb diphosphoinositoldiphosphoinositol polyphosphate polyphosphate phosphohydolase type II

phosphohydolase type II

401223192NM 053598a, diphosphoinositoldiphosphoinositol polyphosphate pp polyphosphate phosphohydolase type II

phosphohydolase type II

40131390 NM 053599c, ephrin A1 ephrin A1 p, v 4024857 NM 053633tt early growth responseearly growth response 402721637NM 053653kk vascular endothelialvascular endothelial growth growth factor C

factor C

40287228 NM 053654jj platelet-activatingplatelet-activating factor factor acetylhydrolase, acetylhydrolase, isoform 1b, alpha1 subunit isoform 1b, alpha1 subunit 40301318 NM_053656g purinergic receptorpurinergic receptor P2X, ligand- P2X, ligand-gated ion gated ion channel,channel, 2 40313454 NM 053662ii, cyclin L c clin L
tt 40313455 NM 053662w, cyclin L cyclin L
tt 403324204NM_053670b, calcitonin gene-relatedcalcitonin gene-related General,peptide- peptide-receptor uu receptor componentcomponent protein protein 40346784 NM 053671v TATA element modulatoryTATA element modulatory factor factor 1 40351957 NM 053674ii phytanoyl-CoA phytanoyl-CoA hydroxylase hydroxylase (Refsum Refsum disease disease TABLE

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Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Tifle ID> ID Acc. Code NO. or N0. RefSeq ID

No:

403616122NM_053698mm CbpIp300-interactingCbp/p300-interacting transactivator, with transactivator, GIulAsp-rich carboxy-terminal with GIu/Asp-richdomain, 2 carboxy-terminal domain, 2 403616123NM 053698ee CbpIp300-interactingCbpIp300-interacting transactivator, with transactivator, GIulAsp-rich carboxy-terminal with GIu/Asp-richdomain, 2 carboxy-terminal domain, 2 403713622NM 053713I Kruppel-like factorKru pel-like factor 4 (gut) 4 (gut) 403722411NM 053713f, Kruppel-like factorKruppel-like factor qq 4 (gut) 4 (gut) 403725379NM 053713qq Kruppel-like factorKruppel-like factor 4 ( ut) 4 (gut) 40404324 NM 053744cc delta-like homologdelta-like homolo (Drosophila) (Drosophila) 40483828 NM 053785b, transmembrane transmembrane 4 superfamily ss 4 superfamily member 4 member 4 40516004 NM 053796rr functional adhesionfunctional adhesion molecule 1 molecule 1 40516005 NM 053796a, functional adhesionfunctional adhesion q, molecule 1 molecule 1 s 405325594NM 053799m aspartyl-tRNA aspartyl-tRNA synthetase synthetase 405415615NM 053800a thioredoxin thioredoxin 405615800NM 053810w, synaptosomal-associatedsynaptosomal-associated cc protein, 29kD

protein, 29kD

406220270NM 053827bb, procollagen-lysine,procollagen-lysine, mm 2- 2-oxoglutarate 5-oxoglutarate 5-dioxygenasedioxygenase (lysine hydroxylase, Ehlers-(lysine hydroxylase,Danlos syndrome type Ehlers- VI) Danlos syndrome type VI) 406317154NM 053835d clathrin, light clathrin, light polypeptide polypeptide (Lcb)(Lcb) 406416590NM 053838v natriuretic peptidenatriuretic peptide receptor 2 receptor 2 406517299NM 053842ww mitogen activatedmitogen activated protein protein kinase kinase 1 40671508 NM 053845e, ureidopropionase,ureidopropionase, beta uu, beta vv 406819018NM_053849y, protein disulfideprotein disulfide isomerase xx isomerase related protein related protein (calcium-binding protein, (calcium-binding intestinal-related) protein, intestinal-related) 406924705NM 053850ww biliverdin reductasebiliverdin reductase A A

40791337 NM 053895p, FGF receptor activatingFGF receptor activating tt protein protein 1 408315706NM 053921a peroxisomal biogenesisperoxisomal biogenesis factor factor 12 40861288 NM 053949I, potassium voltage-gatedpotassium voltage-gated s channel, subfamily channel, subfamilyH (eag-related), member H (eag- 2 related), member 40871029 NM 053953mm interleukin 1 interleukin 1 receptor, receptor, type type II
II

408815822NM 053957Generalamyloid beta (A4)amyloid beta (A4) precursor precursor protein-binding, protein-binding, family B, member 3 family B, member 3 40896538 NM 053959I myc box dependentmyc box dependent interacting interacting protein 1 protein 1 40896539 NM 053959ss, myc box dependentmyc box dependent interacting uu interacting protein 1 rotein 1 TABLE

Attorney Docket No:
44921=5113W0 Document No.1926271.2 SE4 GI:GCGenBankModel Known Gene Name Unigene Sequence Cluster Title .' ID ID Acc. Code N0. or N0. RefSeq ID
-.

No ' -409016552NM 053961Generalendoplasmic retuclumendoplasmic retuclum protein protein 29 409016554NM 053961 endoplasmic retuclumendoplasmic retuclum f protein protein 29 409215135NM 053971w r ibosomal protein ribosomal protein L6 409215136NM 053971h r ibosomal protein ribosomal protein L6 40931764 NM 053974ff, eukaryotic translationeukaryotic translation pp initiation initiation factor 4E

f actor 4E

40961292 NM_053980m ADP-ribosylation ADP-ribosylation factor factor related related protein 1 protein 1 409815642NM 053985d, H3 histone, familyH3 histone, family 3B
r, 3B
kk, rr 409815645NM 053985n, H3 histone, familyH3 histone, family 3B
rr 3B

409918025NM 053989vv pro estin inducedprogestin induced protein protein 410016809NM 053990I, protein tyrosine protein tyrosine phosphatase, oo phosphatase, non-receptor non-receptor typetype 2 410224430NM 053996w proline transporterproline transporter 410316965NM 053999v protein phosphataseprotein phosphatase 2 (formerly 2 (formerly 2A), 2A), regulatory regulatory subunit B
subunit B (PR (PR 52), alpha isoform 52), alpha isoform 410421066NM 054001c, CD36 antigen (collagenCD36 antigen (collagen v, type I type I receptor, ii, rr receptor, thrombospondinthrombospondin receptor)-like receptor)-like 410516566NM 054004a TBP-interactin TBP-interacting protein protein 120A 120A

410617431NM 054006rr unr protein unr protein 411415391NM 057114I peroxiredoxin peroxiredoxin 1 411520254NM 057116ii protein phosphataseprotein phosphatase 2 (formerly 2 (formerly 2A), 2A), regulatory regulatory subunit B
subunit B (PR (PR 52), gamma 52), gamma isoformisoform 411815151NM_057131ss phosphoribosyl phosphoribosyl pyrophosphate pyrophosphate synthetase-synthetase-associatedassociated protein 2 protein 2 41208592 NM 057137q, phenylalkylamine phenylalkylamine Ca2+
xx Ca2+ antagonist antagonist (emopamil)(emopamil) binding protein binding protein 4124358 NM 057146u, complement componentcomplement component vv 9 9 4125706 NM 057147II sec22 homolog sec22 homolog 413123129NM 078622t, phosphate cytidylyltransferasephosphate cytidylyltransferase ff 1, choline, 1, choline, alphaalpha isoform isoform 413523550NM 080698f fibromodulin fibromodulin 414023033NM 080888tt BCL2ladenovirus BCL2ladenovirus E1 B
E1 B 19 kDa- 19 kDa-interacting interacting proteinprotein 3-like 3-like 414123477NM 080891w Fas death domain-associatedFas death domain-associated protein protein 41426143 NM 080892a selenium binding selenium binding protein protein 2 2 41464739 NM_130400ff Dihydrofolate Dihydrofolate reductase reductase 1 1 (active) active TABLE

' Attorney t)ocket No44921-5113W0 Document No.926271:2 SEQ GLGG GenBankModel ~(nown Gene Name Unigene Sequence Clusfer ' Title ID ID Acc. Code N0. or NO. RefSeq ID

No:' 414711421NM_130405w, src associated src associated in mitosis, tt in mitosis, 68 68 kDa kDa 41503579 NM 130409uu complement componentcomplement component factor h factor h 41513458 NM 130412ii stromal cell derivedstromal cell derived factor 4 factor 4 41526909 NM_130413qq src family associatedsrc family associated phosphoprotein 2 phosphoprotein 415518293NM_1304330, acetyl-Coenzyme acetyl-Coenzyme A acyltransferase ii, A 2 ss, xx acyltransferase (mitochondria) 3-oxoacyl-Coenzyme 2 (mitochondria) A

3-oxoacyl-Coenzymehiolase) A thiolase) t 41573880 NM 130749bb MAP/microtubule MAPlmicrotubule affinity-regulating affinity- kinase 3 regulating kinase 415818846NM 130755b, citrate synthase citrate synthase dd 416116767NM_130826o hydroxyacyl-Coenzymehydroxyacyl-Coenzyme A A dehydrogenasel3-dehydrogenasel3-ketoacyl-ketoacyl-Coenzyme A
hiolase/enoyl-Coenzyme A hiolaselenoyl-Coenzyme A hydratase (trifunctional Coenzyme A hydrataseprotein), alpha subunit (trifunctional protein), alpha subunit 416116768NM_1308260, hydroxyacyl-Coenzymehydroxyacyl-Coenzyme ss A A dehydrogenasel3-dehydrogenasel3-ketoacyl-ketoacyl-Coenzyme A
hiolaselenoyl-Coenzyme A hiolase/enoyl-Coenzyme A hydratase (trifunctional Coenzyme A hydrataseprotein), alpha subunit (trifunctional protein), alpha subunit 416925405NM 133307s, protein kinase protein kinase C, delta t, C, delta mm 417817634NM_133418q, solute carrier solute carrier family z, family 25 25 (mitochondria) General,(mitochondria) carrier; dicarboxylate carrier; transporter), member uu dicarboxylate 10 transporter), member 10 417817635NM_133418I, solute carrier solute carrier family x family 25 25 (mitochondria) (mitochondria) carrier; dicarboxylate carrier; transporter), member dicarboxylate 10 transporter), member 10 417817636NM_133418pp solute carrier solute carrier family family 25 25 (mitochondria) (mitochondria) carrier; dicarboxylate carrier; transporter), member dicarboxylate 10 transporter), member 10 417919326NM_133419q, dyskeratosis congenitadyskeratosis congenita ss 1, 1, dyskerin dyskerin 419225821NM 133570cc astrin-releasing astrin-releasin peptide peptide 41981271 NM_133593a adaptor-related adaptor-related protein protein complex complex AP-3, mu 1 AP-3, mu 1 subunitsubunit 41991546 NM_133595a, GTP cyclohydrolaseGTP cyclohydrolase I
s, I feedback feedback regulatory uu, vv re ulatory proteinprotein 420017758NM_133606k, enoyl-Coenzyme enoyl-Coenzyme A, hydratasel3-hydroxyacyl o, A, hydratase/3-v, xx hydroxyacyl CoenzymeCoenzyme A dehydrogenase A

deh dro enase TABLE

' Attorney Docket No:

Document No.1926271.2 SEQGLGC GenBank Model Known Gene Name Unigene Sequence Cluster Title ID'ID Acc. Code.
N0. or .

N0. RefSeq ID ' No:

4203699 NM 133617b, serine (or cysteine)serine (or cysteine) q, proteinase proteinase inhibitor, Generalnhibitor, Glade Glade A (alpha-1 antiproteinase, i A (alpha-1 antitrypsin), antiproteinase, member 10 antitrypsin), member 10 42041728 NM_133618b, hydroxyacyl-Coenzymehydroxyacyl-Coenzyme m, A A dehydrogenase/3-o, cc dehydrogenasel3-ketoacyl-ketoacyl-Coenzyme A
thiolase/enoyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional Coenzyme A hydrataseprotein), beta subunit (trifunctional protein), beta subunit 42071463 NM 134334e, cathepsin D cathepsin D
'j 420816456NM_134346w RAP1 B, member RAP1 B, member of RAS
of RAS oncogene family oncogene family 420816457NM 134346a RAP1 B, member RAP1 B, member of RAS
of RAS oncogene family oncogene family 4209517 NM_134350ee Myxovirus (influenza)myxovirus (influenza virus) resistance 3 resistance, homolog of murine Mx (also interferon-inducible protein IFI78), myxovirus (influenza virusl resistance 3 4210606 NM_134352f, Plasminogen activator,Plasminogen activator, kk, urokinase receptor tt urokinase receptor 421114876NM 134361h small inducible small inducible cytokine cytokine subfamily C, subfamily C, member 1 (lymphotactin) member 1 (I m hotactiN

42141530 NM 134397h, LL5 protein LL5 protein vv 42161557 NM 134403qq, Cca3 protein Cca3 protein ss, vv 42182641 NM_134408w, calcium-independentcalcium-independent Generalalpha- alpha-latrotoxin latrotoxin receptorreceptor homolo 2 homolo 2 42232801 NM 134449j, PKC-delta bindingPKC-delta binding protein j oo protein 42232802 NM 134449c PKC-delta bindingPKC-delta binding protein protein 42275208 NM_138504w, pregnancy-inducedpregnancy-induced growth rr growth inhibitor inhibitor 4230534 NM 138512b, cytochrome P450 cytochrome P450 2c22 a 2c22 423115054NM 138515p cytochrome P450 cytochrome P450 2D18 423224672NM_138517j Rat natural killer (NK) j cell protease 1 (RNKP

1) mRNA, complete Gds 424323166NM 138839m, Vacuole MembraneVacuole Membrane Protein rr Protein 1 1 42441896 NM 138840 traps- of i networktraps- of i network protein 1 protein 1 42441899 NM 138840w traps-gol i networktraps- olgi network protein 1 protein 1 424917530NM_138877s Diaphorase (NADH)Diaphorase (NADH) (cytochrome b-5 (cytochrome b-5 reductase) reductase) 424917532NM 138877I, Diaphorase (NADH)Diaphorase (NADH) (cytochrome z, b-5 General,(cytochrome b-5 reductase) reductase) nn 424917533NM_138877General,Diaphorase (NADH)Diaphorase (NADH) (cytochrome b-5 g, (cytochrome b-5 reductase) hh, reductase) II

424925039NM 138877General,Diaphorase (NADH)Diaphorase (NADH) (cytochrome b-5 ss c tochrome b-5 reductase reductase TABLE

Attorney Docket No.

Documenf No.1926271.2 SEQ GLGCGenBank Model Known Gene Name Unigene SeguenceCluster Title ID D Acc: Code I N0. or N0: RefSeq No.

42514593NM 138881a Best5 protein Best5 protein 42514594NM 138881a, BestS protein Best5 protein qq 42514595NM 138881k Best5 protein Best5 protein 42527395NM_138883p, ATP synthase, ATP synthase, H+ transporting, ff H+ transporting, mitochondria) mitochondria) F1 complex, F1 complex, 0 0 subunit subunit (oligomycin(oligomycin sensitivity sensitivity conferring protein) conferring protein) 425314964NM 138884s, aldo-keto reductasealdo-keto reductase uu family 1, family 1, member D1 member D1 (delta (delta 4-3-ketosteroid-5-beta-reductase) ketosteroid-5-beta-reductase) 425314965NM_138884m aldo-keto reductasealdo-keto reductase family 1, family 1, member D1 member D1 (delta (delta 4-3-ketosteroid-5-beta-reductase) ketosteroid-5-beta-reductase) 425718867NM 138900b, complement componentcomplement component h, 1, s 1, s subcomponent General,subcomponent dd, rr 426217185NM 138919dd unc-50 related unc-50 related protein protein (UNCL) (UNCL) 4263287 NM_139042xx guanylyl cyclase guanylyl cyclase with with kinase-like kinase-like domain, domain, soluble soluble 42651674NM 139086a syncollin syncollin 4267809 NM_139089ee small inducible small inducible cytokine cytokine B B subfamily (Cys-X-subfamily (Cys-X-Cys),Cys), member 10 member 4268737 NM_139093e, CTD-binding SR-likeCTD-binding SR-like tt protein rA9 protein rA9 427417684NM 139102d, dimethylglycine dimethylglycine dehydrogenase h, dehydrogenase precursor uu precursor 427518108NM_139105I, ribonuclease/angiogeninribonuclease/angiogenin w, inhibitor General,inhibitor uu, vv 427618450NM_139106r, ATP synthase, ATP synthase, H+ transporting, ss H+ transporting, mitochondria) mitochondria) F1 complex, F1 complex, deltadelta subunit subunit 42791301NM_139192n stearoyl-Coenzymestearoyl-Coenzyme A
A desaturase 1 desaturase 1 42868717NM_139333gg, neuronal differentiation-relatedneuronal differentiation-related hh gene ene 428923681NM_144746General, Rattus norvegicus protein rr phosphatase 2A B

regulatory subunit delta isoform mRNA, complete cds 43041798NM_145779a, R.norvegicus alpha-1-macroglobulin d, mRNA, m, uu, complete cds vv 430820740NM_145878bb, Rattus norvegicus Sprague-Dawley pp lipid-bindin protein mRNA, complete cds 431316963NM_147214r, Caldesmon 1, proteinCaldesmon 1, protein ee phosphatase 2 phosphatase 2 (formerly 2A), regulatory (formerly 2A), subunit B (PR 52), regulatory subunitalpha isoform B (PR 52), al ha isoform TABLE

Attorney Docket No44921-5113W0 Document No.19262712 SEQ GLGCGenBank Model Known Gene Name Unigepe.Sequence Cluster - Title ID D Accor Code _ NO.
I .

N0 RefSeq ID

No.

431510544NM_152935m Rattus norvegicus outer mitochondrial membrane receptor rTOM20 mRNA, complete cds 431510545NM 152935cc Rattus norvegicus outer mitochondrial membrane receptor rTOM20 mRNA, complete cds 431612700NM 152936w Rat pancreatic secretory trypsin inhibitor ( PSTI-II) mRNA, complete cds type II

43201130NM 153313a, Rat cytochrome P450CMF1 cc b mRNA, complete cds 432114632NM_153314f, Androsterone UDP-Androsterone UDP-glucuronosyltransferase uu lucuronosyltransferase 432114346NM_153314b, Rat UDP-glucuronosyltransferase I, mRNA, j, General, complete cds qq, vv, ww 432114347NM 153314b, Rat UDP-glucuronosyltransferase General, mRNA, vv complete cds 43227789NM_153630d Rattus norvegicus putative four repeat ion channel mRNA, complete cds 434321981S75019 ss, ESTs, Highly similar vv to 854676 antiquitin -rat (fragment) [R.norve icus]

434724469S77858 m, ESTs, Highly similar rr to MLES_RAT Myosin light chain alkali, smooth-muscle isoform (MLC3SM) [R.norvegicus]

436517999019485 a, spp-24 precursor spp-24 precursor g, x, bb, rr 436518000019485 g, spp-24 precursor spp-24 precursor x, cc, dd 4366228 020194 uu Rattus norvegicus complement C8 beta (C8b) mRNA, partial cds 4366229 020194 General Rattus norvegicus complement C8 beta (C8b) mRNA, partial cds 43681537027518 ss Rattus norvegicus UDP-glucuronosyltransferase mRNA, complete cds 437121488032575 e, ~ ESTs, Weakly similar xx to 149523 tumor necrosis factor alpha-induced protein 2 -mouse [M.musculusl 43913387075411 cc Rat Ig active lambda2-like chain mRNA, 3' end 4413672 X13722 ff, Rat mRNA for LDL-receptor jj 441615653X14210 ee, NADH ubiquinone NADH ubiquinone oxidoreductase II subunit oxidoreductase 813 subunit 813 441718541X14671 h, ESTs, Highly similar gg, to RL26_RAT 60S
hh [R.norvegicus]

TABLE

Atkorney Docket No.

~

Document No.1926271.2 SEQ GLGC GenBankModet Known Gene Name Unigene Sequence Cluster Title -(Ds.D Acc. Code I CVO. or .

N0: RefSeq ID

No.

441919244X15013 h, ESTs, Highly similar gg, to RL7A_HUMAN 60S
hh r ibosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) f R.norveqicusl 443018606X53504 h, ESTs, Highly similar j, to RL12_RAT 60S

General, RIBOSOMAL PROTEIN L12 [R.norvegicus]

gg, hh, II

443324577X55153 h, ESTs, Highly similar v, to R6RTP2 acidic General ribosomal protein P2, cytosolic [validated]
-ratfR.norvegicusl 443817175X58389 rr R.norvegicus ASI mRNA
for mammalian equivalent of bacterial large ribosomal subunit protein L22 444421657X61381 b, Rattus norvegicus interferon-inducible x, General, protein variant 10 mRNA, complete cds bb, dd, II, nn, as 445622424X67788 z, villin 2 villin 2 , hh 4458602 X68101 bb R.norve icus trg mRNA

4459588 X69834 a, R,norvegicus mRNA for ii, serine protease rr inhibitor 2.4 446016300X70706 j plastin 3 (T-isoform)plastin 3 (T-isoform) 4468463 X83579 f, cyclin-dependent cyclin-dependent kinase q, kinase 7 7 (M015 homolog, u, ww (M015 homolog, Xenopus laevis, cdk-activating Xenopus kinase) laevis, cdk-activating kinase) 447817146Y07534 b, Serine protease Serine protease inhibitor qq inhibitor 448020695Y09000 gg, Dendrin Dendrin hh 4481407 211995 gg, low density lipoproteinlow density lipoprotein hh receptor- receptor-related related protein protein associated protein associated 1 protein 1 872 16499AA925300d HHs:mitogen-activatedESTs, Weakly similar protein to mitogen activated kinase kinase protein kinase kinase kinase 3 kinase 1 [Rattus norveAicuslfR.norvegicusl 19082069 A1103616bb HHs:ras-related ESTs, Weakly similar C3 botulinum to ras-like protein toxin substrate [Rattus norvegicus]
1 (rho family, [R.norvegicus]

small GTP binding protein Rac1) 26505778 A1233246ii HHs:polymerase ESTs, Weakly similar (RNA) II (DNA to RNA polymerase I

directed) polypeptide(127 kDa subunit) [Rattus B (140kD) norvegicus]

fR.norveaicusl 26545779 AI233350I HHs:polymerase ESTs, Weakly similar (RNA) II (DNA to RNA polymerase I

directed) polypeptide(127 kDa subunit) (Rattus B (140kD) norvegicus]

fR.norvegicusl 438711 U70210 g amyloid beta (A4)amyloid beta (A4) precursor precursor protein-binding, protein-binding, family B, member 2 family B, member 2 123 18115AA800339d, Transferrin Transferrin General, ee, kk TABLE

.Attorney Docket Nor Document No.1926271.2 SEQ GLGC GeriBankModel Known Gene Name Jnigene Sequence Cluster l Title -ID ID Aca. Code N0. or ' NO: RefSeq ID

No.

