KR20100115283A

KR20100115283A - Markers for liver cancer prognosis

Info

Publication number: KR20100115283A
Application number: KR1020090064322A
Authority: KR
Inventors: 박진영; 홍석주; 김종민; 심영택
Original assignee: 씨비에스바이오사이언스 주식회사; 심영택
Priority date: 2009-07-15
Filing date: 2009-07-15
Publication date: 2010-10-27

Abstract

PURPOSE: A marker and method for predicting liver cancer are provided to research liver cancer mechanism. CONSTITUTION: A composition for predicting liver cancer contains a material which specifically detects marker expression level, or expression pattern. A kit for predicting liver cancer contains the composition. A method for predicting liver cancer comprises: a step of treating biological sample with the composition, which is collected from a patient with liver cancer; a step of distinguishing difference of expression level or expression pattern with standard value; and a step of checking promotion or suppression of the marker expression by the candidate.

Description

간암 예후 마커 {MARKERS FOR LIVER CANCER PROGNOSIS}Liver cancer prognosis marker {MARKERS FOR LIVER CANCER PROGNOSIS}

본 발명은 간암 예후 마커, 상기 간암 예후 마커의 발현량 변화를 검출하는 물질을 포함하는 간암 예후 추정용 조성물, 상기 간암 예후 추정용 조성물을 포함하는 간암 예후 추정용 키트, 상기 간암 예후 마커를 이용하는 간암 예후 추정 방법, 상기 간암 예후 마커를 활용한 간암 치료제 스크리닝 방법에 관한 것이다.The present invention is a liver cancer prognostic marker, a composition for estimating liver cancer prognosis comprising a substance for detecting a change in the expression amount of the liver cancer prognostic marker, a kit for estimating liver cancer prognosis comprising the composition for estimating liver cancer prognosis, liver cancer using the liver cancer prognostic marker A method for estimating prognosis and a method for screening a liver cancer therapeutic agent using the liver cancer prognostic markers.

암은 악성 종양과 동일한 의미를 가지며, 다양한 원인으로 세포의 증식 조절 기능에 훼손되고 이러한 비정상적인 세포들이 통제되지 못하고 과다하게 증식하면서 주위 조직 및 장기에 침입하여 종괴를 형성하고 정상 조직을 파괴하는 상태를 의미한다. 인체의 각종 조직에서 발생하는 암은 빠른 성장, 침윤성 (파고들거나 퍼져나감) 성장, 전이 (원래 장소에서 떨어진 곳까지 이동함) 등으로 인하여 생명에 위험을 초래하게 된다.Cancer has the same meaning as a malignant tumor, and for various reasons, it is impaired in the cell's proliferation regulating function, and these abnormal cells proliferate uncontrolled and proliferate excessively, invading surrounding tissues and organs, forming masses and destroying normal tissues. it means. Cancer, which occurs in various tissues of the human body, poses a danger to life due to rapid growth, invasive (digging or spreading) growth, and metastasis (moving from its original place).

암 중에서 간암은 세계적으로 가장 치명적인 암의 하나로 알려져 있으며, 특히 아시아와 사하라 이남 아프리카에서 해마다 약 오십만 명 이상이 간암으로 사망하고 있는 것으로 보고되고 있다. 간암은 크게 간세포 자체로부터 발생한 원발성 간암 (간세포암; hepatocellular carcinoma) 과 다른 조직의 암이 간으로 전이 되어 온 전이성 간암으로 구분할 수 있는데, 간암의 약 90% 이상은 원발성 간암이며, 흔히 간암이라 함은 원발성 간암을 지칭하는 것으로 이해된다.Among cancers, liver cancer is known as one of the most deadly cancers in the world, and more than half a million people die of liver cancer each year, especially in Asia and sub-Saharan Africa. Liver cancer can be classified into primary liver cancer (hepatocellular carcinoma) originating from the liver cells itself and metastatic liver cancer in which cancers of other tissues have spread to the liver. More than 90% of liver cancers are primary liver cancers. It is understood to refer to primary liver cancer.

이러한 간암의 발병 원인 중 대다수는 B형 간염 바이러스 또는 C형 간염 바이러스에 의한 급성 또는 만성적인 감염이라는 것이 보고되고 있지만, 간암의 발병 및 진행에 관한 세포 내의 분자적 메커니즘은 아직도 명확히 규명되지 못한 상태이다. 종래의 연구에 따르면 각종 성장인자 유전자와 같은 전-종양형성유전자 (proto-oncogene) 가 다양한 원인에 의하여 종양형성유전자 (oncogene) 로 돌연변이되어 과발현하거나 과활성을 갖는 경우, 또는 Rb 단백질이나 p53 단백질과 같은 종양형성 억제 유전자 (tumor suppressor gene) 가 다양한 원인에 의하여 돌연변이되어 저발현하거나 기능을 잃는 경우 간암을 비롯한 다양한 암의 발병과 진행을 유발하는 것으로 보고되어 있다. 특히 간암과 관련해서는, 변형된 p53, 베타-카테닌, AXINI, p21(WAF1/CIP1) 및 p27 Kip 등의 유전자가 관련되어 있다는 것이 밝혀지기도 하였다. 그러나, 최근에는 간암을 비롯한 대부분의 암의 발병 및 진행은 특정 몇몇 유전자들만에 의하여 이루어지는 것이 아니라 세포주기, 신호전달 등과 관련된 다양한 각종 유전자들의 복합적인 상호작용에 발병하는 것으로 인식되고 있으며, 따라서 개별적인 유전자나 단백질의 발현이나 기능에만 중점을 두는 것에서 벗어나 다양한 유전자나 단백질에 대한 총체적인 연구의 필요성이 대두되고 있다.Although most of the causes of liver cancer are reported to be acute or chronic infections caused by hepatitis B virus or hepatitis C virus, the molecular mechanisms within the cells regarding the development and progression of liver cancer are still unclear. . Previous studies have shown that proto-oncogenes, such as various growth factor genes, are mutated to oncogenes for various reasons and are overexpressed or overactive, or with Rb or p53 proteins. It has been reported that the same tumor suppressor gene causes the development and progression of various cancers, including liver cancer, when they are mutated by various causes and are underexpressed or lose their function. Especially in relation to liver cancer, it has been found that genes such as modified p53, beta-catenin, AXINI, p21 (WAF1 / CIP1) and p27 Kip are involved. However, in recent years, the onset and progression of most cancers, including liver cancer is recognized not only by a few specific genes but also due to the complex interaction of a variety of genes related to the cell cycle, signaling, etc. Therefore, individual genes In addition to focusing only on the expression and function of proteins, there is a need for a comprehensive study of various genes and proteins.

간암의 예후 (prognosis) 는 간암이 진단된 이후에 간암의 완치가능성, 치료 후 재발가능성, 환자의 생존가능성 등 간암에 따른 환자의 각종 상태를 예측하는 것을 일컫는데, 이는 질병의 심각성, 진단 시점, 치료경과 등의 다양한 조건에 의존하여 달라진다. 간암은 그 예후에 따라 적합하게 다양한 치료방법이 적용되어야만 효율적인 치료가 가능하다. 예를 들어, 예후가 양호할 것으로 추정되는 환자들에 대해서는 공격적인 화학치료나 수술, 방사선 치료 등 환자에게 심각한 부작용을 야기할 가능성이 있는 위험한 치료방법은 지양할 필요가 있고, 상대적으로 온건하고 보존적이며 안전한 치료방법을 선택하여야 한다. 반대로 예후가 불량할 것으로 추정되는 환자들에 대해서는 화학치료나 수술, 방사선 치료와 같은 치료방법을 적극적으로 동원하여 생존의 기간이나 확률을 높이고자 시도하여야 한다.Prognosis of liver cancer refers to predicting various conditions of patients with liver cancer, such as the cure of liver cancer, the possibility of recurrence after treatment, and the patient's survival after the diagnosis of liver cancer. It depends on various conditions such as treatment progress. Liver cancer can be effectively treated only when various treatment methods are applied according to its prognosis. For example, patients with a good prognosis need to avoid risky treatments, such as aggressive chemotherapy, surgery, or radiation therapy, that can cause serious side effects, and should be relatively moderate and conservative. The safe treatment method should be chosen. Conversely, patients who are suspected of having poor prognosis should actively mobilize treatment methods such as chemotherapy, surgery, and radiation therapy to increase the duration or probability of survival.

현재까지의 연구에 따르면, 이미 진행되어버린 간암은 그 예후가 극히 불량하여 진단 후 6개월 이내에 사망하여 평균 생존 기간이 4개월밖에 되지 않는 높은 치명율을 보이는데 비해, 크기가 3cm 미만인 작은 간암은 예후가 양호하여 특별한 치료 없이도 1년간 생존할 확률이 90%에 이르고 수술을 한 경우 5년 생존율이 40-50% 정도가 되는 것으로 알려져 있다. 그러나, 간암 환자의 예후를 정확하게 추정하는 것은 종래의 기술로는 매우 어렵다. 예후의 정확한 추정을 위해서는 환자들을 위험군별로 분류하는 분석방법이 필요한데, 현재까지는 간암의 예후를 정확하게 추정할 수 있는 수단 없이 진단시의 병리임상학적인 간암의 단계와 1차적 외과 치료에만 의존하여 예후를 판단하고 있는 실정이다. 그러나, 불행하게도 간암의 단계만으로는 각 간암 환자에 대한 예후를 정확하게 판단할 수 없다.To date, studies have shown that liver cancer, which has already advanced, has a very poor prognosis and dies within 6 months of diagnosis and has a high mortality rate of only 4 months.However, small liver cancers less than 3cm in size have a prognosis. It is known that the survival rate of 1 year without special treatment reaches 90%, and the 5-year survival rate is 40-50% when operated. However, accurately estimating the prognosis of liver cancer patients is very difficult with conventional techniques. For accurate estimation of the prognosis, an analysis method is needed to classify patients by risk group.To date, the prognosis is determined only by the pathological stage of diagnosis and primary surgical treatment without the means of accurately estimating the prognosis of liver cancer. I'm doing it. Unfortunately, the stage of liver cancer alone cannot accurately determine the prognosis for each liver cancer patient.

CBS 단백질 (cystathionine beta-synthase) 은 호모시스틴 (homocysteine) 을 시스타티오닌 (cystathionine) 으로 변환시키는 효소로서, 트랜스-황화 경로에 서 작용하며 생체 내의 메티오닌 대사에 중요한 역할을 하는 것으로 알려져 있다 [J Biol Chem. 1994 May 20;269(20):14835-40].CBS protein (cystathionine beta-synthase) is an enzyme that converts homocysteine to cystathionine, which is known to act in the trans-sulfurization pathway and play an important role in methionine metabolism in vivo [J Biol Chem. 1994 May 20; 269 (20): 14835-40.

NNMT 단백질 (nicotinamide N-methyltransferase) 은 니코틴아미드와 피리딘의 N-메틸화 작용을 하는 효소로서, 여러가지 약물 및 생체 이물화합물 (xenobiotic compound) 의 대사에 관여하는 것으로 알려져 있다 [Genomics. 1998 Sep 15;52(3):312-24].NNMT protein (nicotinamide N-methyltransferase) is an N-methylation enzyme of nicotinamide and pyridine, and is known to be involved in the metabolism of various drugs and xenobiotic compounds [Genomics. 1998 Sep 15; 52 (3): 312-24.

TKT 단백질 (transketolase) 은 비-산화성 펜토오스-포스페이트 경로에서 핵심적인 역할을 수행하는 효소로서, 그 군의 일원으로는 TKTL1 (transketolase-like 1), TKTL2 (transketolase-like 2) 가 알려져 있다 [J Biol Chem. 1993 Jan 15;268(2):1397-404].TKT protein (transketolase) is an enzyme that plays a key role in the non-oxidative pentose-phosphate pathway. TKTL1 (transketolase-like 1) and TKTL2 (transketolase-like 2) are known as members of the group [J Biol Chem. 1993 Jan 15; 268 (2): 1397-404.

AIFM1 단백질 (apoptosis-inducing factor, mitochondrion-associated, 1) 은 AIF로도 알려져 있는 플라보단백질이며, 세포사멸 (apoptosis) 이 일어나면 이 단백질은 핵으로 이동하여 염색체 응집 및 조각화를 일으키게 되고, 또한 미토콘드리아로부터 시토크롬 c와 카스파아제-9의 분비를 유도하는 것으로 알려져 있다 [Nature. 1999 Feb 4;397(6718):441-6].AIFM1 protein (apoptosis-inducing factor, mitochondrion-associated, 1) is a flavoprotein, also known as AIF, and when apoptosis occurs, the protein moves to the nucleus, causing chromosomal aggregation and fragmentation, and also cytochromes from mitochondria. Induced secretion of c and caspase-9 [Nature. 1999 Feb 4; 397 (6718): 441-6.

AKT 단백질은 AKT2, AKT3와 연관된 단백질이며, 포스파티딜이노시톨 3-키나아제를 통한 성장인자 신호, 즉 혈소판-유래 성장인자 (PDGF), 상피세포 성장인자 (EGF), 인슐린 및 인슐린-유사 성장인자 I (IGF-I) 등의 신호를 전달하는 역할을 하며, 활성화되는 경우 세포사멸 관련 단백질들을 인산화시켜 불활성화 할 수 있는 것으로 알려져 있다 [Proc Natl Acad Sci U S A. 1987 Jul;84(14):5034-7]AKT protein is a protein associated with AKT2, AKT3 and is a growth factor signal through phosphatidylinositol 3-kinase, namely platelet-derived growth factor (PDGF), epithelial growth factor (EGF), insulin and insulin-like growth factor I (IGF). -I), and it is known to be able to inactivate the apoptosis-related proteins when activated by phosphorylation [Proc Natl Acad Sci US A. 1987 Jul; 84 (14): 5034-7 ]

ATG3 단백질 (autophagy related 3 homolog) 은 사람의 ATG8 동족체인 GATE-16, GABARAP, MAP-LC3과 지질과의 결합에 관여하고, ATG3가 결여된 마우스는 오토파고좀 (autophagosome) 을 형성하지 못하고 태어난 후 하루 만에 죽는 것으로 보고되었다 [J Biol Chem. 2002 Apr 19;277(16):13739-44. Epub 2002 Feb 1].ATG3 protein (autophagy related 3 homolog) is involved in the binding of GATE-16, GABARAP, MAP-LC3 to human ATG8 homologues and lipids, and mice lacking ATG3 do not form autophagosomes after birth It was reported to die in one day [J Biol Chem. 2002 Apr 19; 277 (16): 13739-44. Epub 2002 Feb 1].

AGT5 단백질 (autophagy related 5 homolog) 은 자식작용 (autophagy) 에 관여하는데, ATG5는 ATG7과 ATG10의 작용을 통해 ATG12-ATG5 접합을 이루게 되고 이 ATG12-ATG5는 오토파고좀의 막으로 이동하여 ATG8과 포스파티딜에타놀아민의 결합에 작용하며, ATG5가 없는 마우스는 오토파고좀을 형성하지 못하며 태어나면서 죽게되고, 잘려진 ATG5는 미토콘드리아에서 시토크롬 c 분비와 카스파아제 활성화를 유도할 수 있는 것으로 알려져 있다 [Nature 432:1032-1036 (2004)].The AGT5 protein (autophagy related 5 homolog) is involved in autophagy, where ATG5 forms an ATG12-ATG5 junction through the action of ATG7 and ATG10, and this ATG12-ATG5 migrates to the membrane of the autophagosome and causes ATG8 and phosphatidyl It is known that mice without ATG5, which do not form autophagosomes, die at birth, and that truncated ATG5 can induce cytochrome c secretion and caspase activation in mitochondria. [Nature 432: 1032 -1036 (2004)].

ATG7 단백질 (autophagy related 7 homolog) 은 자식작용에 관여하는데, ATG7은 ATG10과 함께 ATG12-ATG5 접합을 이루게 되고, 이는 ATG3와 함께 ATG8과 포스파티딜에탄올아민의 결합에 관여하며, ATG7이 없는 마우스는 오토파고좀을 형성하지 못하며 태어나면서 죽는 것으로 보고되었다 [J Biol Chem. 2001 Jan 19;276(3):1701-6. Epub 2000 Nov 28].The ATG7 protein (autophagy related 7 homolog) is involved in progeny, where ATG7 forms an ATG12-ATG5 junction with ATG10, which is associated with the binding of ATG8 and phosphatidylethanolamine with ATG3, in mice without ATG7 It has been reported to die at birth without forming a moth [J Biol Chem. 2001 Jan 19; 276 (3): 1701-6. Epub 2000 Nov 28].

ATG12 단백질 (autophagy related 12 homolog) 은 자식작용에 관여하는데, ATG12은 ATG7과 ATG10의 작용을 통해 ATG12-ATG5 접합을 이루고 이 ATG12-ATG5는 오토파고좀의 막으로 이동하여 ATG8과 포스파티딜에탄올아민의 결합에 작용한다고 알려져 있다 [J Biol Chem. 1998 Dec 18;273(51):33889-92].ATG12 protein (autophagy related 12 homolog) is involved in the progeny, ATG12 forms ATG12-ATG5 junction through the action of ATG7 and ATG10, and this ATG12-ATG5 migrates to the membrane of autopagosome to bind ATG8 to phosphatidylethanolamine It is known to act on [J Biol Chem. 1998 Dec 18; 273 (51): 33889-92.

BAX 단백질 (BCL2-associated X protein) 은 BCL2 단백질 군 중 하나로서, BCL2와 결합하여 세포사멸 촉진 작용을 하고, 미토콘드리아 막전위 손실과 시토크롬 c 분비에도 관여하는 것으로 알려져 있다 [Cell. 1993 Aug 27;74(4):609-19].BAX protein (BCL2-associated X protein) is a member of the BCL2 protein group, which binds to BCL2 and promotes apoptosis, and is known to be involved in mitochondrial membrane potential loss and cytochrome c secretion [Cell. 1993 Aug 27; 74 (4): 609-19.

BCL2 단백질 (B-cell lymphoma protein 2) 은 미토콘드리아의 막 단백질로서 세포사멸을 억제하는 작용을 하고, 미토콘드리아로부터 시토크롬 c의 분비 억제, 세포사멸-활성화 인자와의 결합을 통해 카스파아제 활성화 및 세포사멸을 억제하는 것으로 알려져 있다 [Proc Natl Acad Sci U S A. 1986 Jul;83(14):5214-8].B-cell lymphoma protein 2 is a membrane protein of mitochondria that acts to inhibit apoptosis, inhibits the secretion of cytochrome c from mitochondria, and binds to apoptosis-activating factors to activate caspase activation and apoptosis. It is known to inhibit [Proc Natl Acad Sci US A. 1986 Jul; 83 (14): 5214-8].

BCL2L1 단백질 (Bcl-2-like 1 protein) 은 BCL2 단백질 군 중 일원으로서, 미토콘드리아 외막에 위치하며 미토콘드리아 막채널 공유에 관여하는 것으로 알려져 있는데, 두 가지 형태의 이소 형태로 존재하며 보다 긴 형태 BCL-XL 은 세포사멸를 억제하고 보다 짧은 형태 BCL-XS는 세포사멸을 촉진하는 것으로 알려져 있다 [Cell. 1993 Aug 27;74(4):597-608].BCL2L1 protein (Bcl-2-like 1 protein) is a member of the BCL2 protein family, which is known to be involved in mitochondrial membrane channel sharing and is located in the mitochondrial outer membrane. Inhibits cell death and the shorter form BCL-XS is known to promote cell death [Cell. 1993 Aug 27; 74 (4): 597-608.

BNIP3 단백질 (BCL2/adenovirus E1B 19kD-interacting protein 3) 은 E1B 19 kDa 단백질 및 BCL2와 결합할 수 있으며, 세포사멸과 자식작용을 유도하는 작용을 하는 것으로 알려져 있다 [J Exp Med. 1997 Dec 15;186(12):1975-83].BNIP3 protein (BCL2 / adenovirus E1B 19kD-interacting protein 3) is capable of binding to E1B 19 kDa protein and BCL2 and is known to induce apoptosis and induction [J Exp Med. 1997 Dec 15; 186 (12): 1975-83.

CASP8 단백질 (caspase 8, apoptosis-related cysteine protease) 은 카스파아제의 군에 속하는 효소로서, FAS에 의한 세포 사멸 기작의 초기에 작용하는 카스파아제이며, 이는 FADD와의 결합 및 단백질 분해성 절단을 통해 활성화 되면 여러 다른 카스파아제를 활성화 시키는 것으로 알려져 있다 [Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14486-91; Biochem J. 1997 Aug 15;326 (Pt 1):1-16)]CASP8 protein (caspase 8, apoptosis-related cysteine protease) is an enzyme belonging to the group of caspases. It is a caspase that acts early in the cell death mechanism by FAS, and when activated through binding to FADD and proteolytic cleavage, It is known to activate other caspases [Proc Natl Acad Sci US A. 1996 Dec 10; 93 (25): 14486-91; Biochem J. 1997 Aug 15; 326 (Pt 1): 1-16)]

CSE1L 단백질 (CSE1 chromosome segregation 1-like) 은 임포틴-α를 핵에서 세포질로 다시 내보내는 역할을 하며, 세포사멸 또는 세포 증식에도 관여하는 것으로 알려져 있다 [Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10427-31].CSE1L protein (CSE1 chromosome segregation 1-like) plays a role in the export of impintin-α from the nucleus back to the cytoplasm and is known to be involved in apoptosis or cell proliferation [Proc Natl Acad Sci US A. 1995 Oct 24; 92 (22): 10427-31.

DIABLO 단백질 (Direct IAP-binding protein with low pI) 는 미토콘드리아에 위치하는 단백질이며 세포사멸이 일어나면 세포질로 이동하여 IAP (inhibitor of Apoptosis protein) 와 결합하여 카스파아제 활성화에 도움을 준다고 알려져 있다 [Cell. 2000 Jul 7;102(1):43-53].DIABLO protein (Direct IAP-binding protein with low pI) is a protein located in the mitochondria and is known to help the caspase activation by binding to IAP (inhibitor of Apoptosis protein) when cell death occurs. 2000 Jul 7; 102 (1): 43-53.

DRAM 단백질 (damage-regulated autophagy modulator) 은 리소좀의 막 단백질이며 p53 종양 억제자 (tumor suppressor) 에 의해 제어되는 자식작용에 관여하고, p53에 의해 제어되는 세포사멸에도 필수적이라고 알려져 있다 [Cell. 2006 Jul 14;126(1):121-34].DRAM protein (damage-regulated autophagy modulator) is a membrane protein of lysosomes and is involved in the progeny controlled by p53 tumor suppressors and is known to be essential for apoptosis controlled by p53 [Cell. 2006 Jul 14; 126 (1): 121-34.

E2F1 단백질 (E2F transcription factor 1) 은 E2F 군의 전사인자의 일원으로서, 세포 주기와 종양 억제자의 제어와 밀접한 관련이 있으며, Rb 단백질과 결합을 하여 세포의 성장을 촉진하거나 p53과 관련한 세포사멸을 유도하는 것으로 알려져 있다 [Gene. 1996 Sep 16;173(2):163-9].E2F1 protein (E2F transcription factor 1) is a member of the E2F family of transcription factors, closely related to the cell cycle and control of tumor suppressors, and binds to the Rb protein to promote cell growth or induce apoptosis associated with p53. It is known that [Gene. 1996 Sep 16; 173 (2): 163-9.

FAS 단백질 (APO-1, CD95, TNFRSF6) 은 TNF 수용체 군의 일원으로서, FAS 리간드의 신호를 받아 FADD (Fas-associated death domain protein), 카스파아제 8, 카스파아제 10 과 함께 DISC (death-inducing signaling complex) 를 구성하며 세포사멸을 유도하는 것으로 알려져 있다 [J Biol Chem. 1992 May 25;267(15):10709-15].FAS proteins (APO-1, CD95, TNFRSF6) are members of the TNF receptor family and receive signal from FAS ligands, together with fas-associated death domain protein (FADD), caspase 8, and caspase 10, and death-inducing signaling. complex and is known to induce apoptosis [J Biol Chem. 1992 May 25; 267 (15): 10709-15.

FRAP1 단백질 (Mammalian target of rapamycin) 은 mTOR로도 알려져 있고, 세포 내의 DNA 손상, 영양 고갈 등의 스트레스에 대한 반응을 매개하며, FRAP1을 포함한 TORC2 복합체는 FKBP12-라파마이신 복합체의 세포 주기 정지와 면역 억제 작용의 타겟이 되는 것으로 알려져 있다 [Nature. 1994 Jun 30;369(6483):756-8].The FRAP1 protein (Mammalian target of rapamycin), also known as mTOR, mediates the response to stresses such as DNA damage and nutrient depletion in cells, and the TORC2 complex, including FRAP1, inhibits cell cycle arrest and immunosuppression of the FKBP12-rapamycin complex. It is known to be the target of [Nature. 1994 Jun 30; 369 (6483): 756-8.

LAMP1 단백질 (lysosomal-associated membrane protein 1) 은 CD107a 항원으로도 알려져 있고, 막 당 단백질의 일종으로 암세포의 전이에 관여하는 것으로 생각된다 [J Biol Chem. 1990 May 5;265(13):7548-51].LAMP1 protein (lysosomal-associated membrane protein 1), also known as CD107a antigen, is a type of protein per membrane that is thought to be involved in metastasis of cancer cells [J Biol Chem. 1990 May 5; 265 (13): 7548-51.

LC3 단백질 (MAP1 light chain 3-like protein 1) 은 미세소관-연관 단백질로서 미세소관과 세포골격의 상호작용에 관여하며, LC3 단백질은 효모의 ATG8 동족체로서 여러 자식작용 단백질들의 작용에 의해 포스파티딜에탄올아민과 결합되어 오토파고좀을 구성하는 것으로 알려져 있다 [J Biol Chem. 1994 Apr 15;269(15):11492-7].LC3 protein (MAP1 light chain 3-like protein 1) is a microtubule-associated protein involved in the interaction of the microtubule with the cytoskeleton, and the LC3 protein is an ATG8 homologue of yeast, which is produced by the action of several offspring proteins. It is known to form an autophagosome in combination with J Biol Chem. 1994 Apr 15; 269 (15): 11492-7.

PRKAA1 단백질 (AMP-activated protein kinase, catalytic, alpha-1) 은 AMPK의 촉매성 서브유닛이고, 이 AMPK는 세포내의 에너지 수준을 감지하는 역할을 하는 단백질로서 AMP/ATP 의 비율이 증가하면 활성화되어 여러 생합성 작용을 제한하는 역할을 하는 것으로 알려져 있다 [FEBS Lett. 1994 Dec 12;356(1):117-21].The PRKAA1 protein (AMP-activated protein kinase, catalytic, alpha-1) is a catalytic subunit of AMPK, which is a protein that senses cellular energy levels and is activated when the ratio of AMP / ATP increases. It is known to play a role in limiting biosynthetic action [FEBS Lett. 1994 Dec 12; 356 (1): 117-21.