184 2143 AA817892e, guanine nucleotideguanine nucleotide binding gg, binding protein beta 2 hh, jj protein beta 2 subunit subunit 420 2263 AA859757a collagen, type collagen, type V, alpha V, alpha 1 1 435 23324AA859980a, T-complex 1 T-complex 1 c, d, jj 435 18578AA859980a, T-complex 1 T-complex 1 c, q, jj, ss 445 17111AA860062ee Albumin Albumin 497 15342AA875172k SH3-domain kinaseSH3-domain kinase binding binding protein 1 protein 1 499 18897AA875207g Hemoglobin, beta Hemoglobin, beta 592 17345AA892014c HLA-B associated HLA-B associated transcript transcript 1A 1A

592 17346AA892014k HLA-B associated HLA-B associated transcript transcript 1A 1A

656 23180AA892649j, gamma-aminobutyricgamma-aminobutyric acid I, acid receptor General,receptor associatedassociated protein protein cc 663 12118AA892775I, Lysozyme Lysozyme General, gg, hh, kk 704 20986AA893242o fatty acid Coenzymefatty acid Coenzyme A ligase, A ligase, long chain l ong chain 2 756 6377 AA894273t, dimethylarginine dimethylarginine dimethylaminohydrolase qq 1 dimethylaminohydrolase 989 19421AA945152n, dimethylarginine dimethylarginine dimethylaminohydrolase ee 1 dimethylaminohydrolase 109424230AA957218ii Cyclin D1 C clip D1 124614583AB008807dd, glutathione S-transferaseESTs, Highly similar uu to GT01 RAT

omega 1 Glutathione transferase omega 1 (GSTO 1-1) (Glutathione-dependent dehydroascorbate reductase)[R.norvegicus]

124917963AB012231h nuclear factor nuclear factor IIB
IIB

125024414AB012234ii Nuclear factor Nuclear factor IIX (CCAAT-binding I/X (CCAAT- ' binding transcriptiontranscription factor) factor) 12514307 AB012600s aryl hydrocarbon aryl hydrocarbon receptor receptor nuclear nuclear translocator-liketranslocator-like 125720438AF009656e, hypoxanthine guaninehypoxanthine guanine a phosphoribosyl phosphoribosyl transferase transferase 12594308 AF015953ww aryl hydrocarbon aryl hydrocarbon receptor receptor nuclear nuclear translocator-liketranslocator-like 127816006AF062594m, nucleosome assemblynucleosome assembly ii protein 1- protein 1-like 1 like 1 ' 13147785 A1008758vv Dipeptidyl peptidaseDipeptidyl peptidase 141016010A1011922a nucleosome assemblynucleosome assembly protein 1- protein 1-like 1 like 1 146517065A1013531qq carbonyl reductasecarbonyl reductase 1 159620983A10449000, fatty acid Coenzymefatty acid Coenzyme v A ligase, A ligase, long chain long chain 2 193818277AI104399t Triose hos hate Triose hos hate isomerase isomerase 1 1 TABLE

Aftorney Docket No44921=5113WD

Document No.1926271.2 SEQ GLGC GenBankModel Kriown Gene Name Uraigene Sequence Cluster Title ID ID Acc. Code N(?: or N0. RefSeq ID

No 196117171AI10513700, Somatostatin ESTs, Highly similar rr to GTK1 RAT

Glutathione S-transferase, mitochondria) (GST 13-13) (Glutathione S-transferase subunit 13) (GST class-kappa) I R.norveaicusl. Somatostatin 203116510AI137583b, Inhibitor of DNA nhibitor of DNA binding w, binding 2, I 2, dominant ii, rr, tt dominant negativenegative helix-loop-helix helix-loop- protein helix protein 223512614AI175294Generalribosomal proteinribosomal protein L21 242419427AI179510pp dimethylarginine dimethylarginine dimethylaminohydrolase dimethylaminohydrolase 246522845A1227887t cell division cell division cycle cycle 42 42 248718612AI228624a, ribosomal proteinribosomal protein L29 c, L29 e, kk 253223041AI230130a ectonucleoside ectonucleoside triphosphate triphosphate diphosphohydrolasediphosphohydrolase 2 276714666AI236912z Ngfi-A binding Ngfi-A binding protein protein 1 1 282319112AI639157w ribosomal proteinribosomal protein L13 28969135 D45247 b, proteasome beta ESTs, Highly similar mm type subunit to PSBS_RAT

Proteasome subunit beta type 5 precursor (Proteasome epsilon chain) (Macropain epsilon chain) (Multicatalytic endopeptidase complex epsilon chain) (Proteasome subunit X) (Proteasome chain 6) [R.norvegicus]

290120984D90109 0, fatty acid Coenzymefatty acid Coenzyme gg, A ligase, A ligase, long chain hh, 2 oo, Ion chain 2 uu 293926368H34047 jj T-complex 1 T-complex 1 296017508L08814 e, Structure specificStructure specific recognition gg, recognition protein 1 hh, 0o protein 1 297821146L35558 gg, Solute carrier Solute carrier family hh family 1 A1 (brain1 A1 (brain glutamate glutamate transporter)transporter) 29891466 M14050 p, Heat shock 70kD ESTs, Heat shock 70kD
q, protein 5 protein 5 General, dd, ff 301721399M36410 Generalsepiapterin reductasesepiapterin reductase 301721400M36410 n, sepiapterin reductasesepiapterin reductase x, General, dd, ee 302713547M63983 a hypoxanthine guanineESTs, Moderately similar to ICA2_MOUSE
_ phosphoribosyl Intercellular adhesion transferase molecule-2 precursor (ICAM-2) (CD102) (Lymphocyte function-associated AG-1 counter-receptor) [M.musculus], hypoxanthine guanine ohosohoribosvl transferase 302810743M64780 I, Agrin Agrin p, z, General 302810744M64780 I, Agrin Agrin p, z, General, ii, nn rr TABLE

Attorney Docket'No.

Document No.1926271 ~2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc. Code _ N0. or .
~

NO. RefSeq ID

Nor' 303121670M80601 f, programmed cell programmed cell death I, death 2 2 z, General 304522513NM 012488nn Alpha-2-macro Alpha-2-macro lobulin lobulin 305220153NM_012503b, AsialoglycoproteinAsialoglycoprotein receptor g, receptor 1 1 (hepatic lectin) v (hepatic lectin) 3057563 NM 012516I, Complement componentComplement component vv 4 4 binding protein, bindin protein, al ha alpha 306216520NM 012532b, Ceruloplasmin Ceruloplasmin (ferroxidase) a (ferroxidase) 306821834NM 012555x Ets avian erythroblastosisEts avian erythroblastosis virus virus E2 E2 oncogene homologoncogene homolog 1 (tumor 1 (tumor progression progression locuslocus 1) 1) 306821835NM 012555y Ets avian erythroblastosisEts avian erythroblastosis virus virus E2 E2 oncogene homologoncogene homolog 1 (tumor 1 (tumor progression progression locuslocus 1) 1) 308220126NM 012591u, Interferon regulatoryInterferon regulatory nn factor 1, factor 1, sirtuin 2 (silent sirtuin 2 (silentmating type information mating type regulation 2, information regulationhomology 2 (S. cerevisiae) 2, homoloa) 2 (S.
cerevisiae) 30971840 NM 012637g protein tyrosine protein tyrosine phosphatase, phosphatase, non-receptor non-receptor typetype 1 30971841 NM 012637ww protein tyrosine protein tyrosine phosphatase, phosphatase, non-receptor non-receptor typetype 1 30971844 NM 012637ww protein tyrosine ESTs, protein tyrosine phosphatase, phosphatase, non-non-receptor typereceptor type 1 310521794NM 012670, m, T-complex 1 T-complex 1 s 312516613NM 012732c Cholesterol esteraseCholesterol esterase (pancreatic) (pancreatic) 312510260NM 012732y Cholesterol esteraseCholesterol esterase (pancreatic) (pancreatic) 312623806NM 012733b, Retinol-binding Retinol-binding protein qq protein 1 1 3130426 NM 012738I, Apolipoprotein Apolipoprotein A'-I
General,A-I

cc, nn, vv 3130427 NM 012738f, Apolipoprotein Apolipoprotein A-I
I, A-I
x, General, nn, vv 31407783 NM 012789qq Dipeptidyl peptidaseDipeptidyl peptidase 31407784 NM 012789General,Dipeptidyl peptidaseDipeptidyl peptidase kk 314124113NM 012791r dual-specificity dual-specificity tyrosine-(Y)-phosphorylation tyrosine-(Y)-phosphorylation regulated kinase 1 a regulated kinase 1a 3145556 NM 012803b, Protein C Protein C
u, x, dd 314621729NM 0128040, ATP-binding cassette,ATP-binding cassette, ff sub- sub-family D (ALD), family D (ALD), member 3 member 3 314621730NM 0128040, ATP-binding cassette,ATP-binding cassette, v sub- sub-family D (ALD), family D (ALD), member 3 member 3 316118767NM 012857qq Lysosomal associatedLysosomal associated membrane protein 1 membrane rotein 120 kDa 1 120 kDa TABLE

Attorney Docket No:

Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster . Title ID ID Ace. Code N0. or N0: RefSeq ID

No.

316118770NM 012857m, Lysosomal associatedLysosomal associated ff, membrane protein 1 ii, rr membrane protein 120 kDa) 1 (120 kDa) ( 316816721NM 0128910, Acyl-Coa dehydrogenase,Acyl-Coa dehydrogenase, General,Very Very long chain cc, ong chain kk, uu l 317423 NM 012907ii Apolipoprotein Apolipoprotein B editing B editing proteinprotein 317524431NM 012912c, Activating transcriptionActivating transcription n, factor 3 factor 3 General, kk, tt 318020755NM 012923m, Cyclin G1 Cyclin G1 a 318413723NM 012935a Crystallin, alphaCrystallin, alpha polypeptide polypeptide 2 2, ESTs, ESTs, Weakly similar to T46637 transcription factor 1, neural - rat [R.norvegicus]

31859109 NM 012939I, Cathepsin H Cathepsin H
General 31981525 NM_012980v Matrix metalloproteinaseMatrix metalloproteinase 11 11 (stromelysin 3) (stromelysin 3) 321518078NM 013030r Solute carrier Rattus norvegicus mRNA
family 17 for NaPi-2 alpha, (sodiumlhydrogen complete cds, Solute exchanger), carrier family 17 member 2 (sodiumlhydroqen exchanger), member 2 3219730 NM 013040cc ATP-binding cassette,ATP-binding cassette, sub- sub-family C

family C (CFTRIMRP),(CFTRIMRP), member 9 member 322616511NM 013060rr Inhibitor of DNA Inhibitor of DNA binding binding 2, 2, dominant dominant negativenegative helix-loop-helix helix-loop- protein helix protein 326524490NM 013178s, Sodium channel, Sodium channel, voltage-gated, cc voltage-gated, type IV, type IV, alpha alpha polypeptide polypeptide 326610499NM 013184r, Neurotrophin 5 ribosomal protein S23 ii (neurotrophin 4I5), ribosomal protein S23 32721693 NM 013199a Dynamin 2 Dynamin 2 328424649NM 016988b, Acid phosphatase Acid phosphatase 2, e, 2, lysozymal lysozymal I, w, General 32871958 NM 016994b, Complement componentComplement component General,3 3 uu, vv 32871959 NM 016994f, Complement componentComplement component u, 3 3 uu 32891698 NM 017000a Diaphorase (NADH/NADPH)Diaphorase (NADH/NADPH) 329218989NM 017013qq, Glutathione-S-transferase,Glutathione-S-transferase, vv alpha type (Yc?) alpha t pe (Yc?) 330024861NM 017033p, PhosphoglucomutasePhosphoglucomutase 1 General1 330024862NM 017033x, PhosphoglucomutasePhosphoglucomutase 1 General1 33081942 NM 017061a Lysyl oxidase Lysyl oxidase 33081946 NM 017061ss Lysyl oxidase Lysyl oxidase 33141262 NM 017077c, Hepatocyte nuclearHepatocyte nuclear factor v, factor 3 3 gamma rr, xx amma TABLE

Attorney Docket No.

Document No.1926271.2 SEQ GLGC GenBankModel Kr~own Gene Name tJnigene Sequence-ClusterTitle ID D Acc. Code I N0. or NO. RefSeq ID
No:' 331623660NM 017080a, Hydroxysteroid Hydroxysteroid dehydrogenase,11 I, dehydrogenase, beta type vv 11 beta type 1 1 33214392 NM 017101mm Peptidylprolyl Peptidylprolyl isomerase ( isomerase A A (cyclophilin A) cyclophilin A) 33214393 NM 017101bb, Peptidylprolyl Peptidylprolyl isomerase mm isomerase A A (cyclophilin A) ( cyclophilin A) 33231548 NM_017112b, hepsin hepsin General 33261435 NM 017125I, Cd63 anti en Cd63 antigen cc, rr 3329169 NM 017131f calsequestrin calsequestrin 2 333510503NM 017143a, coa ulation factorcoagulation factor X
x, X
dd 333510504NM 017143d, coagulation factorcoagulation factor X
dd X

33385351 NM 017150j ribosomal proteinribosomal protein L29 334717686NM 017165o glutathione peroxidaseglutathione peroxidase 33498182 NM 017170a, serum amyloid serum amyloid P-component bb P-component 335020919NM 017172v, zinc finger proteinzinc finger protein nn 36, C3H type- 36, C3H type-like 1 l ike 1 3351114 NM 0171750o protein kinase protein kinase C-like C-like 1 1 33523512 NM_017177d, choline kinase-likecholine kinase-like o, q, v, dd 33523513 NM 017177d, choline kinase-likecholine kinase-like n, dd 33533174 NM 017178qq bone morphogeneticbone morphogenetic protein protein 2 2 335423961NM 017181b, fumarylacetoacetatefumarylacetoacetate uu, hydrolase hydrolase vv 335515434NM 017187y hi h mobility high mobility group group box 2 box 2 335515437NM 017187r, high mobility high mobilit roup box y, roup box 2 2 ww 33589124 NM 017199j, si nal sequence si nal sequence receptor, ii receptor, delta delta 33589125 NM 017199u, signal sequence signal sequence receptor, dd, receptor, delta delta ii, II

33589126 NM 017199g si nal sequence signal sequence receptor, receptor, delta delta 33625005 NM_017209n nuclear receptor nuclear receptor binding binding factor factor 1 337221743NM 017235jj hydroxysteroid hydroxysteroid 17-beta 17-beta dehydrogenase 7 dehydro enase 337221744NM 017235bb, hydroxysteroid ESTs, Highly similar ii, 17-beta to DHB7_RAT
jj dehydrogenase ESTRADIOL 17 BETA-DEHYDROGENASE
7 7 (17-BETA-HSD 7) (17-BETA-HYDROXYSTEROID DEHYDROGENASE
7) (PRL RECEPTOR ASSOCIATED
PROTEIN) (PRAP) [R.norvegicusj 337410427NM 017237bb ubiquitin carboxy-terminalubiquitin carboxy-terminal hydrolase L1 hydrolase L1 337410429NM_017237cc ubiquitin carboxy-terminalubiquitin carboxy-terminal hydrolase L1 hydrolase L1 33751498 NM 017239v myosin heavy chain,myosin heavy chain, polypeptide 6, polypeptide 6, cardiac cardiac muscle, muscle, alpha alpha 337717561NM_017245mm eukaryotic translationeukaryotic translation elongation elongation factor 2 factor 2 TABLE

Attorney Docket No:

Document No.1926271.2 SEQ GLGC GenBankModel Kraown Gene Name Unigene Sequence ClustetTitle , ID ID Acc: Code N0. or N0 RefSeq ID

No.:, 337717562NM 017245h, eukaryotic translationeukaryotic translation t, elongation elongation factor 2, mt factor 2, mitogenmitogen activated protein activated kinase kinase 2 protein kinase kinase 2 337717563NM 017245gg, eukaryotic translationeukaryotic translation hh elongation elongation factor 2 factor 2 337917502NM_017248rr heterogeneous heterogeneous nuclear nuclear ribonucleoprotein A1 ribonucleoprotein 337915012NM 017248kk heterogeneous ESTs, Highly similar nuclear to DDRT helix-ribonucleoproteindestabilizing protein A1 - rat [R.norvegicus], heterogeneous nuclear ribonucleoprotein A1 338319 NM 017258s, B-cell translocationB-cell translocation ss, gene 1, anti- gene 1, anti-proliferative tt proliferative 339515535NM 017283I proteasome (prosome,proteasome (prosome, I macropain) subunit, macropain) subunit,alpha type 6 alpha type 339612523NM_017285tt proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,beta type, 3 beta type, 3 339612524NM_017285kk proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,beta type, 3 beta type, 3 339720579NM 017288a sodium channel, sodium channel, voltage-gated, voltage-gated, type I, beta type I, beta polypeptidepolypeptide 340423130NM_017307j, solute carrier solute carrier family z, family 25 25 (mitochondrial General(mitochondrial carrier; citrate transporter) carrier; citrate member 1 transporter) member 34121630 NM_017325qq, runt related transcriptionrunt related transcription vv factor 1 factor 1 342824785NM 019133n Synapsin I Synapsin I

34391608 NM 019166a synaptogyrin 1 ESTs, Moderately similar to SNG1 RAT

SYNAPTOGYRIN 1 (P29) [R.norvegicus], synaptogyrin 1 344117064NM 019170uu carbonyl reductasecarbonyl reductase 1 3442269 NM 019180d mast cell proteasemast cell protease 6 34512632 NM_019213s jumping translocationjumping translocation breakpoint breakpoint 345315348NM 019222k, coronin, actin coronin, actin binding m binding protein protein 1 B

345620433NM 019232tt, serumlglucocorticoidserumlglucocorticoid xx regulated regulated kinase kinase 345715504NM 019237d procollagen C-proteinaseprocollagen C-proteinase enhancer protein enhancer protein 346017908NM 019242f, interferon-relatedinterferon-related developmental General,developmental regulator 1 ee, regulator 1 pp TABLE

Attorney Docket No.
44921-_5113W0 -Document No.19262712 SEQ GLGC GenBankModel Known.Gene Name Jnigene Sequence Cluster l Title ID ID Acc: Code' . N0. or N0. _ RefSeq ID

No:

34641973 NM 019249h, protein tyrosine protein tyrosine phosphatase, q, phosphatase, receptor-type, r, w, z, eceptor-type, F
General,F
r ee, nn 346713450NM 019255k calcium channel, calcium channel, voltage-dependent, voltage- gamma dependent, gamma subunit 1 subunit 1 34931818 NM 019369a, nter-alpha-inhibitornter-alpha-inhibitor uu H4 heavy i H4 heavy chain i chain 34951323 NM_019371t, EGL nine homolog EGL nine homolog 3 (C.
mm 3 (C. elegans) elegans) 34951324 NM 019371t, EGL nine homolog EGL nine homolog 3 (C.
mm 3 (C. elegans) ele ans) 3507574 NM_019905m calpactin I heavycalpactin I heavy chain, chain, hydroxyacid oxidase hydroxyacid oxidase3 (medium-chain), unknown 3 (medium- Glu-Pro chain), unknown dipeptide repeat protein Glu-Pro dipeptide repeat protein 351212087NM 020082d ribonuclease 4 ribonuclease 4 351919059NM 021587a transforming growthtransforming growth factor-beta factor-beta (TGF-beta) (TGF-beta) maskingmasking protein large protein subunit large subunit 352219679NM 021653a, Thyroxine deiodinase,Thyroxine deiodinase, d, type I ' type I
ii 354423782NM 022183xx topoisomerase topoisomerase (DNA) (DNA) II alpha II alpha 355619422NM 022297j, dimethylarginine dimethylarginine dimethylaminohydrolase z 1 dimethylaminohydrolase 355619423NM_022297I dimethylarginine dimethylarginine dimethylaminohydrolase dimethylaminohydrolase 35738214 NM 022500f, ferritin light ferritin light chain n chain 1 1 35755319 NM 022502r, palmitoyl-proteinpalmitoyl-protein thioesterase u, thioesterase z 35771468 NM 022507dd protein kinase protein kinase C, zeta C, zeta 35894601 NM 022524g sushi-repeat-containingsushi-repeat-containing protein, protein, X

X chromosome chromosome 359920925NM_022594o Peroxisomal enoylPeroxisomal enoyl hydratase-like hydratase- protein like protein 361217661NM 022674c, H2A histone family,H2A histone family, d, member Z member Z
oo, xx 36511785 NM 024130x, dynactin 1 dynactin 1 oo 36891853 NM 030826g Glutathione peroxidaseESTs, Glutathione peroxidase 370020410NM 030990g, Proteolipid proteinProteolipid protein bb, (Pelizaeus- (Pelizaeus-Merzbacher cc Merzbacher disease,disease, spastic paraplegia spastic 2, paraplegia 2, uncomplicated) uncomplicated) 370521165NM 031005mm actinin, alpha actinin, alpha 1 370521166NM 031005t, actinin, alpha actinin, alpha 1 mm 1 3707997 NM 031007a adenylyl cyclase adenylyl cyclase 2 3722690 NM_031034t, guanine nucleotideguanine nucleotide binding v, binding protein (G

General,protein (G protein)protein) alpha 12 alpha 12 mm 3722691 NM 031034t, guanine nucleotideguanine nucleotide binding mm binding protein (G

protein (G protein)protein) alpha 12 alpha 12 37381855 NM 031074d nucleoporin 98 nucleoporin 98 ~

TABLE

Attorney Docket No:
4492~5113W0 Document No.1926279.2 SEQ GLGC GenBankModel Known Gene Name' Unigene Sequence Cluster Title ID ID Acc. Code j N0. or N0. RefSeq ID

No..

374823854NM 031101Generalibosomal protein ibosomal protein L13 r L13 r 375016938NM 031103ee ibosomal protein ibosomal protein L19 r L19 r 375819040NM 031114qq, S-100 related S-100 related protein, vv protein, clone clone 42C

376215539NM 031132v proteasome (prosome,proteasome (prosome, macropain) subunit, macropain) subunit,alpha type 6, transforming alpha type growth factor-b 6, transforming ype II receptor growth factor-b t t ype II receptor 37863519 NM 031334h, Cadherin 1 Cadherin 1 o, dd 379618990NM_031509a Glutathione-S-transferase,Glutathione-S-transferase, alpha type (Yc?) alpha type (Yc?) 379717427NM 031510p Isocitrate dehydrogenasesocitrate dehydrogenase 1, I 1, soluble soluble 380012580NM_031514m, Janus kinase 2 Janus kinase 2 (a protein v (a protein tyrosine kinase) tyrosine kinase) 380220448NM 031530vv Small inducible Small inducible gene gene JE JE

380220449NM 031530vv Small inducible Small inducible ene gene JE JE

3812692 NM_031557g Prostaglandin Prostaglandin 12 (prostacyclin) 12 (prostacyclin)synthase synthase 38169620 NM 031570h, ribosomal proteinribosomal protein S7 General,S7 II

38169621 NM_031570General,ribosomal proteinribosomal protein S7 rr S7 382814295NM 031599f, eukaryotic translationeukaryotic translation I, initiation initiation factor 2 pp alpha factor 2 alpha kinase 3 kinase 3 383721585NM_031620j 3-phosphoglycerate3-phosphoglycerate dehydrogenase dehydrogenase 383721586NM 031620j, 3-phosphoglycerate3-phosphoglycerate dehydrogenase u, dd, dehydrogenase 383721587NM_031620k 3-phosphoglycerate3-phosphoglycerate dehydrogenase dehydrogenase 38381683 NM 031621e, linker of T-cell linker of T-cell receptor ww receptor pathways pathways 383914956NM_031622I mitogen-activatedmitogen-activated protein protein kinase kinase 6 38411639 NM 031627c, nuclear receptor nuclear receptor subfamily x, subfamily 1, 1, group H, General,group H, member member 3 ss 38451727 NM 031642r, core promoter core promoter element tt element binding binding protein protein 385418403NM 031677r four and a half four and a half LIM
LIM domains 2 domains 2 38562327 NM 031683II SMC (segregation SMC (segregation of of mitotic mitotic chromosomes chromosomes 1)-like1)-like 1 (yeast) 1 (yeast) 385720743NM 031684dd solute carrier solute carrier family family 29 29 (nucleoside (nucleoside transporters),transporters), member member 1 385919727NM_031687h, ubiquitin A-52 ubiquitin A-52 residue ff residue ribosomalribosomal protein protein fusion fusion product 1 product 1 1dR
TABLE

Attorney Docket No.
44921-51.13W0 Document No.19262712 SEQ GLGGGenBank Model Known Gene Name nigene Sequence Cluster . U Title lD D-N0.cc. or ode I A = C .