PTEN 단백질 (phosphatase and tensin homolog) 은 종양 억제자로 알려져 있으며, 여러 종류의 암에서 불활성화 되어 있고, 단백질 포스파타아제이면서 포스파티딜이노시톨-3,4,5-트리스포스페이트 3-포스파타아제로서 PI3K-AKT/PKB 신호 전달을 약화시키는 작용을 하는 것으로 알려져 있다 [Nat Genet. 1997 Apr;15(4):356-62].PTEN proteins (phosphatase and tensin homologs) are known as tumor suppressors and are inactivated in many types of cancer and are PI3K-AKT as protein phosphatase and phosphatidylinositol-3,4,5-triphosphate 3-phosphatase. / PKB is known to act to attenuate signal transduction [Nat Genet. 1997 Apr; 15 (4): 356-62.

ULK1 단백질 (Unc-51-like kinase 1) 은 축색돌기 성장에 관련된 세린/트레오닌 키나아제이며, ATG1 동족체로도 알려져 있고, 자식작용과 관련하여 mTOR에 의해 인산화되는 것으로 알려져 있다 [Genomics. 1998 Jul 1;51(1):76-85].ULK1 protein (Unc-51-like kinase 1) is a serine / threonine kinase involved in axon growth, also known as ATG1 homologue, and is known to be phosphorylated by mTOR in relation to progeny [Genomics. 1998 Jul 1; 51 (1): 76-85.

XIAP 단백질 (X-linked inhibitor of apoptosis protein) 은 IAP 군의 일원으로서, IAP 중에서도 강한 세포사멸 억제 효과를 갖고 있으며, 종양 괴사 인자 수용체-연관 인자 TRAF1, TRAF2 와의 결합을 통한 세포사멸 억제, 카스파아제 활성 억제의 작용을 하는 것으로 알려져 있다 [Nature. 1996 Jan 25;379(6563):349-53].XIAP protein (X-linked inhibitor of apoptosis protein) is a member of the IAP group, has a strong apoptosis inhibitory effect among IAP, inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, caspase activity It is known to act as a suppressor [Nature. 1996 Jan 25; 379 (6563): 349-53.

그러나, 상기 단백질들이 구체적으로 간암 조직에서 발현량이나 발현 패턴이 어떻게 변화하는지, 간암의 예후 추정에 있어서 어떻게 활용될 수 있는지에 대해서는 알려지지 않았으며, 현재까지 상기 단백질이나 상기 단백질을 코딩하는 유전자들을 간암 예후 마커로서 사용한 예는 없었다.However, it is not known how these proteins specifically change in expression level or expression pattern in liver cancer tissues, and how they can be used to estimate the prognosis of liver cancer. To date, the proteins or genes encoding the proteins are known as liver cancer. There was no example used as a prognostic marker.

본 발명은 간암의 예후와 관련된 바이오마커를 제공하여, 간암 환자의 예후 추정이 간편하고 정확하게 이루어지도록 하고, 나아가 간암의 치료제 개발에 중요한 시발점을 제공하는 것을 목적으로 한다. 이에 따라 본 발명에서는 간암 예후 마커, 상기 간암 예후 마커의 발현량 변화를 검출하는 물질을 포함하는 간암 예후 추정용 조성물, 상기 간암 예후 추정용 조성물을 포함하는 간암 예후 추정용 키트, 상기 간암 예후 마커를 이용하는 간암 예후 추정 방법, 상기 간암 예후 마커를 활용한 간암 치료제 스크리닝 방법을 제공하고자 한다.An object of the present invention is to provide a biomarker related to the prognosis of liver cancer, to easily and accurately estimate the prognosis of liver cancer patients, and to provide an important starting point for developing a therapeutic agent for liver cancer. Accordingly, in the present invention, a liver cancer prognostic marker, a composition for estimating liver cancer prognosis comprising a substance for detecting a change in expression amount of the liver cancer prognostic marker, a kit for estimating liver cancer prognosis comprising the liver cancer prognostic estimation composition, and a liver cancer prognostic marker It is intended to provide a method for estimating liver cancer prognosis to be used and a method for screening a liver cancer therapeutic agent using the liver cancer prognostic marker.

본 발명자들은 간암의 발병이 확인된 다수의 환자들에게서 채취한 간암 조직들의 유전자 발현 정도를 비교한 후, 각 환자들의 경과에 따라 특이적으로 과량 또는 소량 발현하는 유전자들을 검출하여 간암 예후 추정에 사용될 수 있는 간암 예후 마커들을 발굴해내었다.The present inventors compared the gene expression levels of liver cancer tissues collected from a plurality of patients confirmed that the onset of liver cancer, and then used to estimate the prognosis of liver cancer by detecting genes expressing excessive or small amounts specifically according to the progress of each patient. Possible prognostic markers for liver cancer were identified.

본 발명의 첫번째 국면은 하기 유전자로 이루어진 군으로부터 선택되는 하나 또는 둘 이상의 조합을 포함하는 간암 예후 마커에 관한 것이다:A first aspect of the invention relates to a liver cancer prognostic marker comprising one or more combinations selected from the group consisting of the following genes:

CBS (cystathionine beta-synthase; NCBI GI: 209862802; 서열번호 79);CBS (cystathionine beta-synthase; NCBI GI: 209862802; SEQ ID NO: 79);

NNMT (nicotinamide N-methyltransferase; NCBI GI: 62953139; 서열번호 80);NNMT (nicotinamide N-methyltransferase; NCBI GI: 62953139; SEQ ID NO: 80);

TKT (transketolase; NCBI GI: 205277461; 서열번호 81);TKT (transketolase; NCBI GI: 205277461; SEQ ID NO: 81);

AIFM1 (Apoptosis-inducing factor 1, mitochondrial; NCBI GI: 22202627; 서열번호 82);AIFM1 (Apoptosis-inducing factor 1, mitochondrial; NCBI GI: 22202627; SEQ ID NO: 82);

AKT1 (RAC-alpha serine/threonine-protein kinase; NCBI GI: 62241010; 서열번호 83);AKT1 (RAC-alpha serine / threonine-protein kinase; NCBI GI: 62241010; SEQ ID NO: 83);

ATG3 (Autophagy-related protein 3; NCBI GI: 34147490; 서열번호 84);ATG3 (Autophagy-related protein 3; NCBI GI: 34147490; SEQ ID NO: 84);

ATG5 (Autophagy protein 5; NCBI GI: 92859692; 서열번호 85);ATG5 (Autophagy protein 5; NCBI GI: 92859692; SEQ ID NO: 85);

ATG7 (Autophagy-related protein 7; NCBI GI: 222144225; 서열번호 86);ATG7 (Autophagy-related protein 7; NCBI GI: 222144225; SEQ ID NO: 86);

ATG12 (Autophagy-related protein 12; NCBI GI: 38261968; 서열번호 87);ATG12 (Autophagy-related protein 12; NCBI GI: 38261968; SEQ ID NO: 87);

BAX (Apoptosis regulator BAX; NCBI GI: 34335114; 서열번호 88);Apoptosis regulator BAX; NCBI GI: 34335114; SEQ ID NO: 88);

BCL2 (Apoptosis regulator Bcl-2; NCBI GI: 72198188; 서열번호 89);BCL2 (Apoptosis regulator Bcl-2; NCBI GI: 72198188; SEQ ID NO: 89);

BCL2L1 (Apoptosis regulator Bcl-X; NCBI GI: 20336333; 서열번호 90);BCL2L1 (Apoptosis regulator Bcl-X; NCBI GI: 20336333; SEQ ID NO: 90);

BNIP3 (BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; NCBI GI: 7669480; 서열번호 91);BNIP3 (BCL2 / adenovirus E1B 19 kDa protein-interacting protein 3; NCBI GI: 7669480; SEQ ID NO: 91);

CASP8 (Caspase-8; NCBI GI: 122056470; 서열번호 92);CASP8 (Caspase-8; NCBI GI: 122056470; SEQ ID NO: 92);

CSE1L (Exportin-2; NCBI GI: 29029558; 서열번호 93);CSE1L (Exportin-2; NCBI GI: 29029558; SEQ ID NO: 93);

DIABLO (Diablo homolog, mitochondrial; NCBI GI: 218505810; 서열번호 94);DIABLO (Diablo homolog, mitochondrial; NCBI GI: 218505810; SEQ ID NO: 94);

DRAM (Damage-regulated autophagy modulator; NCBI GI: 110825977; 서열번호 95);DRAM (Damage-regulated autophagy modulator; NCBI GI: 110825977; SEQ ID NO: 95);

E2F1 (Transcription factor E2F1; NCBI GI: 168480109; 서열번호 96);Transcription factor E2F1; NCBI GI: 168480109; SEQ ID NO: 96;

FAS (Tumor necrosis factor receptor superfamily member 6; NCBI GI: 23510419; 서열번호 97);Tumor necrosis factor receptor superfamily member 6; NCBI GI: 23510419; SEQ ID NO: 97;

FRAP1 (FKBP12-rapamycin complex-associated protein; NCBI GI: 206725550; 서열번호 98);FRAP1 (FKBP12-rapamycin complex-associated protein; NCBI GI: 206725550; SEQ ID NO: 98);

LAMP1 (Lysosome-associated membrane glycoprotein 1; NCBI GI: 112380627; 서열번호 99);LAMP1 (Lysosome-associated membrane glycoprotein 1; NCBI GI: 112380627; SEQ ID NO: 99);

LC3[MAP1LC3A] (Microtubule-associated proteins 1A/1B light chain 3A; NCBI GI: 31563519; 서열번호 100);LC3 [MAP1LC3A] (Microtubule-associated proteins 1A / 1B light chain 3A; NCBI GI: 31563519; SEQ ID NO: 100);

PRKAA1 (5'-AMP-activated protein kinase catalytic subunit alpha-1; NCBI GI: 94557300; 서열번호 101);PRKAA1 (5'-AMP-activated protein kinase catalytic subunit alpha-1; NCBI GI: 94557300; SEQ ID NO: 101);

PTEN (Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN; NCBI GI: 110224474; 서열번호 102);PTEN (Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN; NCBI GI: 110224474; SEQ ID NO: 102);

ULK1 (Serine/threonine-protein kinase ULK1; NCBI GI: 225637564; 서열번호 103); 및ULK1 (Serine / threonine-protein kinase ULK1; NCBI GI: 225637564; SEQ ID NO: 103); And

XIAP (Baculoviral IAP repeat-containing protein 4; NCBI GI: 32528298; 서열번호 104).XIAP (Baculoviral IAP repeat-containing protein 4; NCBI GI: 32528298; SEQ ID NO: 104).

간암의 예후는 다양한 관점에서 추정될 수 있지만, 대표적으로 재발가능성, 생존가능성, 무병생존가능성의 관점에서 판단된다. 본 명세서에서 기술된 연구는 다수의 간암 환자의 간암조직에서 유전자 발현 프로파일을 수득하고, 이를 재발가능성, 생존가능성, 무병생존가능성의 관점을 모두 고려한 통계적 데이터 처리 과 정을 거쳐서, 유의성 있게 발현량의 차이가 발생하는 유전자들을 검출하여 간암의 예후 추정이 가능하도록 하는 마커들을 발굴하는 방식으로 진행되었다.The prognosis of liver cancer can be estimated from various points of view, but is typically judged in terms of recurrence, survival, and disease-free survival. The studies described herein obtain a gene expression profile in liver cancer tissues of a number of liver cancer patients and, through statistical data processing, taking into account both recurrence, viability, and disease-free survival, By detecting the genes that cause the difference, we proceeded by identifying the markers that enable us to estimate the prognosis of liver cancer.

본 명세서에서 "간암 예후 마커"는 간암 발병 이후 예후가 양호하거나 불량한 환자를 예측해내는 기준이 되는 유전자 마커를 지칭한다. 본 발명에서 이 마커는 예후가 양호한 환자의 간암 조직 내에서의 발현량이 실험적으로 설정된 기준치와 비교할 때 특징적으로 많거나 적다. 구체적으로, 본 발명에서 이 마커는 예후가 양호한 환자와 불량한 환자의 간암 조직 내에서의 발현 차이에 기초하여 산출되는 p-값이 유의하게 낮다. 바람직하게는, 상기 p-값은 0.05 미만이다.As used herein, "hepatic cancer prognostic marker" refers to a genetic marker that serves as a basis for predicting a patient with a good or poor prognosis after the development of liver cancer. In the present invention, this marker is characteristically more or less when compared with the experimentally established reference value in the liver cancer tissue of a patient with a good prognosis. Specifically, in the present invention, this marker has a significantly low p-value calculated based on the difference in expression in liver cancer tissue of a patient with a good prognosis and a poor prognosis. Preferably, the p-value is less than 0.05.

본 발명은 간암의 발병이 확인된 다수의 환자들의 간암 조직을 대상으로 하여 치료 경과가 양호하거나 불량한 환자의 간암 조직의 유전자 발현 프로파일을 기준치와 비교하여 분석한 것이기 때문에, 이렇게 확인된 마커는 간암의 예후가 양호하거나 불량한 환자를 그렇지 않은 환자와 특이적으로 구분해낼 수 있으며, 따라서 간암의 예후를 추정하는데 유용하게 사용될 수 있다. 나아가, 이렇게 확인된 마커가 특정 예후의 환자의 간암 조직에서 특이적으로 고발현 또는 저발현하는 것이라는 점을 감안한다면, 이 마커의 생리학적 기능은 간암 발병 및 진행, 특히 상기 예후와 관련된 생리학적 기능에 직접적으로 관계된 것일 가능성이 있으며, 따라서 이 마커는 간암 발병 및 진행의 메커니즘을 연구하거나 간암 치료제의 개발을 위한 표적으로서도 유용하게 사용될 수 있다.Since the present invention analyzes gene expression profiles of liver cancer tissues of patients with good or poor treatment progress in comparison to baseline in liver cancer tissues of a large number of patients whose liver cancer has been confirmed, the markers thus identified are those of liver cancer. Patients with a good or poor prognosis can be specifically distinguished from patients who do not, and thus can be usefully used to estimate the prognosis of liver cancer. Furthermore, given that the markers thus identified are specifically high or low expression in liver cancer tissues of patients with a particular prognosis, the physiological function of these markers is the development and progression of liver cancer, in particular the physiological functions associated with the prognosis. There is a possibility that the marker may be directly related to, and thus this marker may be usefully used as a target for studying the mechanism of liver cancer development and progression or for developing a liver cancer therapeutic agent.

특히 본 발명의 첫번째 국면의 간암 예후 마커는 종래 유래가 없는 정도의 다수의 환자의 간암 조직을 통계적으로 분석하여 발굴해낸 것이기 때문에, 극히 일 부 환자의 간암 조직의 유전자 발현 프로파일에 기초하여 발굴된 종래의 간암 관련 마커들에 비하여 더욱 유의성이 있고 임상적으로 활용 가치가 높은 마커들이며, 간암 예후 추정에 있어서 보다 정확한 예측력을 보유하는 것이다.In particular, since the liver cancer prognostic marker of the first aspect of the present invention is obtained by statistically analyzing the liver cancer tissues of a large number of patients with no conventional origin, it has been discovered based on the gene expression profile of the liver cancer tissues of some patients. These markers are more meaningful and clinically useful than liver cancer related markers, and have more accurate predictive power in estimating liver cancer prognosis.

본 발명의 두번째 국면은 상기 첫번째 국면의 간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두를 특이적으로 검출하는 물질을 포함하는 간암 예후 추정용 조성물에 관한 것이다.The second aspect of the present invention relates to a composition for estimating hepatic cancer prognosis comprising a substance that specifically detects the expression level, expression pattern, or both of the liver cancer prognostic marker of the first aspect.

여기서 각 간암 예후 마커의 발현량이나 발현 패턴은 해당 유전자의 전사로 인해 생성된 mRNA의 양이나 패턴을 확인하는 통상적인 생화학적 분석 방법으로써 검출될 수 있다. 이러한 mRNA의 양이나 패턴을 확인하기 위한 분석 방법으로는 RT-PCR, 경쟁적 RT-PCR (Competitive RT-PCR), 실시간 RT-PCR (Real-time RT-PCR), RNase 보호 분석법 (RNase protection assay), 노던 블랏, DNA 마이크로어레이 등이 있으나, 그 외에도 당업계에서 통상적으로 수행되는 어떠한 방법이라도 사용될 수 있다.Here, the expression level or expression pattern of each liver cancer prognostic marker can be detected by a conventional biochemical analysis method for confirming the amount or pattern of mRNA generated by transcription of the gene. Analytical methods for determining the amount or pattern of such mRNAs include RT-PCR, competitive RT-PCR, Real-time RT-PCR, and RNase protection assay. , Northern blots, DNA microarrays, and the like, but any other method commonly performed in the art may be used.

이 분석 방법들을 통하여, 간암 환자의 생물학적 시료에서의 mRNA의 양이나 패턴을 기준치와 비교할 수 있고, 이로부터 본 발명의 간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두의 차이를 검출하며, 간암 환자의 예후를 추정하는 것이 가능하게 된다. 본 명세서에서 "생물학적 시료"란 간암 예후 마커의 발현량이나 발현 패턴, 또는 간암 예후 마커가 코딩하는 단백질의 존재량이나 존재 패턴을 검출할 수 있는 인체로부터 분리된 세포, 조직 등을 의미하며, 뇨, 혈액, 혈장, 혈청 등을 예로 들 수 있지만 특별히 이에 제한되지는 않는다.Through these analytical methods, the amount or pattern of mRNA in a biological sample of liver cancer patients can be compared with a baseline, from which the difference in expression level, expression pattern, or both of liver cancer prognostic markers of the present invention is detected, and liver cancer It is possible to estimate the prognosis of the patient. As used herein, the term "biological sample" refers to a cell or tissue isolated from a human body capable of detecting the amount or pattern of expression of a liver cancer prognostic marker or the amount or pattern of protein encoding a liver cancer prognostic marker. , Blood, plasma, serum, and the like, but is not particularly limited thereto.

mRNA의 양이나 패턴을 RT-PCR로 측정하기 위한 키트는 본 발명의 간암 예후 마커의 mRNA에 특이적인 프라이머를 포함한다. 본 명세서에서 "프라이머"는 템플레이트 (template) 와 상보적으로 결합할 수 있고 역전사효소 또는 DNA 중합효소가 템플레이트의 복제를 개시할 수 있도록 하는 자유 3말단 수산화기 (free 3' hydroxyl group) 를 가지는 핵산 서열을 의미한다. 프라이머는 특정 유전자의 핵산 서열에 상보적인 서열을 가지는 뉴클레오티드로서, 약 7 bp 내지 50 bp의 길이, 바람직하게는 약 10 bp 내지 30 bp 의 길이가 사용될 수 있다. 그 외 RT-PCR 키트는 구체적인 실시 양상에 따라 테스트 튜브 또는 다른 적절한 컨테이너, 반응 완충액, 데옥시뉴클레오티드 (dNTPs), Taq-폴리머라제 및 역전사효소와 같은 효소, DNAse, RNAse 억제제 DEPC-수 (DEPCwater), 멸균수 등을 포함할 수 있다. 프라이머는 적절한 완충용액 및 온도에서 중합반응 (즉, DNA 중합효소 또는 역전사효소) 을 위한 시약 및 상이한 4가지 뉴클레오사이드 트리포스페이트의 존재하에서 DNA 합성을 개시시킬 수 있다. 프라이머는 DNA 합성의 개시점으로 작용하는 프라이머의 기본 성질을 변화시키지 않는 추가의 다른 염기 서열을 포함할 수도 있다. 프라이머는 널리 공지된 방법을 사용하여 화학적으로 합성할 수 있으며, 이러한 핵산 서열은 또한 당해 분야에 공지된 많은 수단을 이용하여 변형시킬 수 있다.Kits for measuring the amount or pattern of mRNA by RT-PCR include primers specific for the mRNA of the liver cancer prognostic markers of the invention. As used herein, a "primer" refers to a nucleic acid sequence having a free 3 'hydroxyl group capable of complementarily binding to a template and allowing reverse transcriptase or DNA polymerase to initiate replication of the template. Means. A primer is a nucleotide having a sequence complementary to the nucleic acid sequence of a particular gene, and may be used in a length of about 7 bp to 50 bp, preferably about 10 bp to 30 bp. Other RT-PCR kits may include test tubes or other suitable containers, reaction buffers, deoxynucleotides (dNTPs), enzymes such as Taq-polymerase and reverse transcriptase, DNAse, RNAse inhibitor DEPC-water (DEPCwater), depending on the specific embodiment. , Sterile water and the like. Primers can initiate DNA synthesis in the presence of four different nucleoside triphosphates and reagents for polymerization (ie, DNA polymerase or reverse transcriptase) at appropriate buffers and temperatures. The primer may also include additional other base sequences that do not change the basic properties of the primer that serve as the starting point for DNA synthesis. Primers can be chemically synthesized using well known methods, and such nucleic acid sequences can also be modified using many means known in the art.

본 발명의 두번째 국면에서의 "간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두를 특이적으로 검출하는 물질"은 해당 간암 예후 마커의 발현량이나 발현 패턴의 분석 방법에 있어서 해당 마커에 특이적으로 사용될 수 있는 임의의 물질 또는 그 둘 이상의 조합일 수 있으며, 반드시 RT-PCR용 프라이머에 제한되는 것은 아니다. 본 발명의 두번째 국면은 대상 간암 환자의 간암 조직에서의 간암 예후 마커의 발현량이나 발현 패턴을 기준치와 비교하여 그 차이를 검출하는 것에 기술적 특징이 있는 것이기 때문에, 이러한 차이의 검출을 가능하게 하는 물질은 어떠한 것이라도 "간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두를 특이적으로 검출하는 물질"로서 사용될 수 있고 발명이 목적하는 기술적 효과를 달성할 수 있으며, 당업자라면 당업계의 평균적인 지식을 참고하여 구체적인 실시양상에 따라 적당한 물질을 선택/선별하여 사용할 수 있을 것이다.In the second aspect of the present invention, "a substance which specifically detects the expression amount, expression pattern, or both of the liver cancer prognostic markers" is specific to the marker in the method for analyzing the expression amount or expression pattern of the liver cancer prognostic markers. Any material that can be used as or a combination of two or more thereof, and is not necessarily limited to primers for RT-PCR. The second aspect of the present invention is a technical feature of detecting the difference by comparing the expression level or expression pattern of liver cancer prognostic markers in liver cancer tissues of the subject liver cancer patients with a reference value, and thus a substance capable of detecting such a difference. Can be used as "a substance that specifically detects the expression level, expression pattern, or both of liver cancer prognostic markers" and the invention can achieve the desired technical effect, and those skilled in the art have the average knowledge Reference may be made to select / select suitable materials according to specific embodiments.

본 발명의 세번째 국면은 상기 첫번째 국면의 간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두를 특이적으로 검출하는 물질을 포함하는 간암 예후 추정용 조성물에 관한 것이다.A third aspect of the present invention relates to a composition for estimating hepatic cancer prognosis comprising a substance that specifically detects an amount of a protein encoded by the liver cancer prognostic marker of the first aspect, a presence pattern, or both.

본 발명의 간암 예후 마커의 발현량이나 발현 패턴은, 상기 본 발명의 두번째 국면과 같이 각 마커의 발현에 따른 mRNA의 양이나 패턴을 검출하는 방법을 사용하는 것 외에도, 시료 내에서 각 마커가 코딩하는 단백질의 존재량이나 존재 패턴을 검출함으로써 각 마커의 발현량이나 발현 패턴을 유추하는 방법을 사용할 수도 있다.The expression amount and expression pattern of the liver cancer prognostic markers of the present invention, in addition to using a method for detecting the amount or pattern of mRNA according to the expression of each marker as in the second aspect of the present invention, each marker is encoded in the sample The method of inferring the expression amount and expression pattern of each marker can also be used by detecting the quantity or expression pattern of the said protein.

본 발명에서 간암 예후 마커가 코딩하는 단백질의 존재량이나 존재 패턴의 특이적인 검출은 생물학적 시료 내에 본 발명의 간암 예후 마커가 코딩하는 단백질이 얼마나 존재하는지 및 어떠한 패턴으로 존재하는지를 확인하는 과정을 의미하며, 예를 들어, 상기 간암 예후 마커가 코딩하는 단백질에 대하여 특이적으로 결합 하는 항체를 이용하여 그 존재량이나 존재 패턴을 확인하는 과정이 활용될 수 있다. 본 명세서에서 "항체"란 항원의 항원결정기 (epitope) 에 특이적으로 결합할 수 있는 단백질을 의미하며, 다클론 항체, 단일클론 항체 및 재조합 항체를 모두 포함하는 개념이다.Specific detection of the amount or pattern of the protein encoded by the liver cancer prognostic marker in the present invention refers to the process of identifying how and in what pattern the protein encoded by the liver cancer prognostic marker of the present invention in a biological sample. For example, a process of confirming the abundance or the presence pattern using an antibody that specifically binds to the protein encoded by the liver cancer prognostic marker may be utilized. As used herein, the term "antibody" refers to a protein that can specifically bind to epitopes of an antigen, and is a concept including all polyclonal antibodies, monoclonal antibodies, and recombinant antibodies.

항체를 이용하여 단백질의 존재량이나 존재 패턴을 측정하는 방법으로는, 웨스턴 블랏, ELISA (enzyme linked immunosorbent assay) , 방사선 면역분석 (Radioimmunoassay), 방사 면역 확산법 (radioimmunodiffusion), 오우크테를로니 (Ouchterlony) 면역 확산법, 로케트 (rocket) 면역 전기영동, 조직 면역 염색, 면역 침전 분석법 (Immunoprecipitation Assay), 보체 고정 분석법 (Complement Fixation Assay), FACS, 단백질 칩 (protein chip) 등이 있으나, 그 외에도 당업계에서 통상적으로 수행되는 어떠한 방법이라도 사용될 수 있다.Methods for measuring the amount or pattern of abundance of proteins using an antibody include Western blot, enzyme linked immunosorbent assay (ELISA), radioimmunoassay, radioimmunodiffusion, and Ouchterlony. Immune diffusion, rocket immunoelectrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, FACS, protein chip, etc. Any method performed by the above can be used.

이 분석 방법들을 통하여, 대상 간암 환자의 생물학적 시료에서의 항원-항체 복합체의 형성량이나 그 형성 패턴과 기준치를 비교할 수 있고, 이로부터 본 발명의 간암 예후 마커가 코딩하는 단백질의 존재량이나 존재 패턴을 판단할 수 있으며, 궁극적으로 간암 환자의 예후를 추정할 수 있게 된다.Through these analytical methods, the amount of antigen-antibody complex formed in a biological sample of a target liver cancer patient and its formation pattern can be compared with the reference value. From this, the amount or presence pattern of the protein encoded by the liver cancer prognostic marker of the present invention can be compared. The prognosis of the liver cancer patient can be estimated ultimately.

여기서 "항원-항체 복합체"란 간암 예후 마커가 코딩하는 단백질과 이에 특이적인 항체의 결합물을 의미하고, 항원-항체 복합체의 형성량이나 형성 패턴은 통상 2차 항체에 연계된 검출 라벨 (detection label) 의 시그널의 크기 및 패턴을 검출함으로써 측정이 가능하다. 이러한 검출 라벨은 효소, 형광물, 리간드, 발광물, 미소입자, 레독스 분자, 방사선 동위원소 등을 예로 들 수 있으나, 반드시 이로 제한되는 것은 아니다. 검출 라벨로서 효소가 사용되는 경우 이용 가능한 효소에는 β-글루쿠로니다제, β-D-글루코시다제, β-D-갈락토시다제, 우레아제, 퍼옥시다아제 또는 알칼라인 포스파타아제, 아세틸콜린에스테라제, 글루코즈 옥시다제, 헥소키나제와 GDPase, RNase, 글루코즈 옥시다제, 루시페라제, 포스포프럭토키나제, 포스포에놀피루베이트 카복실라제, 아스파르테이트 아미노트랜스페라제, 포스페놀피루베이트 데카복실라제, β-라타마제 등이 있으나, 이로 제한되지 않는다. 검출 라벨로서 형광물이 사용되는 경우 이용 가능한 형광물에는 플루오레신, 이소티오시아네이트, 로다민, 피코에리테린, 피코시아닌, 알로피코시아닌, o-프탈데히드, 플루오레스카민 등이 있으나, 이로 제한되지 않는다. 검출 라벨로서 리간드가 사용되는 경우 이용 가능한 리간드에는 바이오틴 유도체 등이 있으나, 이로 제한되지 않는다. 검출 라벨로서 발광물이 사용되는 경우 이용 가능한 발광물에는 아크리디늄 에스테르, 루시페린, 루시퍼라아제 등이 있으나, 이로 제한되지 않는다. 검출 라벨로서 미소입자가 사용되는 경우 이용 가능한 미소입자에는 콜로이드 금, 착색된 라텍스 등이 있으나, 이로 제한되지 않는다. 검출 라벨로서 레독스 분자가 사용되는 경우 이용 가능한 레독스 분자에는 페로센, 루테늄 착화합물, 바이올로젠, 퀴논, Ti 이온, Cs 이온, 디이미드, 1,4-벤조퀴논, 하이드로퀴논, K4W(CN)8, [Os(bpy)3]2+ , [RU(bpy)3]2+, [MO(CN)8]4- 등이 있으나, 이로 제한되지 않는다. 검출 라벨로서 방사성 동위원소가 사용되는 경우 이용 가능한 방사성 동위원소에는 3H, 14C, 32P, 35S, 36Cl, 51Cr, 57Co, 58Co, 59Fe, 90Y, 125I, 131I 또는 186Re 등이 있으나, 이로 제한되지 않는다.The term “antigen-antibody complex” means a combination of a protein encoded by a liver cancer prognostic marker and an antibody specific thereto, and the amount or pattern of formation of the antigen-antibody complex is usually a detection label associated with a secondary antibody. Measurement is possible by detecting the magnitude and pattern of the signal. Such detection labels include, but are not limited to, enzymes, fluorescent materials, ligands, luminescent materials, microparticles, redox molecules, radioisotopes, and the like. When enzymes are used as detection labels, available enzymes include β-glucuronidase, β-D-glucosidase, β-D-galactosidase, urease, peroxidase or alkaline phosphatase, acetylcholinese Therapase, glucose oxidase, hexokinase and GDPase, RNase, glucose oxidase, luciferase, phosphofructokinase, phosphoenolpyruvate carboxylase, aspartate aminotransferase, phosphphenolpyruvate deca Carboxylase, β-latamase, and the like, but are not limited thereto. When fluorescent materials are used as detection labels, available fluorescent materials include fluorescein, isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthalaldehyde, fluorescamine, etc. However, this is not limiting. When a ligand is used as a detection label, available ligands include, but are not limited to, biotin derivatives. When a luminescent material is used as the detection label, available luminescent materials include, but are not limited to, acridinium ester, luciferin, luciferase, and the like. When the microparticles are used as the detection label, the microparticles available include, but are not limited to, colloidal gold and colored latex. When redox molecules are used as detection labels, the available redox molecules include ferrocene, ruthenium complex, biologen, quinone, Ti ion, Cs ion, diimide, 1,4-benzoquinone, hydroquinone, K4W (CN) 8 , [Os (bpy) 3] 2+, [RU (bpy) 3] 2+, [MO (CN) 8] 4- and the like, but are not limited thereto. When radioisotopes are used as detection labels, the radioisotopes available include, but are not limited to, 3H, 14C, 32P, 35S, 36Cl, 51Cr, 57Co, 58Co, 59Fe, 90Y, 125I, 131I or 186Re.

본 발명의 세번째 국면에서의 "간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두를 특이적으로 검출하는 물질"은 간암 예후 마커가 코딩하는 단백질의 존재량이나 존재 패턴을 검출하기 위한 분석 방법에서 그 마커가 코딩하는 단백질에 대하여 특이적으로 사용될 수 있는 임의의 물질일 수 있으며, 반드시 항체로 제한되는 것은 아니다. 본 발명의 세번째 국면은 대상 간암 환자의 생물학적 시료에서 간암 예후 마커가 코딩하는 단백질의 존재량이나 존재 패턴을 기준치와 비교하여 그 차이를 검출하는 것에 기술적 특징이 있는 것이기 때문에, 이러한 차이의 검출을 가능하게 하는 물질이라면 어떠한 것이라도 "간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두를 특이적으로 검출하는 물질"로서 사용될 수 있고 발명이 목적하는 기술적 효과를 달성할 수 있으며, 당업자라면 당업계의 평균적인 지식 및 공지기술을 참고하여 구체적인 실시양상에 따라 적당한 물질을 특별한 어려움 없이 선택/선별하여 사용할 수 있을 것이다.In the third aspect of the present invention, "a substance that specifically detects the amount, pattern, or both of the protein encoded by the liver cancer prognostic marker" is used to detect the amount or pattern of the protein encoded by the liver cancer prognostic marker. In the assay method, the marker may be any substance that can be used specifically for the protein encoding, and is not necessarily limited to the antibody. The third aspect of the present invention is because the technical features of detecting the difference by comparing the amount or pattern of presence of the protein encoded by the liver cancer prognostic marker in the biological sample of the subject liver cancer patient with the reference value, it is possible to detect such a difference Any substance to be used can be used as "a substance which specifically detects the amount of a protein, the pattern of abundance, or both of which the liver cancer prognostic marker encodes", and can achieve the technical effect which this invention aims at, If the reference to the average knowledge and well-known technology in the art can be used to select / select the appropriate material according to the specific embodiment without particular difficulties.

본 발명의 네번째 국면은 상기 본 발명의 두번째 국면 또는 세번째 국면의 간암 예후 추정용 조성물을 포함하는 간암 예후 추정용 키트에 관한 것이다.A fourth aspect of the present invention relates to a kit for estimating liver cancer prognosis comprising a composition for estimating hepatic cancer prognosis of the second or third aspect of the present invention.

본 발명의 간암 예후 추정용 키트는 간암 예후 추정용 조성물에 포함되는 간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두를 특이적으로 검출하는 물질 또는 간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두를 특이적으로 검출하는 물질 외에, 유전자 발현량이나 발현 패턴의 분석 방법 또는 단백질 존재량이나 존재 패턴의 분석 방법에 적합한 한 종류 또는 그 이상의 다른 구성 성분, 용액 또는 장치를 더 포함할 수 있다. 예를 들어, 상기 진단 키트 가 유전자의 발현량이나 발현 패턴을 검출하기 위한 진단 키트인 경우에는, 이 진단 키트는 RT-PCR을 수행하기 위해 필요한 필수 성분을 포함하는 진단 키트일 수 있으며, 이러한 RT-PCR 키트는 마커 유전자의 mRNA에 대한 특이적인 각각의 프라이머 외에도 구체적인 실시 양상에 따라 예를 들어 테스트 튜브 또는 다른 적절한 컨테이너, 반응 완충액, 데옥시뉴클레오티드 (dNTPs), Taq-폴리머라제 및 역전사효소와 같은 효소, DNAse, RNAse 억제제 DEPC-수 (DEPCwater), 멸균수, 정량 대조군으로 사용되는 유전자에 특이적인 프라이머 쌍 등을 포함할 수 있다. 한편, 상기 진단 키트가 단백질의 존재량이나 존재 패턴을 검출하기 위한 진단 키트인 경우에는, 이 진단 키트는 예를 들어 ELISA를 수행하기 위해 필요한 필수 성분을 포함하는 진단 키트일 수 있으며, 이러한 ELISA 키트는 결합된 항체를 검출할 수 있는 성분들, 예를 들어 표지된 2차 항체, 발색단 (chromopores), 효소 (예를 들어, 항체와 접합된 효소) 및 그의 기질, 및 정량 대조군 단백질에 특이적인 항체 등을 포함할 수 있다. 또한, 구체적인 실시 양상에 따라서는, 상기 진단 키트는 DNA 마이크로어레이 또는 단백질 마이크로어레이를 포함할 수 있다.The kit for estimating liver cancer prognosis of the present invention includes a substance that specifically detects the expression amount, expression pattern, or both of the expression of the liver cancer prognostic marker included in the composition for estimating the liver cancer prognosis, or the amount of the protein encoded by the liver cancer prognostic marker, or the presence thereof. In addition to the substance which specifically detects the pattern or both, it further comprises one or more other components, solutions or devices suitable for the method for analyzing the gene expression amount or expression pattern or for the method for analyzing the amount or presence of protein. can do. For example, when the diagnostic kit is a diagnostic kit for detecting the expression level or expression pattern of a gene, the diagnostic kit may be a diagnostic kit including essential components necessary to perform RT-PCR, such RT PCR kits can be used in addition to individual primers specific for mRNA of the marker gene, depending on the specific embodiment, such as, for example, test tubes or other suitable containers, reaction buffers, deoxynucleotides (dNTPs), Taq-polymerases and reverse transcriptases. Enzymes, DNAse, RNAse inhibitor DEPC-water (DEPCwater), sterile water, primer pairs specific for genes used as quantitative controls, and the like. On the other hand, when the diagnostic kit is a diagnostic kit for detecting the amount or pattern of the presence of the protein, the diagnostic kit may be, for example, a diagnostic kit containing essential components necessary to perform the ELISA, such ELISA kit Is an antibody that is specific for components capable of detecting bound antibodies, such as labeled secondary antibodies, chromopores, enzymes (eg, enzymes conjugated with antibodies) and substrates thereof, and quantitative control proteins. And the like. In addition, according to a specific embodiment, the diagnostic kit may comprise a DNA microarray or a protein microarray.

본 발명의 다섯번째 국면은, 상기 본 발명의 두번째 국면의 간암 예후 추정용 조성물을 대상 간암 환자에게서 채취한 생물학적 시료에 처리하는 제 1 단계; 및 제 1 단계의 처리 결과를 기준치와 대비하여 제 1 항의 간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두의 차이를 검출하는 제 2 단계를 포함하는 간암 예후 추정 방법에 관한 것이다. 또한, 추가로, 본 발명의 다섯번째 국면은, 상기 본 발명의 세번째 국면의 간암 예후용 조성물을 간암 예후 추정용 조성물을 간암 환자에게서 채취한 생물학적 시료에 처리하는 제 1 단계; 및 제 1 단계의 처리 결과를 기준치와 대비하여 제 1 항의 간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두의 차이를 검출하는 제 2 단계를 포함하는 간암 예후 추정 방법에 관한 것이다.The fifth aspect of the present invention, the first step of treating the liver cancer prognosis composition of the second aspect of the present invention to a biological sample collected from a target liver cancer patient; And a second step of detecting a difference between the expression level, expression pattern, or both of the liver cancer prognostic marker of claim 1 based on the treatment result of the first step against a reference value. In addition, the fifth aspect of the present invention, the first step of treating the liver cancer prognosis composition of the third aspect of the present invention to a biological sample collected from a liver cancer patient a composition for estimating liver cancer prognosis; And a second step of detecting a difference in the amount of abundance, the presence pattern, or both of the proteins encoded by the liver cancer prognostic marker according to the first step, based on the treatment result of the first step, and the reference value. .

예를 들어, 간암의 예후가 양호한 환자의 간암 조직에서 더 많이 발현하는 간암 예후 마커의 발현량의 차이를 검출하는 경우에는, 만약 대상 간암 환자의 생물학적 시료에서의 상기 마커의 발현량이 기준치보다 많다면 이는 간암의 예후가 상대적으로 양호할 것이라는 점을 제시하는 것이라고 할 수 있을 것이다. 한편, 예를 들어, 간암의 예후가 불량한 환자의 간암 조직에서 더 많이 발현하는 간암 예후 마커의 발현량의 차이를 검출하는 경우에는, 만약 대상 간암 환자의 생물학적 시료에서의 상기 마커의 발현량이 기준치보다 많다면 이는 간암의 예후가 상대적으로 불량할 것이라는 점을 제시하는 것이라고 할 수 있을 것이다.For example, when detecting a difference in the expression level of liver cancer prognostic markers that are expressed more in liver cancer tissues of a patient with a good prognosis of liver cancer, if the expression level of the markers in a biological sample of a subject liver cancer patient is greater than the reference value, This suggests that the prognosis of liver cancer will be relatively good. On the other hand, for example, when detecting the difference in the expression amount of liver cancer prognostic markers expressed more in the liver cancer tissues of patients with poor prognosis of liver cancer, if the expression amount of the markers in the biological sample of the subject liver cancer patients In many cases, this suggests that the prognosis for liver cancer will be relatively poor.

한편, 예를 들어, 간암의 예후가 양호한 환자의 간암 조직에서 더 많이 발현하는 간암 예후 마커가 코딩하는 단백질의 존재량의 차이를 검출하는 경우에는, 만약 대상 간암 환자의 생물학적 시료에서의 상기 마커가 코딩하는 단백질의 존재량이 기준치보다 많다면 이는 간암의 예후가 상대적으로 양호할 것이라는 점을 제시하는 것이라고 할 수 있을 것이다. 한편, 예를 들어, 간암의 예후가 불량한 환자의 간암 조직에서 더 많이 발현하는 간암 예후 마커가 코딩하는 단백질의 존재량의 차이를 검출하는 경우에는, 만약 대상 간암 환자의 생물학적 시료에서의 상기 마커가 코딩하는 단백질의 존재량이 기준치보다 많다면 이는 간암의 예후가 상대적 으로 불량할 것이라는 점을 제시하는 것이라고 할 수 있을 것이다.On the other hand, for example, when detecting a difference in the amount of protein encoded by a liver cancer prognostic marker that is expressed more in liver cancer tissue of a patient with a good prognosis of liver cancer, if the marker in the biological sample of the subject liver cancer patient is If the amount of protein encoding is greater than the baseline, this may indicate that the prognosis of liver cancer will be relatively good. On the other hand, for example, when detecting a difference in the amount of protein encoded by a liver cancer prognostic marker that is expressed more in liver cancer tissue of a patient with a poor prognosis of liver cancer, if the marker in the biological sample of the subject liver cancer patient is If the amount of protein encoding is greater than the baseline, this may indicate that the prognosis for liver cancer will be relatively poor.

본 발명의 여섯번째 국면은 본 발명의 첫번째 국면의 간암 예후 마커를 활용한 간암 치료제의 스크리닝 방법에 관한 것이다. 본 발명의 첫번째 국면의 간암 예후 마커는 간암 환자의 예후에 따른 발현 양상의 차이가 두드러지는 것이기 때문에 간암의 발병이나 진행, 특히 상기 예후와 관련된 생리학적 기능에 직접 관여하는 유전자일 가능성이 있으며, 따라서 상기 마커가 코딩하는 단백질은 간암 발병이나 진행의 메커니즘을 연구하거나 간암 치료제의 개발을 위한 표적 단백질로서도 유용하게 사용될 수 있는 것이다. 즉, 본 발명의 첫번째 국면의 간암 예후 마커는 간암의 치료제 개발의 중요한 전제를 해결한 것이므로, 따라서 이 마커를 이용하여 간암의 치료제를 스크리닝하는 방법도 또한 본 발명의 범주에 속한다.A sixth aspect of the present invention relates to a method for screening a liver cancer therapeutic agent utilizing the liver cancer prognostic marker of the first aspect of the present invention. The hepatic cancer prognostic marker of the first aspect of the present invention may be a gene directly involved in the development or progression of liver cancer, in particular the physiological function associated with the prognosis, since the difference in the expression pattern according to the prognosis of the liver cancer patient is prominent. The protein encoded by the marker may be useful as a target protein for studying the mechanism of liver cancer development or progression, or for the development of a therapeutic agent for liver cancer. That is, since the liver cancer prognostic marker of the first aspect of the present invention solves an important premise of the development of a therapeutic agent for liver cancer, a method for screening a therapeutic agent for liver cancer using this marker is also within the scope of the present invention.

본 발명의 여섯번째 국면의 예로는, 시험 화합물이 본 발명의 첫번째 국면의 간암 예후 마커의 발현을 촉진 또는 억제하는지 여부를 확인하는 단계를 포함하는 간암 치료제의 스크리닝 방법을 들 수 있다. 이러한 치료제를 스크리닝하는 방법으로는, 예를 들어, RT-PCR, 경쟁적 RT-PCR (Competitive RT-PCR), 실시간 RT-PCR (Real-time RT-PCR), RNase 보호 분석법 (RNase protection assay), 노던 블랏, DNA 마이크로어레이, SAGE [Serial Analysis of Gene Expression; Velculescu et al, Science 270:484-7], MPSS [Massively Parellel Signature Sequencing; Brenner et al, PNAS. USA. 97, 1665-1670] 등을 활용할 수 있으나, 그 외에도 필요에 따라 당업계에 알려진 다수의 공지의 방법을 사용할 수 있다.An example of a sixth aspect of the invention is a method of screening for a liver cancer therapeutic agent comprising the step of identifying whether the test compound promotes or inhibits the expression of the liver cancer prognostic marker of the first aspect of the invention. Methods for screening such therapeutic agents include, for example, RT-PCR, competitive RT-PCR, Real-time RT-PCR, RNase protection assay, Northern blots, DNA microarrays, SAGE [Serial Analysis of Gene Expression; Velculescu et al, Science 270: 484-7, MPSS [Massively Parellel Signature Sequencing; Brenner et al, PNAS. USA. 97, 1665-1670, and the like, but in addition, a number of known methods known in the art may be used as necessary.

한편, 본 발명의 여섯번째 국면의 또다른 예로는, 본 발명의 첫번째 국면의 간암 예후 마커가 코딩하는 단백질에 시험 화합물을 결합시키는 제 1 단계; 및 시험 화합물이 상기 단백질의 생리학적 활성을 촉진 또는 억제하는지 여부를 확인하는 제 2 단계를 포함하는 간암 치료제의 스크리닝 방법을 들 수 있다. 이런 치료제를 스크리닝하는 방법으로는, 본 발명의 첫번째 국면의 간암 조기 진단용 단백질성 마커를 어피니티 칼럼에 고정시키고 이를 시료와 접촉시켜 정제하는 방법 [Pandya et al, Virus Res 87: 135-143, 2002], 투-하이브리드 (two-hybrid) 방법을 이용하는 방법, 웨스턴 블랏, 하이스루풋스크리닝 방법 [High-Throughput Screening; Aviezer et al, J Biomol Screen 6: 171-7, 2001] 등을 활용할 수 있으나, 그 외에도 필요에 따라 당업계에 알려진 다수의 공지의 방법을 사용할 수 있다.Meanwhile, another example of the sixth aspect of the present invention may include a first step of binding a test compound to a protein encoded by a liver cancer prognostic marker of the first aspect of the present invention; And a second step of confirming whether the test compound promotes or inhibits the physiological activity of the protein. As a method of screening such a therapeutic agent, a method of fixing the proteinaceous marker for early diagnosis of liver cancer of the first aspect of the present invention in an affinity column and contacting and purifying the sample [Pandya et al, Virus Res 87: 135-143, 2002] ], Using the two-hybrid method, Western blot, high throughput screening method [High-Throughput Screening; Aviezer et al, J Biomol Screen 6: 171-7, 2001, and the like, but in addition, a number of known methods known in the art may be used as necessary.

본 발명의 여섯번째 국면에서 스크리닝에 사용하기 위한 시험 화합물로는, 예를 들어, 조직 추출액, 유전자 라이브러리의 발현산물, 합성 화합물, 합성 펩티드, 천연 화합물 등이 사용될 수 있으나 이에 제한되지는 않는다.As a test compound for use in screening in the sixth aspect of the present invention, for example, tissue extracts, expression products of gene libraries, synthetic compounds, synthetic peptides, natural compounds and the like can be used, but are not limited thereto.

본 발명의 일곱번째 국면은, 본 발명의 첫번째 국면의 간암 예후 마커가 코딩하는 단백질을 특이적으로 인식하는 항체에 관한 것이다.A seventh aspect of the present invention relates to an antibody that specifically recognizes a protein encoded by the liver cancer prognostic marker of the first aspect of the present invention.

본 발명의 첫번째 국면의 간암 예후 마커를 특이적으로 인식하는 항체는 간암 예후 마커가 코딩하는 단백질의 존재량이나 존재 패턴을 특이적으로 검출하는 대표적인 물질이며, 따라서 간암의 예후 추정을 위해 유용하게 사용할 수 있는 물질에 해당한다. 나아가, 경우에 따라서는 간암의 발병이나 진행에 중요한 역할을 담당하는 단백질의 활성을 특이적으로 촉진하거나 억제할 수도 있으며, 이에 따 라 간암에 대한 치료제로서도 활용될 수 있다.Antibodies that specifically recognize the liver cancer prognostic markers of the first aspect of the present invention are representative substances that specifically detect the amount or pattern of the protein encoded by the liver cancer prognostic markers, and thus may be useful for estimating the prognosis of liver cancer. Corresponds to the possible substances. Furthermore, in some cases, it may specifically promote or inhibit the activity of a protein that plays an important role in the development or progression of liver cancer, and thus may be used as a treatment for liver cancer.

본 발명의 첫번째 국면의 간암 예후 마커가 발굴되었으므로, 이를 이용하여 각 간암 예후 마커가 코딩하는 단백질에 대한 다클론 항체, 단일클론 항체 및 재조합 항체를 제조하는 것은 당업계에 널리 공지된 기술을 이용하여 용이하게 수행될 수 있다.Since the liver cancer prognostic markers of the first aspect of the present invention have been discovered, the production of polyclonal antibodies, monoclonal antibodies and recombinant antibodies to the proteins encoded by the respective liver cancer prognostic markers using techniques well known in the art. It can be performed easily.

다클론 항체는 상기한 본 발명의 첫번째 국면의 간암 예후 마커가 코딩하는 단백질 항원을 동물에 주사하고 동물로부터 채혈하여 항체를 포함하는 혈청을 수득하는 당업계에 널리 공지된 방법에 의해 생산할 수 있다. 이러한 다클론 항체는 염소, 토끼, 양, 원숭이, 말, 돼지, 소, 개 등의 다양한 동물 종 숙주로부터 제조 가능하며, 그 제조 방법은 당업계에 잘 알려져 있다.Polyclonal antibodies can be produced by methods well known in the art for injecting into the animal the protein antigen encoded by the liver cancer prognostic marker of the first aspect of the invention described above and collecting blood from the animal to obtain a serum comprising the antibody. Such polyclonal antibodies can be prepared from a variety of animal species hosts such as goats, rabbits, sheep, monkeys, horses, pigs, cattle, dogs, and the like, and methods for their preparation are well known in the art.

단일클론 항체는 당업계에 널리 공지된 하이브리도마 방법 (hybridoma method) (Kohler 및 Milstein (1976) European Jounral of Immunology 6:511-519 참조), 또는 파지 항체 라이브러리 (Clackson et al, Nature, 352:624-628, 1991; Marks et al, J. Mol. Biol., 222:58, 1-597, 1991) 기술 등을 이용하여 제조될 수 있다. 통상적으로, 하이브리도마 방법은 본 발명의 첫번째 국면의 간암 예후 마커가 코딩하는 단백질 항원을 주사한 마우스와 같은 면역학적으로 적합한 숙주 동물로부터의 세포를 이용하고, 나머지 하나의 집단으로는 암 또는 골수종 세포주를 이용한다. 이러한 두 집단의 조직들을 폴리에틸렌글리콜과 같은 당업계에 널리 공지된 방법에 의해 융합시키고 나서 항체-생산 세포를 표준적인 조직 배양 방법에 의해 증식시킨다. 한계 희석법 (limited dilution technique) 에 의한 서브클 로닝에 의해 균일한 세포 집단을 수득한 후, 원하는 항체를 생산할 수 있는 하이브리도마를 공지된 기술에 따라 시험관 내에서 또는 생체내에서 대량으로 배양한다. 파지 항체 라이브러리 방법은 원하는 항체의 유전자를 획득하여 이를 파아지의 표면에 융합 단백질 형태로 발현시킴으로서 항체 라이브러리를 시험관 내에서 제작하고, 이 라이브러리로부터 원하는 단일클론 항체를 분리하여 단일클론 항체를 제작하는 방법이다. 상기 방법으로 제조된 단일클론 항체는 젤 전기영동, 투석, 염 침전, 이온교환 크로마토그래피, 친화성 크로마토그래피 등의 공지된 방법을 이용하여 분리할 수 있다.Monoclonal antibodies are known in the art by the hybridoma method (see Kohler and Milstein (1976) European Jounral of Immunology 6: 511-519), or phage antibody libraries (Clackson et al, Nature, 352: 624-628, 1991; Marks et al, J. Mol. Biol., 222: 58, 1-597, 1991), and the like. Typically, the hybridoma method utilizes cells from an immunologically suitable host animal, such as a mouse, injected with a protein antigen encoded by the liver cancer prognostic marker of the first aspect of the invention, with the other population being cancer or myeloma Use cell lines. These two populations of tissues are fused by methods well known in the art, such as polyethylene glycol, and then antibody-producing cells are propagated by standard tissue culture methods. After obtaining a uniform cell population by subcloning by the limited dilution technique, hybridomas capable of producing the desired antibody are cultured in vitro or in vivo in accordance with known techniques. Phage antibody library method is a method of producing an antibody library in vitro by obtaining a gene of the desired antibody and expressing it in the form of a fusion protein on the surface of the phage, to isolate the desired monoclonal antibody from the library to produce a monoclonal antibody . Monoclonal antibodies prepared by the above method can be separated using known methods such as gel electrophoresis, dialysis, salt precipitation, ion exchange chromatography, affinity chromatography.

본 발명의 일곱번째 국면의 항체는 2개의 전체 길이의 경쇄 및 2개의 전체 길이의 중쇄를 가지는 완전한 형태뿐만 아니라, 항체 분자의 기능적인 단편을 포함한다. 항체 분자의 기능적인 단편이란 항원 결합 기능을 보유하고 있는 단편을 뜻하며, Fab, F(ab'), F(ab')2 및 Fv 등이 있다.Antibodies of the seventh aspect of the invention include functional fragments of antibody molecules, as well as complete forms having two full length light chains and two full length heavy chains. The functional fragment of an antibody molecule means the fragment which has an antigen binding function, and includes Fab, F (ab '), F (ab') 2, and Fv.

본 발명에 의하여, 본 발명은 간암 예후 마커, 상기 간암 예후 마커의 발현량 변화를 검출하는 물질을 포함하는 간암 예후 추정용 조성물, 상기 간암 예후 추정용 조성물을 포함하는 간암 예후 추정용 키트, 상기 간암 예후 마커를 이용하는 간암 예후 추정 방법, 상기 간암 예후 마커를 활용한 간암 치료제 스크리닝 방법이 제공된다.According to the present invention, the present invention is a liver cancer prognostic marker, a composition for estimating liver cancer prognosis comprising a substance for detecting a change in the expression amount of the liver cancer prognostic marker, a kit for estimating liver cancer prognosis comprising the composition for estimating liver cancer prognosis, the liver cancer Provided are a method for estimating liver cancer prognosis using a prognostic marker, and a method for screening a liver cancer therapeutic agent using the liver cancer prognostic marker.