N0. RefSeq - ID .

No. -3862 3706NM 031699s c laudin 1 c laudin 1 1 s 3864 25652NM 031704q s yntaxin 5a s yntaxin 5a 3864 20718NM 031704n s yntaxin 5a s yntaxin 5a 3864 20719NM 031704b, syntaxin 5a syntaxin 5a q, y, dd 3874 17554NM 0317360, solute carrier solute carrier family vv family 27 (fatty27 (fatty acid acid transporter),ransporter), member 2 member 2 t 3886 15647NM 031773, y RNA polymerase RNA polymerase I (127 I I (127 kDa kDa subunit) subunit) 3896 2114NM 031798u, solute carrier solute carrier family kk family 12, member12, member 2 3901 10676NM 031818t intracellular intracellular chloride chloride ion ion channel protein channel protein p64H1 p64H1 3902 2655NM 031821I, serum-inducible serum-inducible kinase kk, kinase nn, tt 3904 4748NM 031834k, sulfotransferasesulfotransferase family cc, family 1A, 1A, phenol-vv phenol-preferring,preferring, member 1 member 1 3904 4749NM 031834b, Aryl sulfotransferaseAryl sulfotransferase k, cytosolic, cytosolic,1A, phenol-I, ii 1A, phenol-preferring,preferring, member 3, member sulfotransferase 3, sulfotransferasefamily 1A, phenol-preferring, family 1A, member 1 phenol-preferring, member 1 3910 15069NM 031840k, Farnesyl diphosphateFarnesyl diphosphate s, synthase synthase jj 3910 15070NM 031840ii, Farnesyl diphosphateFarnesyl diphosphate jj, synthase synthase rr 3910 25460NM 031840k, Farnesyl diphosphateFarnesyl diphosphate jj synthase synthase 3930 860 NM 032063mm delta (Drosophila)-likedelta (Drosophila)-like 3931 18494NM 032079n, DnaJ (Hsp40) DnaJ (Hsp40) homolog, ff, homolog, subfamily A, pp subfamily A, member 2 member 2 3934 12299NM 032416a, aldehyde dehydrogenasealdehyde dehydrogenase General2, 2, mitochondria) mitochondria) 3940 17829NM 033234v Hemo lobin, betaHemoglobin, beta 3952 1311NM 053291j, phospho lyceratephosphoglycerate kinase s, kinase 1 1 t 3958 1063NM 053328p, basic helix-loop-helixbasic helix-loop-helix t, domain domain containing, ff containing, classclass B2 3960 14928NM 053330ff, ribosomal proteinribosomal protein L21 gg, L21 hh 3965 14042NM 053348cc fetuin beta fetuin beta 4007 20831NM 053589g GTPase Rab14 GTPase Rab14 4020 1178NM 053620II Cdc42-binding Cdc42-binding protein protein kinase kinase beta b eta 4072 17728NM 053867n, tumor protein, tumor protein, translationally-controlled ee translationally-1 controlled 1 4073 19781NM 053883, tt dual specificitydual specificity phosphatase phosphatase 6 4075 14992NM 053886dd lectin, mannose-bindinlectin, mannose-binding,1 ,1 4107 23250NM 057097m vesicle-associatedvesicle-associated membrane membrane protein 3 protein 3 4122 2413NM 057141I, heterogeneous heterogeneous nuclear n nuclear ribonucleoprotein K

ribonucleoprotein K

4122 2416NM 057141w heterogeneous heterogeneous nuclear nuclear ribonucleoprotein K

ribonucleo rotein K

1~1~
TABLE

:
Attorney Docket No.

Document No.1926271.2 SEQ
GLGC
GenBank:
Model Known Gene Name Unigene Sequence Cluster Title Y

lD
IDN0.
Acc.
or Code N0.
l2efSeq ID
.

No:
, 41288641 NM 057211f Kruppel-like factorKruppel-like factor 413010498'NM 078617w, ribosomal proteinribosomal protein S23 y S23 41688436 NM 133299b, erosisomal 2-enoyl-CoAperosisomal 2-enoyl-CoA
General, reductase p vv reductase 4175656 NM 133380x Interleukin 4 Interleukin 4 receptor receptor 420617112NM_134326ee Albumin, GlutathioneAlbumin, Glutathione peroxidase 1 peroxidase 1 423915189NM 138826q, Metallothionein Metallothionein w 1 A

423915190NM 138826n, Metallothionein Metallothionein w, 1 A
ii 424516354NM 138843v, ercaptopyruvate mercaptopyruvate sulfurtransferase xx m sulfurtransferase 42509896 NM_138878p Neural precursor Neural precursor cell cell expressed, expressed, developmentally developmentally down-regulated down-regulated gene 8 gene 8 _ 42601858 NM_1389070, acyl-CoA thioesteraseacyl-CoA thioesterase q, 1, 1, cytosolic, jj, xx cytosolic, mitochondria)mitochondria) acyl-CoA
acyl- thioesterase 1 CoA thioesterase 432519429847028 n dimethylarginine dimethylarginine dimethylaminohydrolase dimethylaminohydrolase 43338210 S61960 a ferritin light ferritin light chain chain 1 1 43611392 010188 j Polo-like kinase Polo-like kinase homolog homolog 438317078053859 k, calpain, small calpain, small subunit jj subunit 1 1 438317079053859 jj calpain, small calpain, small subunit subunit 1 1 438525608053927 t, cationic amino cationic amino acid ff acid transporter-transporter-2A

442210819X51536 h, ibosomal protein ESTs, Highly similar k S3 to RS3_MOUSE 40S
r r ibosomal protein S3 [R.norvegicus]

44341037 X57523 a, Transporter 1, Transporter 1, ABC (ATP
qq ABC (ATP binding cassette) b inding cassette) 443718611X58200 h, ibosomal protein ibosomal protein L29 I, L29 r r General, ee 44451587562145 ee, ibosomal protein STs, Highly similar X gg, L8 E to RL8 HUMAN 60S
hh r r ibosomal protein L8 [R.norvegicus]

44502082162671 II inkel-Biskis-ReillySTs, Highly similar X F murine E to UBIM_RAT

s arcoma virus (FBR-MuSV)BIQUITIN-LIKE PROTEIN
U FUBI

u biquitously expressedR.norvegicus]
(fox [

d erived) 44526376 62951 xx imethylarginine imethylarginine dimethylaminohydrolase X d d 1 d imethylaminoh drolase 1 44541641365036 0o lpha 7A inte rin lpha 7A integrin X a a 44541641465036 a a lpha 7A inte rin lpha 7A integrin X a 44631260 77934 , mm myloid protein myloid protein precursor-like 1 X t A precursor-like protein 2 A

p rotein 2 80 21042A799814p H Mm:MAP kinase-activatedSTs, Weakly similar A E to A34366 p rotein kinase a2+/calmodulin-dependent 2 C protein kinase ( EC 2.7.1.123) II delta chain - rat R.norve icus TABLE

:
Attorney Docket No:

Document No.19262712 SE GLGC GenBankModef Known Gene Name Unigene Sequence Cluster : 4 Title ID ID-N0.Acc. Code or NO RefSeq ID

No.;

119 19020AA800291e, HMm:guanylate ESTs, Weakly similar h, kinase 1 to discs, large n homolog 3 (Drosophila) [Rattus norvegicus]

[ R.norvegicusl 665 22537AA892799kk HMm:glyoxylate ESTs, Weakly similar to 3-phosphoglycerate reductase/hydroxypyruvatedehydrogenase [Rattus norvegicus]

reductase [ R.norvegicusl 665 22538AA892799z HMm:glyoxylate ESTs, Weakly similar to 3-phosphoglycerate reductaselhydroxypyruvatedehydrogenase [Rattus norvegicus]

reductase [R.norvegicusl 850 22540AA924630ff HMm:glyoxylate ESTs, Weakly similar to 3-phosphoglycerate reductaselhydroxypyruvatedehydrogenase [Rattus norvegicus]

reductase [R.norvegicusl 873 21010AA925306o HMm:carnitine ESTs, Weakly similar acetyltransferaseto 1701410A choline acetyltransferase [Rattus norvegicus]

[R.norvegicusl 11652915 AA996782ww HMm:lamin B2 ESTs, Moderately similar to lamin B1 [Rattus norve icus]
[R.norve icus]

129521563A1007750gg, HMm:ubiquitin-conjugatingESTs, Weakly similar hh to ubiquitin-enzyme E2L 3 conjugating enzyme E2D
2 [Rattus norvegicusl R.norvegicusl 137312310A1010362gg, HMm:cullin 1 ESTs, Weakly similar hh to vasopressin-activated calcium-mobilizing receptor protein fRattus norvegicusl [R.norvegicusl 142920817A1012589c lutathione S-transferase,glutathione S-transferase, pi 2 pi 2 18942364 AI103379GeneralHMm:ubiquitin-activatingESTs, Highly similar to 163168 gene Ube1x enzyme E1, Chr protein - rat (fra ment) X [R.norvegicus]

208417812AI169075uu HMm:glutathione ESTs, Weakly similar transferase to GT01 RAT

zeta 1 (maleylacetoacetateGlutathione transferase omega 1 (GSTO 1-isomerase) 1) (Glutathione-dependent dehydroascorbate reductase)[R.norvegicus]

232014384A1177096a HMm:adenine phosphoribosylESTs, Highly similar to APT_RAT ADENINE

transferase PHOSPHORIBOSYLTRANSFERASE

(APRT) [R.norvegicus]

23368949 AI177593I, HMm:ATPase, H+ ESTs, Weakly similar Generaltransporting, to VATL_MOUSE

lysosomal 21 kDa,Vacuolar ATP synthase VO subunit B 16 kDa proteolipid subunit [R.norvegicusl 246921505AI228005bb HMm:deoxyguanosineESTs, Weakly similar kinase to deoxycytidine kinase [Rattus norvegicus]
[R.norvegicus]

259122542AI232066ff HMm:glyoxylate ESTs, Weakly similar to 3-phosphoglycerate reductaselhydroxypyruvatedehydrogenase [Rattus norvegicus]

reductase [R.norvegicusl 279321043A1237813mm HMm:MAP kinase-activatedESTs, Weakly similar to A34366 protein kinase Ca2+Icalmodulin-dependent 2 protein kinase (EC 2.7.1.123) II delta chain - rat iR.norveaicusl 338917715NM 017274ss, glycerol-3-phosphateglycerol-3-phosphate xx acyltransferase, ac Itransferase mitochondria) mitochondria) TABLE

Attorney Docket No.'44921-5113W0 Document No.19262712 SEQ GLGC GenBankModel Known-Gene Name Unigene Sequence Cluster Title fD fD Aca. Code N0: or N0. RefSeq ID

No.

338920282NM 017274y glycerol-3-phosphateglycerol-3-phosphate acyltransferase, acyltransferase, mitochondria) mitochondria) 342514979NM 019126u, Carcinoembryonic Carcinoembryonic antigen bb, antigen gene gene family jj f amily (CGM3) ( CGM3) 3504904 NM 019620d, Kruppel associatedKruppel associated box n, box (KRAB) (KRAB) zinc finger gg, 1 hh, zinc finger 1 kk, tt 360221023NM 022599h, synaptojanin 2 synaptojanin 2 binding I, binding protein protein General 376821624NM 031144mm actin, beta actin, beta 376821625NM 031144z actin, beta actin, beta 42422100 NM 138829I golgi reassembly golgi reassembly stacking I stacking protein 2 protein 2 426018082NM_138907nn mitochondria) mitochondria) acyl-CoA
acyl-CoA thioesterase 1 t hioesterase 1 426018083NM_138907m, mitochondria) mitochondria) acyl-CoA
o, acyl-CoA thioesterase 1 jj, nn, xx thioesterase 1 439723926086635 d, glutathione S-transferase,lutathione S-transferase, oo mu 5 mu 5 33 17613AA799511ww ESTs, Weakly similar to DDRT helix-destabilizing protein - rat [R.norvegicus]

38 17599AA799539o ESTs, Weakly similar to KEAP_RAT Kelch-l ike ECH-associated protein 1 (Cytosolic i nhibitor of Nrf2) (INrf2) [R.norveqicusl 45 18361AA799591, tt ESTs, Highly similar j to TBB1 RAT TUBULIN

BETA CHAIN (T BETA-15) [R.norvegicus]

56 20982AA799657x, ESTs, Weakly similar qq to 568418 protein phosphatase 1 M chain M110 isoform - rat (fragment) [R.norvegicusl 77 20998AA799803b, ESTs, Weakly similar General to JC6554 complement subcomponent C1s (EC

3.4.21.42) precursor [similarity] - rat IR.norveqicusl 97 16712AA800015v integrin-linked integrin-linked kinase kinase 117 21665AA800272e, ESTs, Highly similar s to RM03_RAT

Mitochondria) 60S ribosomal protein L3 [R.norvegicusl 124 9089 AA800389d ESTs, Weakly similar to A48157 renal transcription factor Kid-1- rat [R.norvegicus]

126 6892 AA800551p DnaJ-like proteinDnaJ-like protein 140 12072AA800680g ESTs, Weakly similar to S68418 protein phosphatase 1 M chain M110 isoform - rat (fragment) [R.norvegicusl 165 21415AA800948I, ESTs, Highly similar mm to 0812252A tubulin alpha [Rattus norvegicus]
[R.norvegicus]

189 9840 AA817964g paraoxonase 1 paraoxonase 1 199 6526 AA818118gg, ESTs, Weakly similar hh to cold inducible RNA-binding protein [Rattus norvegicus]

R.norve icus TABLE

Attorney:Docket No"

Document No.1926271-:2 SEQ GLGG GenBank'Model Known Gene Name Jnigene Sequence GlusterTitle l lD ID Acc. Code NO. or a NO'., Ref~eq )D

No.

201 6016 AA818163x ESTs, Weakly similar to PON1 RAT Serum paraoxonase/arylesterase 1 (PON 1) (Serum aryldiakylphosphatase 1) (A-esterase 1) ( Aromatic esterase 1) [R.norvegicus]

202 17771AA818224I Rat mRNA for beta-tubulin T beta15 269 17614AA848306t, ESTs, Weakly similar II, to DDRT helix-tt destabilizin protein - rat [R.norve icus]

277 23355AA848530I, ESTs, Weakly similar bb to retinoblastoma binding protein 7 [Rattus norvegicus]

f R.norvegicusl 297 6635 AA849786bb, ESTs, Weakly similar II to CLK3_RAT Protein kinase CLK3 (CDC-like kinase 3) [R.norvegicusl 316 14324AA850402n ESTs, Moderately similar to S21348 probable pol polyprotein-related protein 4 -ratfR.norvegicus 372 14987AA858640o heat shock proteinRattus norvegicus CDK110 60 (liver) mRNA, heat shock protein 60 (liver) 390 19105AA859230v, ESTs, Weakly similar x to HG17_RAT

NONHISTONE CHROMOSOMAL
PROTEIN

HMG-17 [R.norvegicusl 410 11317AA8596310o ESTs, Weakly similar to ZF37_RAT Zinc finger protein 37 (Zfp-37) [R.norve icus]

411 16318AA859648c ESTs, Weakly similar to DJA1 MOUSE

DnaJ homolog subfamily A member 1 (Heat shock 40 kDa protein 4) (DnaJ protein homoloa 2) (HSJ-2) fR.norveaicusl 433 23301AA859975w 2-oxoglutarate 2-oxo lutarate carrier carrier 439 19332AA860014a EST, Moderately similar to 2206405A

hemoglobin:SUBUNIT=zeta [Rattus norvegicuslfR.norvegicusl 465 16082AA874887ww ESTs, Weakly similar to segregation of mitotic chromosomes b; SMC (segregation of mitotic chromosomes 1 )-like 1 (yeast) fRattus norveaicusl fR.norveaicusl 478 14951AA875037y ESTs, Weakly similar to plasminogen activator inhibitor 2 type A [Rattus norvegicusl [R.norvegicusl 482 16327AA875050c, ESTs, Weakly similar oo to KICE_RAT

Cholinelethanolamine kinase [Includes:

Choline kinase (CK);
Ethanolamine kinase (EK)1 fR.norveqicusl 486 20701AA875097b, EST, Highly similar m, to FIBA_RAT Fibrinogen General alphalalpha-E chain precursor [R.norvegicusl 501 15933AA875253 ADP-ribos lation ADP-ribos lation factor-like factor-like 1 1 TABLE

Attorney Docket No44921=5113W0 Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster -= Title ID ID Aca. Code N0. or' NO RefSeq ID

No:v 516 16516AA875563x ESTs, Weakly similar to 156519 taipoxin-associated calcium binding protein-49 precursor - rat [R.norveqicusl 533 9136 AA891226rr, ESTs, Highly similar tt to PSBS_RAT

Proteasome subunit beta type 5 precursor (Proteasome epsilon chain) (Macropain epsilon chain) (Multicatalytic endopeptidase complex epsilon chain) (Proteasome subunit X) (Proteasome chain 6) [R.norvegicus]

547 2753 AA891589a sarcosine dehydroESTs, sarcosine dehydrogenase enase 562 18269AA891769z ESTs, Weakly similar to SC65 synaptonemal complex protein [Rattus norvegicusl [R.norvegicusl 606 17350AA892240k ESTs, Weakly similar to 2008109A set gene [Rattus norvegicus]
[R.norvegicus]

613 4486 AA892298w ESTs, Weakly similar to matrin cyclophilin (matrin-cyp) [Rattus norvegicus]

[R.norvegicusl 621 13647AA892367z, ESTs, Highly similar General, to RL3_RAT 60S

ii, RIBOSOMAL PROTEIN L3 rr (L4) [R.norveaicusl 623 19226AA892394a ESTs, Weakly similar to ELV4_RAT ELAV-like protein 4 (Paraneoplastic encephalomyelitis antigen HuD) (Hu-antigen D) fR.norveaicusl 623 19227AA892394a, ESTs, Weakly similar w to ELV4 RAT ELAV-_ like protein 4 (Paraneoplastic encephalomyelitis antigen HuD) (Hu-antigen D)fR.norveqicust 631 9254 AA892470j, ESTs, Highly similar q, to S03644 histone nn, oo H2A.Z - rat [R.norve icus]

632 11992AA892485kk dihydrolipoamide dihydrolipoamide acetyltransferase acetyltransferase 649 15876AA892582I, ESTs, Highly similar General to RL8_HUMAN 60S

ribosomal protein L8 [R.norvegicus]

658 4487 AA892680e, ESTs, Weakly similar p to matrin cyclophilin (matrin-cyp) [Rattus norvegicus]

[R.norvegicusl 667 6951 AA892820bb ESTs, Weakly similar to S70642 ubiquitin ligase Nedd4 - rat (fragment) [R.norvegicus]

671 7148 AA892842gg, ESTs, Weakly similar hh to CAZ3_RAT F-actin capping protein alpha-3 subunit (CAPZ

alpha-3) [R.norvegicusl 679 3438 AA892921r ESTs, Weakly similar to A55143 calpain (EC

3.4.22.17) light chain - rat (fragment) R.norve icus TABLE

Attorney Docket No.

Document No.1-926271.2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster - ' Tifle ID ID Acc. Code N0. or N0. RefSeq ID

No 68016482AA892940x ESTs, Weakly similar to EF2_RAT

Elon ation factor 2 (EF-2) [R.norve icus]

69124179AA893091nn, ESTs, Weakly similar tt to TC17_RAT Zinc finger protein 354A
(Transcription factor 17) (Renal transcription factor Kid-1) (Kidney, ischemia, and developmentally regulated protein-11 IR.norveaicusl 72517836AA893626uu ESTs, Weakly similar to guanine nucleotide-binding protein, beta-1#
subunit [Rattus norvegicusl[R.norvegicusl 7437637 AA894089k, rotein carrying rotein carrying the x the RING-H2 RING-H2 sequence motif sequence motif 74618419AA894130n, ESTs, Weakly similar General, to 2019243A amyloid ww precursor-like protein 2 [Rattus norvegicus]

[R.norvegicusl 75415274'AA894258General,ubiquitin-conjugatingubiquitin-conjugating enzyme enzyme E2D 3 kk E2D 3 (homologous(homologous to yeast to yeast UBC4/5) UBC4/5) 7553908 AA894259j ESTs, Weakly similar to hypoxia induced gene 1 [Rattus norvegicus]
[R.norvegicus]

7956483 AA900461v ESTs, Weakly similar to OBRG_RAT Leptin receptor gene-related protein (OB-R gene related protein) (OB-RGRP) [R.norvegicus]

80418547AA900722ii solute carrier solute carrier family family 9 9 (sodium/hydrogen (sodiumlhydrogen exchanger), isoform exchanger), 3 regulator 2 isoform 3 regulator 82422980AA923973y seven in absentiaseven in absentia 1A

8555019 AA924768b ESTs, Weakly similar to DnaJ (Hsp40) homolog, subfamily A, member 2 [Rattus norvegicusl[R.norvegicusl 86723261AA925145b, ESTs, Weakly similar uu, to betaine-vv homocysteine methyltransferase [Rattus norveqicusl R.norvegicusl 86810666AA925212kk siah binding proteinsiah binding protein 1; FBP 1; FBP interacting interacting repressor;repressor; pyrimidine pyrimidine tract binding splicing tract binding factor; Ro ribonucleoprotein-binding splicing factor; protein Ro ribonucleoprotein-binding1 protein 1 96414763AA944481s, ESTs, Weakly similar ff, to FCN2_RAT Ficolin nn 2 precursor (Collagenlfibrinogen domain-containing protein 2) (Ficolin-B) (Ficolin B) (Serum lectin P35) (EBP-37) (Hucolin) fR.norve4icusl 9772893 AA944833kk ESTs, Weakly similar to ROD RAT

Heterogeneous nuclear ribonucleoprotein DO

(hnRNP DO) (AU-rich element RNA-binding rotein 1 R.norve icus TABLE

Attorney Docket No:

Document No.1926271.2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster - Title lD ID Acc. Code ' NO. or N0. RefSeq ID

No.