상기 간암 예후 마커는 간암 환자의 간편하고 정확한 예후 추정에 유용하게 사용될 수 있다. 나아가, 이 마커의 생리학적 기능은 간암의 발병이나 진행에 직접적으로 관계된 것일 가능성이 있으며, 따라서 이 마커는 간암 발병 또는 진행의 메커니즘을 연구하거나 간암 치료제의 개발을 위한 표적으로서도 유용하게 사용될 수 있다.The hepatic cancer prognostic marker may be useful for simple and accurate prognostic estimation of liver cancer patients. Furthermore, the physiological function of this marker may be directly related to the onset or progression of liver cancer, and thus the marker may be useful as a target for studying the mechanism of liver cancer development or progression or for developing a liver cancer therapeutic agent.

상기 간암 예후 마커는 종래 유래가 없는 정도의 다수의 환자의 간암 조직을 통계적으로 분석하여 발굴해낸 것이기 때문에 더욱 유의성이 있고 임상적으로 활용 가치가 높은 마커들이며, 간암 예후 추정에 있어서 보다 정확한 예측력을 보유하는 것이다.The hepatic cancer prognostic markers are statistically significant and clinically valuable markers because they have been statistically analyzed and found in liver cancer tissues of a large number of patients without a conventional origin, and have more accurate predictive power in estimating the prognosis of liver cancer. It is.

이하, 본 발명을 실시예에 의해 보다 구체적으로 설명하나, 이는 본 발명의 이해를 돕기 위한 것일 뿐 본 발명의 범위를 어떤 식으로든 제한하고자 하는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, which are intended to aid the understanding of the present invention but are not intended to limit the scope of the present invention in any way.

실시예 1: RNA 추출 및 cDNA 합성Example 1 RNA Extraction and cDNA Synthesis

간암 발병이 진단되고 진행 경과가 확인된 120명의 간암 환자의 간암 조직 및 주변 정상 조직을 입수하였다. 하기의 방식에 따라 각 조직의 RNA를 추출하고 cDNA를 합성하였다.Hepatocellular carcinoma and surrounding normal tissue were obtained from 120 liver cancer patients whose liver cancer was diagnosed and progress was confirmed. RNA of each tissue was extracted and cDNA was synthesized in the following manner.

RNeasy Minikit (독일 Qiagen 사) 를 사용하여 사용자 설명서에 따라 간암 조직 및 주변 정상 조직으로부터 전체 RNA를 추출하였다. 수득된 RNA 추출물을 Bioanalyzer 2100 (미국 Agilent Technologies 사) 를 사용하여 전체 RNA를 정량하였다. 추출 단계에서 DNase I을 처리하여 RNA 추출물에 오염된 게놈 DNA를 제거하였다. 전체 RNA 4 μg 을 포함하는 샘플을 1 μM 올리고d(T)18 프라이머 (한국 Genotech 사) 2 μl 과 함께 70℃에서 7분간 배양하였고, 얼음 위에서 5분간 식혔다. 효소 혼합액 [0.1 M DTT (네덜란드 Duchefa 사) 2 μl, 10× 역전사 완충액 2 μl, 2 mM dNTP 5 μl, 200 U/μl MMLV 역전사효소 1 μl, 및 40 U/μl RNase 저해자 (한국 Enzynomics 사) 1 μl; 총 11 μl] 을 별도로 준비하였다. 효소 혼합액을 상기 RNA를 포함하는 샘플에 첨가하였고, 42℃에서 90분간 배양하였으며, 이어서 80℃에서 10분간 배양하여 역전사효소를 불활성화시켰다. 상기 샘플에 디에틸피로카르보네이트(DEPC)-처리한 물을 첨가하여 최종 부피가 400 μl 가 되도록 하였다.Total RNA was extracted from liver cancer tissue and surrounding normal tissue using the RNeasy Minikit (Qiagen, Germany) according to the user instructions. The obtained RNA extract was quantitated total RNA using Bioanalyzer 2100 (Agilent Technologies, USA). DNase I was treated in the extraction step to remove genomic DNA contaminated with RNA extract. Samples containing 4 μg of total RNA were incubated for 7 minutes at 70 ° C. with 2 μl of 1 μM oligod (T) 18 primer (Genotech, Korea) and cooled on ice for 5 minutes. Enzyme mixture [2 μl of 0.1 M DTT (Duchefa, Netherlands), 2 μl of 10 × reverse transcript buffer, 5 μl of 2 mM dNTP, 1 μl of 200 U / μl MMLV reverse transcriptase, and 40 U / μl RNase inhibitor (Korea Enzynomics) 1 μl; 11 μl total] was prepared separately. The enzyme mixture was added to the sample containing the RNA, incubated at 42 ° C. for 90 minutes, and then incubated at 80 ° C. for 10 minutes to inactivate reverse transcriptase. Diethylpyrocarbonate (DEPC) -treated water was added to the sample to a final volume of 400 μl.

실시예 2: 정량적 실시간 PCRExample 2: Quantitative Real-Time PCR

실시예 1에서 수득된 cDNA 샘플 각각에 대하여 PRISM 7900HT (미국 Applied Biosystems 사) 을 사용하여 사용자 설명서에 따라 하기 2 종의 유전자 마커에 대하여 실시간 PCR 증폭을 수행하였다:For each cDNA sample obtained in Example 1, real-time PCR amplification was performed on the following two genetic markers according to the user manual using PRISM 7900HT (Applied Biosystems, USA):

CBS (cystathionine beta-synthase; NCBI GI: 209862802; 서열번호 79); 및CBS (cystathionine beta-synthase; NCBI GI: 209862802; SEQ ID NO: 79); And

NNMT (nicotinamide N-methyltransferase; NCBI GI: 62953139; 서열번호 80).NNMT (nicotinamide N-methyltransferase; NCBI GI: 62953139; SEQ ID NO: 80).

실시간 PCR 분석은 2× 태크만 유전자 발현 주혼합액 (미국 Applied Biosystems 사) 5 μl, 5 μM 포워드 및 리버스 프라이머 각 1 μl, 1 μM 프로브 (한국 Genotech 사) 1 μl, cDNA 2 μl (대조군의 경우 동량의 물) 로 이루어진 총 10 μl 의 부피에서 실시간 PCR 분석을 수행하였다. 95℃에서 10분간 해리 단계를 거친 후, 95℃에서 15초간 해리, 60℃에서 1분간 합성의 순환을 통하여 증폭 시켰다. 프라이머와 프로브 서열은 Primer Express 3.0 (미국 Applied Biosystems 사) 를 사용하여 고안하였고 모든 프로브 서열은 5' 말단에 FAM 및 3' 말단에 TAMRA로 표지하였다. 각 마커에 대하여, 하기 표 1과 같은 프라이머 및 프로브 서열이 사용되었다:Real-time PCR analysis was performed using 5 μl of 2 × Takman gene expression main mixture (Applied Biosystems, USA), 1 μl of 5 μM forward and reverse primer, 1 μl of 1 μM probe (Genotech Korea), 2 μl of cDNA (control equivalent) Real time PCR analysis was carried out in a total volume of 10 μl. After 10 minutes of dissociation step at 95 ℃, dissociation for 15 seconds at 95 ℃, amplification through the circulation of synthesis for 1 minute at 60 ℃. Primer and probe sequences were designed using Primer Express 3.0 (Applied Biosystems, USA) and all probe sequences were labeled with FAM at the 5 'end and TAMRA at the 3' end. For each marker, primers and probe sequences as shown in Table 1 were used:

각 마커 유전자의 발현을 3회 반복하여 측정하였고, 5 종의 참조 유전자 (B2M, GAPDH, HMBS, HPRT1, 및 SDHA) 의 평균적인 발현을 공제하여 표준화하였다. 각 마커의 CT (기준치를 달성하는데 소요되는 사이클 횟수) 를 측정하였고, ΔCT 값 (각 마커의 CT - 참조 유전자의 평균 CT) 을 계산하였으며, mRNA의 카피수는 2^-ΔCT로 계산되었다. cDNA 샘플의 연속적 희석물의 동시적 증폭의 결과로부터 표준 곡선을 완성하였다.The expression of each marker gene was measured three times and normalized by subtracting the average expression of five reference genes (B2M, GAPDH, HMBS, HPRT1, and SDHA). The CT of each marker (the number of cycles required to achieve the baseline) was measured, the ΔCT value (CT-average CT of the reference gene of each marker) was calculated and the copy number of mRNA was calculated as 2 ^−ΔCT . Standard curves were completed from the results of simultaneous amplification of serial dilutions of cDNA samples.

실시예 3: 통계적 분석Example 3: Statistical Analysis

실시예 2에서 수득된 각 마커에 대한 표준화된 발현, 및 각 조직을 제공한 환자의 경과를 고려하여, 카플란-마이어 곡선을 완성한 후 유의성 검정을 수행하였다.Significance assays were performed after completing the Kaplan-Meier curves, taking into account normalized expression for each marker obtained in Example 2, and the course of the patients who provided each tissue.

간암 조직을 제공한 120명의 환자의 경과를 토대로 재발, 생존, 무병생존 각각에 대하여 기간이 짧은 순서대로 나열하였다. 생존한 환자 (또는 재발한 환자) 를 위험에 노출된 대상 환자수로 나누어 구간 생존율 (또는 구간 재발율) 을 구하였다. 누적 생존율 (또는 누적 재발율) 은 조건부 확률이며, 이전까지의 누적 생존율 (또는 누적 재발율) 에 현재의 구간 생존율 (또는 구간 재발율) 을 곱하여 구하였다. 가로축을 생존시간 (또는 관찰기간), 세로축을 누적 생존율 (또는 누적 재발율) 로 하여 계단 함수로 그려서 카플란-마이어 곡선을 완성하였다.Based on the progress of 120 patients who presented with liver cancer tissue, the recurrence, survival, and disease-free survival were listed in short order. The interval survival (or interval recurrence rate) was determined by dividing surviving patients (or relapsed patients) by the number of subjects at risk. Cumulative survival (or cumulative relapse rate) is a conditional probability, which is obtained by multiplying the previous cumulative survival rate (or cumulative relapse rate) by the current interval survival rate (or interval recurrence rate). Kaplan-Meier curves were completed by plotting the abscissa as the survival time (or observation period) and the ordinate as the cumulative survival rate (or cumulative relapse rate) as a step function.

각 마커에 대하여, 재발, 생존, 무병생존에 관한 카플란-마이어 곡선을 완성하였다. 실시예 2에서 측정된 각 마커의 발현을, 실험적으로 결정된 통계적으로 유의한 기준치에 의거하여 고발현 및 저발현으로 분류하였으며, 각 마커에 대하여 고발현 및 저발현의 경우를 분리하여 카플란-마이어 곡선을 완성하였다. 완성된 카플란-마이어 곡선을 도 1에 나타내었다.For each marker, Kaplan-Meier curves for relapse, survival, and disease free survival were completed. The expression of each marker measured in Example 2 was classified into high and low expression based on the statistically significant reference value determined experimentally, and Kaplan-Meier curves were separated for the high and low expression for each marker. Was completed. The completed Kaplan-Meier curve is shown in FIG. 1.

도 1에서 확인할 수 있다시피, 재발 (Recurrence), 생존 (Overall Survival), 무병생존 (Disease-free Survival) 의 측면에서 완성된 카플란-마이어 곡선에 있어서, 각 마커들은 고발현의 경우와 저발현의 경우가 뚜렷하게 구분되는 곡선을 형성하였다. 이는 각 마커들이 고발현하는 경우와 저발현하는 경우 구간 재발율이나 구간 생존율, 및 이에 기초한 누적 재발율이나 누적 생존율에 현저한 차이가 발생한다는 것을 의미하며, 결과적으로 각 마커의 발현 양상이 차후 환자의 재발가능성이나 생존가능성을 시사하는 지표가 될 수 있음을 의미하는 것이다.As can be seen in FIG. 1, in the Kaplan-Meier curve completed in terms of recurrence, overall survival, and disease-free survival, each marker represents a case of high and low expression. The case formed a distinct curve. This means that there is a significant difference in the rate of interval recurrence or interval survival, and the cumulative relapse rate or cumulative survival rate based on the high and low expression levels of each marker. In other words, it can be an indicator of the viability.

각 마커 및 그 둘의 조합에 대하여 재발 또는 사망이 일어난 시점마다 관찰값과 기대값을 계산하여 교차분석 (Chi-square test) 통계량을 구하는 방식으로 로그순위 (log-rank) 법에 의한 유의성 검정을 시행하여 p-값을 산출하였다. 산출된 p-값은 하기 표 2와 같다.For each marker and a combination of the two, the significance test by the log-rank method is performed by calculating the chi-square test statistics by calculating the observation and expectation values at each time point of relapse or death. Was performed to calculate the p-value. The calculated p-values are shown in Table 2 below.

상기 표 2에서 확인할 수 있다시피, 각 마커 또는 그 둘의 조합은 재발, 생존, 무병생존 모두에 대하여 유의한 정도로 낮은 p-값을 나타내었다. 특히, 두 마커의 조합의 경우 재발, 생존, 및 무병생존에 대한 모든 p-값이 0.05 미만으로 바람직하였다. p-값이 낮으면 낮을수록 통계적 유의성은 커지는 것인바, 상기 낮은 p-값은 각 마커 또는 그 둘의 조합에 따른 간암 예후 추정이 정확도가 높을 것이라는 점을 시사한다.As can be seen in Table 2 above, each marker or combination of both showed a significantly lower p-value for both relapse, survival and disease free survival. In particular, all p-values for relapse, survival, and disease-free survival for the combination of the two markers were preferred below 0.05. The lower the p-value, the greater the statistical significance. The lower p-value suggests that the hepatic cancer prognosis according to each marker or combination of both will be more accurate.

실시예 4: 추가의 마커 발굴Example 4: Further Marker Discovery

185명의 간암 환자의 간암 조직 및 그 주변 정상 조직을 입수하여 실험한 것을 제외하고는 상기 실시예 1 내지 3과 동일한 방식으로 실험하여, 하기 유전자를 마커로 사용한 카플란-마이어 곡선과 p-값을 수득하였다:Experiments were performed in the same manner as in Examples 1 to 3, except that liver cancer tissues and normal tissues surrounding 185 liver cancer patients were obtained and obtained, and Kaplan-Meier curves and p-values using the following genes as markers were obtained. Was:

TKT (transketolase; NCBI GI: 205277461; 서열번호 81).TKT (transketolase; NCBI GI: 205277461; SEQ ID NO: 81).

사용된 프라이머 및 프로브는 하기 표 3과 같고, 카플란-마이어 곡선은 도 2와 같으며, 산출된 p-값은 표 4와 같다.Primers and probes used are shown in Table 3 below, the Kaplan-Meier curve is shown in FIG. 2, and the calculated p-values are shown in Table 4 below.

도 2에서 확인할 수 있다시피, 재발, 생존, 무병생존의 측면에서 완성된 카플란-마이어 곡선에 있어서, 상기 마커는 고발현의 경우와 저발현의 경우가 뚜렷하게 구분되는 곡선을 형성하였다. 이는 상기 마커가 고발현하는 경우와 저발현하는 경우 구간 재발율이나 구간 생존율, 및 이에 기초한 누적 재발율이나 누적 생존율에 현저한 차이가 발생한다는 것을 의미하며, 결과적으로 상기 마커의 발현 양상이 차후 환자의 재발가능성이나 생존가능성을 시사하는 지표가 될 수 있음을 의미하는 것이다.As can be seen in Figure 2, in the Kaplan-Meier curve completed in terms of recurrence, survival, disease-free survival, the marker formed a curve that is distinctly distinguished between the case of high and low expression. This means that there is a significant difference in the interval recurrence rate or interval survival rate, and the cumulative recurrence rate or cumulative survival rate based on the high and low expression of the marker, and as a result, the expression pattern of the marker is likely to recur later in the patient. In other words, it can be an indicator of the viability.

상기 표 4에서 확인할 수 있다시피, 상기 마커는 재발, 생존, 무병생존 모두에 대하여 p-값이 0.05 미만을 나타내어, 바람직한 수준으로 낮은 p-값을 나타내었다. p-값이 낮으면 낮을수록 통계적 유의성은 커지는 것인바, 상기 낮은 p-값은 상기 마커에 따른 간암 예후 추정이 정확도가 높을 것이라는 점을 시사한다.As can be seen in Table 4, the markers showed p-values less than 0.05 for both relapse, survival, and disease-free survival, indicating a low p-value at the desired level. The lower the p-value, the greater the statistical significance. The lower p-value suggests that the hepatic cancer prognosis according to the marker will be more accurate.

실시예 5: 추가의 마커 발굴Example 5: Finding Additional Markers

369명의 간암 환자의 간암 조직 및 그 주변 정상 조직을 입수하여 실험한 것을 제외하고는 상기 실시예 1 내지 3과 동일한 방식으로 실험하여, 하기 23종의 유전자를 마커로 사용한 카플란-마이어 곡선과 p-값을 수득하였다:The experiment was performed in the same manner as in Examples 1 to 3, except that the liver cancer tissues and normal tissues of 369 liver cancer patients were obtained and tested, and the Kaplan-Meier curve and p- using the following 23 genes as markers The value was obtained:

XIAP (Baculoviral IAP repeat-containing protein 4; NCBI GI: 32528298; 서열번호 104)XIAP (Baculoviral IAP repeat-containing protein 4; NCBI GI: 32528298; SEQ ID NO: 104)

사용된 프라이머 및 프로브는 하기 표 5와 같고, 카플란-마이어 곡선은 도 3 내지 10과 같으며, 각 마커에 대하여 산출된 p-값은 표 6과 같다. 2 종의 마커가 임의로 조합된 경우 산출된 p-값은 표 7과 같다.Primers and probes used are shown in Table 5 below, the Kaplan-Meier curves are shown in FIGS. 3 to 10, and the p-values calculated for each marker are shown in Table 6. The calculated p-values when two markers are arbitrarily combined are shown in Table 7.

도 3내지 10에서 확인할 수 있다시피, 재발, 생존, 무병생존의 측면에서 완성된 카플란-마이어 곡선에 있어서, 각 마커는 고발현의 경우와 저발현의 경우가 뚜렷하게 구분되는 곡선을 형성하였다. 이는 각 마커가 고발현하는 경우와 저발현하는 경우 구간 재발율이나 구간 생존율, 및 이에 기초한 누적 재발율이나 누적 생존율에 현저한 차이가 발생한다는 것을 의미하며, 결과적으로 각 마커의 발현 양상이 차후 환자의 재발가능성이나 생존가능성을 시사하는 지표가 될 수 있음을 의미하는 것이다.As can be seen in Figures 3 to 10, in the Kaplan-Meier curve completed in terms of recurrence, survival, disease-free survival, each marker formed a distinct curve between high and low expression cases. This means that there is a significant difference in the rate of interval recurrence or interval survival, and the cumulative relapse rate or cumulative survival rate based on the high and low expression of each marker. In other words, it can be an indicator of the viability.

상기 표 6 및 7에서 확인할 수 있다시피, 각 마커 또는 2 종의 마커의 모든 조합은 재발, 생존, 무병생존 모두에 대하여 유의한 정도로 낮은 p-값을 나타내었다. p-값이 낮으면 낮을수록 통계적 유의성은 커지는 것인바, 상기 낮은 p-값은 각 마커 또는 이들의 조합에 따른 간암 예후 추정이 정확할 것이라는 점을 시사한다. 특히, 각 마커 또는 2 종의 마커의 임의의 조합은 대부분 0.05 미만의 바람직하게 낮은 p-값을 나타내었다.As can be seen in Tables 6 and 7, each marker or combination of two markers showed a significantly lower p-value for both relapse, survival and disease free survival. The lower the p-value, the greater the statistical significance. The lower p-value suggests that the hepatic cancer prognostic estimates for each marker or combination thereof will be accurate. In particular, each marker or any combination of two markers exhibited preferably low p-values of mostly less than 0.05.

3종 이상의 마커의 조합에 관한 p-값은 모두 0.05 미만이었다. 가장 p-값이 낮은 단일 마커나 둘 이상의 마커의 조합 및 해당 p-값은 하기 표 8과 같다.The p-values for the combination of three or more markers were all less than 0.05. The single lowest p-value or combination of two or more markers and corresponding p-values are shown in Table 8 below.

상기 표 8로부터, 본 발명의 마커들이 조합되면 조합될수록 p-값이 낮아진다는 점을 알 수 있다. 이는 본 발명의 마커들이 조합되면 조합될수록 더욱 유의한 정도로 낮은 p-값을 나타낸다는 것으로서, 이 마커들의 조합에 기초한 예후 추정의 정확도는 더욱 향상될 것이라는 점을 알 수 있다.From Table 8, it can be seen that as the markers of the present invention are combined, the p-value is lowered. This indicates that the more combined the markers of the present invention show a significantly lower p-value, the better the accuracy of the prognostic estimation based on the combination of these markers.

실시예 6: 교차 검증Example 6: Cross Validation

실시예 5에서 통계적으로 유의하게 나타난 마커들의 조합에 대하여, 교차 검증을 수행하였다.For the combination of markers that were statistically significant in Example 5, cross validation was performed.

369명의 간암 환자를 무작위로 두 군 (양성군: 185명; 시험군: 184명) 으로 나누고, 양성군에 대하여 상기 실시예 3에서와 동일한 방식으로 통계적으로 유의하게 나타나는 기준치를 실험적으로 설정하여 고발현과 저발현을 분류하였다. 이렇게 설정된 기준치를 고정한채 시험군에 대하여 재발, 생존, 무병생존의 측면에서 p<0.05 또는 p<0.001 의 수준으로 예측 정확도를 계산하였다.369 patients with liver cancer were randomly divided into two groups (positive group: 185; test group: 184). Strings and low-expressions were classified. Predicting accuracy was calculated at the level of p <0.05 or p <0.001 in terms of recurrence, survival, and disease-free survival for the test group with the fixed baseline.

재발, 생존, 무병생존의 각 측면에서 우수한 예측 정확도를 나타낸 대표적인 예는 다음과 같다.Representative examples of good predictive accuracy in terms of relapse, survival, and disease free survival are as follows.

재발: AIFM1_AKT1_LC3 (p<0.05 수준에서 77.3%)Relapse: AIFM1_AKT1_LC3 (77.3% at p <0.05)

생존: ATG5_DRAM_FAS_XIAP (p<0.001 수준에서 87.3%)Survival: ATG5_DRAM_FAS_XIAP (87.3% at p <0.001)

무병생존: AIFM1_AKT1_LC3 (p<0.05 수준에서 71.3%)Disease free survival: AIFM1_AKT1_LC3 (71.3% at p <0.05)

도 1 내지 10은 본원 발명의 간암 예후 마커들을 재발, 생존, 무병생존의 측면에서 측정하여 도시한 카플란-마이어 곡선이다.1 to 10 are Kaplan-Meier curves showing the liver cancer prognostic markers of the present invention measured in terms of recurrence, survival, and disease free survival.