99922607AA945580b ESTs, Weakly similar to ARG2_RAT

Arginase II, mitochondria) precursor (Non-hepatic arginase) (Kidney-type arginase) i R.norveaicusl 101217721AA945762General ESTs, Weakly similar to 2102279A protein Tyr phosphatase [Rattus norvegicus]

[ R.norvegicus]

101722680AA945883j ESTs, Weakly similar to JC5598 mucin - rat [ R.norvegicus]

103022753AA946300I, Rattus norvegicus cytochrome General P450-like protein mRNA, partial cds 1041643 AA946439c, ESTs, Highly similar ii, to HSRT4 histone H4 tt -rat [R.norvegicus]

104823584AA955071ff retinoid X receptorretinoid X receptor gamma ( gamma 105222596AA955298c ESTs, Weakly similar to T46637 transcription factor 1, neural - rat fR.norvegicusl 105523542AA955389pp ESTs, Weakly similar to GRB2_HUMAN

Growth factor receptor-bound protein 2 (GRB2 adapter protein) (SH2/SH3 adapter GRB2) (ASH protein) fR.norveqicusl 107911050AA956164ii ESTs, Weakly similar to JQ0866 T-complex protein 1 - rat [R.norvegicus]

108223747AA956329gg, ESTs, Moderately similar hh to delta-6 fatty acid desaturase [Rattus norvegicus]

fR.norvegicus]

108425112AA956437d ESTs, Weakly similar to TERA_RAT

TRANSITIONAL ENDOPLASMIC

RETICULUM ATPASE (TER
ATPASE) (15S

MG(2+)-ATPASE P97 SUBUNIT) (VALOSIN

CONTAINING PROTEIN) (VCP) [CONTAINS: VALOSIN]
[R.norvegicus]

10916174 AA957063tt ESTs, Weakly similar ~ to E2BE_RAT
_ TRANSLATION INITIATION
FACTOR EIF-2B EPSILON SUBUNIT (EIF-2B
GDP-GTP

EXCHANGE FACTOR) [R.norvegicus]

109924050AA957449v ESTs, Weakly similar to SNK_RAT

Serine/threonine-protein kinase SNK (Serum inducible kinase) [R.norvegicus]

110112479AA957557a, ESTs, Weakly similar vv to ITH3_RAT Inter-alpha-trypsin inhibitor heavy chain H3 precursor (ITI heavy chain H3) R.norve icus 1.5R
TABLE

Attorney Docket No.

Document No.1926271.2 SEQ GLGC Genl3ankModet Known Gene Name Unigene Sequence Clusfer Title ID ID Acc. Code NO. or N0. RefSeq ID_ No.

111023541AA957999f, I, ESTs, Weakly similar nn to TXTP_RAT

Tricarboxylate transport protein, mitochondria) precursor (Citrate transport protein) (CTP) (Tricarboxylate carrier protein) IR.norveaicusl 119013330AA997716II Kelch-like ECH-associatedKelch-like ECH-associated protein 1 protein 1 12133746 AA998268b, bb ESTs, Weakly similar to SYPH_RAT

SYNAPTOPHYSIN (MAJOR
SYNAPTIC

VESICLE PROTEIN P38) [R.norveqicus]

121614379AA998415rr ESTs, Weakly similar to A40016 matrin 3 -rat [R.norve icus]

124411745AB006450gg, translocator translocator of inner hh of inner mitochondria) mitochondria) membrane 17 kDa, a membrane 17 kDa, a 125518192AF000899s, tt nucleoporin p58 Rattus norvegicus p58/p45 mRNA, alternatively spliced form, clone H6, 3' end, nucleoporin p58 126019649AF016387pp retinoid X receptorretinoid X receptor ammo gamma ( 126019650AF016387s retinoid X receptorretinoid X receptor gamma gamma ( 12708008 AF039584xx decay-accelaratingdecay-accelaratin factor factor 127415715AF053092ii Rattus norvegicus polo-like kinase isoform mRNA, partial cds 12813896 AF077000m protein tyrosineprotein tyrosine phosphatase phosphatase TD14 128320741AF084186nn alpha-fodrin alpha-fodrin 12882947 AF099093f, kk ubiquitin-conjugatingubiquitin-conjugating enzyme enzyme UBC7 128912932AF102552x ankyrin 3 (G) ankyrin 3 (G) 129211251A1007666i ESTs, Weakly similar i to JC4647 KW8 protein - rat [R.norve icus]

129422332A1007748f ESTs, Weakly similar f to OZF_RAT Zinc f inger protein OZF (POZF-1) [R.norvegicus]

132221838A1009131ee, aminin, gamma aminin, ammo 1 kk 1 l l 133310820A1009411ee ESTs, Highly similar to RS3_MOUSE 40S

r ibosomal protein S3 [R.norve icus]

13399746 A1009555d, g Rattus norvegicus dynein light intermediate c hain 1 mRNA, complete cds 135022545A1009747z t ransducer of ransducer of ERBB2, 1 ERBB2, 1 t 136523540A1010110x S H3-domain GRB2-likeH3-domain GRB2-like 1 x 1 S

140116112A1011706t E STs, Weakly similar to t SFRS_RAT Splicing f actor, arginine/serine-rich 5 (Pre-mRNA

s plicing factor SRP40) (Insulin-induced g rowth response protein CL-4) (Delayed-e arly protein HRS) [R.norvegicus]

1 ~7 TABLE

Attorney Docket No.

Document No.1926271:2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster Title ID D Acc. Code - N0. or ~
~~
I

N0. RefS
eq ID

_ No.

141521796A1012221v ESTs, Weakly similar v to intracellular chloride ion channel protein p64H1 [Rattus norvegicusl[R.norvegicusl 14223417A1012337h, ESTs, Highly similar w to NHPX_RAT NHP2-l ike protein 1 (High mobility group-like nuclear protein 2 homolog 1) ([U41U6.U5] tri-snRNP 15.5 kDa protein) (OTK27) IR.norveaicusl 14271263A1012567bb ESTs, Weakly similar to ZF94_RAT Zinc -finger protein 94 (Zfp-94) (Zinc finger protein Y1) (RLZF-Y) [R.norvegicusl 14346489A1012636d ESTs, Weakly similar to RBMA_RAT RNA-binding protein 10 (RNA
binding motif protein 10) (S1-1 protein) [R.norvegicus]

14627258A1013475h ESTs, Moderately similar to SORT_RAT

Sortilin (Glycoprotein 110) (Gp110) [R.norvegicus]

147224239A1013781d ESTs, Weakly similar to S19586 N-methyl-D-aspartate receptor glutamate-binding chain -rat [R.norvegicusl 154823949A1031019q translation initiationtranslation initiation factor eIF- factor eIF-2B alpha-2B alpha-subunit subunit 154823950A1031019n, translation initiationtranslation initiation q, factor eIF- factor eIF-2B alpha-x, II

2B alpha-subunit subunit 15725431A1044257I ESTs, Weakly similar to syntenin [Rattus norvegicus] [R.norve icus]

159118205A1044836h ESTs, Weakly similar to NUCL_RAT
-Nucleolin (Protein C23) [R.norvegicus]

164710533A1058430qq ESTs, Highly similar to HG17_RAT

NONHISTONE CHROMOSOMAL
PROTEIN

HMG-17 [R.norvegicusl 16628584A1058911cc, ESTs, Weakly similar ii, to FIBA_RAT
rr Fibrinogen alphalalpha-E
chain precursor [R.norvegicusl 167014984A1059174h Rattus norvegicus CDK110 mRNA

16866370A1059568g ESTs, Highly similar to B48213 syntaxin rat [R.norvegicus]

173326184A1070784m ESTs, Weakly similar to OZF_RAT Zinc finger protein OZF (POZF-1) [R.norvegicus]

174110999A1071110t ESTs, Weakly similar to A44437 regenerating liver inhibitory factor RLIIF-1 -rat[R.norvegicusl 176221839A1071644f laminin, amma laminin, gamma 1 17647092A1071668c ' ESTs, Weakly similar to E2BE_RAT

TRANSLATION INITIATION
FACTOR EIF-2B EPSILON SUBUNIT (EIF-2B
GDP-GTP

EXCHANGE FACTOR) [R.norvegicus]

15~
TABLE

Attorney Docket No.
44921=5113W0 Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID D Acc. Code I N0. or N0. RefSeq ID _ No. , 177116376A1071866a, Rattus norvegicus Nclone10 a mRNA

179421797A1072439qq ESTs, Weakly similar to intracellular chloride ion channel protein p64H1 [Rattus norveqicus][R.norveqicus]

18021501 A1072634e, Rattus norvegicus cytokeratin-18 I, mRNA, t, bb, dd, partial cds ww 182511183AI100768b ESTs, Weakly similar to CAH2_RAT
_ Carbonic anhydrase II
(Carbonate dehydratase II) (CA-II) [R.norveqicusl 18326321 AI101256i, ESTs, Weakly similar i II to S09017 heterogeneous ribonuclear particle protein type C - rat (fragment) [R.norveqicusl 185118649AI101926q ESTs, Weakly similar to HS9B_RAT Heat _ shock protein HSP 90-beta (HSP 84) [R.norveqicus]

187523538A1102727I, solute carrier solute carrier family n, family 20 20 (phosphate p (phosphate transporter),transporter), member member 1 188515026AI103094Generalras-related proteinras-related protein _ 15981AI103150nn ESTs, Weakly similar 1889 to ubiquitin conjugating enzyme [Rattus norvegicus]

[R.norveaicusl 18958919 A1103388dd, ESTs, Weakly similar kk to ARF6_HUMAN ADP

ribosylation factor 6 [R.norvegicus]

189614981AI103396ee Rattus norvegicus CDK110 mRNA

1935_ AI104357a ESTs, Highly similar 18831 to ACTB_HUMAN

Actin, cytoplasmic 1 (Beta-actin) [R.norveqicusl 194412342AI1046580o ESTs, Weakly similar to A48152 zinc finger protein Gfi-1 - rat [R.norve icus]

195615065AI105050p, ATP synthase, ATP synthase, H+ transporting, ii, H+ transporting, II

mitochondrial mitochondrial F1 complex, F1 complex, beta beta polypeptide poIVPeptide 197911192AI11198(ig ESTs, Weakly similar to S41067 collagen alpha 1 (III) chain - rat [R.norvegicus]

200611735AI136540j ESTs, Highly similar to TRT3_RAT Troponin T, fast skeletal muscle isoforms betalalpha (Betalalpha TnTF) [R.nonregicus]

200710780AI136555j Rattus norvegicus mRNA
for Castration Induced Prostatic Apoptosis Related protein-1 (CIPAR-1) 20238924 AI137283z ESTs, Weakly similar to TC17_RAT Zinc finger protein 354A
(Transcription factor 17) (Renal transcription factor Kid-1) (Kidney, ischemia, and developmentally regulated protein-1) [R.norveQicusl 20721358 AI146154mm hos hatid linositol4-kinasehos hatid linositol4-kinase TABLE

.
Attorney Docket No.

Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster - Title ID D Accor Code I NO.

NO RefSeq ID

No..

20851335 AI169105ss ESTs, Weakly similar to PON1 RAT Serum paraoxonase/arylesterase 1 (PON 1) (Serum aryldiakylphosphatase 1) (A-esterase 1) (Aromatic esterase 1) [R.norvegicus]

209418641AI169225ee Rattus norvegicus mRNA
for ribosomal protein L35 209622661AI169265t, ATPase, H+ transporting,ATPase, H+ transporting, mm lysosomal lysosomal (vacuolar(vacuolar proton pump), proton subunit 1 pump), subunit 213114938AI170362qq ESTs, Weakly similar to 167414 nuclear factor kappa B - rat (fragment) [R.norvegicus]

214515403AI170714m, ESTs, Weakly similar dd to A40389 translation elongation factor eEF-1 alpha chain (clone pS1) - rat [R.norvegicus 215518535AI170979dd, ESTs, Weakly similar oo to REQN_RAT Zinc-finger protein neuro-d4 [R.norve icus]

216017783AI171206vv ESTs, Weakly similar to 2118320A

neurodegeneration-associated protein 1 [Rattus norvegicus]
[R.norvegicus]

217011419A1171365k ESTs, Weakly similar to A57514 RNA

helicase HEL117 - rat [R.norve icus]

21816879 AI171674t Very low density Very low density lipoprotein lipoprotein receptor receptor 22046630 AI172184b ESTs, Weakly similar to SYPH_RAT

SYNAPTOPHYSIN (MAJOR
SYNAPTIC

VESICLE PROTEIN P38) f R.norvegicus]

221623325AI172405bb ESTs, Highly similar to 2008109A set gene [Rattus norvegicus]
[R.norvegicus]

224715404AI175760dd ESTs, Weakly similar to A40389 translation elongation factor eEF-1 alpha chain (clone pS1) - rat [R.norvegicusl 227113339AI176308r ESTs, Weakly similar to C01 B RAT Coronin _ 1 B (Coronin 2) [R.norvegicus]

233517773AI177513y ESTs, Weakly similar to CLK3_RAT Protein _ kinase CLK3 (CDC-like kinase 3) [R.norvegicus]

23554979 AI178133ss ESTs, Weakly similar to LIS1 MOUSE

Platelet-activating factor acetylhydrolase IB

alpha subunit (PAF acetylhydrolase 45 kDa subunit) (PAF-AH 45 kDa subunit) (PAF-AH

alpha) (PAFAH alpha) (Lissencephaly-1 protein) (LIS-1) [R.norvegicus]

238412408AI178762qq ESTs, Moderately similar to delta-6 fatty acid desaturase [Rattus norvegicus]

R.norve icus TABLE

v Aftorneypocket No.
44921'~5113W0 Document No:1926271:2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID ID Acc, Code=
NO. or N0. Ref$eq ID

No 239523043AI178968nn ESTs, Weakly similar to S70642 ubiquitin ligase Nedd4 - rat (fragment) [R.norvegicus]

240317890AI179123j, ESTs, Weakly similar mm to NF-E2-related factor 2 Rattus norve icus] [R.norvegicus]

242916656AI179634h ESTs, Weakly similar to Gasz [Rattus norve icus] [R.norve icus]

24406455 AI179984vv ESTs, Weakly similar to CPI3_RAT

CONTRAPSIN-LIKE PROTEASE

(CPI-23) (SERINE PROTEASE INHIBITOR
1) (SPI-1) fR.norveaicusl 246812413AI227953t, ESTs, Weakly similar mm to K6A1 RAT

Ribosomal protein S6 kinase alpha 1 (S6K-alpha 1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (Ribosomal S6 kinase 1) (RSK-1) (pp90RSK1) [R.norvegicus]

25056604 AI229192xx ESTs, Weakly similar to 2209311A

coagulation factor X
[Rattus norvegicus]

[R.norveqicusl 251523858AI229450r ESTs, Weakly similar to A57514 RNA

helicase HEL117 - rat [R.norvegicus]

253018650AI230121q, ESTs, Weakly similar ii, to HS9B_RAT Heat II

shock protein HSP 90-beta (HSP 84) [R.norvegicus]

256621816A1231217ee ESTs, Highly similar to S611 HUMAN

Protein transport protein Sec61 alpha subunit isoform 1 (Sec61 alpha-1) fR.norveaicusl 26058390 AI232288ww ESTs, Weakly similar to retinoblastoma binding protein 7 [Rattus norvegicus]

[R.norvegicusl 26245602 AI2326110, ESTs, Weakly similar ff, to MTE1 RAT Acyl xx coenzyme A thioester hydrolase, mitochondrial precursor (Very-long-chain acyl-CoA thioesterase) (MTE-I) iR.norveaicusl 263612873AI232984tt ESTs, Weakly similar to OZF_RAT Zinc finger protein OZF (POZF-1) [R.norvegicus]

26414442 AI233163gg, ESTs, Highly similar hh to RL11 HUMAN 60S

ribosomal protein L11 [R.norvegicus]

271322070AI235528jj ESTs, Weakly similar to synuclein, gamma Rattus norve icus R.norve icus TABLE

Attorney Docket No44921-5113WQ

Document No.1926271~2 SEQGLGC GenBankModel Kriawn Gene Name Unigene Sequence Cluster Title ID ID Acc. Code NO. or N0. RefSeq ID
' No 27267307 AI235935g, ESTs, Weakly similar oo to C1TC_RAT C-1-tetrahydrofolate synthase, cytoplasmic (C1-THF synthase) [Includes:

Methylenetetrahydrofolate dehydrogenase ;

Methenyltetrahydrofolate cyclohydrolase ;

Formyltetrahydrofolate synthetase ]

IR.norveaicusl 27307604 AI236039II reticulocalbin reticulocalbin 274013911AI236262ww Rattus norvegicus epidermal Langerhans cell rotein LCP1 mRNA, complete cds 274210667AI236366dd siah binding proteinsiah binding protein 1; FBP 1; FBP interacting interacting repressor;repressor; pyrimidine pyrimidine tract binding splicing tract binding factor; Ro ribonucleoprotein-binding splicing factor; protein Ro ribonucleoprotein-binding1 protein 1 27556207 AI236681gg, ESTs, Weakly similar hh to SUIS RAT Sucrase-isomaltase, intestinal [Contains: Sucrase ;

Isomaltase 1 fR.norveAicusl 276217618AI236786p, ESTs, Weakly similar rr to FK506 binding protein 2 (13 kDa) [Rattus norvegicus]

fR.norveaicus~

277823076A1237388q, ESTs, Weakly similar dd to IFR1 RAT

INTERFERON-RELATED

DEVELOPMENTAL REGULATOR

(NERVE GROWTH FACTOR-INDUCIBLE

PROTEIN PC4) (IRPRI
IR.norveaicusl 285118338AI639422g ESTs, Moderately similar to CAQC_RAT

CALSEQUESTRIN, CARDIAC
MUSCLE

ISOFORM PRECURSOR ~R.norvegicusl 285826012AI639478pp ESTs, Weakly similar to PDI RAT Protein disulfide isomerase precursor (PDI) (Prolyl hydroxylase beta subunit) (Cellular thyroid hormone binding protein) (Thyroxine deiodinase) (lodothyronine 5'-monodeiodinasel (5'-MDl fR.norveaicusl 28678107 AI639534pp ESTs, Weakly similar to ATS4_RAT

ADAMTS-4 precursor (A
disintegrin and metalloproteinase with thrombospondin motifs 4) (ADAM-TS 4) (ADAM-TS4) (Aaarecanase 11 fR.norveaicusl 28727602 AJ001929b, reticulocalbin reticulocalbin q, v, ii, II, xx 287620519C06598 v, ESTs, Weakly similar w to FK506 binding protein 2 (13 kDa) [Rattus norvegicus]

[R.norveqicusl 28775048 D00092 0o dihydrolipoamide dihydrolipoamide acetyltransferase acetyltransferase 28815049 D10655 m dihydrolipoamide dihydrolipoamide acetyltransferase acet Itransferase Ti4BLE
~( Attorney Docket.No.

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence GlusterTitle IDw ID Acc. Code N0. or NO. RefSeq ID

No:.

28865082 D14015 ii, Cyclin E1 ESTs, Highly similar ww to CGE1 RAT G1lS-specific cyclin E1 [R.norve icus]

28981041 D78610 x Protein tyrosine Protein tyrosine phosphatase, phosphatase, receptor type, receptor type, epsilon polypeptide epsilon polypeptide 28991356 D83538 y phosphatidylinositol4-kinasephosphatidylinositol4-kinase 29002744 D87991 b, ESTs, Highly similar e, to JC5026 UDP-q, dd galactose transporter related protein 1-rat [ R.norvegicus]

29154352 H31692 x GERp95 GERp95 29199745 H31847 c, Rattus norvegicus dynein h light intermediate chain 1 mRNA, complete cds 29213815 H31907 a G protein pathwayG protein pathway suppressor suppressor 1 1 295214968K02815 f butyrophilin-likebutyrophilin-like 2 2 (MHC class (MHC class II associated) II

associated) 2964107 L14001 General, Rattus norvegicus clone 15 polymeric mm i mmunoglobulin receptor mRNA, 3'UTR

microsatellite repeats 2965108 L14002 I, Rattus norvegicus clone m, 15 polymeric u, General,i mmunoglobulin receptor ~ mRNA, 3'UTR

cc, microsatellite repeats kk, vv 2967109 L14004 b, Rattus norvegicus clone General, 15 polymeric vv immunoglobulin receptor mRNA, 3'UTR

microsatellite repeats 297224518L19927 t, ATP synthase, ATP synthase, H+ transporting, y, H+ transporting, mm mitochondria) mitochondria) F1 complex, F1 complex, gamma gamma polypeptidepolypeptide 1 298118620L40364 gg, Rattus norvegicus MHC
hh class I RT1.0 type -149 processed pseudogene mRNA

298225389L41684 II FAT tumor suppressorFAT tumor suppressor (Drosophila) homolog (Drosophila) homolog 298417883M11851 ss Rat heart myosin light chain 2 (MLC2) mRNA, 3' end 298824554M13749 m Chorionic somatomammotropinChorionic somatomammotropin hormone 2;

hormone 2; PlacentalPlacental lactogen-2 lactogen-2 301517211M34331 ee, Rattus norvegicus mRNA
II for ribosomal protein L35 301526030M34331 bb, Rattus norvegicus mRNA
II for ribosomal protein L35 30402694 M92340 rr Interleukin 6 Interleukin 6 signal si nal transducertransducer 309918726NM 012645b, Rattus norvegicus MHC
q, class Ib RT1.S3 v, General, (RT1.S3) mRNA, partial cds dd, oo, rr 31097101 NM 012679nn Clusterin Clusterin 31321478 NM 012744kk Pyruvate carboxylasePyruvate carboxylase 31338829 NM 012749q, Nucleolin Nucleolin xx 31338831 NM 012749 Nucleolin Nucleolin T=ABLE

Attorney.D~cket No.
44921=5113W0 Document No:1926271.2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence ClusterTitle - ' ID ID Acc. Code=
CVa. or , N0: RefSeq ID

No:

3138721 NM 012780tt Aryl hydrocarbon Aryl hydrocarbon receptor receptor nuclear nuclear translocatortranslocator 1 316420945NM 012875gg, Ribosomal proteinRibosomal protein L39 hh L39 319119106NM 012963ss Hi h mobility Hi h mobility roup 1 roup 1 319119107NM 012963cc High mobility High mobility group group 1 1 319119108NM 012963ii Hi h mobility High mobility group grow 1 1 319119109NM 012963ee Hi h mobility Hi h mobility roup 1 roup 1 319119110NM 012963jj High mobility Hi h mobility group roup 1 1 323124607NM 013075n Homeo box A1 Homeo box A1 32368898 NM 013087q, CD81 antigen (targetCD81 antigen (target tt of of antiproliferative antiproliferativeantibody 1) antibody 1) 325524867NM_013155t, Very low density Very low density lipoprotein mm lipoprotein receptor receptor 32583465 NM 013160ww ESTs, Moderately similar to MXI1 RAT MAX

interacting protein 1 (MXI1 protein) [R.norvegicusl 32701969 NM 013194k, Myosin, heavy Myosin, heavy polypeptide t, polypeptide 9, 9, non-muscle mm non-muscle 32701970 NM 013194t, Myosin, heavy Myosin, heavy polypeptide mm polypeptide 9, 9, non-muscle non-muscle 327818230NM 013221r ESTs, Moderately similar to 158311 HMG-box containing protein 1- rat [R.norvegicus]

32781495 NM_013221f, HMG-box containingHMG-box containing protein General,protein 1 1 qq, vv 330018139NM 017033General ESTs, Highly similar to PMRT

phosphoglucomutase (EC
5.4.2.2) 1- rat [R.norveqicus) 341720848NM 017343x Rat mRNA for myosin regulatory light chain (RLC) 341720849NM 017343r, ' Rat mRNA for myosin ff regulatory light chain (RLC) 3419537 NM 017351h, pre-alpha-inhibitor,pre-alpha-inhibitor, ss, heavy chain heavy chain 3 uu 342124428NM 017356nn neural visinin-likeneural visinin-like Ca2+-binding Ca2+-binding protein type protein type 3 3 342624732NM 019130 Insulin 2 Insulin 2 343220351NM 019142kk 5'-AMP-activated 5'-AMP-activated protein protein kinase kinase alpha-1 alpha-1 catalyticcatalytic subunit subunit 34492933 NM_019204e, ESTs, Highly similar m to BACE_RAT Beta-secretase precursor (Beta-site APP cleaving enzyme) (Beta-site amyloid precursor protein cleaving enzyme) (Aspartyl protease 2) (Asp 2) (ASP2) (Membrane-associated aspartic protease 2) (Memapsin-2) IR. orveai 1 348024883NM 019293e, carbonic anhydrasecarbonic anhydrase 5 k, 5 a TABLE

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Attorney Docket No.

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bocument No.1926271.2 SEQGLGC GenBankModel Known Gene.Name Unigene Sequence Cluster ' Title ID ID Acc. Code=
NO. or .

N0. RefSeq ID

No:

34821099 NM 019303y Cytochrome P450,Cytochrome P450, subfamily subfamily IIF, polypeptide IIF, polypeptide1 348316330NM 019331General,Paired basic Paired basic amino acid amino acid cleaving enzyme kk cleaving enzyme furin) (furin) ( 348316331NM 019331h, m, Paired basic Paired basic amino acid amino acid cleaving enzyme General,cleaving enzyme furin) (furin) ( mm 348616697NM 019349s SerinelthreonineSerine/threonine kinase kinase 2 2 348616698NM 019349a SerinelthreonineSerine/threonine kinase kinase 2 2 349023226NM 019360v, y, cytochrome oxidasecytochrome oxidase subunit gg, subunit Vlc Vlc hh 351320635NM 020099ee OB-receptor geneOB-receptor gene related related protein (OB-protein (OB-RGRP)RGRP) 351818724NM 021585b, ss Rattus norvegicus MHC
class Ib RT1.S3 (RT1.S3) mRNA, partial cds 352117340NM_021594General,ERM-binding phosphoproteinERM-binding phosphoprotein dd 352319173NM_021661n regulator of regulator of G-protein G-protein signallingsignalling 19 354720248NM 022205y Chemokine receptorChemokine receptor (LCR1) (LCR1) 354720249NM 022205tt Chemokine receptorChemokine receptor (LCR1) (LCR1) 356115932NM 022385q, x, ADP-ribosylationADP-ribosylation factor-like dd factor-like 1 356522412NM 022392f, p, growth response growth response protein s, protein (CL-6) (CL-6) General, ee, ft 356522413NM 022392a, f, growth response growth response protein p, protein (CL-6) (CL-6) General, ee, ff, qq 356522414NM_022392ff growth response growth response protein protein (CL-6) (CL-6) 356522415NM 022392p, General,growth response growth response protein protein (CL-6) (CL-6) ff 35681141 NM 022401f, n, plectin plectin r, z 35833902 NM 022516ss polypyrimidine polypyrimidine tract tract binding binding protein protein 35918097 NM 022536j, q, cyclophilin B cyclophilin B
w, x 35928597 NM 022538h, I phosphatidate phosphatidate phosphohydrolase type 2a phosphohydrolase type 2a 35928598 NM 022538d phosphatidate phosphatidate phosphohydrolase type 2a phosphohydrolase type 2a 359412422NM 022546bb Death-associatedDeath-associated like like kinase kinase 359512606NM 022547General,10-formyltetrahydrofolate10-formyltetrahydrofolate dehydrogenase vv dehydrogenase 359820820NM 022593a elongation factorelongation factor SIII
SIII p15 p15 subunit subunit 360912542NM_022647c, d, ESTs, Highly similar qq to 0506206A histone H2B Rattus norve icus R.norve icus TABLE

Attorney Docket No.

Document No:1926271~2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title.

ID 1D Acc. Code N0. or N0. RefSeq ID

No;

361024442NM 022667u, Matrin FlG Matrin F/G
General, rr 362224423NM 022703m, small glutamine-richsmall glutamine-rich r, tetratricopeptide repeat gg, hh, tetratricopeptide(TPR) containing protein pp repeat (TPR) (SGT) containing protein (SGT) 362324458NM 022706b GABA(A) receptor-associatedGABA(A) receptor-associated protein like 2 protein like 2 36316891 NM 022934t, DnaJ-like proteinDnaJ-like protein , hh 364020681NM 022952a clathrin-associatedclathrin-associated protein 17 protein 17 365815367NM 024149r ADP-ribosylation ADP-ribosylation factor factor 5 5 366021696NM 024152f, ADP-ribosylation ADP-ribosylation factor oo factor 6 6 368323386NM 024404gg, RNA binding proteinRNA binding protein hh p45AUF1 p45AUF1 368325682NM 024404c, RNA bindin proteinRNA binding protein w p45AUF1 p45AUF1 36941995 NM 030850d, betaine-homocysteinebetaine-homocysteine h, methyltransferase uu methyltransferase 369615186NM 030861g, N- N-acetylglucosaminyltransferase p, I

General,acetylglucosaminyltransferase rr I

369615187NM 030861n, N- N-acetylglucosaminyltransferase z, I

General,acetylglucosaminyltransferase rr I

369615188NM 030861d, N- N-acetylglucosaminyltransferase s, I

Generalacetylglucosaminyltransferase I

369821800NM_030987r, Guanine nucleotide-bindingGuanine nucleotide-binding w, protein beta 1 z protein beta 1 369821801NM 030987gg, Guanine nucleotide-bindingGuanine nucleotide-binding hh protein beta 1 protein beta 1 369821806NM 030987s, Guanine nucleotide-bindingGuanine nucleotide-binding a protein beta 1 protein beta 1 370817302NM 031008tt alpha-c large alpha-c large chain chain of the of the protein complex protein complex AP-2 associated with AP-2 clathrin associated with clathrin 37111538 NM 031012k, alanyl (membrane)alanyl (membrane) aminopeptidase mm aminopeptidase 37111540 NM_031012n, alanyl (membrane)alanyl (membrane) aminopeptidase dd, ee aminopeptidase 371616560NM 031020t p38 mitogen activatedp38 mitogen activated protein protein kinase kinase 371616562NM_031020I, p38 mitogen activatedp38 mitogen activated p, protein protein kinase ss, uu kinase 371616564NM_031020k, p38 mitogen activatedp38 mitogen activated I protein protein kinase kinase 371616565NM 031020t p38 mitogen activatedp38 mitogen activated protein protein kinase kinase 371916210NM 031026r, LIC-2 dynein lightLIC-2 dynein light intermediate w intermediate chain 53/55 chain 53155 372915137NM 031051w, macrophage migrationmacrophage migration y, inhibitory inhibitory factor ee, tt factor TABLE

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Document No:1926271.2 SEQ GLGC GenBank Model Knowri Gene NameUnigene=Sequence Cluster Title ID ID:NO.Acc. Code or N0. RefSeq ID

No:

373011899NM 031052rr mitochondria) mitochondria) intermediate intermediate peptidase peptidase 37396348 NM 031077mm PCTAIRE-1 proteinCTAIRE-1 protein kinase, kinase, P alternatively alternatively spliced spliced 374217173NM 031090u, ras-related proteinras-related protein cc 374720812NM 031100y, ribosomal proteinribosomal protein L10 ee L10 375220807NM 031106h ribosomal proteinribosomal protein L37 375510878NM 031110, Generalribosomal proteinribosomal protein S11 j S11 376016671NM 031125tt syntaxin 4 syntaxin 4 376515487NM 031137q, tripeptidylpeptidasetripeptidylpeptidase ww II II

376515489NM 031137bb, ripeptidylpeptidasetripeptidylpeptidase II, II II
ww t 376617378NM 031138q ubiquitin conjugatingubiquitin conjugating enzyme enzyme 376617379NM 031138Generalubiquitin conjugatinubiquitin conju ating enzyme enzyme 376923097NM 031145h, calcium- and calcium- and integrin-binding bb integrin-bindingprotein protein 3772164 NM 031151v malate dehydrogenasemalate dehydrogenase mitochondria) mitochondria) 3773238 NM 031152ee RAB11a, member RAB11a, member RAS oncogene RAS family oncogene family 3773240 NM 031152x RAB11a, member RAB11a, member RAS oncogene RAS family oncogene family 377715277NM 031237n ubiquitin-conjugatingubiquitin-conjugating enzyme enzyme E2D 3 (homologous(homologous to yeast to yeast UBC4/5) UBC415) 378715360NM 031335p, polymerase II EST, Moderately similar v D to RPB6_RAT
NA-directed RNA polymerase ll 14.4 kDa polypeptide (RPB6) (RPB14.4) f R.norveaicush polvmerase II

38111822 NM 031553c, CCAAT binding CCAAT binding transcription ww transcription factor of CBF-f actor of CBF-B/NFY-BBINFY-B

383020840NM 031604d ATPase, H+ transporting,ATPase, H+ transporting, lysosomal l ysosomal (vacuolarvacuolar proton pump) proton ( noncatalytic pump) noncatalyticaccessory protein 1 accessory (1101160 kDa) protein 1 (1101160 kDa) 383020841NM 031604bb ATPase, H+ transporting,ATPase, H+ transporting, lysosomal l ysosomal (vacuolarvacuolar proton pump) proton ( noncatalytic p ump) noncatalyticaccessory protein 1 accessory (1101160 kDa) p rotein 1 (1101160 kDa) 388520752NM 031763i p latelet-activatingplatelet-activating i factor factor acetylhydrolase a cetylhydrolase eta subunit (PAF-AH
beta subunit beta) b ( PAF-AH beta) 388520753NM 031763, General,latelet-activatinglatelet-activating factor I p factor p acetylhydrolase d d, cetylhydrolase eta subunit (PAF-AH
pp beta subunit beta) a b ( PAF-AH beta) 389216178NM_031785i ATPase, H+ transporting,ATPase, H+ transporting, i lysosomal l ysosomal (vacuolarvacuolar proton pump), proton ( subunit 1 p ump), subunit 38931169 NM 031789, w, NF-E2-related NF-E2-related factor d bb, factor 2 2 II

38931170 NM 031789, II NF-E2-related NF-E2-related factor . d factor 2 2 TABLE

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Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID' ID Acc. Code N0. or N0. RefSeq ID

No.

390810267NM 031838h ribosomal proteinribosomal protein S2 390810269NM 031838w ribosomal proteinribosomal protein S2 390910949NM 031839rr arachidonic acid arachidonic acid epoxy epoxy enase enase 391422301NM 031967d development-relateddevelopment-related protein protein 392619768NM 031986pp syntenin syntenin 39331573 NM 032083bb, chimerin (chimaerin)chimerin (chimaerin) ss 1 1 39471410 NM 052798o zinc finger proteinzinc finger protein 397823811NM 053436ww staufen (Drosophila,staufen (Drosophila, RNA- RNA-binding protein) binding protein) 398014670NM 053439ee RAN, member RAS RAN, member RAS oncogene oncogene family family 401020902NM 053593cc cyclin-dependent cyclin-dependent kinase kinase 4 4 402620951NM 053651nn NK2 transcriptionNK2 transcription factor factor related, related, locus 5 locus 5 (Drosophila)(Drosophila) 403215735NM 053665n, A kinase (PRKA) A kinase (PRKA) anchor ee anchor protein protein 1 403215738NM_053665cc A kinase (PRKA) A kinase (PRKA) anchor anchor protein protein 1 404310909NM 053756o ATP synthase, ATP synthase, H+ transporting, H+ transporting, mitochondria) mitochondria) FO complex, FO complex, subunit c (subunit subunit c (subunit9) isoform 3 9) isoform 3 404714015NM_053770n, Arg/Abl-interactingArglAbl-interacting w protein protein ArgBP2 ArgBP2 404714016NM_053770xx Arg/Abl-interactingArg/Abl-interacting protein protein ArgBP2 ArgBP2 40506290 NM 053795tt kinase D-interactingkinase D-interacting substance substance of 220 kDa of 220 kDa 405516921NM 053806gg, ESTs, Weakly similar hh, to S18140 jj hypoxanthine phosphoribosyltransferase EC 2.4.2.8) - rat fR.norvegicusl 405519827NM 0538060o ESTs, Weakly similar to OZF_RAT Zinc finger protein OZF (POZF-1) [R.norvegicus]

405920421NM 053821a, v-ral simian leukemiav-ral simian leukemia vv viral viral oncogene oncogene homolog homolog B (ras related) B (ras related) 40606110 NM 053824x casein kinase casein kinase II, alpha II, alpha 1 1 polypeptide polypeptide 40611601 NM 053826t pyruvate dehydrogenasepyruvate dehydrogenase kinase, isoenzyme kinase, isoenzyme1 40701570 NM 053857k, eukaryotic translationeukaryotic translation I, initiation initiation factor 4E
m, Generalfactor 4E bindingbinding protein 1 protein 1 40701571 NM 053857I, eukaryotic translationeukaryotic translation m, initiation initiation factor 4E
q, General,factor 4E bindingbinding protein 1 protein 1 dd 407118358NM 053864x valosin-containingvalosin-containing protein protein 40761453 NM 053887ff mitogen activatedmitogen activated protein protein kinase kinase kinase kinase kinase kinase 1 TABLE

Attorney Docket No.
44921=5113W0 Document No19262712 SEQGLGC GenBankModel Known Gene Name lJnigene Sequence Cluster Title ID ID Acc. Code N0. or N0. RefSeq ID

No, 40761454 NM 053887gg, mitogen activatedmitogen activated protein hh protein kinase kinase kinase kinase kinase kinase 1 40771660 NM_053891bb, cyclin-dependent cyclin-dependent kinase II, kinase 5, 5, regulatory ww regulatory subunitsubunit 1 (p35) 1 (p35) 407816147NM 053892y phospholipase phospholipase A2, group A2, group VI VI

409016190NM_053961o ESTs, Weakly similar to F Chain F, 2-Enoyl-Coa Hydratase, Data Collected At 100 K, Ph 6.5 fR.norveqicusl 409116546NM 0539650, solute carrier solute carrier family ii family 25 25 (carnitinelacylcarnitine(carnitine/acylcarnitine translocase), member translocase), 20 member 20 409116547NM 053965o solute carrier solute carrier family family 25 25 (carnitine/acylcarn'itine(carnitine/acylcarnitine translocase), member translocase), 20 member 20 409417279NM 053977t, cadherin 17 cadherin 17 mm 409417280NM 053977mm cadherin 17 cadherin 17 409515325NM 053979j ADP-ribosylation ADP-ribosylation factor-like factor-like 5 5 410117739NM_053995h, 3-hydroxybutyrate3-hydroxybutyrate dehydrogenase General, (heart, qq dehydrogenase mitochondrial) (heart, mitochondrial) 410916043NM 057100jj ESTs, Highly similar to growth arrest specific 6 [Rattus norvegicusj [R.norvegicusj 411017709NM 057101y Tenascin X Tenascin X

411623310NM 057119w splicing factor, splicing factor, argininelserine-rich argininelserine-rich (transformer(transformer 2 Drosophila 2 Drosophila homology 10 homology 10 412315839NM 057143bb, fertility proteinfertility protein SP22 kk SP22 412718122NM 057208ee tropomyosin 3, tropomyosin 3, gamma gamma 41293831 NM 057213e, ATPase, H+ transporting,ATPase, H+ transporting, General, lysosomal cc, lysosomal (vacuolar(vacuolar proton pump), qq proton beta 56/58 kDa, pump), beta 56/58isoform 2 kDa, isoform 41449952 NM 080902xx hypoxia induced hypoxia induced ene gene 1 1 415418810NM 130430w, mitochondrial mitochondrial H+-ATP
ss H+-ATP synthase synthase alpha alpha subunit subunit 41607864 NM_130823c, ATPase, H+ transporting,ATPase, H+ transporting, gg, lysosomal hh, oo, lysosomal (vacuolar(vacuolar proton pump) qq proton 16 kDa pump) 16 kDa 4170505 NM 133309ss calpain 8 calpain 8 4173252 NM 133323d zinc fin er proteinzinc finger protein 418010660NM 133423r, splicing factor splicing factor YT521-B
w YT521-B

418116736NM 133427j flavohemoprotein flavohemoprotein b5+b5R
b5+b5R

41825686 NM 133428dd histidine-rich histidine-rich glycoprotein lycoprotein 41861791 NM_133541ww general transcriptiongeneral transcription factor III C factor III C 1 41891558 NM 133554e, solute carrier solute carrier family pp family 17 vesicular17 vesicular glutamate glutamate transporter),transporter), member member 1 TABLE

Attot'ney Docket No.

Document No.1926271.2 SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster - Title lD-ID Acc. Code N0. or N0. RefSeq ID
'-No.

41891559 NM_133554a solute carrier solute carrier family family 17 vesicular17 vesicular glutamate glutamate transporter),transporter), member member 1 4191745 NM 133567cc centaurin, alpha centaurin, alpha 1 419316993NM_133583a, N-myc downstream-regulatedN-myc downstream-regulated d, gene 2 m gene 2 419315029NM 1335830o N-myc downstream-regulatedN-myc downstream-regulated gene 2 gene 2 41941164 NM 133584g phosphodiesterasephosphodiesterase 5A, 5A, cGMP- cGMP-specific specific 41954312 NM_133586y, carboxylesterase carboxylesterase 2 (intestine, rr, 2 (intestine, liver) ww liver) 419619822NM_133590x Ras-related GTP-bindingRas-related GTP-binding protein protein Rab29 Rab29 41971308 NM_133591a rabphilin 3A-likerabphilin 3A-like (without (without C2 C2 domains) domains) 420225200NM 133610cc potassium voltage-gatedpotassium voltage-gated channel, subfamily channel, subfamilyH (eag-related), member H (eag- 5 related), member 42138692 NM 134387a diacetyI/L-xylulosediacetyI/L-xylulose reductase reductase 42153074 NM 134399kk Mk1 protein Mk1 protein 421723321NM_134407ss aldo-keto reductasealdo-keto reductase family 7, family 7, member A2 member A2 (aflatoxin(aflatoxin aldehyde aldehyde reductase) reductase) 42241440 NM 134456a SH2-B PH domain SH2-B PH domain containing containing signaling signalin mediatormediator 1 42251373 NM_134468n calcium/calmodulin-dependentcalcium/calmodulin-dependent protein protein kinase kinase I
I

422961 NM_138510a 20 alpha-hydroxysteroid20 alpha-hydroxysteroid dehydrogenase dehydrogenase 42355283 NM 138535xx glutamate receptorglutamate receptor interacting interacting protein 2 protein 2 423716922NM 138549x synaptic glycoproteinsynaptic lycoprotein 423725479NM 138549e, synaptic glycoproteinsynaptic glycoprotein x SC2 SC2 4247891 NM 138863x, dithiolethione-inducibledithiolethione-inducible bb gene-1 gene-1 42545655 NM 138885f, golgi-associated golgi-associated protein q, protein GCP360 ff 42545656 NM 138885d, golgi-associated golgi-associated protein q protein GCP360 42553015 NM 138895h, polyubiquitin polyubiquitin w 42567636 NM_138896s rotein carrying rotein carrying the the RING-H2 RING-H2 sequence motif sequence motif 425917115NM_138905I, ER transmembrane ER transmembrane protein m, protein Dri Dri 42 General,42 kk 426121915NM 138910dd defender against defender against cell cell death 1 death 1 426121916NM 138910II defender a ainst defender a ainst cell cell death 1 death 1 4269734 NM_139094d CTD-binding SR-likeCTD-binding SR-like protein rA8 protein rA8 ~~n TABLE

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Document No.1926271:2 SEQ GLGGGenBank Model-Known Gene Name Unigene Sequence Cluster Title ID D Acc. Coded - N0. or F -I

N0. Ref$eq ID ' . -No. ~ . .
~ .

4270 7119NM 139098p RNA helicase RNA helicase 4277 5023NM 139113n, nuclear receptornuclear receptor subfamily 1 z, subfamily 2, 2, group F, General,group F, member member 6 kk, pp 4278 15239NM_139114h, ibosomal proteinribosomal protein L15 I, L15 v, r General 4281 22970NM 139254c, ubulin, beta tubulin, beta 3 d, 3 a t 4285 1962NM 139329i CCA2 protein CCA2 protein i 4287 4949NM_139338s Na+IPi-cotransporterRattus norvegicus mRNA
type Ilc for Na+IPi-cotransporter type I
Ic, complete cds 4290 15703NM_144750f, LysophospholipaseRattus norvegicus mRNA
n, for gg, hh, Lysophospholipase, complete pp cds 4291 11493NM_144755f, ESTs, Weakly similar q, to A53621 AMP-z, dd, oo, activated protein kinase qq - rat [R.norve icus]

4291 11494NM_144755f, ESTs, Weakly similar I, to A53621 AMP-q;
v, z, General, activated protein kinase - rat [R.norvegicus]

dd, 4292 1623NM_144757s Cys21His2 zinc Rattus norvegicus Cys21His2 finger protein zinc finger (rKr1) protein (rKr1) mRNA, complete cds 4296 1949NM_145092f, Rattus norvegicus lamina I, associated ii, nn polypeptide 1C (LAP1C) mRNA, complete cds, Rattus norvegicus lamina-associated polypeptide 1 C (LAP1 C) mRNA, complete cds 4298 1562NM_145097j, Rattus norvegicus kallistatin o, mRNA, x, uu complete cds 4302 16343NM_145724uu Rattus norvegicus zinc finger protein Y1 (RLZF-Y) mRNA, complete cds 4302 16345NM_145724j, Rattus norvegicus zinc uu finger protein Y1 (RLZF-Y) mRNA, complete cds 4303 22975NM 145778jj Rattus norvegicus mRNA
for tubulin, complete cds 4338 18647S69316 q, ESTs, Weakly similar dd to HS9B_RAT Heat shock protein HSP 90-beta (HSP 84) (R.norvegicusl 4345 1460S76054 t, ESTs, Highly similar General, to K2C8_RAT Keratin, ll, type II cytoskeletal ww 8 (Cytokeratin 8) (Cytokeratin endo A) (R.norveqicusl 4348 17626S78556 qq ESTs, Highly similar to 156581 dnaK-type molecular chaperone grp75 precursor - rat [R.norveqicusl 4354 110 001145 I, Rattus norvegicus clone General, 15 polymeric kk immunoglobulin receptor mRNA, 3'UTR

microsatellite repeats 4356 347 001914 s, A kinase anchor A kinase anchor protein tt protein 8 8 4357 111 002506 b, , Rattus norvegicus clone General 15 polymeric kk, immunoglobulin receptor vv mRNA, 3'UTR

microsatellite re eats TABLE

Attorney Docket No.

Document No.192627~1~3 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster Title ID D Acc.'or Code I N0.