<110> CBSBIOSCIENCE, CO., LTD <120> MARKERS FOR LIVER CANCER PROGNOSIS <130> Y09KP-027 <160> 104 <170> KopatentIn 1.71 <210> 1 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CBS forward primer <400> 1 gttggcaaag tcatctacaa gca 23 <210> 2 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> CBS reverse primer <400> 2 gggcgaagtg gtccatctc 19 <210> 3 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> CBS probe <400> 3 acgctgggca ggctctcgca c 21 <210> 4 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NNMT forward primer <400> 4 ttgaggtgat ctcgcaaagt tatt 24 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> NNMT reverse primer <400> 5 ctcgccacca gggagaaa 18 <210> 6 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NNMT probe <400> 6 ccaccatggc caacaacgaa ggac 24 <210> 7 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TKT forward primer <400> 7 gaggctgtgt ccagtgcagt ag 22 <210> 8 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TKT reverse primer <400> 8 ccacttcttg gtacccggtt aa 22 <210> 9 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> TKT probe <400> 9 cctggcatca ctgtcaccca cctg 24 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> BCL2 forward primer <400> 10 catgtgtgtg gagagcgtca a 21 <210> 11 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> BCL2 reverse primer <400> 11 gccggttcag gtactcagtc a 21 <210> 12 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BCL2 probe <400> 12 cctggtggac aacatcgccc tgt 23 <210> 13 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> FAS forward primer <400> 13 aatggtgtca atgaagccaa aat 23 <210> 14 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> FAS reverse primer <400> 14 gtcatacgct tctttctttc catga 25 <210> 15 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> FAS probe <400> 15 tgacaatgtc caagacacag cagaacagaa 30 <210> 16 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAX forward primer <400> 16 ggttgtcgcc cttttctact ttg 23 <210> 17 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> BAX reverse primer <400> 17 cagttccggc accttggt 18 <210> 18 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BAX probe <400> 18 cagcaaactg gtgctcaagg ccct 24 <210> 19 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BCL2L1 forward primer <400> 19 gattgccttt gttttgatgt ttgt 24 <210> 20 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BCL2L1 reverse primer <400> 20 ggaaagggaa cccaggttag tg 22 <210> 21 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> BCL2L1 probe <400> 21 cagaattgat cattttcccc ccactctcc 29 <210> 22 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> AIFM1 forward primer <400> 22 tgaagatctc aatgaagtag ccaaactat 29 <210> 23 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> AIFM1 reverse primer <400> 23 ctgcagtggg tttgccaat 19 <210> 24 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> AIFM1 probe <400> 24 caacattcat gaagactgaa gccccaca 28 <210> 25 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CASP8 forward primer <400> 25 ccttctgatt gatggtgcta ttttg 25 <210> 26 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> CASP8 reverse primer <400> 26 gcggtgagcc gagatcac 18 <210> 27 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> CASP8 probe <400> 27 cagaatctcg ctctgtcgcc cagg 24 <210> 28 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CSE1L forward primer <400> 28 gcatgatcct gtaggtcaaa tgg 23 <210> 29 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CSE1L reverse primer <400> 29 caggcggtag acaacttgtg aa 22 <210> 30 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> CSE1L probe <400> 30 aataacccca aaattcacct ggcacagtca 30 <210> 31 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> XIAP forward primer <400> 31 gacaggccat ctgagacaca tg 22 <210> 32 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> XIAP reverse primer <400> 32 agcatagtct ggccagttct gaa 23 <210> 33 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> XIAP probe <400> 33 agacaccata tacccgagga accctgcc 28 <210> 34 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> DIABLO forward primer <400> 34 aatcacattc agctggtgaa actg 24 <210> 35 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> DIABLO reverse primer <400> 35 tgccagcttg gtttctgctt 20 <210> 36 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> DIABLO probe <400> 36 aagaggtgca ccagctctcc cgg 23 <210> 37 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> AKT1 forward primer <400> 37 tctcgggtgc atttgagaga a 21 <210> 38 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> AKT1 reverse primer <400> 38 acagcacaaa aacgtctttc ca 22 <210> 39 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> AKT1 probe <400> 39 ccacgctgtc ctctcgagcc ca 22 <210> 40 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> PTEN forward primer <400> 40 tggcggaact tgcaatcc 18 <210> 41 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> PTEN reverse primer <400> 41 gctgagggaa ctcaaagtac atga 24 <210> 42 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> PTEN probe <400> 42 atattcctcc aattcaggac ccacacgac 29 <210> 43 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> FRAP1 forward primer <400> 43 aggccgcatt gtctctatca a 21 <210> 44 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> FRAP1 reverse primer <400> 44 gcagtaaatg caggtagtca tcca 24 <210> 45 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> FRAP1 probe <400> 45 tgcaatccag ctgtttggcg cc 22 <210> 46 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> PRKAA1 forward primer <400> 46 ggcagttgcc taccatctca taa 23 <210> 47 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PRKAA1 reverse primer <400> 47 gccgagtcag gtgatgatca 20 <210> 48 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> PRKAA1 probe <400> 48 tctatttggc gacaagccca cctgatt 27 <210> 49 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ATG3 forward primer <400> 49 ccattgaaaa tcaccctcat ctg 23 <210> 50 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> ATG3 reverse primer <400> 50 cacctcagca tgcctgcat 19 <210> 51 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ATG3 probe <400> 51 caccacctcc catgtgttca gttcacc 27 <210> 52 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ATG12 forward primer <400> 52 cgacagcttc gatttgaatg ac 22 <210> 53 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> ATG12 reverse primer <400> 53 gggagcgtcg caaagga 17 <210> 54 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ATG12 probe <400> 54 tgtaattgcg tccccctact ccggc 25 <210> 55 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ATG5 forward primer <400> 55 tttcctccac tgccatcatt aa 22 <210> 56 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ATG5 reverse primer <400> 56 ggccaaaggt ttcagcttca 20 <210> 57 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ATG5 probe <400> 57 cctcagctgt gacatgaaag acttaccgg 29 <210> 58 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> ATG7 forward primer <400> 58 cggatgaatg agcctccaa 19 <210> 59 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ATG7 reverse primer <400> 59 ggacattatc aaaccgtgaa agaa 24 <210> 60 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ATG7 probe <400> 60 tcttgggctt gtgcctcacc agatc 25 <210> 61 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BNIP3 forward primer <400> 61 ttccccccaa ggagttcct 19 <210> 62 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BNIP3 reverse primer <400> 62 cgctcgtgtt cctcatgct 19 <210> 63 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BNIP3 probe <400> 63 acccgaagcg cacggccac 19 <210> 64 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> DRAM forward primer <400> 64 cagccgcctt cattatctcc ta 22 <210> 65 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> DRAM reverse primer <400> 65 tggaggtgtt gttcccgtat c 21 <210> 66 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> DRAM probe <400> 66 tgctctccgg gcacgtcaac c 21 <210> 67 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> LAMP1 forward primer <400> 67 tgcactcaga tttaagcctt acaaa 25 <210> 68 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> LAMP1 reverse primer <400> 68 tcaccacgag tgaccttcat g 21 <210> 69 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LAMP1 probe <400> 69 aagcctctgg ccgtcacacg tagg 24 <210> 70 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> LC3 forward primer <400> 70 aaccagcaca gcatggtgag t 21 <210> 71 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LC3 reverse primer <400> 71 cctcgtcttt ctcctgctcg ta 22 <210> 72 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> LC3 probe <400> 72 tccacgccca tcgcggaca 19 <210> 73 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> ULK1 forward primer <400> 73 tcgcggccgc atgt 14 <210> 74 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ULK1 reverse primer <400> 74 aagggtccag cactatcaag aga 23 <210> 75 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ULK1 probe <400> 75 agcaggtcct gggcgcctca ac 22 <210> 76 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> E2F1 forward primer <400> 76 ctggaccacc tgatgaatat ctgt 24 <210> 77 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> E2F1 reverse primer <400> 77 caatgctacg aaggtcctga ca 22 <210> 78 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> E2F1 probe <400> 78 cagctgcgcc tgctctccga 20 <210> 79 <211> 2609 <212> DNA <213> Homo sapiens <400> 79 acattggccg gcgccggcct ccgcccccgc ctctccgcca atcaccgccc gcctgctccc 60 ctcgccgtgg gtccccgcga ggccgccacc ccggggtcgc cgtctccgcc tcgccgcagt 120 cggggcagcc gctcgcccct cttttccatg tatccgtcca ggatcccatg acagattctg 180 ttgtcacgtc tccttacaga gtttgagcgg tgctgaactg tcagcaccat ctgtccggtc 240 ccagcatgcc ttctgagacc ccccaggcag aagtggggcc cacaggctgc ccccaccgct 300 cagggccaca ctcggcgaag gggagcctgg agaaggggtc cccagaggat aaggaagcca 360 aggagcccct gtggatccgg cccgatgctc cgagcaggtg cacctggcag ctgggccggc 420 ctgcctccga gtccccacat caccacactg ccccggcaaa atctccaaaa atcttgccag 480 atattctgaa gaaaatcggg gacaccccta tggtcagaat caacaagatt gggaagaagt 540 tcggcctgaa gtgtgagctc ttggccaagt gtgagttctt caacgcgggc gggagcgtga 600 aggaccgcat cagcctgcgg atgattgagg atgctgagcg cgacgggacg ctgaagcccg 660 gggacacgat tatcgagccg acatccggga acaccgggat cgggctggcc ctggctgcgg 720 cagtgagggg ctatcgctgc atcatcgtga tgccagagaa gatgagctcc gagaaggtgg 780 acgtgctgcg ggcactgggg gctgagattg tgaggacgcc caccaatgcc aggttcgact 840 ccccggagtc acacgtgggg gtggcctggc ggctgaagaa cgaaatcccc aattctcaca 900 tcctagacca gtaccgcaac gccagcaacc ccctggctca ctacgacacc accgctgatg 960 agatcctgca gcagtgtgat gggaagctgg acatgctggt ggcttcagtg ggcacgggcg 1020 gcaccatcac gggcattgcc aggaagctga aggagaagtg tcctggatgc aggatcattg 1080 gggtggatcc cgaagggtcc atcctcgcag agccggagga gctgaaccag acggagcaga 1140 caacctacga ggtggaaggg atcggctacg acttcatccc cacggtgctg gacaggacgg 1200 tggtggacaa gtggttcaag agcaacgatg aggaggcgtt cacctttgcc cgcatgctga 1260 tcgcgcaaga ggggctgctg tgcggtggca gtgctggcag cacggtggcg gtggccgtga 1320 aggccgcgca ggagctgcag gagggccagc gctgcgtggt cattctgccc gactcagtgc 1380 ggaactacat gaccaagttc ctgagcgaca ggtggatgct gcagaagggc tttctgaagg 1440 aggaggacct cacggagaag aagccctggt ggtggcacct ccgtgttcag gagctgggcc 1500 tgtcagcccc gctgaccgtg ctcccgacca tcacctgtgg gcacaccatc gagatcctcc 1560 gggagaaggg cttcgaccag gcgcccgtgg tggatgaggc gggggtaatc ctgggaatgg 1620 tgacgcttgg gaacatgctc tcgtccctgc ttgccgggaa ggtgcagccg tcagaccaag 1680 ttggcaaagt catctacaag cagttcaaac agatccgcct cacggacacg ctgggcaggc 1740 tctcgcacat cctggagatg gaccacttcg ccctggtggt gcacgagcag atccagtacc 1800 acagcaccgg gaagtccagt cagcggcaga tggtgttcgg ggtggtcacc gccattgact 1860 tgctgaactt cgtggccgcc caggagcggg accagaagtg aagtccggag cgctgggcgg 1920 tgcggagcgg gcccgccacc cttgcccact tctccttcgc tttcctgagc cctaaacaca 1980 cgcgtgattg gtaactgcct ggcctggcac cgttatccct gcacacggca cagagcatcc 2040 gtctcccctc gttaacacat ggcttcctaa atggccctgt ttacggccta tgagatgaaa 2100 tatgtgattt tctctaatgt aacttcctct taggatgttt caccaaggaa atattgagag 2160 agaagtcggc caggtaggat gaacacaggc aatgactgcg cagagtggat taaaggcaaa 2220 agagagaaga gtccaggaag gggcggggag aagcctgggt ggctcagcat cctccacggg 2280 ctgcgccgtc tgctcggggc tgagctggcg ggagcagttt gcgtgtttgg gttttttaat 2340 tgagatgaaa ttcaaataac ctaaaaatca atcacttgaa agtgaacaat cagcggcatt 2400 tagtacatcc agaaagttgt gtaggcacca cctctgtcac gttctggaac attctgtcat 2460 caccccgtga agcaatcatt tcccctcccg tcttcctcct cccctggcaa ctgctgatcg 2520 actttgtgtc tctgttgtct aaaataggtt ttccctgttc tggacatttc atataaatgg 2580 aatcacacaa aaaaaaaaaa aaaaaaaaa 2609 <210> 80 <211> 1579 <212> DNA <213> Homo sapiens <400> 80 gaggaggtgc ttgccagaca ctgggtcatg gcagtggtcg gtgaagctgc agttgcctag 60 ggcagggatg gagagagagt ctgggcatga ggagagggtc tcgggatgtt tggctggact 120 agattttaca gaaagcctta tccaggcttt taaaattact ctttccagac ttcatctgag 180 actccttctt cagccaacat tccttagccc tgaatacatt tcctatcctc atctttccct 240 tctttttttt cctttctttt acatgtttaa atttaaacca ttcttcgtga ccccttttct 300 tgggagattc atggcaagaa cgagaagaat gatggtgctt gttaggggat gtcctgtctc 360 tctgaacttt ggggtcctat gcattaaata attttcctga cgagctcaag tgctccctct 420 ggtctacaat ccctggcggc tggccttcat cccttgggca agcattgcat acagctcatg 480 gccctccctc taccataccc tccacccccg ttcgcctaag ctcccttctc cgggaatttc 540 atcatttcct agaacagcca gaacatttgt ggtctatttc tctgttagtg tttaaccaac 600 catctgttct aaaagaaggg ctgaactgat ggaaggaatg ctgttagcct gagactcagg 660 aagacaactt ctgcagggtc actccctggc ttctggagga aagagaagga gggcagtgct 720 ccagtggtac agaagtgaga cataatggaa tcaggcttca cctccaagga cacctatcta 780 agccatttta accctcggga ttacctagaa aaatattaca agtttggttc taggcactct 840 gcagaaagcc agattcttaa gcaccttctg aaaaatcttt tcaagatatt ctgcctagac 900 ggtgtgaagg gagacctgct gattgacatc ggctctggcc ccactatcta tcagctcctc 960 tctgcttgtg aatcctttaa ggagatcgtc gtcactgact actcagacca gaacctgcag 1020 gagctggaga agtggctgaa gaaagagcca gaggcctttg actggtcccc agtggtgacc 1080 tatgtgtgtg atcttgaagg gaacagagtc aagggtccag agaaggagga gaagttgaga 1140 caggcggtca agcaggtgct gaagtgtgat gtgactcaga gccagccact gggggccgtc 1200 cccttacccc cggctgactg cgtgctcagc acactgtgtc tggatgccgc ctgcccagac 1260 ctccccacct actgcagggc gctcaggaac ctcggcagcc tactgaagcc agggggcttc 1320 ctggtgatca tggatgcgct caagagcagc tactacatga ttggtgagca gaagttctcc 1380 agcctccccc tgggccggga ggcagtagag gctgctgtga aagaggctgg ctacacaatc 1440 gaatggtttg aggtgatctc gcaaagttat tcttccacca tggccaacaa cgaaggactt 1500 ttctccctgg tggcgaggaa gctgagcaga cccctgtgat gcctgtgacc tcaattaaag 1560 caattccttt gacctgtca 1579 <210> 81 <211> 2117 <212> DNA <213> Homo sapiens <400> 81 gacttaacgc gcccccgccc cgcgcccggc ctcggcagcc gcctgtcgcc gcgggagcag 60 ccgctatctc tgtgtgtccg cgtgtgcgcc cggtccccgc ctgccgcacc atggagagct 120 accacaagcc tgaccagcag aagctgcagg ccttgaagga cacggccaac cgcctacgta 180 tcagctccat ccaggccacc actgcggcgg gctctggcca ccccacgtca tgctgcagcg 240 ccgcagagat catggctgtc ctctttttcc acaccatgcg ctacaagtcc caggaccccc 300 ggaatccgca caatgaccgc tttgtgctct ccaagggcca tgcagctccc atcctctacg 360 cggtctgggc tgaagctggt ttcctggccg aggcggagct gctgaacctg aggaagatca 420 gctccgactt ggacgggcac ccggtcccga aacaagcttt caccgacgtg gccactggct 480 ccctgggcca gggcctcggg gccgcttgtg ggatggccta caccggcaaa tacttcgaca 540 aggccagcta ccgagtctat tgcttgctgg gagacgggga gctgtcagag ggctctgtat 600 gggaggccat ggccttcgcc agcatctata agctggacaa ccttgtggcc attctagaca 660 tcaatcgcct gggccagagt gacccggccc cactgcagca ccagatggac atctaccaga 720 agcggtgcga ggccttcggt tggcatgcca tcatcgtgga tggacacagc gtggaggagc 780 tgtgcaaggc ctttggccag gccaagcacc agccaacagc catcattgcc aagaccttca 840 agggccgagg gatcacgggg gtagaagata aggagtcttg gcatgggaag cccctcccca 900 aaaacatggc tgagcagatc atccaggaga tctacagcca gatccagagc aaaaagaaga 960 tcctggcaac ccctccacag gaggacgcac cctcagtgga cattgccaac atccgcatgc 1020 ccagcctgcc cagctacaaa gttggggaca agatagccac ccgcaaggcc tacgggcagg 1080 cactggccaa gctgggccat gccagtgacc gcatcatcgc cctggatggg gacaccaaaa 1140 attccacctt ctcggagatc ttcaaaaagg agcacccgga ccgcttcatc gagtgctaca 1200 ttgctgagca gaacatggtg agcatcgcgg tgggctgtgc cacccgcaac aggacggtgc 1260 ccttctgcag cacttttgca gccttcttca cgcgggcctt tgaccagatt cgcatggccg 1320 ccatctccga gagcaacatc aacctctgcg gctcccactg cggcgtttcc atcggggaag 1380 acgggccctc ccagatggcc ctagaagatc tggctatgtt tcggtcagtc cccacatcaa 1440 ctgtctttta cccaagtgat ggcgttgcta cagagaaggc agtggaacta gccgccaata 1500 caaagggtat ctgcttcatc cggaccagcc gcccagaaaa tgccatcatc tataacaaca 1560 atgaggactt ccaggtcgga caagccaagg tggtcctgaa gagcaaggat gaccaggtga 1620 ccgttatcgg ggctggggtg accctgcacg aggccttggc cgctgccgaa ctgctgaaga 1680 aagaaaagat caacatccgc gtgctggacc ccttcaccat caagcccctg gacagaaaac 1740 tcattctcga cagcgctcgt gccaccaagg gcaggatcct caccgtggag gaccattatt 1800 atgaaggtgg cattggtgag gctgtgtcca gtgcagtagt gggcgagcct ggcatcactg 1860 tcacccacct ggcagttaac cgggtaccaa gaagtgggaa gccggctgag ctgctgaaga 1920 tgtttggtat cgacagggat gccattgcac aagctgtgag gggcctcatc accaaggcct 1980 agggcgggta tgaagtgtgg ggcgggggtc tatacattcc tgagattctg ggaaaggtgc 2040 tcaaagatgt actgagagga ggggtaaata tatgttttga gaaaaatgaa ttggccctga 2100 aaaaaaaaaa aaaaaaa 2117 <210> 82 <211> 2215 <212> DNA <213> Homo sapiens <400> 82 ttccccggct ctagcaggcc ggcttctctg tccaatgccc acccggagct gggaggagga 60 gtctgcgtaa tgtgcgtgtg aagagactgg gggagctggc cggggctcac ggtgtttgac 120 ccgtcggtcg tgcgtgagag gaaagggaag gaggaggtcc cgaatagcgg tcgccgaaat 180 gttccggtgt ggaggcctgg cggcgggtgc tttgaagcag aagctggtgc ccttggtgcg 240 gaccgtgtgc gtccgaagcc cgaggcagag gaaccggctc ccaggcaact tgttccagcg 300 atggcatgtt cctctagaac tccagatgac aagacaaatg gctagctctg gtgcatcagg 360 gggcaaaatc gataattctg tgttagtcct tattgtgggc ttatcaacag taggagctgg 420 tgcctatgcc tacaagacta tgaaagagga tgaaaaaaga tacaatgaaa gaatttcagg 480 gttagggctg acaccagaac agaaacagaa aaaggccgcg ttatctgctt cagaaggaga 540 ggaagttcct caagacaagg cgccaagtca tgttcctttc ctgctaattg gtggaggcac 600 agctgctttt gctgcagcca gatccatccg ggctcgggat cctggggcca gggtactgat 660 tgtatctgaa gatcctgagc tgccgtacat gcgacctcct ctttcaaaag aactgtggtt 720 ttcagatgac ccaaatgtca caaagacact gcgattcaaa cagtggaatg gaaaagagag 780 aagcatatat ttccagccac cttctttcta tgtctctgct caggacctgc ctcatattga 840 gaatggtggt gtggctgtcc tcactgggaa gaaggtagta cagctggatg tgagagacaa 900 catggtgaaa cttaatgatg gctctcaaat aacctatgaa aagtgcttga ttgcaacagg 960 aggtactcca agaagtctgt ctgccattga tagggctgga gcagaggtga agagtagaac 1020 aacgcttttc agaaagattg gagactttag aagcttggag aagatttcac gggaagtcaa 1080 atcaattacg attatcggtg ggggcttcct tggtagcgaa ctggcctgtg ctcttggcag 1140 aaaggctcga gccttgggca cagaagtgat tcaactcttc cccgagaaag gaaatatggg 1200 aaagatcctc cccgaatacc tcagcaactg gaccatggaa aaagtcagac gagagggggt 1260 taaggtgatg cccaatgcta ttgtgcaatc cgttggagtc agcagtggca agttacttat 1320 caagctgaaa gacggcagga aggtagaaac tgaccacata gtggcagctg tgggcctgga 1380 gcccaatgtt gagttggcca agactggtgg cctggaaata gactcagatt ttggtggctt 1440 ccgggtaaat gcagagctac aagcacgctc taacatctgg gtggcaggag atgctgcatg 1500 cttctacgat ataaagttgg gaaggaggcg ggtagagcac catgatcacg ctgttgtgag 1560 tggaagattg gctggagaaa atatgactgg agctgctaag ccgtactggc atcagtcaat 1620 gttctggagt gatttgggcc ccgatgttgg ctatgaagct attggtcttg tggacagtag 1680 tttgcccaca gttggtgttt ttgcaaaagc aactgcacaa gacaacccca aatctgccac 1740 agagcagtca ggaactggta tccgatcaga gagtgagaca gagtccgagg cctcagaaat 1800 tactattcct cccagcaccc cggcagttcc acaggctccc gtccaggggg aggactacgg 1860 caaaggtgtc atcttctacc tcagggacaa agtggtcgtg gggattgtgc tatggaacat 1920 ctttaaccga atgccaatag caaggaagat cattaaggac ggtgagcagc atgaagatct 1980 caatgaagta gccaaactat tcaacattca tgaagactga agccccacag tggaattggc 2040 aaacccactg cagcccctga gaggaggtcg aatgggtaaa ggagcatttt tttattcagc 2100 agactttctc tgtgtatgag tgtgaatgat caagtccttt gtgaatattt tcaactatgt 2160 aggtaaattc ttaatgttca catagtgaaa taaattctga ttcttctaaa ttaaa 2215 <210> 83 <211> 3008 <212> DNA <213> Homo sapiens <400> 83 taattatggg tctgtaacca ccctggactg ggtgctcctc actgacggac ttgtctgaac 60 ctctctttgt ctccagcgcc cagcactggg cctggcaaaa cctgagacgc ccggtacatg 120 ttggccaaat gaatgaacca gattcagacc ggcaggggcg ctgtggttta ggaggggcct 180 ggggtttctc ccaggaggtt tttgggcttg cgctggaggg ctctggactc ccgtttgcgc 240 cagtggcctg catcctggtc ctgtcttcct catgtttgaa tttctttgct ttcctagtct 300 ggggagcagg gaggagccct gtgccctgtc ccaggatcca tgggtaggaa caccatggac 360 agggagagca aacggggcca tctgtcacca ggggcttagg gaaggccgag ccagcctggg 420 tcaaagaagt caaaggggct gcctggagga ggcagcctgt cagctggtgc atcagaggct 480 gtggccaggc cagctgggct cggggagcgc cagcctgaga ggagcgcgtg agcgtcgcgg 540 gagcctcggg caccatgagc gacgtggcta ttgtgaagga gggttggctg cacaaacgag 600 gggagtacat caagacctgg cggccacgct acttcctcct caagaatgat ggcaccttca 660 ttggctacaa ggagcggccg caggatgtgg accaacgtga ggctcccctc aacaacttct 720 ctgtggcgca gtgccagctg atgaagacgg agcggccccg gcccaacacc ttcatcatcc 780 gctgcctgca gtggaccact gtcatcgaac gcaccttcca tgtggagact cctgaggagc 840 gggaggagtg gacaaccgcc atccagactg tggctgacgg cctcaagaag caggaggagg 900 aggagatgga cttccggtcg ggctcaccca gtgacaactc aggggctgaa gagatggagg 960 tgtccctggc caagcccaag caccgcgtga ccatgaacga gtttgagtac ctgaagctgc 1020 tgggcaaggg cactttcggc aaggtgatcc tggtgaagga gaaggccaca ggccgctact 1080 acgccatgaa gatcctcaag aaggaagtca tcgtggccaa ggacgaggtg gcccacacac 1140 tcaccgagaa ccgcgtcctg cagaactcca ggcacccctt cctcacagcc ctgaagtact 1200 ctttccagac ccacgaccgc ctctgctttg tcatggagta cgccaacggg ggcgagctgt 1260 tcttccacct gtcccgggag cgtgtgttct ccgaggaccg ggcccgcttc tatggcgctg 1320 agattgtgtc agccctggac tacctgcact cggagaagaa cgtggtgtac cgggacctca 1380 agctggagaa cctcatgctg gacaaggacg ggcacattaa gatcacagac ttcgggctgt 1440 gcaaggaggg gatcaaggac ggtgccacca tgaagacctt ttgcggcaca cctgagtacc 1500 tggcccccga ggtgctggag gacaatgact acggccgtgc agtggactgg tgggggctgg 1560 gcgtggtcat gtacgagatg atgtgcggtc gcctgccctt ctacaaccag gaccatgaga 1620 agctttttga gctcatcctc atggaggaga tccgcttccc gcgcacgctt ggtcccgagg 1680 ccaagtcctt gctttcaggg ctgctcaaga aggaccccaa gcagaggctt ggcgggggct 1740 ccgaggacgc caaggagatc atgcagcatc gcttctttgc cggtatcgtg tggcagcacg 1800 tgtacgagaa gaagctcagc ccacccttca agccccaggt cacgtcggag actgacacca 1860 ggtattttga tgaggagttc acggcccaga tgatcaccat cacaccacct gaccaagatg 1920 acagcatgga gtgtgtggac agcgagcgca ggccccactt cccccagttc tcctactcgg 1980 ccagcggcac ggcctgaggc ggcggtggac tgcgctggac gatagcttgg agggatggag 2040 aggcggcctc gtgccatgat ctgtatttaa tggtttttat ttctcgggtg catttgagag 2100 aagccacgct gtcctctcga gcccagatgg aaagacgttt ttgtgctgtg ggcagcaccc 2160 tcccccgcag cggggtaggg aagaaaacta tcctgcgggt tttaatttat ttcatccagt 2220 ttgttctccg ggtgtggcct cagccctcag aacaatccga ttcacgtagg gaaatgttaa 2280 ggacttctgc agctatgcgc aatgtggcat tggggggccg ggcaggtcct gcccatgtgt 2340 cccctcactc tgtcagccag ccgccctggg ctgtctgtca ccagctatct gtcatctctc 2400 tggggccctg ggcctcagtt caacctggtg gcaccagatg caacctcact atggtatgct 2460 ggccagcacc ctctcctggg ggtggcaggc acacagcagc cccccagcac taaggccgtg 2520 tctctgagga cgtcatcgga ggctgggccc ctgggatggg accagggatg ggggatgggc 2580 cagggtttac ccagtgggac agaggagcaa ggtttaaatt tgttattgtg tattatgttg 2640 ttcaaatgca ttttgggggt ttttaatctt tgtgacagga aagccctccc ccttcccctt 2700 ctgtgtcaca gttcttggtg actgtcccac cgggagcctc cccctcagat gatctctcca 2760 cggtagcact tgaccttttc gacgcttaac ctttccgctg tcgccccagg ccctccctga 2820 ctccctgtgg gggtggccat ccctgggccc ctccacgcct cctggccaga cgctgccgct 2880 gccgctgcac cacggcgttt ttttacaaca ttcaacttta gtatttttac tattataata 2940 taatatggaa ccttccctcc aaattcttca ataaaagttg cttttcaaaa aaaaaaaaaa 3000 aaaaaaaa 3008 <210> 84 <211> 1372 <212> DNA <213> Homo sapiens <400> 84 cgggtgctga tgcgagtcgg tggcagcgag gacattttct gactccctgg cccctgacac 60 ggctgcactt tccatcccgt cgcggggccg gccgctactc cggccccagg atgcagaatg 120 tgattaatac tgtgaaggga aaggcactgg aagtggctga gtacctgacc ccggtcctca 180 aggaatcaaa gtttaaggaa acaggtgtaa ttaccccaga agagtttgtg gcagctggag 240 atcacctagt ccaccactgt ccaacatggc aatgggctac aggggaagaa ttgaaagtga 300 aggcatacct accaacaggc aaacaatttt tggtaaccaa aaatgtgccg tgctataagc 360 ggtgcaaaca gatggaatat tcagatgaat tggaagctat cattgaagaa gatgatggtg 420 atggcggatg ggtagataca tatcacaaca caggtattac aggaataacg gaagccgtta 480 aagagatcac actggaaaat aaggacaata taaggcttca agattgctca gcactatgtg 540 aagaggaaga agatgaagat gaaggagaag ctgcagatat ggaagaatat gaagagagtg 600 gattgttgga aacagatgag gctaccctag atacaaggaa aatagtagaa gcttgtaaag 660 ccaaaactga tgctggcggt gaagatgcta ttttgcaaac cagaacttat gacctttaca 720 tcacttatga taaatattac cagactccac gattatggtt gtttggctat gatgagcaac 780 ggcagccttt aacagttgag cacatgtatg aagacatcag tcaggatcat gtgaagaaaa 840 cagtgaccat tgaaaatcac cctcatctgc caccacctcc catgtgttca gttcacccat 900 gcaggcatgc tgaggtgatg aagaaaatca ttgagactgt tgcagaagga gggggagaac 960 ttggagttca tatgtatctt cttattttct tgaaatttgt acaagctgtc attccaacaa 1020 tagaatatga ctacacaaga cacttcacaa tgtaatgaag agagcataaa atctatccta 1080 attattggtt ctgattttta aagaattaac ccatagatgt gaccattgac catattcatc 1140 aatatataca gtttctctaa taagggactt atatgtttat gcattaaata aaaatatgtt 1200 ccactaccag ccttacttgt ttaataaaaa tcagtgcaaa gaaaaaaaaa aaaaaaaaaa 1260 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1320 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 1372 <210> 85 <211> 3244 <212> DNA <213> Homo sapiens <400> 85 gtgacgtcat ctccgggcgc cgagggtgac tggacttgtg gtgcgctgcc agggctccgc 60 agcgttgccg gttgtattcg ctggatacca gagggcggaa gtgcagcagg gttcagctcc 120 gacctccgcg ccggtgcttt ttgcggctgc gcgggcttcc tggagtcctg ctaccgcgtc 180 cccgcaggac agtgtgtcag gcgggcagct tgccccgccg ccccaccgga gcgcggaatc 240 tgggcgtccc caccagtgcg gggagccgga aggaggagcc atagcttgga gtaggtttgg 300 ctttggttga aataagaatt tagcctgtat gtactgcttt aactcctgga agaatgacag 360 atgacaaaga tgtgcttcga gatgtgtggt ttggacgaat tccaacttgt ttcacgctat 420 atcaggatga gataactgaa agggaagcag aaccatacta tttgcttttg ccaagagtaa 480 gttatttgac gttggtaact gacaaagtga aaaagcactt tcagaaggtt atgagacaag 540 aagacattag tgagatatgg tttgaatatg aaggcacacc actgaaatgg cattatccaa 600 ttggtttgct atttgatctt cttgcatcaa gttcagctct tccttggaac atcacagtac 660 attttaagag ttttccagaa aaagaccttc tgcactgtcc atctaaggat gcaattgaag 720 ctcattttat gtcatgtatg aaagaagctg atgctttaaa acataaaagt caagtaatca 780 atgaaatgca gaaaaaagat cacaagcaac tctggatggg attgcaaaat gacagatttg 840 accagttttg ggccatcaat cggaaactca tggaatatcc tgcagaagaa aatggatttc 900 gttatatccc ctttagaata tatcagacaa cgactgaaag acctttcatt cagaagctgt 960 ttcgtcctgt ggctgcagat ggacagttgc acacactagg agatctcctc aaagaagttt 1020 gtccttctgc tattgatcct gaagatgggg aaaaaaagaa tcaagtgatg attcatggaa 1080 ttgagccaat gttggaaaca cctctgcagt ggctgagtga acatctgagc tacccggata 1140 attttcttca tattagtatc atcccacagc caacagattg aaggatcaac tatttgcctg 1200 aacagaatca tccttaaatg ggatttatca gagcatgtca cccttttgct tcaatcaggt 1260 ttggtggagg caacctgacc agaaacactt cgctgctgca agccagacag gaaaaagatt 1320 ccatgtcaga taaggcaact gggctggtct tactttgcat cacctctgct ttcctccact 1380 gccatcatta aacctcagct gtgacatgaa agacttaccg gaccactgaa ggtcttctgt 1440 aaaatataat gaagctgaaa cctttggcct aagaagaaaa tggaagtatg tgccactcga 1500 tttgtatttc tgattaacaa ataaacaggg gtatttccta aggtgaccat ggttgaactt 1560 tagctcatga aagtggaaac attggtttaa ttttcaagag aattaagaaa gtaaaagaga 1620 aattctgtta tcaataactt gcaagtaatt ttttgtaaaa gattgaatta cagtaaaccc 1680 atctttcctt aacgaaaatt tcctatgttt acagtctgtc tattggtatg caatcttgta 1740 actttgataa tgaacagtga gagattttta aataaagcct ctaaatatgt tttgtcattt 1800 aataacatac agttttgtca cttttcaagt actttctgac tcacatacag tagatcactt 1860 tttactctgt gttaccattt tgactggtcg tcattggcat ggggtggata tagggcatag 1920 gattacttgt ctcagaagct gtcatagaat ttcttgctgc caattaaaaa acctgtgttc 1980 tttacacact acacgtataa atattgtaac tgttcatctt tgttgtttta tcactgtaag 2040 cctgtcaaat catagtatcc taagcatctg taaatgctaa ttttgcattt ttggaaaaac 2100 ccattccttc caagctagtg tttttcattg gctccaggtc taatttttca ctgtggtccc 2160 tggcagccag tcttttgaag tttaaagatt acctgtctct tgactgcagt accttttctt 2220 taatttttac caaaaatatc cagaggttac tggagttctt attcaatata aggaaagttt 2280 gctgcacttt attaccaagc ctctgggatt ttaccagtca aacatatttg tgcattacat 2340 ttcatttctt gtgagctagc tggctgtcca tattgaatgt tgacccattt gagtacgcta 2400 aaaggcttac agtatcagac acgatcatgg ttttagatcc cataataaaa atgaatgttt 2460 ttcttataaa aaattataca aatgctgaag tgagattcta ctattgttca ttgcttcctt 2520 ttctttttcc ttttgcgatt ttcactgatt aatagcacat ttcttcacaa aattagataa 2580 agttggtcaa agaccagata ttctggaatg gaaattgtaa agcttaatca aaaagaatag 2640 ccagtacagc atacaatctc agaaacttag aagcaagtag aaaataattg gttgatgtaa 2700 acgaaagtgc cattttagta aaggcaggaa aaaaatagca atatttgagt tatgtaagga 2760 taaaaaatcc actgacttgt atttttgcac aagaggctgg tctgaatatg attgttcaca 2820 ttaagagtgt ttattcgtcg gttcattttg gggattttcc cccttgatgt tttgacagat 2880 tgaagtgagc tttagtgagc aaaaggatca gaatgcaggg aacactaagc tgtgatgaag 2940 aaagtgtggt aaaaagccag agtagtttta tacagacaaa accagtgtca ggcctttgca 3000 gtaggcttga gtgaacttct gatctagatt tgaaagtaaa ttttatgaag acattgccca 3060 tttttacttc ctcattcatt attgtaccag catcatagct ttattactct aatcccaggt 3120 aagtcaagcc tacaatgccc tagaggaaga gtaaaaccag aaattcatgc tggcttaaat 3180 aatctatttt tgtttctttt catttgaata tttaaatttt atggtttatt aaaaaattaa 3240 ataa 3244 <210> 86 <211> 5059 <212> DNA <213> Homo sapiens <400> 86 ctttgcgcac gcgcgccgct tcccagtggc aagcgcgggc aggaccgcgt tgcgtcatcg 60 gggcgcgcgc ctcagagaga gctgtggttg ccggaagttg agcggcggca agaaataatg 120 gcggcagcta cgggggatcc tggactctct aaactgcagt ttgccccttt tagtagtgcc 180 ttggatgttg ggttttggca tgagttgacc cagaagaagc tgaacgagta tcggctggat 240 gaagctccca aggacattaa gggttattac tacaatggtg actctgctgg gctgccagct 300 cgcttaacat tggagttcag tgcttttgac atgagtgctc ccaccccagc ccgttgctgc 360 ccagctattg gaacactgta taacaccaac acactcgagt ctttcaagac tgcagataag 420 aagctccttt tggaacaagc agcaaatgag atatgggaat ccataaaatc aggcactgct 480 cttgaaaacc ctgtactcct caacaagttc ctcctcttga catttgcaga tctaaagaag 540 taccacttct actattggtt ttgctatcct gccctctgtc ttccagagag tttacctctc 600 attcaggggc cagtgggttt ggatcaaagg ttttcactaa aacagattga agcactagag 660 tgtgcatatg ataatctttg tcaaacagaa ggagtcacag ctcttcctta cttcttaatc 720 aagtatgatg agaacatggt gctggtttcc ttgcttaaac actacagtga tttcttccaa 780 ggtcaaagga cgaagataac aattggtgta tatgatccct gtaacttagc ccagtaccct 840 ggatggcctt tgaggaattt tttggtccta gcagcccaca gatggagtag cagtttccag 900 tctgttgaag ttgtttgctt ccgtgaccgt accatgcagg gggcgagaga cgttgcccac 960 agcatcatct tcgaagtgaa gcttccagaa atggcattta gcccagattg tcctaaagca 1020 gttggatggg aaaagaacca gaaaggaggc atgggaccaa ggatggtgaa cctcagtgaa 1080 tgtatggacc ctaaaaggtt agctgagtca tcagtggatc taaatctcaa actgatgtgt 1140 tggagattgg ttcctacttt agacttggac aaggttgtgt ctgtcaaatg tctgctgctt 1200 ggagccggca ccttgggttg caatgtagct aggacgttga tgggttgggg cgtgagacac 1260 atcacatttg tggacaatgc caagatctcc tactccaatc ctgtgaggca gcctctctat 1320 gagtttgaag attgcctagg gggtggtaag cccaaggctc tggcagcagc ggaccggctc 1380 cagaaaatat tccccggtgt gaatgccaga ggattcaaca tgagcatacc tatgcctggg 1440 catccagtga acttctccag tgtcactctg gagcaagccc gcagagatgt ggagcaactg 1500 gagcagctca tcgaaagcca tgatgtcgtc ttcctattga tggacaccag ggagagccgg 1560 tggcttcctg ccgtcattgc tgcaagcaag agaaagctgg tcatcaatgc tgctttggga 1620 tttgacacat ttgttgtcat gagacatggt ctgaagaaac caaagcagca aggagctggg 1680 gacttgtgtc caaaccaccc tgtggcatct gctgacctcc tgggctcatc gctttttgcc 1740 aacatccctg gttacaagct tggctgctac ttctgcaatg atgtggtggc cccaggagat 1800 tcaaccagag accggacctt ggaccagcag tgcactgtga gtcgtccagg actggccgtg 1860 attgcaggag ccctggccgt ggaattgatg gtatctgttt tgcagcatcc agaagggggc 1920 tatgccattg ccagcagcag tgacgatcgg atgaatgagc ctccaacctc tcttgggctt 1980 gtgcctcacc agatccgggg atttctttca cggtttgata atgtccttcc cgtcagcctg 2040 gcatttgaca aatgtacagc ttgttcttcc aaagttcttg atcaatatga acgagaagga 2100 tttaacttcc tagccaaggt gtttaattct tcacattcct tcttagaaga cttgactggt 2160 cttacattgc tgcatcaaga aacccaagct gctgagatct gggacatgag cgatgatgag 2220 accatctgag atggccccgc tgtggggctg acttctcccc ggccgcctgc tgaggagctc 2280 tccatcgcca gagcaggact gctgacccca ggcctggtga ttctgggccc ctcctccata 2340 ccccgaggtc tgggattccc ccctctgctg cccaggagtg gccagtgttc ggcgttgctc 2400 gggattcaag ataccaccag ttcagagcta aataataacc ttggccttgg ccttgctatt 2460 gacctgggac ttggtcctcc atgcagtttt tatttcttgt cacagtgact gatagccatc 2520 ccccaggatc ctttcccctt ggccctgagg gggtgaccca acacagacca aatggggaaa 2580 tgagcaacca gctcctgccc agagccactg cgggaggtgg caccctcatc cccggaatgt 2640 gctgcccacc gcaccgcagg ctcctcctgt gggggccctg ggcatgggtg agggtgggac 2700 cccgtgagcg cactgcaccc tggccctggt ggagcgggag gaggaggaga gccgagctgg 2760 gtacgagact aaagggccca catgacccag tgacgccaga tttccaccaa ggactgagtg 2820 agctgctcag acatggcttt ctgcctccca gcctgtcctc cactgtgggc atagcatctg 2880 tgcctgcctg cctgcttgag ggagaggagt ttctgctgct gccttgagct ggggggaaga 2940 gcccaggggc agatcctggc agctgcctgg atggggctcc tccctgccct tatgagcagg 3000 ccaggcccag aaaggccgag cctgggctgc cttcctgccc cagccgaggg aggggtcaga 3060 cggctctacc atgggtaact caggcaagag ctggttttcc tctttattct gggtgtgtgc 3120 agctgtgagg ccccaaccca ggagaggcca tggcctaggt acctgtgacc accctgcccc 3180 cgtgtagagg gcatcgtctt tcctgctatt ttattctttc agcttttgtc ttaggcccag 3240 aatcaaagtg aaaattgagt cgagctgacc cttacaacag taggatttag tagggtagat 3300 ttcaaatgag gcttcgcttc tcccaaagta gccagtccaa gttccagtgg ctgtcgttca 3360 gctcatggga gcttcatggg gacacagccg gcacaggtgc agggcccgag tccgcccacc 3420 cagcctggcg ctgaaactgc acacgtacac tatgtggttt aagagcactt tattattgtt 3480 cttaaggcta cttttaagta caaaaaaaga tggcctgcca aacctttttt tttcttcttc 3540 caggaaaaac aggccacaga gaatggtata ttacagattt acacacatga agagaaggtc 3600 agagcgcact gcaggcagcg cggctctggg aagaacttca cggagcccct tcttagagca 3660 gggagggggc tttctcagtg aaatgtttgg ttttctgctg cctcctctgc cccaggcccc 3720 cctccagggt actgcctatc ccagataggt cagtgcacca gggacccggc cgccagcacc 3780 gccgacccct cccagagtga cgcccttgtt cactgacaaa gagacctgtc ccaggagtgt 3840 cctccaccga gccggtcagc tgtgggtggt tttcctgtta cgacgctcag tagcctgtag 3900 caataacaaa ctcgtggcta tgaatgcaga tgcagtgttc tcatagaata actgttcctg 3960 cacttttaca gacaaatcta cgacaaaaaa aaagatcaac tttttttttc cgaacaacaa 4020 aaaaaatgaa tgattacaat aggaaaggga aaaattaaat agctacatat cattaacaaa 4080 ttaatgttct tcaaaaaata cctacaaatt tctctgtaca ttctttacgc acagcgtaac 4140 gatggtctca aaatcaccca tatagaaaag tgttctcaac gatttttcct acagaaaata 4200 taggggcctg aatgccaaag cttggaagcc cagtacagtg ggagtgaaat gtgtgcgggg 4260 caaggagaag ggcttttctt tcctccactt ttcaaaggcc tgcagccact ctgtgactac 4320 aagagccagt cctccgacct tttcacccag tgccaatttc caaaattcaa cagctaaaaa 4380 ctgtaaaacc gggggtcata cggtgtgcag agtccacaaa gccttgcagg tgaggtgacc 4440 acgcccacgt cacctggtca ggtgccatcg tcgtgagcct ctggtgggcc aggtgggaca 4500 cagcacaccc cagggggagg ggatagaaac gctcattgac caaaaaggag cagctgtgac 4560 ctccacagct gtgtctgtca tgcttgcttc atctaatttc tagttagtag ctattaatat 4620 agcaaataat aaatgcagta ataacagtat aaagtcagag gaatgtatac tgccttggcc 4680 ccagcgtacg aggaagcgta taaaacacca tatcacagat tgtctgtcag taatctgctg 4740 ttcagccaag agagttcaaa gggagcagtt tctgcatgta gggaagttgg aagacacaaa 4800 ccccacctcc cctgggagct tgtaacaaag cagacaggga tgcaaaaata aatgatgtca 4860 gcctgcagcc aaactccagc atcccacacc gcagctgacc cactgctcat cgcgagggcc 4920 tgccaggagc tggcctcccg cactacttgt gagtaaagtg aatatcaaat accaatctta 4980 gagtacaact gtaccagcag taagtatatc taggactgta actgacaaaa ataaactaat 5040 tctgaaaaga aaaaaaaaa 5059 <210> 87 <211> 2359 <212> DNA <213> Homo sapiens <400> 87 cgaccgagca cagacacgtt gcccaccgct cctctcccga ggtctgtagt cgcggagaaa 60 cacatgttgc gttactaacg ttcagaggtc tgcgacagct tcgatttgaa tgactagccg 120 ggaacaccaa gtttcactgt gtaattgcgt ccccctactc cggcgcctcc tttgcgacgc 180 tccctggaga aaagcacgcc cactgcacgc gctcagtcgc tacttccgct ctcgagtgtc 240 tccaagcaag atggcggagg agccgcagtc tgtgttgcag cttcctactt caattgctgc 300 tggaggggaa ggacttacgg atgtctcccc agaaacaacc accccggagc ccccgtcttc 360 cgctgcagtt tccccgggaa cagaggaacc tgctggcgac accaagaaaa aaattgacat 420 tttgctaaag gctgtgggag acactcctat tatgaaaaca aagaagtggg cagtagagcg 480 aacacgaacc atccaaggac tcattgactt catcaaaaag tttcttaaac ttgtggcctc 540 agaacagttg tttatttatg tgaatcagtc ctttgctcct tccccagacc aagaagttgg 600 aactctctat gagtgttttg gcagtgatgg taaactggtt ttacattact gcaagtctca 660 ggcgtgggga tgaaccacaa agaaaatcaa cttgctacta catgaaatgg attttcacgg 720 aagagacagc tctgaaaagt tttgatgctt gtggcaagag acttaacaga tgtgatctat 780 ttagtatgtg tctactctat gtttatgcat aagaaaacat ccatagcatg aatggactca 840 gaaaaatgtg atttgtatta atgcaccagt catcataaaa gatggtcatg atagtacacc 900 cattgctcct acttgttact attattgctg cagatctgcc tccaaggttg aaaaggagac 960 taagactgta taaacatctt cattgtcagt tctcaaaatg actgaaattg ttttcatggt 1020 aaaagttaat atactaaagg gttccttttt ttttaatgtt tacatttatc tctatgttta 1080 cctttttagt cacattgacc tgctggctga atacctcaaa tagtccagta gagggcagtc 1140 caccaggcag aaaaggttag gcgttttggt ttcacatctt tgctggggaa taatagggga 1200 aatggctgtt tttgctaatt tttagctaat atctagccag gagagcaagc acataggaca 1260 gactgaaaga ctgtaatttt acacaataca catggcttaa ttattttatt gggatacaga 1320 aaaatataaa ttctggacaa ataagtcata tacctgtttt cagtcctaac atttaaggat 1380 tcttgagtcc caatcacata actgtggtgt tactctgtca tttatatggt gtcaaaagca 1440 cttgatgagt aaacccagta gcatcttttt gagtgtttca taatgcattt tccaacttga 1500 aaacaataat tgaaaaatag ccttattgta tattttatgc catgactaaa agtgccattt 1560 ttactgatgc tattagactg ataatttctt gaagtgaaat ttaacctttt tttctcttta 1620 gtattatgtt tataatgcca tatttttaga aagcattcca gatcaggcat ggtggcttac 1680 acctgtaatc ccagcacttt ggaaggctga ggtgtgggga ttgcgtgaag ccacaagttt 1740 gagaccagcc tggttagcaa ggcaagatcc ccaactctac aaaaaaataa aaattaaaaa 1800 aaaattatta ggctgcagag gcaagaggat cccctgagcc cagaagttca agggtatagt 1860 gagtcgtgat tgtaccactg cattcctgct gagcaacaga gtgagacccc atctcaaaaa 1920 agaaaaaaaa aggcattcta gtaaatcgaa tgtaatgtga atggaatttc aaaacaggat 1980 ctaagatggt atgtagtaga attcaaagta atatcatttt aaagttaaat gagtatggaa 2040 aaggtctgtt ctctagtttt gtccagttca gtttactgaa ggaatatatt taattatatt 2100 catatattta acaaataaaa atatgttgaa ttttcgtatt gtttgccact gagggttcag 2160 atgatagacc tcaaaaaatc gaaaatactg gttgaaattt gtagcatcca tttagttatt 2220 ctttttgacc taaataactt aatagtttat taaatctaag gttagctaaa tatgtagcta 2280 accttatttg ttttctttcc taacaactct gaagaataca taggactttg cacttttttt 2340 tttttttttt ttttttaaa 2359 <210> 88 <211> 891 <212> DNA <213> Homo sapiens <400> 88 tcacgtgacc cgggcgcgct gcggccgccc gcgcggaccc ggcgagaggc ggcggcggga 60 gcggcggtga tggacgggtc cggggagcag cccagaggcg gggggcccac cagctctgag 120 cagatcatga agacaggggc ccttttgctt cagggtttca tccaggatcg agcagggcga 180 atgggggggg aggcacccga gctggccctg gacccggtgc ctcaggatgc gtccaccaag 240 aagctgagcg agtgtctcaa gcgcatcggg gacgaactgg acagtaacat ggagctgcag 300 aggatgattg ccgccgtgga cacagactcc ccccgagagg tctttttccg agtggcagct 360 gacatgtttt ctgacggcaa cttcaactgg ggccgggttg tcgccctttt ctactttgcc 420 agcaaactgg tgctcaaggc cctgtgcacc aaggtgccgg aactgatcag aaccatcatg 480 ggctggacat tggacttcct ccgggagcgg ctgttgggct ggatccaaga ccagggtggt 540 tgggtgagac tcctcaagcc tcctcacccc caccaccgcg ccctcaccac cgcccctgcc 600 ccaccgtccc tgccccccgc cactcctctg ggaccctggg ccttctggag caggtcacag 660 tggtgccctc tccccatctt cagatcatca gatgtggtct ataatgcgtt ttccttacgt 720 gtctgatcaa tccccgattc atctaccctg ctgacctccc agtgacccct gacctcactg 780 tgaccttgac ttgattagtg ccttctgccc tccctggagc ctccactgcc tctggaattg 840 ctcaagttca ttgatgaccc tctgacccta gctctttcct tttttttttt t 891 <210> 89 <211> 6492 <212> DNA <213> Homo sapiens <400> 89 tttctgtgaa gcagaagtct gggaatcgat ctggaaatcc tcctaatttt tactccctct 60 ccccgcgact cctgattcat tgggaagttt caaatcagct ataactggag agtgctgaag 120 attgatggga tcgttgcctt atgcatttgt tttggtttta caaaaaggaa acttgacaga 180 ggatcatgct gtacttaaaa aatacaacat cacagaggaa gtagactgat attaacaata 240 cttactaata ataacgtgcc tcatgaaata aagatccgaa aggaattgga ataaaaattt 300 cctgcatctc atgccaaggg ggaaacacca gaatcaagtg ttccgcgtga ttgaagacac 360 cccctcgtcc aagaatgcaa