NO. RefSeq ID

No:

43582010005675 y, Rattus norvegicus Sprague-Dawley vv fibrinogen B beta chain mRNA, complete cds 4370399 031668 ww, E2F transcriptionE2F transcription factor xx factor 5 5 43751357039572 mm phosphatidylinositol4-kinasephosphatidylinositol4-kinase 437618038039943 x Rattus norvegicus cytochrome pseudogene (CYP2J3P1) mRNA

438615516068544 b Rattus norvegicus cyclophilin D mRNA, nuclear gene encoding mitochondria) protein, complete cds 43981153089280 h, Rattus norvegicus oxidative n 17 beta hydroxysteroid dehydrogenase type 6 mRNA, complete cds 44009841094856 w paraoxonase 1 paraoxonase 1 44009842094856 pp paraoxonase 1 paraoxonase 1 441419584X13905 General,, ESTs, Moderately similar to TVRTYP GTP-mm binding protein Rab1 - rat [R.norve icus]

444018924X58830 g ~ Bone morphogeneticBone morphogenetic protein protein 6 6 44464441X62146 ee ESTs, Highly similar to RL11 HUMAN 60S

ribosomal protein L11 [R.norve icus]

444713646X62166 I, ESTs, Highly similar m, to RL3_RAT 60S
s, z, General, RIBOSOMAL PROTEIN L3 (L4) bb, [R.norvegicus]
cc, ii, 4q, rr 444815387X62482 h, ESTs, Highly similar gg, to R3RT25 ribosomal hh protein S25, cytosolic [validated] - rat [R.norvegicus]

445520844X65228 y, ESTs, Highly similar II to R3RT3A ribosomal protein L23a, cytosolic [validated] - rat [R.norvegicusl 446423302X78949 ff, prolyl 4-hydroxylaseprolyl 4-hydroxylase xx alpha alpha subunit subunit 447318031X94551 y laminin, gamma laminin, amma 1 250 10157AA819527rr HHs:amyloid beta ESTs, Highly similar (A4) to S23094 beta-amyloid precursor proteinprotein precursor -(protease rat [R.norvegicus]

nexin-II, Alzheimer disease) 235210156AI178039bb HHs:amyloid beta ESTs, Highly similar (A4) to S23094 beta-amyloid precursor proteinprotein precursor -(protease rat [R.norvegicus]

nexin-II, Alzheimer disease) 441010154X07648 m HHs:amyloid beta ESTs, Highly similar (A4) to S23094 beta-amyloid precursor proteinprotein precursor -(protease rat [R.norvegicus]

nexin-II, Alzheimer disease) 442420872X51707 h ribosomal proteinESTs, Highly similar S19 to R3RT19 ribosomal protein S19, cytosolic [validated] - rat R.norve icus 17~
TABLE

Attorney Docket No:'44921-5113W0 Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID D Aocor Code I NO..

NO: RefSeq ID
;

No.

221818498AI172452m, ESTs, Weakly similar ii, to COXJ RAT
II, uu Cytochrome c oxidase polypeptide Vlla-l iverlheart, mitochondria) precursor (Cytochrome c oxidase subunit Vlla-L) IR.norveaicusl 232416175A1177145w ESTs, Weakly similar to CAG7_RAT ALPHA-N-ACETYLGALACTOSAMINIDE
ALPHA-2,6 SIALYLTRANSFERASE (ST6GALNACI11) (STY) fR.norveaicusl 239812033AI179066ee ESTs, Highly similar to SL52_RAT
-SODIUMIGLUCOSE COTRANSPORTER

(NA(+)/GLUCOSE COTRANSPORTER
2) (LOW AFFINITY SODIUM-GLUCOSE

COTRANSPORTER) (R.norveaicusl 255620055AI230762rr ESTs, Weakly similar to A53742 calponin, acidic - rat [R.norve icusl 260718497AI232307c ESTs, Weakly similar to COXJ_RAT

Cytochrome c oxidase polypeptide Vlla-liverlheart, mitochondria) precursor (Cytochrome c oxidase subunit Vlla-L) (R,norveaicusl 350122726NM 019383r ATP synthase subunitATP synthase subunit d d 36082250 NM_022643c, ESTs, Highly similar d, to 0506206A histone m, cc, kk, H2B [Rattus norvegicus]
qq, [R.norvegicus]
vv 375619161NM 031111j, ribosomal proteinribosomal protein S21 ee S21 409715468NM 053982h, ribosomal proteinribosomal protein S15a g, S15a hh 409719544NM_053982h, EST, Moderately similar I, to JC2234 qq ribosomal protein S15a, cytosolic [validated]

rat [R.norveaicusl 42999845 NM_145672m ESTs, Weakly similar to JN0572 neutrophil chemo-attractant Gro protein precursor -rat [R.norvegicusl 442816716X53054 c Rat mRNA for RT1.D beta chain 488 4339 AA875121d CCAAT binding CCAAT binding factor factor of CBF- of CBF-CINFY-C

C/NFY-C

130417353A1008020o Malic enzyme 1, Malic enzyme 1, soluble soluble 16818330 A1059434g peroxisome proliferativeperoxisome proliferative activated receptor, activated receptor,gamma, coactivator 1 gamma, coactivator 1 182918838AI101102ee Prosaposin (sulfatedProsaposin (sulfated glycoprotein, glycoprotein, sphingolipid hydrolase sphingolipid activator) hydrolase activator) 189011486AI103162j Glycoprotein-4-beta-Glycoprotein-4-beta-galactosyltransferase galactosyltransferase 21126479 AI169690h, Fibrinogen, gammaFibrinogen, gamma polypeptide I, polypeptide q 245521296AI227641j Myosin, light Myosin, light polypeptide polypeptide 2, 2, alkali;

alkali ventricularventricular skeletal skeletal slow slow TABLE

Afforney Dockef No44921=5118W0 t)ocument No.
X926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence-Clustex Title ID l) Acc. Code _- N0. or I

N0. RefSe_q iD
' No.

255213618AI230724kk, SAC1 (supressor SAC1 (supressor of actin tt of actin mutations 1, mutations 1, homology-likehomology-like (S. cerevisiae) (S.

cerevisiae) 272421414AI235842x Superoxide dismutaseSuperoxide dismutase 2, 2, mitochondria) mitochondria) 2961790 L10073 g 5-hydroxytryptamine5-hydroxytryptamine (serotonin) (serotonin) receptor receptor 5B, ER01-like (S.

cerevisiae), Lysosomal associated membrane protein 1 (120 kDa), apoptotic protease activating factor 1, ceroid-lipofuscinosis, neuronal 2, cysteine-sulfinate rianarhnxvlasP

296916119L16532 q 2',3'- Cyclic 2',3'- Cyclic nucleotide nucleotide 3'- 3'-phosphodiesterase phosphodiesterase 299221053M15481 qq Insulin-like growthInsulin-like rowth factor factor I I

_ 6477 NM_012559dd Fibrinogen, gammaFibrinogen, gamma polypeptide 3071 polypeptide 3073619 NM 012565h, Glucokinase Glucokinase r, kk 307620744NM 012571e, Glutamic-oxaloaceticGlutamic-oxaloacetic II, transaminase 1, oo transaminase 1, soluble (aspartate aminotransferase, soluble (aspartate aminotransferase,cytosolic) see also D1Mgh12 cvtosolic) see also D1Mah12 308718746NM 012600gg, Malic enzyme 1, Malic enzyme 1, soluble hh soluble 30909174 NM 012612g Natriuretic peptideNatriuretic peptide precursor A, precursor A, (pronatriodilatin,(pronatriodilatin, also also Anf, Pnd) Anf, Pnd) 310216198NM 012663kk, Vesicle-associatedVesicle-associated membrane tt membrane protein protein (synaptobrevin(synaptobrevin 2) 2) 310216199NM 012663bb, Vesicle-associatedVesicle-associated membrane kk membrane protein protein (synaptobrevin(synaptobrevin 2) 2) 310216200NM_012663ii Vesicle-associatedVesicle-associated membrane membrane protein protein (synaptobrevin(synaptobrevin 2) 2) 3119503 NM_012704k Rat kidney prostaglandinRat kidney prostaglandin EP3 EP3 receptor receptor 312124545NM 012713s Protein kinase Protein kinase C beta C beta 31311260 NM_012743d Hepatocyte nuclearHepatocyte nuclear factor factor 3 3 beta beta 315411138NM_012839jj Cytochrome C, Cytochrome C, expressed expressed in in somatic tissues somatic tissues 3162395 NM_012864v Matrix metalloproteinaseMatrix metalloproteinase 7 7 (matrilysin) (matrilysin) 31634338 NM 012866II CCAAT binding CCAAT binding factor factor of CBF- of CBF-CINFY-C

CINFY-C

31881720 NM 012943cc Distal-less homeoboxDistal-less homeobox 320519391NM 012998t, Protein disulfideProtein disulfide isomerase y, isomerase (Prolyl 4-mm (Prolyl 4-hydroxylase,hydroxylase, beta polypeptide) beta of a tide TABLE

Attorney Docket Nor 44921=5113W0 Document No.19262713 SEQ GLGC GenBankModel Known Gene Name Unigene-Sequence ClusferTitle ID ID.NO.Ace. Code or N0. RefSeq ID

No.

320519392NM 012998j, Protein disulfideProtein disulfide isomerase gg, isomerase (Prolyl 4-hh (Prolyl 4-hydroxylase,hydroxylase, beta polypeptide) beta polypeptide) 320519393NM 012998gg, Protein disulfideProtein disulfide hh, isomerase somerase (Prolyl 4-II i (Prolyl 4-hydroxylase,hydroxylase, beta polypeptide) beta polypeptide) 320923543NM 013013w, Prosaposin (sulfatedProsaposin (sulfated y glycoprotein, glycoprotein, sphingolipid hydrolase sphingolipid activator) hydrolase activator) 320923544NM 013013c Prosaposin (sulfatedProsaposin (sulfated glycoprotein, glycoprotein, sphingolipid hydrolase sphingolipid activator) hydrolase activator) 3211208 NM 013025vv Macrophage inflammatoryMacrophage inflammatory protein 1 alpha protein 1 alpha (Small inducible cytokine (Small inducible A3) cytokine A3) 32331583 NM 013079a, Asparagine synthetaseAsparagine synthetase m, s, General, dd 3306910 NM 017059bb, Bcl2-associated Bcl2-associated X protein ss X protein 3306911 NM 017059ss Bcl2-associated Bcl2-associated X protein X protein 3306912 NM 017059qq Bcl2-associated Bcl2-associated X protein X protein 333620859NM 017144cc Troponin I Troponin I

33571541 NM 017193ee kynurenine aminotransferasekynurenine aminotransferase II II

336413938NM 017212g microtubule-associatedmicrotubule-associated protein protein tau tau 339812347NM 017290j ATPase, Ca++ transporting,ATPase, Ca++ transporting, j cardiac muscle, cardiac muscle, slow twitch 2 slow twitch 2 339812348NM 017290f, ATPase, Ca++ transporting,ATPase, Ca++ transporting, f pp cardiac muscle, cardiac muscle, slow twitch 2 slow twitch 2 339812349NM 017290 ATPase, Ca++ transporting,ATPase, Ca++ transporting, I cardiac muscle, cardiac muscle, slow twitch 2 slow twitch 2 34595661 NM 019241a gap junction membranegap junction membrane channel channel protein beta protein beta 5 5 34921070 NM 019368, q, blocked early blocked early in transport f z in transport 1 1 omolog h homolo (S.cerevisiaeS.cerevisiae) - like - like ( 349715680NM 019376i, 14-3-3 protein 4-3-3 protein gamma-subtype i II gamma-subtype 350815911NM 019907ww postsynaptic proteinpostsynaptic protein Cript Cript 351615335NM_021264General,ribosomal proteinibosomal protein L35a L35a r kk 354023151NM_022005a FXYD domain-containingFXYD domain-containing ion ion transport transport regulatoregulator 6 6 r 358525681NM_022519 serine (or cysteine)erine (or cysteine) r proteinase s proteinase inhibitor, i nhibitor, Glade lade A (alpha-1 antiproteinase, A (alpha-1 G antitrypsin), antiproteinase, member 1 antitrypsin), member 1 35854212 NM 022519a serine (or cysteine)erine (or proteinase s ysteine) proteinase c inhibitor, i nhibitor, Glade lade A (alpha-1 antiproteinase, A (alpha-1 G antitrypsin), antiproteinase, member 1 antitrypsin), member 1 TABLE

Aftorney Docket Nor Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster ' Title ID D Accor Code I N0.

NO RefSeq=ID

No.' 35854213 NM 022519ee serine (or cysteine)serine (or cysteine) proteinase proteinase inhibitor, i nhibitor, Glade Glade A (alpha-1 antiproteinase, A (alpha-1 antitrypsin), antiproteinase, member 1 antitrypsin), member 1 35905666 NM 022529r mitochondrial mitochondrial ribosomal ribosomal proteinprotein L23 362658 NM 022715nn major vault proteinmajor vault protein 363618098NM 0229470o suppressor of suppressor of K+ transport K+ transport defect 3 defect 3 364215755NM_022960k neutral solute neutral solute channel channel aquaporin 9 aquaporin 9 3703248 NM_030998gg, anti-Mullerian anti-Mullerian hormone hh hormone type type 2 receptor receptor 372015805NM 031028g gamma-aminobutyricgamma-aminobutyric acid acid (GABA) B

(GAGA) B receptor,receptor, 1 372015807NM 031028s gamma-aminobutyricgamma-aminobutyric acid acid (GABA) B

(GABA) B receptor,receptor,1 379924710NM 031512vv Interleukin 1 Interleukin 1 beta beta 38074010 NM 031543e, Cytochrome P450, Cytochrome P450, subfamily r subfamily 2e1 (ethanol-2e1 (ethanol-inducible)inducible) 38074011 NM 031543j, Cytochrome P450, Cytochrome P450, subfamily w subfamily 2e1 (ethanol-2e1 (ethanol-inducible)inducible) 38074012 NM 031543e, Cytochrome P450, Cytochrome P450, subfamily rr subfamily 2e1 (ethanol-2e1 (ethanol-inducible)inducible 38181920 NM 031576c, P450 (cytochrome)P450 (cytochrome) oxidoreductase cc oxidoreductase 3819939 NM 031577z growth hormone growth hormone releasing releasing hormone hormone 382714542NM_031596a squamous cell squamous cell carcinoma carcinoma antigen antigen recognizedrecognized by T-cells by T-cells 382714543NM 031596jj squamous cell squamous cell carcinoma carcinoma antigen anti en reco nizedrecognized by T-cells by T-cells 3843906 NM 031633ss forkhead box M1 forkhead box M1 38489427 NM 031656c, syntaxin-like syntaxin-like protein kk protein 3135 3135 38489428 NM 031656p syntaxin-like syntaxin-like protein protein 3135 3135 385020467NM 031662r, calcium/calmodulin-dependentcalcium/calmodulin-dependent ee protein protein kinase kinase kinase 1, alpha kinase 1, alpha 385223656NM 031673bb calpain 10 calpain 10 393617933NM_032615m, membrane interactingmembrane interacting o, protein of protein of RGS16 z, General,RGS16 dd, rr 393617934NM 0326150, membrane interactingmembrane interacting z, protein of protein of RGS16 General,RGS16 nn 393617935NM 0326150, membrane interactingmembrane interacting s protein of protein of RGS16 399114380NM 053536tt Kruppel-like factorKruppel-like factor 15 (kidney) 15 (kidney) 402213005NM 053623a fatty acid-Coenzymefatty acid-Coenzyme A ligase, A ligase, long chain Ion chain 4 TABLE

Attorney Docket No:
44921-5~131N0 Document No.19262712 SEO.GLGC GenBankModel fnown Gene Name Unigene Sequence Cluster I Title ID D Accor Code - N0.
I

N0~ RefSeq ID

No. _ _ 40523677 NM 053798x SAC1 (supressor SAC1 (supressor of actin of actin mutations 1, mutations 1, homology-likehomology-like (S. cerevisiae) (S.

cerevisiae) 405816311NM 053818 glycine transporterlycine transporter 1 j 1 406620868NM 053843y, Fc receptor, I Fc receptor, IgG, low xx G, low affinity affinity III
III

4137132 NM 080782I, cyclin-dependent cyclin-dependent kinase I tt kinase inhibitor 1A (P21) i nhibitor 1A (P21) 4137133 NM 080782p, cyclin-dependent cyclin-dependent kinase II, kinase inhibitor 1A (P21) ss i nhibitor 1A (P21) 416417560NM_133283e, eukaryotic translationmitogen activated protein t, elongation kinase kinase 2 mm factor 2, mitogen activated protein kinase kinase 2 416417564NM_133283ff mitogen activatedmitogen activated protein protein kinase kinase kinase 2 kinase 2 416421848NM_133283v, mitogen activatedmitogen activated protein y protein kinase kinase kinase 2 kinase 2 416421849NM_133283ff mitogen activatedmitogen activated protein protein kinase kinase kinase 2 kinase 2 417610195NM_133383w retinoid-inducibleretinoid-inducible serine serine caroboxypetidase caroboxypetidase 43241937 846934 k amelogenin amelogenin 440621054X06107 g, Insulin-like rowthInsulin-like growth v factor I factor I

60 2040 AA799700w HMmaelenophosphateESTs, Highly similar to SPS2_MOUSE

synthetase 2 Selenide,water dikinase 2 (Selenophosphate synthetase 2) (Selenium donor protein 2) fM.musculusl 209 12160AA8184120, cytochrome P450, cytochrome P450, 2b19 qq 2b19 495 10936AA875146f HMm:ubiquitin ESTs, Highly similar conjugating to ubiquitin conjugating enzyme 6 enzyme 6; Ubc6p homolog [Mus musculus]

~M.musculusl 590 2107 AA892006a HMm:ATPase, H+ ESTs, Highly similar transporting, to VAA1 MOUSE

lysosomal 70kD, Vacuolar ATP synthase V1 subunit A, catalytic subunit A, isoform 1 ubiquitous isoform (V-ATPase A subunit 1) (Vacuolar proton pump alpha subunit 1) (V-ATPase 69 kDa subunit 1) fM.musculusl 815 3959 AA901338z HMm:eukaryotic ESTs, Highly similar translation to eukaryotic initiation factortranslation initiation 2, subunit 2 factor 2, subunit 2 (beta, (beta, 38kDa) 38kDa) fMus musculus) [M.musculusl 10962702 AA957307I, HMmaeryl-aminoacyl-tRNAESTs, Highly similar I, to A41019 serine--tRNA
p, z, General,synthetase 1 ligase (EC 6.1.1.11) - mouse (fragment) dd, [M.musculus]
ii, pp, aa, rr 15172108 A1029960ee HMm:ATPase, H+ ESTs, Highly similar transporting, to VAA1 MOUSE

lysosomal 70kD, Vacuolar ATP synthase V1 subunit A, catalytic subunit A, isoform 1 ubiquitous isoform (V-ATPase A subunit 1) (Vacuolar proton pump alpha subunit 1) (V-ATPase 9 kD subuni 1 M.musculu TABLE

:
Attorney Docket No~

Document No.19262712 $EC GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title fD ID Acc. Code N0. or :

N0. RefSeq ID

NQ.:

208917914AI169159I HMm:ATPase, H+ ESTs, Moderately similar I transporting, to VATE_MOUSE

' lysosomal 31 kDa,Vacuolar ATP synthase V1 subunit E subunit E (V-ATPase E subunit) (Vacuolar proton pump E

subunit) (V-ATPase 31 kDa subunit) (P31) [ M.musculusl 231215588AI176916dd HMm:phosphomannomutaseESTs, Highly similar 1 to PMM1 MOUSE

Phosphomannomutase 1 (PMM 1) [ M.musculusl 294812156K00996 o cytochrome P450, cytochrome P450, 2b19 2b19 295012157K01721 o cytochrome P450, cytochrome P450, 2b19 2b19 296823897L15011 g cortexin cortexin 31786107 NM 012915b, ATPase inhibitor ATPase inhibitor (rat General,(rat mitochondria) IF1 gg, mitochondria) protein) hh, IF1 protein) uu 31786108 NM 012915b, ATPase inhibitor ATPase inhibitor (rat General,(rat mitochondria) IF1 uu mitochondria) protein) IF1 protein) 31786109 NM 012915n ATPase inhibitor ATPase inhibitor (rat (rat mitochondria) IF1 mitochondria) protein) IF1 protein) 3196956 NM 012976GeneralLectin, galactoseLectin, galactose binding, binding, soluble 9 (Galectin ' soluble 5 (Galectin-5),9) Lectin, galactose binding, soluble 9 (Galectin-9) 3197958 NM 012977b, Lectin, galactoseLectin, galactose binding, tt binding, soluble 9 (Galectin soluble 9 (Galectin-9)9) 354120309NM 022175gg, Homeobox gene Homeobox gene Pem hh Pem 3655504 NM 024136x epididymal retinoicepididymal retinoic acid-binding acid-binding protein protein 3796635 NM 031509vv Glutathione-S-transferase,Glutathione-S-transferase, alpha type (Ya) alpha type (Ya) 4312683 NM_147206ii HMm:cytochrome Rattus norvegicus cytochrome P450, steroid P450 3A9 inducible 3a13 mRNA, complete cds 4439 AA685175h, ESTs, Moderately similar m, to ribosome s, General binding protein 1 isoform mRRp61 [Mus musculusl [M.musculusl 14 19222AA799279d, ESTs, Highly similar f, to mitochondria) carrier I, General, homolog 2 [Mus musculus]
[M.musculus]

pp 37 15560AA799538z ESTs, Highly similar to SFR2_MOUSE

Splicing factor, argininelserine-rich (Splicing factor SC35) (SC-35) (Splicing component, 35 kDa) (PR264 protein) [M.musculusl 85 21006AA799861rr ESTs, Highly similar to IRF7_MOUSE

Interferon regulatory factor 7 (IRF-7) [M.musculusl 85 21007AA799861g ESTs, Highly similar to IRF7_MOUSE

Interferon regulatory factor 7 (IRF-7) M.musculus ~ ~n TABLE

Attorney=Docket No.
44921=5113WQ

Document No.1926271:2 SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster ID ID Acc. . Title N0. or Code N0. RefSeq ID :

No 101 15394AA800039z, ESTs, Weakly similar II to FAF1 MOUSE FAS

associated factor 1 (FAF1 protein) fM.musculus]

121 24228AA8003180o ESTs, Moderately similar to IC1 MOUSE

Plasma protease C1 inhibitor precursor (C1 Inh) (C1lnh) [M.musculus]

147 17648AA800735I ESTs, Weakly similar to VIL1 MOUSE Villin 1 [M.musculus]

147 17649AA800735w, ESTs, Weakly similar gg, to VIL1 MOUSE Villin hh 1 [M.musculus]

174 2425AA817722mm ESTs, Highly similar to CTN1 MOUSE

Alpha-1 catenin (102 kDa cadherin-associated protein) (CAP102) (Alpha E-catenin) fM.musculusl 186 11215AA817921xx ESTs, Highly similar ' to ubiquitin-like 5 [Mus musculus] [M.musculus]

191 10623AA817987c, Sulfotransferase Sulfotransferase hydroxysteroid - f, hydroxysteroid gene 2 n, v ene 2 204 6522AA818261c ' ESTs, Moderately similar to A47318 RNA-bindin protein Raly - mouse [M.musculus]

222 18868AA818759dd ESTs, Moderately similar to S12207 hypothetical protein (B2 element) - mouse f M.musculusl 233 6132AA819055v, ESTs, Weakly similar uu to 635070 apolipoprotein H-related protein 1361 -mouse [M.musculusl 249 9987AA819502c ESTs, Weakly similar to ELL MOUSE RNA

POLYMERASE II ELONGATION
FACTOR

ELL (ELEVEN-NINETEEN
LYSINE-RICH

LEUKEMIA PROTEIN) fM.musculusl 258 6297AA819681General, ESTs, Highly similar to RIKEN cDNA

uu 1 200014P03 [Mus musculus]
[M
musculus]

.

283 16128AA848807I, ESTs, Highly similar r, to RIKEN cDNA
nn 2 410017118 [Mus musculus]
[M.musculus]

307 12129AA849966n ESTs, Moderately similar to Mpv17 t ransgene, kidney disease mutant-like [Mus musculusl fM.musculus]

319 19621AA850634v E STs, Moderately similar to S12207 h ypothetical protein (B2 element) - mouse f M.musculusl 330 8872AA851050v, lutathione reductaselutathione reductase qq g 334 15561AA851202II E STs, Highly similar to SFR2_MOUSE

S plicing factor, arginine/serine-rich ( Splicing factor SC35) (SC-35) (Splicing c omponent, 35 kDa) (PR264 protein) f M.musculusl 337 17699AA851233gg, E STs, Highly similar hh to RIKEN cDNA

4 930548607 Mus musculus M.musculus TABLE

~' Attorney Docket No.
44921-51131Na Document No.1926271:2 SEQ GLGC GeriBankModel Kr~own Gene Name Jnigene Sequence ClusterTitle _ t ID D Acc: Code' : NO. or I

N0. RefSeq ID

No.

371 1801 AA858636r, ESTs, Highly similar rr to mini chromosome maintenance deficient 7 (S. cerevisiae) [Mus musculus] [M.musculusl 386 18765AA859019a ESTs, Weakly similar to 635070 apolipoprotein H-related protein 1361 -mouse [M.musculusl 398 6464 AA859401II ESTs, Highly similar to JC7321 N-acetylneuraminic acid 9-phosphate synthase (EC 4.1.3.-) - mouse [M.musculus]

419 22670AA859750y ESTs, Weakly similar to ERF_MOUSE ETS-domain transcription factor ERF

[M.musculusl 421 14213AA859827bb, ESTs, Moderately similar dd, to URK1 MOUSE
jj, oo, URIDINE KINASE (URIDINE
pp MONOPHOSPHOKINASE) [M.musculus]

432 19377AA859971I ESTs, Highly similar to RIKEN cDNA

0610010112 [Mus musculus]
[M.musculus]

459 9391 AA866477d ESTs, Moderately similar to COXM_MOUSE

Cytochrome c oxidase polypeptide Vllb, mitochondria) precursor [M.musculus]

476 16241AA875019pp ESTs, Highly similar to ZAP3_MOUSE

Nuclear protein ZAP3 [M.musculus]

487 16416AA875098j, ESTs, Highly similar q, to RIKEN cDNA
dd 1110002023 [Mus musculus]
[M.musculus]

509 18864AA875470a ESTs, Highly similar to COP9 (constitutive photomorphogenic) homolog, subunit 7a (Arabidopsis thaliana);
DNA segment, Chr 6, ERATO Doi 35, expressed;
COP9 complex S7a; COP9 (constitutive photomorphogenic), subunit 7a (Arabidopsis) [Mus musculus]

fM.m ulusl 515 15558AA875537tt ESTs, Highly similar to SFR2_MOUSE
-Splicing factor, argininelserine-rich (Splicing factor SC35) (SC-35) (Splicing component, 35 kDa) (PR264 protein) IM.musculusl 524 15688AA875664x ESTs, Highly similar to mitochondria associated granulocyte macrophage CSF

signaling molecule [Mus musculus]

fM.musculusl 526 17057AA891049General ESTs, Highly similar to PFD2_MOUSE
-Prefoldin subunit 2 [M.musculus]

531 24814AA891209m ESTs, Highly similar to interleukin 25;

lymphocyte antigen 6 complex, locus E

li and Mus musculus M.musculus TABLE

~
Attorney Docket No44921=5113W0 Document No.1926271:2 SEQ GLGC Genl3ankModel Known Gene Name Unigene Sequence Cluster : Title 117yID Acc. Code' X10..or-N0. RefSeq G
ID= v~

No:
,. _ 574 16602AA891864t, ESTs, Highly similar mm to RIKEN cDNA

2900054013 gene; nuclear ATP/GTP-binding protein; Purkinje cell degeneration [Mus musculusl [M.musculusl 594 6362 AA892053q ESTs, Highly similar to T42204 chromatin structural protein homolog SuptShp - mouse [M.musculus]

628 18150AA892422a ESTs, Moderately similar to RIKEN cDNA

2410001 P07; RIKEN cDNA

gene [Mus musculus]
(M.musculus]

633 1522 AA892486e, ESTs, Weakly similar ii, to A36690 sucrose rr, uu alpha-glucosidase (EC
3.2.1.48) - rat (fragment) R.norveqicusl 648 18274AA892572bb ESTs, Highly similar to RIKEN cDNA

1110001J03 [Mus musculus]
[M.musculus]

666 20359AA892817f, EST, Weakly similar s to S12207 hypothetical protein (B2 element) - mouse [M.musculus]

684 11189AA892960ee ESTs, Highly similar to RIKEN cDNA

1200011118 Mus musculus]
[M.musculus]

696 19745AA893199t ESTs, Highly similar to RIKEN cDNA

1500004D14 [Mus musculus]
[M.musculus]

701 548 AA893235c, ESTs, Highly similar ww, to GOS2_MOUSE
xx Putative lymphocyte GO/G1 switch protein (GOS2-like protein) [M.musculusl 720 17698AA893596ww ESTs, Highly similar to RIKEN cDNA

4930548607 [Mus musculus]
[M.musculus]

745 3217 AA894101jj ESTs, Moderately similar to PNAD_MOUSE

PROTEIN N-TERMINAL ASPARAGINE

AMIDOHYDROLASE (PROTEIN

TERMINAL ASPARAGINE
DEAMIDASE) (NTN-AMIDASE) (PNAD) (PROTEIN NH2-TERMINAL ASPARAGINE

AMIDOHYDROLASE) (PNAA) [M.musculus]

764 3910 AA894345b, ESTs, Weakly similar k, to 2021425A MAT1 I, cc ene [Mus musculus] [M.musculus]

765 18094AA899051rr SH-PTP2 protein SH-PTP2 protein tyrosine tyrosine phosphatase, non-phosphatase, non-receptorreceptor type 11 type 807 22666AA900974r, ESTs, Highly similar y, to p34SEl-1; PHD zinc kk finger- and bromodomain-interacting protein 1 [Mus musculus] [M.musculusl 840 18434AA924413kk, ESTs, Moderately similar tt to hypothetical protein MNCb-0169 [Mus musculus]

M.musculus TABLE

Attorney Docket No~
44921=5113W0 Document No.1926271:2 SEQ GLGC GenBankModel Knowrt Gene Name Unigene Sequence Cluster Title ID. 1D Acc. Code NO.~ or ~

N0, RefSeq ID

No:

843 3631 AA924460m ESTs, Weakly similar to PMC1 MOUSE

Polymyositislscleroderma autoantigen 1 ( Autoantigen PM/Scl 1 ) ( Polymyositislscleroderma autoantigen 75 kDa) (PM/Scl-75) (P75 polymyositis-scleroderma overlap syndrome associated aut nti nl fM.musculusl 864 5073 AA925061d ESTs, Moderately similar to S20710 hypothetical protein, 16K - mouse [ M.musculus 916 16909AA942704bb ESTs, Moderately similar to SUR2_MOUSE

Surfeit locus protein 2 (Surf 2) [M.musculusj 918 6039 AA942716nn ESTs, Highly similar to hematological and neurological expressed sequence 1 [Mus musculus] [M.musculusl 976 21581AA944828ff ESTs, Highly similar to RIKEN cDNA

2610524607 [Mus musculus]
[M.musculus]

984 22667AA945069r ESTs, Highly similar to p34SEl-1; PHD zinc finger- and bromodomain-interacting protein 1 [Mus musculus] [M.musculus]

102612321AA946166d ESTs, Highly similar to RIKEN cDNA

2410003020 [Mus musculus]
[M.musculus]

105715329AA955427k ESTs, Highly similar to LMA1 MOUSE

Laminin alpha-1 chain precursor (Laminin A

chain) [M.musculusl 10609984 AA955536c ESTs, Weakly similar to ELL_MOUSE RNA

POLYMERASE II ELONGATION
FACTOR

ELL (ELEVEN-NINETEEN
LYSINE-RICH

LEUKEMIA PROTEIN) fM.musculusl 10609985 AA955536c ESTs, Weakly similar to ELL_MOUSE RNA

POLYMERASE II ELONGATION
FACTOR

ELL (ELEVEN-NINETEEN
LYSINE-RICH

LEUKEMIA PROTEIN) fM.musculusl 106623662AA955640jj ESTs, Highly similar to RIKEN cDNA

2610002M06 [Mus musculus]
[M.musculus]

108823805AA956558jj ESTs, Moderately similar to MTG8_MOUSE

MTG8 protein [M.musculus]

112316603AA964059mm ESTs, Highly similar to RIKEN cDNA

2900054013 gene; nuclear ATPIGTP-binding protein; Purkinje cell degeneration fMus musculusl IM.musculusl 112912166AA964426a ESTs, Moderately similar to RIKEN cDNA

2810433K01 [Mus musculus]
[M.musculus]

115521008AA965186II ESTs, Highly similar to IRF7_MOUSE

Interferon regulatory factor 7 (IRF-7) M.musculus 1R~
TABLE

Attorney Docket No.

Document No:19262712 SEGtGLGC GenBankModel:Known Gene Name Unigene-SequenceClusterTitle ID' DNO. Acc: Code I of N0 RefSeq ID

No, 11772988 AA997030rr ESTs, Moderately similar to guanine nucleotide exchange factor (RCC1 related) [ Mus musculusl [M.musculusl 11933269 AA997800k ESTs, Moderately similar to T30249 cell proliferation antigen Ki-67 - mouse [M.musculus]

12033357 AA998078v ESTs, Moderately similar to RaIBP1 associated Eps domain containing protein [Mus musculusl [M.musculus]

12333069 AA998910ss ESTs, Highly similar to endoplasmic reticulum chaperone SIL1 homolog (S.

cerevisiae) [Mus musculus]
fM.musculusl 126523044AF034218s, hyaluronidase hyaluronidase 2 kk, 2 pp 12984740 A1007847k ESTs, Weakly similar to S26689 hypothetical protein hc1 - mouse (fragment) f M.musculusl 13403464 A1009589ww ESTs, Highly similar to RIKEN cDNA

4921524J17 [Mus musculus]
[M.musculus]

1345994 A1009693bb ESTs, Highly similar to RIKEN cDNA

2310050K10 [Mus musculus]
[M.musculus]

13626874 A1010057g EST, Weakly similar to A26621 retrovirus-related endonuclease (EC 3.1.-.-) - mouse (fragment) [M.musculusl 13786943 A1010637ss ESTs, Moderately similar to peptide N-glycanase; peptide:N-glycanase [Mus musculus] fM.musculusl 15102340 A1029499s, ESTs, Weakly similar oo to JC4524 aldehyde dehydrogenase (NAD(P)+) (EC 1.2.1.5) - rat [R.norve icusl 151122469A1029506dd ESTs, Moderately similar to COG2_MOUSE

Coatomer gamma-2 subunit (Gamma-2 coat protein) (Gamma-2 COP) [M.musculus]

15617916 A1043855s, sterol-C5-desaturasesterol-C5-desaturase t (fungal (fungal ERG3, delta-5-ERG3, delta-5-desaturase)-likedesaturase)-like 15699829 A1044063x ESTs, Weakly similar to carcinoma related gene [Mus musculus]
[M.musculus]

158924174A1044826gg, ESTs, Highly similar hh to CC45_MOUSE

CDC45-related protein (PORC-PI-1) [M.musculusl 161019782A1045333r ESTs, Moderately similar to tumor necrosis factor induced protein 1 [Mus musculus]

[M.musculusl 163523712A1045827h ESTs, Weakly similar to T00043 BH-protocadherin-a - mouse [M.musculus]

165210084A1058674s ESTs, Highly similar to MTR3_MOUSE

Myotubularin-related protein 3 [M.musculus]

ERR
T;~BLE

AttoKney Dobket No.
'44921=5113W0 Document No.19262712 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence_ClusterTitle ID D Acc. Code ' N0. or I .

N0. RefSeq ID

No.

168214518A1059477gg, ESTs, Moderately similar hh to POL3_MOUSE

Retrovirus-related POL
polyprotein (Endonuclease) [M.musculus]

172611821A1070350mm ESTs, Weakly similar to JC4667 TB21DP1 protein homolo - mouse [M.musculus]

17479079 A1071251b, ESTs, Moderately similar x to A57050 K-~

lypican recursor- mouse [M.musculus]

175716788A1071557ii Orthodenticle Orthodenticle (Drosophila) (Drosophila) homolog 1 homolo 1 17656521 A1071688c, ESTs, Moderately similar w to A47318 RNA-bindin protein Raly - mouse [M.musculus]

17889162 A1072392jj ESTs, Highly similar to C2MS classical-complement-pathway C3/C5 convertase (EC

3 .4.21.43) C2 component precursor - mouse [M.musculusl 182623124AI100785y, ESTs, Highly similar nn to germ cell-less homolog (Drosophila) [Mus musculus]

[M.musculusl 187419379AI102711d, ESTs, Highly similar j to RIKEN cDNA

0610010112 [Mus musculus]
[M.musculus]

19367223 AI104373x ESTs, Highly similar to RIKEN cDNA

2810428115 [Mus musculus]
M.musculus]

19425084 AI104587z ESTs, Moderately similar to RIKEN cDNA

1810008A14 [Mus musculus]
M.musculus]

19772539 AI111960y ESTs, Weakly similar to FKBS_MOUSE 51 kDa FK506-binding protein (FKBP51) (Peptidyl-prolyl cis-trans isomerase) - (PPiase) (Rotamase) [M.musculusl 199711180AI11300300, ESTs, Highly similar vv to gene rich cluster, ene [Mus musculus] [M.musculus]

201416187AI136838gg, ESTs, Highly similar hh to A55053 endothelial monocyte-activating protein I I precursor -mouse [M.musculus]

201523851AI136862v ESTs, Highly similar to carcinoma related gene [Mus musculus]
[M.musculus]

202713129AI137413p ESTs, Weakly similar to T14318 ubiquitin-protein ligase E3-alpha - mouse [M.musculus]

20341556 AI137790xx R.norvegicus mRNA from Leydig cell hypercalcemic tumour 204122987AI138061s ESTs, Moderately similar to JC4761 recombination activating gene 1 inducing protein - mouse [M.musculusl 205213190AI144981c ESTs, Weakly similar to Fas-activated serinelthreonine kinase [Mus musculus]

[M.musculus]

205323106AI145081ww ESTs, Highly similar to S56766 replication licensing factor MCM4 - mouse M.musculus TABLE

Attorriey_Docket No:

_ Document No.1926271.2 SEQ GLGC GenBankModel Known Geae Name Unigene Sequence'ClusterTitle .

ID D Acc: Code ' NO. or I

N0: RefSeq ID

No:

206818522AI145870, ff ESTs, Moderately similar t to RIKEN cDNA

1110025H10 [Mus musculus]
M.musculus]

207013401AI146008pp ESTs, Moderately similar to S12207 hypothetical protein (B2 element) - mouse [M.musculusl 207514519AI168947tt ESTs, Moderately similar to POL3_MOUSE
_ Retrovirus-related POL
polyprotein (Endonuclease) M.musculusl 20835683 AI169034p DEADIH (Asp-Glu-Ala-Asp/His)DEADIH (Asp-Glu-Ala-AspIHis) box box polypeptide polypeptide 20,103kD
20,103kD

20876392 AI169154q ESTs, Weakly similar to SSXT_MOUSE

SSXT protein (SYT protein) (Synovial sarcoma associated Ss18-alpha) f M.musculusl 20932607 AI169211c ESTs, Highly similar to A47318 RNA-binding protein Ral - mouse [M.musculus]

2095806 AI169231r ESTs, Highly similar to G33_RAT GENE 33 POLYPEPTIDE [R.norvegicus]

211015665AI169611I ESTs, Moderately similar to steroid receptor RNA activator 1 [Mus musculus]

[M.musculus]

211320466AI169735h Rat cytochrome P45011B3 (P45011B

subfamily) mRNA, complete cds 2115804 AI169756n, ESTs, Highly similar r, to G33_RAT GENE 33 ee POLYPEPTIDE [R.norve icus]

21254368 AI170265xx ESTs, Highly similar to RIKEN cDNA

1700006006 [Mus musculus]
[M.musculus]

217621698A1171574tt ESTs, Highly similar to RNA and export factor binding protein 1; Tcra enhancer-binding factor interacting protein 1 [Mus musculusl iM.musculusl 218710087AI171803w, methylmalonate methylmalonate semialdehyde semialdehyde General,dehydrogenase dehydrogenase gene gene uu 219122239A1171982qq ESTs, Moderately similar to 148672 p8 MTCP-1 - mouse [M.musculus]

22015080 AI172106qq ESTs, Highly similar to cDNA sequence AB028863; Mmrp19 [Mus musculus]

[M.musculusl 221415382AI172302rr ESTs, Weakly similar to S43056 hypothetical protein - mouse [M.musculus]

22235044 AI172572m ESTs, Moderately similar to expressed sequence tag mouse EST
12 [Mus musculusl [M.musculus]

225422451AI175992d, ESTs, Highly similar t to beta-catenin-interacting protein ICAT [Mus musculus]

- M.musculus TABLE

-Attorney Docket No:

Document No.1926271.2 S~QGLGC GenBankModel Knov~n Gene Name tJnigene Sequence Cluster Title -ID ID Acc. Code' N0. or N0. RefSeq ID

Nor 232921279AI177356bb ESTs, Highly similar to mitochondria) ribosomal protein 64 [Mus musculus]

fM.musculus]

233218095AI177482rr SH-PTP2 protein SH-PTP2 protein tyrosine tyrosine phosphatase, non-phosphatase,non-receptortypereceptortype 11 234422249A1177809I zyxin zyxin 241212011AI1793800o ESTs, Highly similar to open reading frame 12 [Mus musculus] [M.musculus]

241319783AI179388y ESTs, Highly similar to RIKEN cDNA

0610040D20 [Mus musculus]
[M.musculus]

242223515AI179498I ESTs, Highly similar to SEC23B (S.

cerevisiae) [Mus musculus]
[M.musculus]

243017865AI179636ss ESTs, Highly similar to RIKEN cDNA

0610009822 [Mus musculus]
[M.musculus]

244817089AI180281h ESTs, Moderately similar to JC4978 oxidative stress protein A170 - mouse [M.musculus]

248521898AI228595ss ESTs, Moderately similar to CN07_MOUSE

CCR4-NOT transcription complex, subunit 7 (CCR4-associated factor 1) (CAF1) IM.musculusl 249415873AI228798pp ESTs, Weakly similar to 152657 seizure-related protein SEZ-6 precursor - mouse [M.musculus]

249723824AI229059h, ESTs, Moderately similar q, to retinoic acid x, dd induced 12; Clone 13u [Mus musculus]

[M.musculus]

24995143 AI229087s ESTs, Highly similar to TPS1 MOUSE

Protein-tyrosine sulfotransferase (Tyrosylprotein sulfotransferase-1) (TPST-1) fM.musculusl 250119063AI229166nn ESTs, Highly similar to mitochondria) ribosomal protein S14;
1810032L21 Rik [Mus musculus][M.musculusl 251421237A1229430cc Rattus norvegicus Tclone4 mRNA

253418088AI230199xx ESTs, Weakly similar to POL3_MOUSE

Retrovirus-related POL
polyprotein (Endonuclease) [M.musculusl 255014388AI230702q, ESTs, Highly similar bb to hematological and neurological expressed sequence 1 [Mus musculusl [M.musculusl 255919765AI230945j, ESTs, Highly similar bb to synbindin; syndecan binding protein 2 [Mus musculus]

[M.musculusl 25852339 A1231798x ESTs, Highly similar to T-complex expressed gene 2 [Mus musculus]

M.musculus Attorney Docket No:

' Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Jnigene Sequence Cluster t Title ID ID Acc. Code N0. or N0: RefSeq ID

No."

261414521AI232350m ESTs, Moderately similar to POL3_MOUSE

Retrovirus-related POL
polyprotein ( Endonuclease) [M.musculus]

262921664AI232734kk ESTs, Highly similar to DD15 MOUSE

Putative pre-mRNA splicing factor RNA

helicase (DEAN box protein 15) f M.musculusl 267515085AI233829x, P11 protein P11 protein ff, ii 271022805AI235403v ESTs, Highly similar to adaptor-related protein complex AP-3, delta subunit [Mus musculus] [M.musculusl 272115200AI235736a ESTs, Moderately similar to CD34_MOUSE

Hematopoietic progenitor cell antigen CD34 precursor [M.musculus]

273415467AI236106jj ESTs, Moderately similar to S15785 heat-stable antigen-related hypothetical protein HSA-C - mouse fM.musculusl 275620992AI236719k ESTs, Highly similar to N-acetylglucosamine kinase; GIcNAc kinase [Mus musculus]

[M.musculusl 275816609AI23674pp 8 ESTs, Moderately similar to CENB_MOUSE

MAJOR CENTROMERE AUTOANTIGEN
B

(CENTROMERE PROTEIN
B) (CENP-B) [M.musculusl 277616063AI237314q ESTs, Highly similar to zinc finger like protein 1 [Mus musculus]
[M.musculus]

280220000AI638989j ESTs, Moderately similar to T14273 zinc fin er protein 106 -mouse [M.musculus]

281510071AI639058y, ESTs, Highly similar xx to Nedd4 WW binding#

protein 4; Nedd4 WW-binding protein 4 [Mus musculus] [M.musculusl 28195545 AI639117h, ESTs, Highly similar cc, to CFAB_MOUSE
ii, vv Complement factor B
precursor (C3/C5 convertase) [M.musculusl 291211358H31610 00, ESTs, Highly similar pp to JW0059 mtprd protein - mouse [M.musculus]

293618281H33459 ss ESTs, Highly similar to SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1;

integrase interactor 1 [Mus musculus]

fM.musculusl 294416256J02861 dd, cytochrome P450 cytochrome P450 2c13, rr 2c13, cytochrome P450, cytochrome P450, 2c38 2c38 295117270K02111 jj Rat embryonic myosin heavy chain gene, partial 5' region, mRNA

299620464M20406 I, Rat cytochrome P45011B3 v, (P45011B
vv subfamil mRNA com lete cds TABLE

Aftorney Docket No.