agcacatcca ataaaatagc tggattataa ctcctcttct 420 ttctctgggg gccgtggggt gggagctggg gcgagaggtg ccgttggccc ccgttgcttt 480 tcctctggga aggatggcgc acgctgggag aacagggtac gataaccggg agatagtgat 540 gaagtacatc cattataagc tgtcgcagag gggctacgag tgggatgcgg gagatgtggg 600 cgccgcgccc ccgggggccg cccccgcacc gggcatcttc tcctcccagc ccgggcacac 660 gccccatcca gccgcatccc gggacccggt cgccaggacc tcgccgctgc agaccccggc 720 tgcccccggc gccgccgcgg ggcctgcgct cagcccggtg ccacctgtgg tccacctgac 780 cctccgccag gccggcgacg acttctcccg ccgctaccgc cgcgacttcg ccgagatgtc 840 cagccagctg cacctgacgc ccttcaccgc gcggggacgc tttgccacgg tggtggagga 900 gctcttcagg gacggggtga actgggggag gattgtggcc ttctttgagt tcggtggggt 960 catgtgtgtg gagagcgtca accgggagat gtcgcccctg gtggacaaca tcgccctgtg 1020 gatgactgag tacctgaacc ggcacctgca cacctggatc caggataacg gaggctggga 1080 tgcctttgtg gaactgtacg gccccagcat gcggcctctg tttgatttct cctggctgtc 1140 tctgaagact ctgctcagtt tggccctggt gggagcttgc atcaccctgg gtgcctatct 1200 gggccacaag tgaagtcaac atgcctgccc caaacaaata tgcaaaaggt tcactaaagc 1260 agtagaaata atatgcattg tcagtgatgt accatgaaac aaagctgcag gctgtttaag 1320 aaaaaataac acacatataa acatcacaca cacagacaga cacacacaca cacaacaatt 1380 aacagtcttc aggcaaaacg tcgaatcagc tatttactgc caaagggaaa tatcatttat 1440 tttttacatt attaagaaaa aaagatttat ttatttaaga cagtcccatc aaaactcctg 1500 tctttggaaa tccgaccact aattgccaag caccgcttcg tgtggctcca cctggatgtt 1560 ctgtgcctgt aaacatagat tcgctttcca tgttgttggc cggatcacca tctgaagagc 1620 agacggatgg aaaaaggacc tgatcattgg ggaagctggc tttctggctg ctggaggctg 1680 gggagaaggt gttcattcac ttgcatttct ttgccctggg ggctgtgata ttaacagagg 1740 gagggttcct gtggggggaa gtccatgcct ccctggcctg aagaagagac tctttgcata 1800 tgactcacat gatgcatacc tggtgggagg aaaagagttg ggaacttcag atggacctag 1860 tacccactga gatttccacg ccgaaggaca gcgatgggaa aaatgccctt aaatcatagg 1920 aaagtatttt tttaagctac caattgtgcc gagaaaagca ttttagcaat ttatacaata 1980 tcatccagta ccttaagccc tgattgtgta tattcatata ttttggatac gcacccccca 2040 actcccaata ctggctctgt ctgagtaaga aacagaatcc tctggaactt gaggaagtga 2100 acatttcggt gacttccgca tcaggaaggc tagagttacc cagagcatca ggccgccaca 2160 agtgcctgct tttaggagac cgaagtccgc agaacctgcc tgtgtcccag cttggaggcc 2220 tggtcctgga actgagccgg ggccctcact ggcctcctcc agggatgatc aacagggcag 2280 tgtggtctcc gaatgtctgg aagctgatgg agctcagaat tccactgtca agaaagagca 2340 gtagaggggt gtggctgggc ctgtcaccct ggggccctcc aggtaggccc gttttcacgt 2400 ggagcatggg agccacgacc cttcttaaga catgtatcac tgtagaggga aggaacagag 2460 gccctgggcc cttcctatca gaaggacatg gtgaaggctg ggaacgtgag gagaggcaat 2520 ggccacggcc cattttggct gtagcacatg gcacgttggc tgtgtggcct tggcccacct 2580 gtgagtttaa agcaaggctt taaatgactt tggagagggt cacaaatcct aaaagaagca 2640 ttgaagtgag gtgtcatgga ttaattgacc cctgtctatg gaattacatg taaaacatta 2700 tcttgtcact gtagtttggt tttatttgaa aacctgacaa aaaaaaagtt ccaggtgtgg 2760 aatatggggg ttatctgtac atcctggggc attaaaaaaa aaatcaatgg tggggaacta 2820 taaagaagta acaaaagaag tgacatcttc agcaaataaa ctaggaaatt tttttttctt 2880 ccagtttaga atcagccttg aaacattgat ggaataactc tgtggcatta ttgcattata 2940 taccatttat ctgtattaac tttggaatgt actctgttca atgtttaatg ctgtggttga 3000 tatttcgaaa gctgctttaa aaaaatacat gcatctcagc gtttttttgt ttttaattgt 3060 atttagttat ggcctataca ctatttgtga gcaaaggtga tcgttttctg tttgagattt 3120 ttatctcttg attcttcaaa agcattctga gaaggtgaga taagccctga gtctcagcta 3180 cctaagaaaa acctggatgt cactggccac tgaggagctt tgtttcaacc aagtcatgtg 3240 catttccacg tcaacagaat tgtttattgt gacagttata tctgttgtcc ctttgacctt 3300 gtttcttgaa ggtttcctcg tccctgggca attccgcatt taattcatgg tattcaggat 3360 tacatgcatg tttggttaaa cccatgagat tcattcagtt aaaaatccag atggcaaatg 3420 accagcagat tcaaatctat ggtggtttga cctttagaga gttgctttac gtggcctgtt 3480 tcaacacaga cccacccaga gccctcctgc cctccttccg cgggggcttt ctcatggctg 3540 tccttcaggg tcttcctgaa atgcagtggt gcttacgctc caccaagaaa gcaggaaacc 3600 tgtggtatga agccagacct ccccggcggg cctcagggaa cagaatgatc agacctttga 3660 atgattctaa tttttaagca aaatattatt ttatgaaagg tttacattgt caaagtgatg 3720 aatatggaat atccaatcct gtgctgctat cctgccaaaa tcattttaat ggagtcagtt 3780 tgcagtatgc tccacgtggt aagatcctcc aagctgcttt agaagtaaca atgaagaacg 3840 tggacgtttt taatataaag cctgttttgt cttttgttgt tgttcaaacg ggattcacag 3900 agtatttgaa aaatgtatat atattaagag gtcacggggg ctaattgctg gctggctgcc 3960 ttttgctgtg gggttttgtt acctggtttt aataacagta aatgtgccca gcctcttggc 4020 cccagaactg tacagtattg tggctgcact tgctctaaga gtagttgatg ttgcattttc 4080 cttattgtta aaaacatgtt agaagcaatg aatgtatata aaagcctcaa ctagtcattt 4140 ttttctcctc ttcttttttt tcattatatc taattatttt gcagttgggc aacagagaac 4200 catccctatt ttgtattgaa gagggattca catctgcatc ttaactgctc tttatgaatg 4260 aaaaaacagt cctctgtatg tactcctctt tacactggcc agggtcagag ttaaatagag 4320 tatatgcact ttccaaattg gggacaaggg ctctaaaaaa agccccaaaa ggagaagaac 4380 atctgagaac ctcctcggcc ctcccagtcc ctcgctgcac aaatactccg caagagaggc 4440 cagaatgaca gctgacaggg tctatggcca tcgggtcgtc tccgaagatt tggcaggggc 4500 agaaaactct ggcaggctta agatttggaa taaagtcaca gaattaagga agcacctcaa 4560 tttagttcaa acaagacgcc aacattctct ccacagctca cttacctctc tgtgttcaga 4620 tgtggccttc catttatatg tgatctttgt tttattagta aatgcttatc atctaaagat 4680 gtagctctgg cccagtggga aaaattagga agtgattata aatcgagagg agttataata 4740 atcaagatta aatgtaaata atcagggcaa tcccaacaca tgtctagctt tcacctccag 4800 gatctattga gtgaacagaa ttgcaaatag tctctatttg taattgaact tatcctaaaa 4860 caaatagttt ataaatgtga acttaaactc taattaattc caactgtact tttaaggcag 4920 tggctgtttt tagactttct tatcacttat agttagtaat gtacacctac tctatcagag 4980 aaaaacagga aaggctcgaa atacaagcca ttctaaggaa attagggagt cagttgaaat 5040 tctattctga tcttattctg tggtgtcttt tgcagcccag acaaatgtgg ttacacactt 5100 tttaagaaat acaattctac attgtcaagc ttatgaaggt tccaatcaga tctttattgt 5160 tattcaattt ggatctttca gggatttttt ttttaaatta ttatgggaca aaggacattt 5220 gttggagggg tgggagggag gaagaatttt taaatgtaaa acattcccaa gtttggatca 5280 gggagttgga agttttcaga ataaccagaa ctaagggtat gaaggacctg tattggggtc 5340 gatgtgatgc ctctgcgaag aaccttgtgt gacaaatgag aaacattttg aagtttgtgg 5400 tacgaccttt agattccaga gacatcagca tggctcaaag tgcagctccg tttggcagtg 5460 caatggtata aatttcaagc tggatatgtc taatgggtat ttaaacaata aatgtgcagt 5520 tttaactaac aggatattta atgacaacct tctggttggt agggacatct gtttctaaat 5580 gtttattatg tacaatacag aaaaaaattt tataaaatta agcaatgtga aactgaattg 5640 gagagtgata atacaagtcc tttagtctta cccagtgaat cattctgttc catgtctttg 5700 gacaaccatg accttggaca atcatgaaat atgcatctca ctggatgcaa agaaaatcag 5760 atggagcatg aatggtactg taccggttca tctggactgc cccagaaaaa taacttcaag 5820 caaacatcct atcaacaaca aggttgttct gcataccaag ctgagcacag aagatgggaa 5880 cactggtgga ggatggaaag gctcgctcaa tcaagaaaat tctgagacta ttaataaata 5940 agactgtagt gtagatactg agtaaatcca tgcacctaaa ccttttggaa aatctgccgt 6000 gggccctcca gatagctcat ttcattaagt ttttccctcc aaggtagaat ttgcaagagt 6060 gacagtggat tgcatttctt ttggggaagc tttcttttgg tggttttgtt tattatacct 6120 tcttaagttt tcaaccaagg tttgcttttg ttttgagtta ctggggttat ttttgtttta 6180 aataaaaata agtgtacaat aagtgttttt gtattgaaag cttttgttat caagattttc 6240 atacttttac cttccatggc tctttttaag attgatactt ttaagaggtg gctgatattc 6300 tgcaacactg tacacataaa aaatacggta aggatacttt acatggttaa ggtaaagtaa 6360 gtctccagtt ggccaccatt agctataatg gcactttgtt tgtgttgttg gaaaaagtca 6420 cattgccatt aaactttcct tgtctgtcta gttaatattg tgaagaaaaa taaagtacag 6480 tgtgagatac tg 6492 <210> 90 <211> 2386 <212> DNA <213> Homo sapiens <400> 90 ggaggaggaa gcaagcgagg gggctggttc ctgagcttcg caattcctgt gtcgccttct 60 gggctcccag cctgccgggt cgcatgatcc ctccggccgg agctggtttt tttgccagcc 120 accgcgaggc cggctgagtt accggcatcc ccgcagccac ctcctctccc gacctgtgat 180 acaaaagatc ttccgggggc tgcacctgcc tgcctttgcc taaggcggat ttgaatctct 240 ttctctccct tcagaatctt atcttggctt tggatcttag aagagaatca ctaaccagag 300 acgagactca gtgagtgagc aggtgttttg gacaatggac tggttgagcc catccctatt 360 ataaaaatgt ctcagagcaa ccgggagctg gtggttgact ttctctccta caagctttcc 420 cagaaaggat acagctggag tcagtttagt gatgtggaag agaacaggac tgaggcccca 480 gaagggactg aatcggagat ggagaccccc agtgccatca atggcaaccc atcctggcac 540 ctggcagaca gccccgcggt gaatggagcc actggccaca gcagcagttt ggatgcccgg 600 gaggtgatcc ccatggcagc agtaaagcaa gcgctgaggg aggcaggcga cgagtttgaa 660 ctgcggtacc ggcgggcatt cagtgacctg acatcccagc tccacatcac cccagggaca 720 gcatatcaga gctttgaaca ggatactttt gtggaactct atgggaacaa tgcagcagcc 780 gagagccgaa agggccagga acgcttcaac cgctggttcc tgacgggcat gactgtggcc 840 ggcgtggttc tgctgggctc actcttcagt cggaaatgac cagacactga ccatccactc 900 taccctccca cccccttctc tgctccacca catcctccgt ccagccgcca ttgccaccag 960 gagaaccact acatgcagcc catgcccacc tgcccatcac agggttgggc ccagatctgg 1020 tcccttgcag ctagttttct agaatttatc acacttctgt gagaccccca cacctcagtt 1080 cccttggcct cagaattcac aaaatttcca caaaatctgt ccaaaggagg ctggcaggta 1140 tggaagggtt tgtggctggg ggcaggaggg ccctacctga ttggtgcaac ccttacccct 1200 tagcctccct gaaaatgttt ttctgccagg gagcttgaaa gttttcagaa cctcttcccc 1260 agaaaggaga ctagattgcc tttgttttga tgtttgtggc ctcagaattg atcattttcc 1320 ccccactctc cccacactaa cctgggttcc ctttccttcc atccctaccc cctaagagcc 1380 atttaggggc cacttttgac tagggattca ggctgcttgg gataaagatg caaggaccag 1440 gactccctcc tcacctctgg actggctaga gtcctcactc ccagtccaaa tgtcctccag 1500 aagcctctgg ctagaggcca gccccaccca ggagggaggg ggctatagct acaggaagca 1560 ccccatgcca aagctagggt ggcccttgca gttcagcacc accctagtcc cttcccctcc 1620 ctggctccca tgaccatact gagggaccaa ctgggcccaa gacagatgcc ccagagctgt 1680 ttatggcctc agctgcctca cttcctacaa gagcagcctg tggcatcttt gccttgggct 1740 gctcctcatg gtgggttcag gggactcagc cctgaggtga aagggagcta tcaggaacag 1800 ctatgggagc cccagggtct tccctacctc aggcaggaag ggcaggaagg agagcctgct 1860 gcatggggtg gggtagggct gactagaagg gccagtcctg cctggccagg cagatctgtg 1920 ccccatgcct gtccagcctg ggcagccagg ctgccaaggc cagagtggcc tggccaggag 1980 ctcttcaggc ctccctctct cttctgctcc acccttggcc tgtctcatcc ccaggggtcc 2040 cagccacccc gggctctctg ctgtacatat ttgagactag tttttattcc ttgtgaagat 2100 gatatactat ttttgttaag cgtgtctgta tttatgtgtg aggagctgct ggcttgcagt 2160 gcgcgtgcac gtggagagct ggtgcccgga gattggacgg cctgatgctc cctcccctgc 2220 cctggtccag ggaagctggc cgagggtcct ggctcctgag gggcatctgc ccctccccca 2280 acccccaccc cacacttgtt ccagctcttt gaaatagtct gtgtgaaggt gaaagtgcag 2340 ttcagtaata aactgtgttt actcagtgaa aaaaaaaaaa aaaaaa 2386 <210> 91 <211> 1535 <212> DNA <213> Homo sapiens <400> 91 cctccgctca gtccgggagc gcacgtgggc cgcggcgctc cgacctccgc tttcccaccg 60 cccgcagctg aagcacatcc cgcagcccgg cgcggactcc gatcgccgca gttgccctct 120 ggcgccatgt cgcagaacgg agcgcccggg atgcaggagg agagcctgca gggctcctgg 180 gtagaactgc acttcagcaa taatgggaac gggggcagcg ttccagcctc ggtttctatt 240 tataatggag acatggaaaa aatactgctg gacgcacagc atgagtctgg acggagtagc 300 tccaagagct ctcactgtga cagcccacct cgctcgcaga caccacaaga taccaacagg 360 gcttctgaaa cagataccca tagcattgga gagaaaaaca gctcacagtc tgaggaagat 420 gatattgaaa gaaggaaaga agttgaaagc atcttgaaga aaaactcaga ttggatatgg 480 gattggtcaa gtcggccgga aaatattccc cccaaggagt tcctctttaa acacccgaag 540 cgcacggcca ccctcagcat gaggaacacg agcgtcatga agaaaggggg catattctct 600 gcagaatttc tgaaagtttt ccttccatct ctgctgctct ctcatttgct ggccatcgga 660 ttggggatct atattggaag gcgtctgaca acctccacca gcaccttttg atgaagaact 720 ggagtctgac ttggttcgtt agtggattac ttctgagctt gcaacatagc tcactgaaga 780 gctgttagat cctggggtgg ccacgtcact tgtgtttatt tgttctgtaa atgctgcgtt 840 cctaatttag taaaataaaa gaatagacac taaaatcatg ttgatctata attacaccta 900 tgggatcaat aagcatgtca gactgattaa tgtctactgt gaaaatttgg tagtaaattt 960 tcatttgata ttagatataa atatctgaat ataaataatt ttaatatact agtcatgatg 1020 tgtgttgtat tttaaaaatt atctgcaacc ttaattcagc tgaagtactt tatatttcaa 1080 aagaatgaat aacattgata ataaaatcgc tactttaagg ggtttgtcca aaataaatat 1140 tgtggcctta tatatcacac tattgtagaa agtattattt aatttaaatg gatgcaggtt 1200 gtctactaaa gaaagattat atataactat gctaattgtt cataatcaac agaaaccaag 1260 atagagctac aaactcagct gtacagttcg tacactaaac tcttcttgct tttgcattat 1320 aaggaattaa gtctccgatt attaggtgat caccctggat gatcagtttt ctgctgaagg 1380 cacctactca gtatcttttc ctctttatca ctctgcattg gtgaatttaa tcctctcctt 1440 tgtgttcaac ttttgtgtgc ttttaaaatc agctttattc taagcaaatc tgtgtctact 1500 ttaaaaaact ggaaatggaa aaaaaaataa atctt 1535 <210> 92 <211> 2914 <212> DNA <213> Homo sapiens <400> 92 gtgctctgag tttttggttt ctgtttcacc ttgtgtctga gctggtctga aggctggttg 60 ttcagactga gcttcctgcc tgcctgtacc ccgccaacag cttcagaaga aggtgactgg 120 tggctgcctg aggaatacca gtgggcaaga gaattagcat ttctggagca tctgctgtct 180 gagcagcccc tgggtgcgtc cactttctgg gcacgtgagg ttgggccttg gccgcctgag 240 cccttgagtt ggtcacttga accttgggaa tattgagatt atattctcct gccttttaaa 300 aagatggact tcagcagaaa tctttatgat attggggaac aactggacag tgaagatctg 360 gcctccctca agttcctgag cctggactac attccgcaaa ggaagcaaga acccatcaag 420 gatgccttga tgttattcca gagactccag gaaaagagaa tgttggagga aagcaatctg 480 tccttcctga aggagctgct cttccgaatt aatagactgg atttgctgat tacctaccta 540 aacactagaa aggaggagat ggaaagggaa cttcagacac caggcagggc tcaaatttct 600 gcctacaggt tccacttctg ccgcatgagc tgggctgaag caaacagcca gtgccagaca 660 cagtctgtac ctttctggcg gagggtcgat catctattaa taagggtcat gctctatcag 720 atttcagaag aagtgagcag atcagaattg aggtctttta agtttctttt gcaagaggaa 780 atctccaaat gcaaactgga tgatgacatg aacctgctgg atattttcat agagatggag 840 aagagggtca tcctgggaga aggaaagttg gacatcctga aaagagtctg tgcccaaatc 900 aacaagagcc tgctgaagat aatcaacgac tatgaagaat tcagcaaagg ggaggagttg 960 tgtggggtaa tgacaatctc ggactctcca agagaacagg atagtgaatc acagactttg 1020 gacaaagttt accaaatgaa aagcaaacct cggggatact gtctgatcat caacaatcac 1080 aattttgcaa aagcacggga gaaagtgccc aaacttcaca gcattaggga caggaatgga 1140 acacacttgg atgcaggggc tttgaccacg acctttgaag agcttcattt tgagatcaag 1200 ccccacgatg actgcacagt agagcaaatc tatgagattt tgaaaatcta ccaactcatg 1260 gaccacagta acatggactg cttcatctgc tgtatcctct cccatggaga caagggcatc 1320 atctatggca ctgatggaca ggaggccccc atctatgagc tgacatctca gttcactggt 1380 ttgaagtgcc cttcccttgc tggaaaaccc aaagtgtttt ttattcaggc ttgtcagggg 1440 gataactacc agaaaggtat acctgttgag actgattcag aggagcaacc ctatttagaa 1500 atggatttat catcacctca aacgagatat atcccggatg aggctgactt tctgctgggg 1560 atggccactg tgaataactg tgtttcctac cgaaaccctg cagagggaac ctggtacatc 1620 cagtcacttt gccagagcct gagagagcga tgtcctcgag gcgatgatat tctcaccatc 1680 ctgactgaag tgaactatga agtaagcaac aaggatgaca agaaaaacat ggggaaacag 1740 atgcctcagc ctactttcac actaagaaaa aaacttgtct tcccttctga ttgatggtgc 1800 tattttgttt gttttgtttt gttttgtttt tttgagacag aatctcgctc tgtcgcccag 1860 gctggagtgc agtggcgtga tctcggctca ccgcaagctc cgcctcccgg gttcaggcca 1920 ttctcctgcc tcagcctccc gagtagctgg gactacaggg gcccgccacc acacctggct 1980 aattttttaa aaatattttt agtagagaca gggtttcact gtgttagcca gggtggtctt 2040 gatctcctga cctcgtgatc cacccacctc ggcctcccaa agtgctggga ttacaggcgt 2100 gagccaccgc gcctggccga tggtactatt tagatataac actatgttta tttactaatt 2160 ttctagattt tctactttat taattgtttt gcactttttt ataagagcta aagttaaata 2220 ggatattaac aacaataaca ctgtctcctt tctcttatgc ttaaggcttt gggaatgttt 2280 ttagctggtg gcaataaata ccagacacgt acaaaatcca gctatgaata tagagggctt 2340 atgattcaga ttgttatcta tcaactataa gcccactgtt aatattctat taactttaat 2400 tctctttcaa agctaaattc cacactacca cattaaaaaa attagaaagt agccacgtat 2460 ggtggctcat gtctataatc ccagcacttt gggaggttga ggtgggagga ttgcttgaac 2520 ccaagaggtc aaggctgcag tgagccatgt tcacaccgct gcactcaagc ttgggtgaca 2580 gaacaagacc ccgtctcaaa aaaaattttt tttttaataa aacaaaattt gtttgaaatc 2640 ttttaaaaat tcaaatgatt tttacaagtt ttaaataagc tctccccaaa cttgctttat 2700 gccttcttat tgcttttatg atatatatat gcttggctaa ctatatttgc tttttgctaa 2760 caatgctctg gggtcttttt atgcatttgc atttgctctt tcatctctgc ttggattatt 2820 ttaaatcatt aggaattaag ttatctttaa aatttaagta tcttttttca aaaacatttt 2880 ttaatagaat aaaatataat ttgatcttat taaa 2914 <210> 93 <211> 3579 <212> DNA <213> Homo sapiens <400> 93 tcaggctcgc tgtcgcgcca ttttgccggg gtttgaatgt gaggcggagc ggcggcagga 60 gcgggtagtg ccagctacgg tccgcggctg gggttccctc ctccgtttct gtatccccac 120 gagatcctat agcaatggaa ctcagcgatg caaatctgca aacactaaca gaatatttaa 180 agaaaacact tgatcctgat cctgccatcc gacgtccagc tgagaaattt cttgaatctg 240 ttgaaggaaa tcagaattat ccactgttgc ttttgacatt actggagaag tcccaggata 300 atgttatcaa agtatgtgct tcagtaacat tcaaaaacta tattaaaagg aactggagaa 360 ttgttgaaga tgaaccaaac aaaatttgtg aagccgatcg agtggccatt aaagccaaca 420 tagtgcactt gatgcttagc agcccagagc aaattcagaa gcagttaagt gatgcaatta 480 gcattattgg cagagaagat tttccacaga aatggcctga cttgctgaca gaaatggtga 540 atcgctttca gagtggagat ttccatgtta ttaatggagt cctccgtaca gcacattcat 600 tatttaaaag ataccgtcat gaatttaagt caaacgagtt atggactgaa attaagcttg 660 ttctggatgc ctttgctttg cctttgacta atctttttaa ggccactatt gaactctgca 720 gtacccatgc aaatgatgcc tctgccctga ggattctgtt ttcttccctg atcctgatct 780 caaaattgtt ctatagttta aactttcagg atctccctga attttttgaa gataatatgg 840 aaacttggat gaataatttt catactctct taacattgga taataagctt ttacaaactg 900 atgatgaaga ggaagccggc ttattggagc tcttaaaatc ccagatttgt gataatgccg 960 cactctatgc acaaaagtac gatgaagaat tccagcgata cctgcctcgt tttgttacag 1020 ccatctggaa tttactagtt acaacgggtc aagaggttaa atatgatttg ttggtaagta 1080 atgcaattca atttctggct tcagtttgtg agagacctca ttataagaat ctatttgagg 1140 accagaacac gctgacaagt atctgtgaaa aggttattgt gcctaacatg gaatttagag 1200 ctgctgatga agaagcattt gaagataatt ctgaggagta cataaggaga gatttggaag 1260 gatctgatat tgatactaga cgcagggctg cttgtgatct ggtacgagga ttatgcaagt 1320 tttttgaggg acctgtgaca ggaatcttct ctggttatgt taattccatg ctgcaggaat 1380 acgcaaaaaa tccatctgtc aactggaaac acaaagatgc agccatctac ctagtgacat 1440 ctttggcatc aaaagcccaa acacagaagc atggaattac acaagcaaat gaacttgtaa 1500 acctaactga gttctttgtg aatcacatcc tccctgattt aaaatcagct aatgtgaatg 1560 aatttcctgt ccttaaagct gacggtatca aatatattat gatttttaga aatcaagtgc 1620 caaaagaaca tcttttagtc tcgattcctc tcttgattaa tcatcttcaa gctgaaagta 1680 ttgttgttca tacttacgca gctcatgctc ttgaacggct ctttactatg cgagggccta 1740 acaatgccac tctctttaca gctgcagaaa tcgcaccgtt tgttgagatt ctgctaacaa 1800 accttttcaa agctctcaca cttcctggct cttcagaaaa tgaatatatt atgaaagcta 1860 tcatgagaag tttttctctc ctacaagaag ccataatccc ctacatccct actctcatca 1920 ctcagcttac acagaagcta ttagctgtta gtaagaaccc aagcaaacct cactttaatc 1980 actacatgtt tgaagcaata tgtttatcca taagaataac ttgcaaagct aaccctgctg 2040 ctgttgtaaa ttttgaggag gctttgtttt tggtgtttac tgaaatctta caaaatgatg 2100 tgcaagaatt tattccatac gtctttcaag tgatgtcttt gcttctggaa acacacaaaa 2160 atgacatccc gtcttcctat atggccttat ttcctcatct ccttcagcca gtgctttggg 2220 aaagaacagg aaatattcct gctctagtga ggcttcttca agcattctta gaacgcggtt 2280 caaacacaat agcaagtgct gcagctgaca aaattcctgg gttactaggt gtctttcaga 2340 agctgattgc atccaaagca aatgaccacc aaggttttta tcttctaaac agtataatag 2400 agcacatgcc tcctgaatca gttgaccaat ataggaaaca aatcttcatt ctgctattcc 2460 agagacttca gaattccaaa acaaccaagt ttatcaagag ttttttagtc tttattaatt 2520 tgtattgcat aaaatatggg gcactagcac tacaagaaat atttgatggt atacaaccaa 2580 aaatgtttgg aatggttttg gaaaaaatta ttattcctga aattcagaag gtatctggaa 2640 atgtagagaa aaagatctgt gcggttggca taaccaaatt actaacagaa tgtcccccaa 2700 tgatggacac tgagtatacc aaactgtgga ctccattatt acagtctttg attggtcttt 2760 ttgagttacc cgaagatgat accattcctg atgaggaaca ttttattgac atagaagata 2820 caccaggata tcagactgcc ttctcacagt tggcatttgc tgggaaaaaa gagcatgatc 2880 ctgtaggtca aatggtgaat aaccccaaaa ttcacctggc acagtcactt cacaagttgt 2940 ctaccgcctg tccaggaagg gttccatcaa tggtgagcac cagcctgaat gcagaagcgc 3000 tccagtatct ccaagggtac cttcaggcag ccagtgtgac actgctttaa actgcatttt 3060 tctaatgggc taaacccaga tggtttccta ggaaatcaca ggcttctgag cacagctgca 3120 ttaaaacaaa ggaagttctc cttttgaact tgtcacgaat tccatcttgt aaaggatatt 3180 aaatgttgct ttaacctgaa ccttgagcaa attagttggt ttgtgtgatc atacagttat 3240 gtgggtggct tctagtttgc aacttcaagg gacaagtatt aatagttcag tgtatggcgt 3300 tggtttgtgt tgagcgtttg cacggtttgg ataatcttaa attttgacgg acactgtgga 3360 gactttctgt tactaaatcc ttttgttttg aagctgttgc tatttgtatt tctcttgtcc 3420 tttatatttt ttgtctgttt atttacgctt