Document No.1926271.2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequertca Cluster . Title ID ID Acc. Code N0. or N0. RefSeq ID

No:

301216305M33312 0, Cytochrome P450 Cytochrome P450 IIA1 GeneralIIA1 (hepatic (hepatic steroid steroid hydroxylasehydroxylase IIA1) gene IIA1) gene 303316255M82855 g, cytochrome P450 cytochrome P450 2c13, dd 2c13, cytochrome P450, cytochrome P450, 2c38 2c38 307016895NM 012558a, Fructose-1,6- Fructose-1,6- biphosphatase cc, biphosphatase gg, hh, ss, uu 310724589NM 012674d, Serine protease Serine protease inhibitor, kk inhibitor, kanzalkanzal type 1/

type 1/ Trypsin Trypsin inhibitor-like inhibitor-like protein, pancreatic protein, pancreatic 311316306NM 012692uu Cytochrome P450 Cytochrome P450 IIA1 IIA1 (hepatic (hepatic steroid steroid hydroxylasehydroxylase IIA1) gene, IIA1) gene, Cytochrome P450 Cytochrome P450 IIA2 311424707NM 012693c, Cytochrome P450 Cytochrome P450 IIA2 r, IIA2 s 311510622NM_012695f, Sulfotransferase Sulfotransferase hydroxysteroid n hydroxysteroid gene 2 ene 2 311510624NM 012695n, Sulfotransferase Sulfotransferase hydroxysteroid xx hydroxysteroid gene 2 gene 2 311510625NM 012695k, Sulfotransferase Sulfotransferase hydroxysteroid n, hydroxysteroid gene 2 ii gene 2 311510626NM 012695f Sulfotransferase Sulfotransferase hydroxysteroid hydroxysteroid gene 2 gene 2 315021350NM 012823a Annexin A3 Annexin A3 3235357 NM 013086w CAMP responsive CAMP responsive element element modulator modulator 323718096NM 013088ff SH-PTP2 protein SH-PTP2 protein tyrosine tyrosine phosphatase, non-phosphatase, non-receptorreceptor type 11 type 3259200 NM 013161k, Pancreatic lipasePancreatic lipase v 32632012 NM 013173r Solute carrier Solute carrier family family 11 member 11 member 2 (natural 2 (natural resistance-associatedesistance-associated r macrophage protein macrophage protein2) 2) 32632013 NM_013173r Solute carrier Solute carrier family family 11 member 11 member 2 (natural 2 (natural resistance-associatedesistance-associated r macrophage protein macrophage protein2) 2) 330718973NM 017060kk E STs, Moderately similar to S14234 h ypothetical protein - mouse [M.musculus]

336621903M 017220ss cytochrome P450, ytochrome P450, 2c37 N 2c37 c 338820914M 017272, o, aldehyde dehydrogenaseldehyde dehydrogenase N j v, family a family 1, subfamily vv 1, subfamily A4 A4 341616148M_0173400, acyl-coA oxidase cyl-coA oxidase N y, a jj, ss, x x 341616150M 017340, jj acyl-coA oxidase cyl-coA oxidase N 0 a 34431173 M 019184, rr Cytochrome ytochrome P450, subfamily N j P 450, subfamily IIC
IIC C

( mephenytoin 4-hydroxylase)mephenytoin 4-hydroxylase) ( 1 StR
TABLE

Attorney Docket No.

' Document No.19262712 SEQ GLGC G-enBankModel Known Gene Name nigene Sequence Cluster ' U Title ID. ID Acc. Code N0. or N0. RefSeq . ' No 34431174 NM 019184rr Cytochrome P450, Cytochrome P450, subfamily subfamily IIC IIC

(mephenytoin 4-hydroxylase)(mephenytoin 4-hydroxylase) 348020553NM 019293I, ESTs, Moderately similar p to S12207 hypothetical protein (B2 element) - mouse [M.musculus]

349918032NM 019380w stromal cell derivedtromal cell derived factor s factor receptor 1 receptor 1 355443 NM 022287General,sulfate anion sulfate anion transporter transporter dd, ff, rr 360321072NM_022601k pyridoxine 5'-phosphatepyridoxine 5'-phosphate oxidase oxidase 360521203NM 022606a protein phosphataseprotein phosphatase 360521204NM 022606a protein phosphataseprotein phosphatase 36075336 NM 022631v ESTs, Highly similar to synembryn [Mus musculus] [M.musculus]

362923606NM 022867ii microtubule-associatedicrotubule-associated proteins m proteins 1A/1B light 1AI1 B light chainchain 3 362923608NM 022867II microtubule-associatedmicrotubule-associated proteins proteins 1A/1B light 1A/1 B li ht chainchain 3 364417486NM 023092g, unconventional unconventional myosin cc myosin Myr2 I Myr2 I heavy chain heavy chain 364417487NM_023092mm unconventional unconventional myosin myosin Myr2 I Myr2 I heavy chain heavy chain 36772811 NM 024386j 3-hydroxy-3-methylglutaryl3-hydroxy-3-methylglutaryl j C0A CoA lyase lyase 36772812 NM 024386rr 3-hydroxy-3-methylglutaryl-hydroxy-3-methylglutaryl CoA 3 CoA lyase lyase 36772813 NM 0243860, 3-hydroxy-3-methylglutaryl-hydroxy-3-methylglutaryl ii C0A 3 CoA lyase lyase 368416141NM 024405nn GSK-3beta interactingGSK-3beta interacting protein protein rAxin rAxin 36914057 NM 030844a islet cell autoantigenislet cell autoanti 1, 69 kDa en 1, 69 kDa 3714485 NM 031017c cAMP response cAMP response element element binding binding protein 1 , protein 1 373217269NM 031057General,methylmalonate methylmalonate semialdehyde semialdehyde kk dehydro enase dehydrogenase gene gene 37411403 NM 031087j presenilin-2 j presenilin-2 37431175 NM 031093x, Cytochrome P450, Cytochrome xx subfamily IIC 450, subfamily IIC
P

(mephenytoin 4-hydroxylase)(mephenytoin 4-hydroxylase) 377415238NM 031153 shank-interactingshank-interactin protein I protein 37788149 NM 031242i CDP-diacylglycerolCDP-diacylglycerol synthase i s ynthase (phosphatidate (phosphatidate cytidylyltransferase) cytidylyltransferase) 378923358NM 031342r lysophospholipaselysophospholipase II
r II

382515803NM 031593bb s na tic vesicle s na tic vesicle rotein rotein 2C 2C

TABLE

Attoiney Docket No:
4.4921~5113W0 Document No.1926271:2 SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster Title ID D Acc: Code ' NO_ or I

N0. RefSeq ID

No.

389021646NM 031781General,amyloid beta (A4)amyloid beta (A4) precursor II precursor protein-binding, protein-binding, amily A, member 3 (X11-like family A, f 2) member 3 (X11-like 2) 389415794NM 031796qq UDP-GaINAc:polypeptideUDP-GaINAc:polypeptide N- N-acetylgalactosaminyltransferaseacetylgalactosaminyltransferase 390015759NM 031815kk activin beta E activin beta E

39057914 NM 031835b, beta-alanine-pyruvatebeta-alanine-pyruvate h, aminotransferase I, General,aminotransferase nn 393821102NM 033021q vesicle associatedvesicle associated protein protein 393821103NM 033021q, vesicle associatedvesicle associated protein x protein 397523338NM 053416n, double-stranded double-stranded RNA-binding rr RNA-binding protein p74 protein p74 397914621NM 0534370, diacylglycerol diacyl lycerol acyltransferase ss acyltransferase 400621534NM 053588f Trif ene Trif gene 40151126 NM 053605v, sphingomyelin sphingomyelin phosphodiesterase y, 3, neutral oo phosphodiesterase 3, neutral 402315777NM 053630v potassium voltage-gatedpotassium voltage-gated channel, subfamily channel, subfamilyH (eag-related), member H (eag- 4 related), member 405715103NM 053814I, Rho interacting Rho interacting protein bb protein 3 3 408117090NM 053906t, glutathione reductaseglutathione reductase mm 408117091NM 053906qq glutathione reductaseglutathione reductase 4119968 NM 057133I, nuclear receptor nuclear receptor subfamily v, subfamily 0, 0, group B, bb group B, member member 2 41714956 NM_133315n solute carrier solute carrier family family 39 (iron- 39 (iron-regulated regulated transporter),transporter), member member 1 41714957 NM_133315f, solute carrier solute carrier family n, family 39 (iron- 39 (iron-regulated y, ll regulated transporter),transporter), member member 1 417721576NM 1333980o LYRIC LYRIC

418711483NM_133546f, myeloid differentiationmyeloid differentiation n, primary primary response General,response gene gene 116 kk 418718043NM_133546w, myeloid differentiationmyeloid differentiation z, primary primary response General,response gene gene 116 kk, tt 418813968NM_133553kk UDP-Gal:betaGIcNAcUDP-Gal:betaGIcNAc beta beta 1,3- 1,3-galactosyltransferase,galactosyltransferase, polypeptide 4 polypeptide 4 418813969NM_133553a UDP-Gal:betaGIcNAcUDP-Gal:betaGIcNAc beta beta 1,3- 1,3-galactosyltransferase,galactosyltransferase, polypeptide 4 polypeptide 4 419017886NM 133561t, brain protein brain protein 44-like g, 44-like hh 419017887NM 133561q brain protein brain protein 44-like 44-like 42204849 NM 134415h, CDK105 rotein CDK105 rotein TABLE
1;
Attorney Docket No, 44921=5113W0 Document No.1926271.2 SEQGLGC GerlBankModel Known Gene Name Unigene Sequence Cluster ' Title ID ID Acc. Code N0. or N0. RefSeq ID

No.

423648 NM 138547b 3-alpha-hydroxysteroid3-alpha-hydroxysteroid dehydrogenase dehydro enase 423625475NM_138547b 3-alpha-hydroxysteroid3-alpha-hydroxysteroid dehydrogenase dehydrogenase 42469796 NM_138847f, Saccharomyces Saccharomyces cerevisiae q cerevisiae Nip7p homolog Nip7p homolog 424811435NM 138865tt testis specific testis specific protein protein 428211502NM_139255I, RDCR-0918-3 proteinRDCR-0918-3 protein p, q, y, ww 431423070NM_148891m, ESTs, Highly similar to NMT1 MOUSE

General, Glycylpeptide N-tetradecanoyltransferase ee, (Peptide N-myristoyltransferase oo 1 ) (Myristoyl CoA:protein N-myristoyltransferase 1) (NMT

1) (Type I N-myristoyltransferase) IM.musculusl 431917995NM_153312e, Rattus norvegicus Sprague j Dawley testosterone 6-beta-hydroxylase, cytochrome P450I6-beta-A, (CYP3A2) mRNA, complete cds 435915462U06230 ii protein S protein S

436217281U10697 j, carboxylesterase carboxylesterase 1 x, 1 dd, rr 437218302U33500 n, Rattus norvegicus retinol tt dehydrogenase type II mRNA, complete cds 4374212 U36895 cc Rattus norvegicus putative pheromone receptor VN3 mRNA, complete cds 443515106X57529 v ESTs, Highly similar to RS18 HUMAN 40S

ribosomal protein S18 (KE-3) (KE3) f R.norvegicus) 4457436 X67877 pp R.norvegicus mRNA for cytosolic resiniferatoxin-binding protein 447925777Y08355 h, oxidative stress oxidative stress induced I, induced General, uu, xx 194023574AI104520II Cytochrome c oxidaseCytochrome c oxidase subunit subunit Vla (liver) Vla (liver) 2592573 AI232087h, hydroxyacid oxidasehydroxyacid oxidase I, 3 (medium- 3 (medium-chain) m, qq chain) 292621011H32189 nn Glutathione-S-transferase,Glutathione-S-transferase, mu mu type 2 (Yb2) type 2 (Yb2) 294221012J02592 b, Glutathione-S-transferase,Glutathione-S-transferase, I, mu mu type 2 (Yb2) General,type 2 (Yb2) gg, hh, kk, II

294521014J03914 b, Glutathione-S-transferase,Glutathione-S-transferase, I, mu mu type 2 (Yb2) o, x, General,type 2 (Yb2) II, rr _302519823M61725 0o Transcription Transcription factor factor UBF UBF

31812830 NM 012925I, CD59 anti en CD59 anti en , nn 1q1 TABLE

Attorney Docket No.

Document No.1926271:2 SEQ GL.GCGenBank Model Known Gene Name Unigene Sequence:Cluster Title ID D Acc. Code I N0. or NO. RefSeq . ID

No.

329321013NM 017014cc Glutathione-S-transferase,Glutathione-S-transferase, mu mu type 2 (Yb2) type 2 (Yb2) 329321015NM 017014s, Glutathione-S-transferase,Glutathione-S-transferase, cc mu mu type 2 (Yb2) type 2 (Yb2) 334221975NM 017154 xanthine dehydrogenasexanthine dehydrogenase I

343624362NM 019156a vitronectin vitronectin 347021443NM 019262nn complement componentcomplement component 1, q 1, q subcomponent, subcomponent, beta polypeptide beta polypeptide 351520816NM 021261e, thymosin, beta thymosin, beta 10 ii, 10 II

3627180 NM_022853s solute carrier solute carrier family family 30 (zinc 30 (zinc transporter), transporter), member 1 member 1 3666844 NM 024352h, Macrophage stimulatingMacrophage stimulating I, 1 1 (hepatocyte n, uu (hepatocyte growthgrowth factor-like) factor-like) 3687862 NM 024487w GrpE-like 1, mitochondria)GrpE-like 1, mitochondria) 38723548NM 031723u, signal peptidase signal peptidase complex ww complex (18kD) (18kD) 38723549NM 031723r, signal peptidase signal peptidase complex tt complex (18kD) (18kD) 391216535NM 031853bb Diazepam binding Diazepam binding inhibitor inhibitor (GABA receptor (GABA receptor modulator, acyl-Coenxyme modulator, acyl- A binding Coenxyme A bindingprotein) protein) 404218174NM 053752o succinate-CoA succinate-CoA ligase, ligase, GDP- GDP-forming, alpha forming, alpha subunit subunit 426415134NM_139081c Ornithine decarboxylaseESTs, Highly similar to OAZ_RAT Ornithine antizyme 1 decarboxylase antizyme (ODC-Az) [R.norveqicus]

226 4877AA818887nn Rattus norvegicus MHC
class I mRNA, complete cds 545 13307AA891576d ESTs, Weakly similar to S49158 complement protein C1q beta chain precursor - rat [R.norveqicusl 844 15577AA924557p ESTs, Highly similar to vesicle-associated calmodulin-binding protein [Rattus norvegicusl fR.norveqicusl 871 5110AA925274ii ESTs, Highly similar to OIfRT2R protein kinase (EC 2.7.1.37), cAMP-dependent, type II-alpha regulatory chain - rat (fragment) [R.norveaicusl 15597912A104383600 ESTs, Weakly similar to S53340 CD59 protein - rat [R.norve icus]

185211636AI101967r amyotrophic lateralamyotrophic lateral sclerosis 2 sclerosis 2 (juvenile) Quvenile) chromosomechromosome region, candidate region, 3 candidate 3 DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

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Claims (62)

WE CLAIM:

1. A method of determining whether a compound induces at least one toxic effect on a tissue or cell, comprising:

(a) preparing a gene expression profile of a tissue or cell sample exposed to said compound; and (b) comparing the gene expression profile to a database comprising an adequate amount of the data or information of Tables 5A-5XX to determine whether the compound induces at least one toxic effect on the tissue or cell.

2. A method of claim 1, wherein the gene expression profile prepared from the tissue or cell sample comprises the level of expression for at least one gene.

3. A method of claim 2, wherein the level of expression is compared to a Tox Mean and/or Non-tox Mean value in Tables 5A-5XX.

4. A method of claim 3, wherein the level of expression is normalized prior to comparison.

5. A method of claim 1, wherein the database comprises substantially all of the data or information in Tables 5A-5XX.

6. A method of predicting at least one toxic effect of a compound, comprising:
(a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 5A-5XX; wherein differential expression of the genes in Tables 5A-5XX is indicative of at least one toxic effect.

7. A method of predicting the progression of a toxic effect of a compound, comprising:
(a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 5A-5XX; wherein differential expression of the genes in Tables 5A-5XX is indicative of toxicity progression.

8. A method of predicting the hepatotoxicity of a compound, comprising:

(a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 5A-5XX; wherein differential expression of the genes in Tables 5A-5XX is indicative of hepatotoxicity.

9. A method of identifying an agent that modulates the onset or progression of a toxic response, comprising:
(a) exposing a cell to the agent and a known toxin; and (b) detecting the expression level of two or more genes from Tables 5A-5XX;
wherein differential expression of the genes in Tables 5A-5XX is indicative of toxicity.

10. A method of predicting the cellular pathways that a compound modulates in a cell, comprising:
(a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 5A-5XX; wherein differential expression of the genes in Tables 5A-5XX is associated the modulation of at least one cellular pathway.

11. The method of any one of claims 6-10, wherein the expression levels of at least 3 genes are detected.

12. The method of any one of claims 6-10, wherein the expression levels of at least 5 genes are detected.

13. The method of any one of claims 6-10, wherein the expression levels of at least 10 genes are detected.

14. The method of any one of claims 6-10, wherein the expression levels of at least 50 genes are detected.

15. The method of any one of claims 6-10, wherein the expression levels of at least 100 genes are detected.

16. The method of any one of claims 6-10, wherein the expression levels of at least 500 genes are detected.

17. A method of any one of claims 6-10, wherein substantially all of the genes in Tables 5A-5XX are detected.

18. A method of claim 51, wherein all of the genes in at least one of Tables 5A-5XX are detected.

19. A method of any one of claims 6-10, wherein the compound exposure is in vitro.

20. A method of claim 19, wherein the cell sample comprises rat hepatocytes.

21. A method of any one of claims 6-10, wherein the level of expression is detected by an amplification or hybridization assay.

22. A method of claim 21, wherein the amplification assay is quantitative or semi-quantitative PCR.

23. A method of claim 21, wherein the hybridization assay is selected from the group consisting of Northern blot, dot or slot blot, nuclease protection and microarray assays.

24. The method of any one of claims 6-10, wherein the detected level of expression is compared to that found in cells exposed to a known toxin.

25. The method of claim 24, wherein the toxin is selected from the group consisting of amiodarone, alpha-naphthylisothiocyante (ANIT), acetaminophen (APAP), AY-25329, carbamazepine, carbon tetrachloride, chlorpromazine, CI-1000, clofibrate, cyproterone acetate (CPA), diclofenac, diflunisal, dimethylnitrosamine (DMN), 17.alpha.-ethinylestradiol, gemfibrozil, hydrazine, imipramine, indomethacin, lipopolysaccharide, lovastatin, methotrexate, phenobarbital, tacrine, tamoxifen, tetracycline, valproate and Wy-14643.

26. The method of claim 25, wherein the level of expression is compared to that found in Tables 5A-5XX.

27. The method of claim 26, wherein the cells are primary hepatocytes.

28. The method of claim 27, wherein the cells are rat primary hepatocytes.

29. A method of claim 6 or 7, wherein the effect is selected from the group consisting of genotoxic and non-genotoxic carcinogenesis, cholestasis, direct-acting toxicity, hepatitis, liver enlargement, inflammation, necrosis, necrosis with steatosis, peroxisome proliferation, steatosis, and steatosis with hepatitis.

30. A method of claim 8, wherein the hepatotoxicity is associated with at least one liver disease pathology selected from the group consisting of genotoxic and non-genotoxic carcinogenesis, cholestasis, direct-acting toxicity, hepatitis, liver enlargement, inflammation, necrosis, necrosis with steatosis, peroxisome proliferation, steatosis, and steatosis with hepatitis.

31. A method of claim 10, wherein the cellular pathway is modulated by a toxin selected from the group consisting of amiodarone, alpha-naphthylisothiocyante (ANIT), acetaminophen (APAP), AY-25329, carbamazepine, carbon tetrachloride, chlorpromazine, CI-1000, clofibrate, cyproterone acetate (CPA), diclofenac, diflunisal, dimethylnitrosamine (DMN), 17.alpha.-ethinylestradiol, gemfibrozil, hydrazine, imipramine, indomethacin, lipopolysaccharide, lovastatin, methotrexate, phenobarbital, tacrine, tamoxifen, tetracycline, valproate and Wy-14643.

32. A set of at least two probes, wherein each of the probes comprises a sequence that specifically hybridizes to a gene in Tables 5A-5XX.

33. A set of probes according to claim 32, wherein the set comprises probes that hybridize to at least 3 genes.

34. A set of probes according to claim 32, wherein the set comprises probes that hybridize to at least 10 genes.

35. A set of probes according to claim 32, wherein the set comprises probes that hybridize to at least 100 genes.

36. A set of probes according to claim 32, wherein the set comprises probes that hybridize to at least 500 genes.

37. A set of probes according to any one of claims 32-36, wherein the probes are attached to a solid support.

38. A set of probes according to claim 37, wherein the solid support is selected from the group consisting of a membrane, a glass support and a silicon support.

39. A solid support comprising at least two probes, wherein each of the probes comprises a sequence that specifically hybridizes to a gene in Tables 5A-5XX.

40. A solid support of claim 39, wherein the solid support is an array comprising at least different oligonucleotides in discrete locations per square centimeter.

41. A solid support of claim 39, wherein the array comprises at least about 100 different oligonucleotides in discrete locations per square centimeter.

42. A solid support of claim 39, wherein the array comprises at least about 1000 different oligonucleotides in discrete locations per square centimeter.

43. A solid support of claim 39, wherein the array comprises at least about 10,000 different oligonucleotides in discrete locations per square centimeter.

44. A computer system comprising:
(a) a database containing information identifying the expression level in a tissue or cell sample exposed to a hepatotoxin of a set of genes comprising at least two genes in Tables 1-5XX; and (b) a user interface to view the information.

45. The computer system of claim 44, wherein the cell samples are rat primary hepatocytes.

46. A computer system of claim 44, wherein the database further comprises sequence information for the genes.

47. A computer system of claim 44, wherein the database further comprises information identifying the expression level for the set of genes in the tissue or cell sample before exposure to a hepatotoxin.

48. A computer system of claim 44, wherein the database further comprises information identifying the expression level of the set of genes in a tissue or cell sample exposed to at least a second hepatotoxin.

49. A computer system of any of claims 44-48, further comprising records including descriptive information from an external database, which information correlates said genes to records in the external database.

50. A computer system of claim 49, wherein the external database is GenBank.

51. A method of using a computer system of any one of claims 44-48 to present information identifying the expression level in a tissue or cell of at least one gene in Tables 5A-5XX, comprising:
(a) comparing the expression level of at least one gene in Tables 5A-5XX in a tissue or cell exposed to a test agent to the level of expression of the gene in the database.

52. A method of claim 51, wherein the expression levels of at least 2 genes are compared.

53. A method of claim 51, wherein the expression levels of at least 10 genes are compared.

54. A method of claim 51, wherein the expression levels of at least 100 genes are compared.

55. A method of claim 51, further comprising the step of displaying the level of expression of at least one gene in the tissue or cell sample compared to the expression level when exposed to a toxin.

56. A kit comprising at least one solid support of any one of claims 39-43 packaged with gene expression information for said genes.

57. A kit of claim 56, wherein the gene expression information comprises gene expression levels in a tissue or cell sample exposed to a hepatotoxin.

58. A kit of claim 57, wherein the gene expression information is in an electronic format.

59. A method of identifying an agent that modulates at least one activity of a protein encoded by a gene in Tables 5A-5XX comprising:
(a) exposing the protein to the agent; and (b) assaying at least one activity of said protein.

60. A method of claim 59, wherein the agent is exposed to a cell expressing the protein.

61. A method of claim 60, wherein the cell is exposed to a known toxin.

62. A method of claim 61, wherein the toxin modulates the expression of the protein.