ttattggaaa tgtgaataag taaagaatta 3480 cttgtgttac ttgccaagca gtgcacattt catagtttca aatctgtaat cagcaataaa 3540 aatcctaaaa tatgtaccta aaaaaaaaaa aaaaaaaaa 3579 <210> 94 <211> 2265 <212> DNA <213> Homo sapiens <400> 94 acgcggaggt tgtaattggt ctctagacca cacctagttg ttgagtgccg ctgcttgaaa 60 atctcagttc tgccgagatc gcagaataca cacaagctac ctttgggcac cagagcagac 120 agaaccgcgg agcttcaggg tggaagattc gtggaaactt tgccaaggcc aggacctcgt 180 gtgttcccgt ccgcccctct gggacggcgc cagcccggca ggccgccgac cgtcctgggg 240 ctcccgcgca gcgcgatgcc ggcctcgtcc accgtccacg tgctgcagct gctgcgggag 300 ctgctcgcct tcgtgctcct cagctacacg gtgctcatcg gggcgctgct gctggccggc 360 tggaccactt acttcctggt gctgaagtga cagcgccgtc gccgcgcccg gccccgcctc 420 ccgcccggcc ccgcctcccg cccggccccg cctccctaac tcaccaggaa attcccttca 480 agccctggcc cgaactgagt ccccgcccac ccgccagcgt cacggcgccc gactcagctc 540 cgcgccggac ccacctccgc gccctcaggc cctgcatatg ccccgccccg cgcggaagtt 600 ccggcggttg gttgccttgc gcggccgtta cagcctttgc cctaagcctc gccccctttc 660 cccctgcctg cccaatcccg actgcttcct tgggtggggg cgtggctatg gggcgaggcg 720 ctctcaggtg gaggccgtgc cccgctccgc gctcacgaag ctgcgtcact tccggcgtgt 780 gcgtctggcg tccgcgcgct gcacaatggc ggctctgaag agttggctgt cgcgcagcgt 840 aacttcattc ttcaggtaca gacagtgttt gtgtgttcct gttgtggcta actttaagaa 900 gcggtgtttc tcagaattga taagaccatg gcacaaaact gtgacgattg gctttggagt 960 aaccctgtgt gcggttccta ttgcacagaa atcagagcct cattccctta gtagtgaagc 1020 attgatgagg agagcagtgt ctttggtaac agatagcacc tctacctttc tctctcagac 1080 cacatatgcg ttgattgaag ctattactga atatactaag gctgtttata ccttaacttc 1140 tctttaccga caatatacaa gtttacttgg gaaaatgaat tcagaggagg aagatgaagt 1200 gtggcaggtg atcataggag ccagagctga gatgacttca aaacaccaag agtacttgaa 1260 gctggaaacc acttggatga ctgcagttgg tctttcagag atggcagcag aagctgcata 1320 tcaaactggc gcagatcagg cctctataac cgccaggaat cacattcagc tggtgaaact 1380 gcaggtggaa gaggtgcacc agctctcccg gaaagcagaa accaagctgg cagaagcaca 1440 gatagaagag ctccgtcaga aaacacagga ggaaggggag gagcgggctg agtcggagca 1500 ggaggcctac ctgcgtgagg attgagggcc tgagcacact gccctgtctc cccactcagt 1560 ggggaaagca ggggcagatg ccaccctgcc cagggttggc atgactgtct gtgcaccgag 1620 aagaggcggc agatcctgcc ctggccaatc aggcgagacg cctttgtgag ctgtgagtgc 1680 ctcctgtggt ctcaggcttg cgctggacct ggttcttagc ccttgggcac tgcaccctgt 1740 ttaacatttc accccactct gtacagctgc tcttacccat tttttttacc tcacacccaa 1800 agcattttgc ctacctgggt cagagagagg agtccttttt gtcatgccct taagttcagc 1860 aactgtttaa cctgttttca gtcttattta cgtcgtcaaa aatgatttag tacttgttcc 1920 ctctgttggg atgccagttg tggcaggggg aggggaacct gtccagtttg tacgatttct 1980 ttgtatgtat ttctgatgtg ttctctgatc tgcccccact gtcctgtgag gacagctgag 2040 gccaaggagt gaaaaaccta ttactactaa gagaaggggt gcagagtgtt tacctggtgc 2100 tctcaacagg acttaacatc aacaggactt aacacaggcc tcttgttcct tcctttcttt 2160 ccgtttctct attgtatcca aaggagaaga gtgtaagatt ttgtttgcat ctgaaagaga 2220 aaatgcgtct ctcctggggt cctaaaaaaa aaaaaaaaaa aaaaa 2265 <210> 95 <211> 3553 <212> DNA <213> Homo sapiens <400> 95 gagccagcgc ggtagggcca gagtgggaag gccagagcgg gcgtccccgc cagtgacccc 60 acgccgcccg tccgcgccca acccggcctc cgccgagtgt ccaaaccaaa agcgaaagga 120 acccgacccc gcgtcccctc cggcggctcc gtagtcgcgt ccgcttggag ctcgccgggc 180 gcctccgacc ctgccgggcc gctttgtgac ttcactcgtt tcgcaacaag cccgggcagc 240 ccgcgcccca cccactctgg cccggcagcc tcgccgcccg cagcctcgct ccgctcctcg 300 cgcttcccct ccctccgggg ctgggcctgc cccggccgtc gcggagcctc ccctcccacc 360 gtccgtgagt gtacgcgccc ggccgccgcc tccaggcagc ccggagcaac ccggcgcccg 420 gccccgctgg gcgcagcact ccgtcggcgg cggcggcggc gcgatgctgt gcttcctgag 480 gggaatggct ttcgtcccct tcctcttggt gacctggtcg tcagccgcct tcattatctc 540 ctacgtggtc gccgtgctct ccgggcacgt caaccccttc ctcccgtata tcagtgatac 600 gggaacaaca cctccagaga gtggtatttt tggatttatg ataaacttct ctgcatttct 660 tggtgcagcc acgatgtata caagatacaa aatagtacag aagcaaaatc aaacctgcta 720 tttcagcact cctgttttta acttggtgtc tttagtgctt ggattggtgg gatgtttcgg 780 aatgggcatt gtcgccaatt ttcaggagtt agctgtgcca gtggttcatg acgggggcgc 840 tcttttggcc tttgtctgtg gtgtcgtgta cacgctccta cagtccatca tctcttacaa 900 atcatgtccc cagtggaaca gtctctcgac atgccacata cggatggtca tctctgccgt 960 ttcttgcgca gctgtcatcc ccatgattgt ctgtgcttca ctaatttcca taaccaagct 1020 ggagtggaat ccaagagaaa aggattatgt atatcacgta gtgagtgcga tctgtgaatg 1080 gacagtggcc tttggtttta ttttctactt cctaactttc atccaagatt tccagagtgt 1140 caccctaagg atatccacag aaatcaatgg tgatatttga agaaagaaga attcagtctc 1200 actcagtgaa tgtcgcaggc catttctaaa agtgctacag aggacagaca gggttttgag 1260 gccaccctga ttattgggat gcatctgcag cacatccagg acttgaattt cattacgagt 1320 tcctaatagt tgtatttcta aagatgtgtt tcctagagaa tgtacagcct tatgacactg 1380 tagtgatgtt tttataattt tctaagtaga tttttttata ttaacaaatt catatacaga 1440 aaaaataagg tgttacaaaa aatggagagc tcttattttt gtacagattc tgtcgttttt 1500 gttttatttg tgtgagattt atggaaatac actaaatgag taattcaggt tcagtacatt 1560 tattacaaag tgaaatcagg ggatattcat ttgtaaattt tattcttagt gaatgaactg 1620 tataattttt tttatcagga gagcacttat aaaattcaat ttataaagat catataccca 1680 aatcataaag atttagttga tacattaaca ctaagatact ctgattttta gccgaactaa 1740 acaaagtgct tctactgaga ggcctttata ccaccatgta cagtaactct aagtgaatac 1800 ggaagacctt ggttttgaaa ttctgccacc ttgtttctcc ctgctcatga ggtcgcacct 1860 tttgctcttg ctgctaattg cccattcgta gtgggtgtaa tgccaggtgg aatggtttca 1920 acaagtcagg tgaaaaccat cctttattgt tgctggcaca acttgatata tagtctgact 1980 cagaactgaa gctcacatct caaattcatt tcatgccagt aaatgtggca aagagaagaa 2040 aggcccaaga gcgagacaag aagaatggag aagggggcag ccaagaagaa cttctgggtt 2100 cagggtactg tttatttgct ccttctcttc atgcctgtgg ctggatgtcc cacaacacta 2160 taagaaatat aagtcaagcc ctttgtgtta agcaagaact acagactcca tcttttcacc 2220 caaatcatga atgaccaata aaaagcaagt tattccagag gaagaagcag cccttgaaat 2280 gttaaggctt aggcttgaaa ggtgaagagc aggaattctc tctttcaaat cctagagcat 2340 aaacccatgt gtggccaagt gagatcagcc ctcaagggca catgccaagg gcagagcagc 2400 ccatgtagac agcttcggag ggcatggggg tgtagggagt tcggggtagc tcctcattaa 2460 ctatttgttg ggtgagtaaa ggggtgaggc tcagtggcag gtacctctgc aatgacaagc 2520 tgcctcccct ctatgtgttt agcatatgtt attagaacat gtccgacacc cctaccgctg 2580 ccatttgggc cctttaataa agccaagtag agaaatctgg caataaaagg caaatgtaag 2640 catgctttct ttaagacgca tcataaatgg ttttctttaa gtgaatggaa gagtttgaca 2700 gagatacacc tttgtaagaa aacattaaga atgctggctg gctgtggtgg ctcacacctg 2760 tattcccagc actttgggag gcctaggcag gaggattgct tgagcctggg acttcgagac 2820 cagactggga aacatggcaa aatcccatct ctacaacaaa aatacaaaaa ttagccaagt 2880 gcggtggtgt gcctgtagtc ctagttactt gggaggctga ggtgggagaa tcacctgagc 2940 ccaggaggtg gaggctgcag tgagccatgc caatgcactc cagtctgggc aacagagtga 3000 gaccctgtct caaaaataaa taaataaata aatgaataaa gagaatgcta atcatttctg 3060 ggttcactgc gactcactgt agtgctgggg atcccccttg taacactgga actgaaagac 3120 agtgatgaaa gctatgtcaa gcattcatta ttctgaagag gaggagaaat gccacatacc 3180 tttcccatgg gacctgtggt ggaatgaatc catacttctg cctcacttcg agcagacttt 3240 tgttctcggc gctcctcacg atggagtttc atgcttcatt ttcacatctc tctgcacaat 3300 tagattggga gctccttgag ggcagagtac gtgccttaat ctttatcttt gtaatgccac 3360 aatgaacaga gtgcctcctg gtacactgta ggagcttaag aaatactcac tgaatgcatg 3420 aatgaatgaa tgaacaaatg aaggaatgac taaggatgtt tgtagtgcta taatatagaa 3480 tgggatttac tctgctttac cagttagttt cataataaac aaatagtctg tatcgcctgg 3540 taaaaaaaaa aaa 3553 <210> 96 <211> 2722 <212> DNA <213> Homo sapiens <400> 96 ttggcgcgta aaagtggccg ggactttgca ggcagcggcg gccgggggcg gagcgggatc 60 gagccctcgc cgaggcctgc cgccatgggc ccgcgccgcc gccgccgcct gtcacccggg 120 ccgcgcgggc cgtgagcgtc atggccttgg ccggggcccc tgcgggcggc ccatgcgcgc 180 cggcgctgga ggccctgctc ggggccggcg cgctgcggct gctcgactcc tcgcagatcg 240 tcatcatctc cgccgcgcag gacgccagcg ccccgccggc tcccaccggc cccgcggcgc 300 ccgccgccgg cccctgcgac cctgacctgc tgctcttcgc cacaccgcag gcgccccggc 360 ccacacccag tgcgccgcgg cccgcgctcg gccgcccgcc ggtgaagcgg aggctggacc 420 tggaaactga ccatcagtac ctggccgaga gcagtgggcc agctcggggc agaggccgcc 480 atccaggaaa aggtgtgaaa tccccggggg agaagtcacg ctatgagacc tcactgaatc 540 tgaccaccaa gcgcttcctg gagctgctga gccactcggc tgacggtgtc gtcgacctga 600 actgggctgc cgaggtgctg aaggtgcaga agcggcgcat ctatgacatc accaacgtcc 660 ttgagggcat ccagctcatt gccaagaagt ccaagaacca catccagtgg ctgggcagcc 720 acaccacagt gggcgtcggc ggacggcttg aggggttgac ccaggacctc cgacagctgc 780 aggagagcga gcagcagctg gaccacctga tgaatatctg tactacgcag ctgcgcctgc 840 tctccgagga cactgacagc cagcgcctgg cctacgtgac gtgtcaggac cttcgtagca 900 ttgcagaccc tgcagagcag atggttatgg tgatcaaagc ccctcctgag acccagctcc 960 aagccgtgga ctcttcggag aactttcaga tctcccttaa gagcaaacaa ggcccgatcg 1020 atgttttcct gtgccctgag gagaccgtag gtgggatcag ccctgggaag accccatccc 1080 aggaggtcac ttctgaggag gagaacaggg ccactgactc tgccaccata gtgtcaccac 1140 caccatcatc tcccccctca tccctcacca cagatcccag ccagtctcta ctcagcctgg 1200 agcaagaacc gctgttgtcc cggatgggca gcctgcgggc tcccgtggac gaggaccgcc 1260 tgtccccgct ggtggcggcc gactcgctcc tggagcatgt gcgggaggac ttctccggcc 1320 tcctccctga ggagttcatc agcctttccc caccccacga ggccctcgac taccacttcg 1380 gcctcgagga gggcgagggc atcagagacc tcttcgactg tgactttggg gacctcaccc 1440 ccctggattt ctgacagggc ttggagggac cagggtttcc agagatgctc accttgtctc 1500 tgcagccctg gagccccctg tccctggccg tcctcccagc ctgtttggaa acatttaatt 1560 tatacccctc tcctctgtct ccagaagctt ctagctctgg ggtctggcta ccgctaggag 1620 gctgagcaag ccaggaaggg aaggagtctg tgtggtgtgt atgtgcatgc agcctacacc 1680 cacacgtgtg taccgggggt gaatgtgtgt gagcatgtgt gtgtgcatgt accggggaat 1740 gaaggtgaac atacacctct gtgtgtgcac tgcagacacg ccccagtgtg tccacatgtg 1800 tgtgcatgag tccatgtgtg cgcgtggggg ggctctaact gcactttcgg cccttttgct 1860 ctgggggtcc cacaaggccc agggcagtgc ctgctcccag aatctggtgc tctgaccagg 1920 ccaggtgggg aggctttggc tggctgggcg tgtaggacgg tgagagcact tctgtcttaa 1980 aggttttttc tgattgaagc tttaatggag cgttatttat ttatcgaggc ctctttggtg 2040 agcctgggga atcagcaaag gggaggaggg gtgtggggtt gataccccaa ctccctctac 2100 ccttgagcaa gggcaggggt ccctgagctg ttcttctgcc ccatactgaa ggaactgagg 2160 cctgggtgat ttatttattg ggaaagtgag ggagggagac agactgactg acagccatgg 2220 gtggtcagat ggtggggtgg gccctctcca gggggccagt tcagggcccc agctgccccc 2280 caggatggat atgagatggg agaggtgagt gggggacctt cactgatgtg ggcaggaggg 2340 gtggtgaagg cctcccccag cccagaccct gtggtccctc ctgcagtgtc tgaagcgcct 2400 gcctccccac tgctctgccc caccctccaa tctgcacttt gatttgcttc ctaacagctc 2460 tgttccctcc tgctttggtt ttaataaata ttttgatgac gtttgggccg ggttttggga 2520 ctctgttggg aacatttcgg ggcgggagag gccaaggttg ctggggaaat gcccattctc 2580 cacttccctt ctccctgtcc gtgcccgatt tgatttgagc ctcataactc gaagaaaggt 2640 cagcttcctc gctgttttgg tcctaactca aaagcagatc cagtaaaggt ttttgttgta 2700 aaaaaaaaaa aaaaaaaaaa aa 2722 <210> 97 <211> 2755 <212> DNA <213> Homo sapiens <400> 97 cctacccgcg cgcaggccaa gttgctgaat caatggagcc ctccccaacc cgggcgttcc 60 ccagcgaggc ttccttccca tcctcctgac caccggggct tttcgtgagc tcgtctctga 120 tctcgcgcaa gagtgacaca caggtgttca aagacgcttc tggggagtga gggaagcggt 180 ttacgagtga cttggctgga gcctcagggg cgggcactgg cacggaacac accctgaggc 240 cagccctggc tgcccaggcg gagctgcctc ttctcccgcg ggttggtgga cccgctcagt 300 acggagttgg ggaagctctt tcacttcgga ggattgctca acaaccatgc tgggcatctg 360 gaccctccta cctctggttc ttacgtctgt tgctagatta tcgtccaaaa gtgttaatgc 420 ccaagtgact gacatcaact ccaagggatt ggaattgagg aagactgtta ctacagttga 480 gactcagaac ttggaaggcc tgcatcatga tggccaattc tgccataagc cctgtcctcc 540 aggtgaaagg aaagctaggg actgcacagt caatggggat gaaccagact gcgtgccctg 600 ccaagaaggg aaggagtaca cagacaaagc ccatttttct tccaaatgca gaagatgtag 660 attgtgtgat gaaggacatg gcttagaagt ggaaataaac tgcacccgga cccagaatac 720 caagtgcaga tgtaaaccaa actttttttg taactctact gtatgtgaac actgtgaccc 780 ttgcaccaaa tgtgaacatg gaatcatcaa ggaatgcaca ctcaccagca acaccaagtg 840 caaagaggaa ggatccagat ctaacttggg gtggctttgt cttcttcttt tgccaattcc 900 actaattgtt tgggtgaaga gaaaggaagt acagaaaaca tgcagaaagc acagaaagga 960 aaaccaaggt tctcatgaat ctccaacctt aaatcctgaa acagtggcaa taaatttatc 1020 tgatgttgac ttgagtaaat atatcaccac tattgctgga gtcatgacac taagtcaagt 1080 taaaggcttt gttcgaaaga atggtgtcaa tgaagccaaa atagatgaga tcaagaatga 1140 caatgtccaa gacacagcag aacagaaagt tcaactgctt cgtaattggc atcaacttca 1200 tggaaagaaa gaagcgtatg acacattgat taaagatctc aaaaaagcca atctttgtac 1260 tcttgcagag aaaattcaga ctatcatcct caaggacatt actagtgact cagaaaattc 1320 aaacttcaga aatgaaatcc aaagcttggt ctagagtgaa aaacaacaaa ttcagttctg 1380 agtatatgca attagtgttt gaaaagattc ttaatagctg gctgtaaata ctgcttggtt 1440 ttttactggg tacattttat catttattag cgctgaagag ccaacatatt tgtagatttt 1500 taatatctca tgattctgcc tccaaggatg tttaaaatct agttgggaaa acaaacttca 1560 tcaagagtaa atgcagtggc atgctaagta cccaaatagg agtgtatgca gaggatgaaa 1620 gattaagatt atgctctggc atctaacata tgattctgta gtatgaatgt aatcagtgta 1680 tgttagtaca aatgtctatc cacaggctaa ccccactcta tgaatcaata gaagaagcta 1740 tgaccttttg ctgaaatatc agttactgaa caggcaggcc actttgcctc taaattacct 1800 ctgataattc tagagatttt accatatttc taaactttgt ttataactct gagaagatca 1860 tatttatgta aagtatatgt atttgagtgc agaatttaaa taaggctcta cctcaaagac 1920 ctttgcacag tttattggtg tcatattata caatatttca attgtgaatt cacatagaaa 1980 acattaaatt ataatgtttg actattatat atgtgtatgc attttactgg ctcaaaacta 2040 cctacttctt tctcaggcat caaaagcatt ttgagcagga gagtattact agagctttgc 2100 cacctctcca tttttgcctt ggtgctcatc ttaatggcct aatgcacccc caaacatgga 2160 aatatcacca aaaaatactt aatagtccac caaaaggcaa gactgccctt agaaattcta 2220 gcctggtttg gagatactaa ctgctctcag agaaagtagc tttgtgacat gtcatgaacc 2280 catgtttgca atcaaagatg ataaaataga ttcttatttt tcccccaccc ccgaaaatgt 2340 tcaataatgt cccatgtaaa acctgctaca aatggcagct tatacatagc aatggtaaaa 2400 tcatcatctg gatttaggaa ttgctcttgt cataccccca agtttctaag atttaagatt 2460 ctccttacta ctatcctacg tttaaatatc tttgaaagtt tgtattaaat gtgaatttta 2520 agaaataata tttatatttc tgtaaatgta aactgtgaag atagttataa actgaagcag 2580 atacctggaa ccacctaaag aacttccatt tatggaggat ttttttgccc cttgtgtttg 2640 gaattataaa atataggtaa aagtacgtaa ttaaataatg tttttggtaa aaaaaaaaaa 2700 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2755 <210> 98 <211> 8733 <212> DNA <213> Homo sapiens <400> 98 gctcccggct tagaggacag cggggaaggc gggcggtggg gcagggggcc tgaagcggcg 60 gtaccggtgc tggcggcggc agctgaggcc ttggccgaag ccgcgcgaac ctcagggcaa 120 gatgcttgga accggacctg ccgccgccac caccgctgcc accacatcta gcaatgtgag 180 cgtcctgcag cagtttgcca gtggcctaaa gagccggaat gaggaaacca gggccaaagc 240 cgccaaggag ctccagcact atgtcaccat ggaactccga gagatgagtc aagaggagtc 300 tactcgcttc tatgaccaac tgaaccatca catttttgaa ttggtttcca gctcagatgc 360 caatgagagg aaaggtggca tcttggccat agctagcctc ataggagtgg aaggtgggaa 420 tgccacccga attggcagat ttgccaacta tcttcggaac ctcctcccct ccaatgaccc 480 agttgtcatg gaaatggcat ccaaggccat tggccgtctt gccatggcag gggacacttt 540 taccgctgag tacgtggaat ttgaggtgaa gcgagccctg gaatggctgg gtgctgaccg 600 caatgagggc cggagacatg cagctgtcct ggttctccgt gagctggcca tcagcgtccc 660 taccttcttc ttccagcaag tgcaaccctt ctttgacaac atttttgtgg ccgtgtggga 720 ccccaaacag gccatccgtg agggagctgt agccgccctt cgtgcctgtc tgattctcac 780 aacccagcgt gagccgaagg agatgcagaa gcctcagtgg tacaggcaca catttgaaga 840 agcagagaag ggatttgatg agaccttggc caaagagaag ggcatgaatc gggatgatcg 900 gatccatgga gccttgttga tccttaacga gctggtccga atcagcagca tggagggaga 960 gcgtctgaga gaagaaatgg aagaaatcac acagcagcag ctggtacacg acaagtactg 1020 caaagatctc atgggcttcg gaacaaaacc tcgtcacatt acccccttca ccagtttcca 1080 ggctgtacag ccccagcagt caaatgcctt ggtggggctg ctggggtaca gctctcacca 1140 aggcctcatg ggatttggga cctcccccag tccagctaag tccaccctgg tggagagccg 1200 gtgttgcaga gacttgatgg aggagaaatt tgatcaggtg tgccagtggg tgctgaaatg 1260 caggaatagc aagaactcgc tgatccaaat gacaatcctt aatttgttgc cccgcttggc 1320 tgcattccga ccttctgcct tcacagatac ccagtatctc caagatacca tgaaccatgt 1380 cctaagctgt gtcaagaagg agaaggaacg tacagcggcc ttccaagccc tggggctact 1440 ttctgtggct gtgaggtctg agtttaaggt ctatttgcct cgcgtgctgg acatcatccg 1500 agcggccctg cccccaaagg acttcgccca taagaggcag aaggcaatgc aggtggatgc 1560 cacagtcttc acttgcatca gcatgctggc tcgagcaatg gggccaggca tccagcagga 1620 tatcaaggag ctgctggagc ccatgctggc agtgggacta agccctgccc tcactgcagt 1680 gctctacgac ctgagccgtc agattccaca gctaaagaag gacattcaag atgggctact 1740 gaaaatgctg tccctggtcc ttatgcacaa accccttcgc cacccaggca tgcccaaggg 1800 cctggcccat cagctggcct ctcctggcct cacgaccctc cctgaggcca gcgatgtggg 1860 cagcatcact cttgccctcc gaacgcttgg cagctttgaa tttgaaggcc actctctgac 1920 ccaatttgtt cgccactgtg cggatcattt cctgaacagt gagcacaagg agatccgcat 1980 ggaggctgcc cgcacctgct cccgcctgct cacaccctcc atccacctca tcagtggcca 2040 tgctcatgtg gttagccaga ccgcagtgca agtggtggca gatgtgctta gcaaactgct 2100 cgtagttggg ataacagatc ctgaccctga cattcgctac tgtgtcttgg cgtccctgga 2160 cgagcgcttt gatgcacacc tggcccaggc ggagaacttg caggccttgt ttgtggctct 2220 gaatgaccag gtgtttgaga tccgggagct ggccatctgc actgtgggcc gactcagtag 2280 catgaaccct gcctttgtca tgcctttcct gcgcaagatg ctcatccaga ttttgacaga 2340 gttggagcac agtgggattg gaagaatcaa agagcagagt gcccgcatgc tggggcacct 2400 ggtctccaat gccccccgac tcatccgccc ctacatggag cctattctga aggcattaat 2460 tttgaaactg aaagatccag accctgatcc aaacccaggt gtgatcaata atgtcctggc 2520 aacaatagga gaattggcac aggttagtgg cctggaaatg aggaaatggg ttgatgaact 2580 ttttattatc atcatggaca tgctccagga ttcctctttg ttggccaaaa ggcaggtggc 2640 tctgtggacc ctgggacagt tggtggccag cactggctat gtagtagagc cctacaggaa 2700 gtaccctact ttgcttgagg tgctactgaa ttttctgaag actgagcaga accagggtac 2760 acgcagagag gccatccgtg tgttagggct tttaggggct ttggatcctt acaagcacaa 2820 agtgaacatt ggcatgatag accagtcccg ggatgcctct gctgtcagcc tgtcagaatc 2880 caagtcaagt caggattcct ctgactatag cactagtgaa atgctggtca acatgggaaa 2940 cttgcctctg gatgagttct acccagctgt gtccatggtg gccctgatgc ggatcttccg 3000 agaccagtca ctctctcatc atcacaccat ggttgtccag gccatcacct tcatcttcaa 3060 gtccctggga ctcaaatgtg tgcagttcct gccccaggtc atgcccacgt tccttaacgt 3120 cattcgagtc tgtgatgggg ccatccggga atttttgttc cagcagctgg gaatgttggt 3180 gtcctttgtg aagagccaca tcagacctta tatggatgaa atagtcaccc tcatgagaga 3240 attctgggtc atgaacacct caattcagag cacgatcatt cttctcattg agcaaattgt 3300 ggtagctctt gggggtgaat ttaagctcta cctgccccag ctgatcccac acatgctgcg 3360 tgtcttcatg catgacaaca gcccaggccg cattgtctct atcaagttac tggctgcaat 3420 ccagctgttt ggcgccaacc tggatgacta cctgcattta ctgctgcctc ctattgttaa 3480 gttgtttgat gcccctgaag ctccactgcc atctcgaaag gcagcgctag agactgtgga 3540 ccgcctgacg gagtccctgg atttcactga ctatgcctcc cggatcattc accctattgt 3600 tcgaacactg gaccagagcc cagaactgcg ctccacagcc atggacacgc tgtcttcact 3660 tgtttttcag ctggggaaga agtaccaaat tttcattcca atggtgaata aagttctggt 3720 gcgacaccga atcaatcatc agcgctatga tgtgctcatc tgcagaattg tcaagggata 3780 cacacttgct gatgaagagg aggatccttt gatttaccag catcggatgc ttaggagtgg 3840 ccaaggggat gcattggcta gtggaccagt ggaaacagga cccatgaaga aactgcacgt 3900 cagcaccatc aacctccaaa aggcctgggg cgctgccagg agggtctcca aagatgactg 3960 gctggaatgg ctgagacggc tgagcctgga gctgctgaag gactcatcat cgccctccct 4020 gcgctcctgc tgggccctgg cacaggccta caacccgatg gccagggatc tcttcaatgc 4080 tgcatttgtg tcctgctggt ctgaactgaa tgaagatcaa caggatgagc tcatcagaag 4140 catcgagttg gccctcacct cacaagacat cgctgaagtc acacagaccc tcttaaactt 4200 ggctgaattc atggaacaca gtgacaaggg ccccctgcca ctgagagatg acaatggcat 4260 tgttctgctg ggtgagagag ctgccaagtg ccgagcatat gccaaagcac tacactacaa 4320 agaactggag ttccagaaag gccccacccc tgccattcta gaatctctca tcagcattaa 4380 taataagcta cagcagccgg aggcagcggc cggagtgtta gaatatgcca tgaaacactt 4440 tggagagctg gagatccagg ctacctggta tgagaaactg cacgagtggg aggatgccct 4500 tgtggcctat gacaagaaaa tggacaccaa caaggacgac ccagagctga tgctgggccg 4560 catgcgctgc ctcgaggcct tgggggaatg gggtcaactc caccagcagt gctgtgaaaa 4620 gtggaccctg gttaatgatg agacccaagc caagatggcc cggatggctg ctgcagctgc 4680 atggggttta ggtcagtggg acagcatgga agaatacacc tgtatgatcc ctcgggacac 4740 ccatgatggg gcattttata gagctgtgct ggcactgcat caggacctct tctccttggc 4800 acaacagtgc attgacaagg ccagggacct gctggatgct gaattaactg cgatggcagg 4860 agagagttac agtcgggcat atggggccat ggtttcttgc cacatgctgt ccgagctgga 4920 ggaggttatc cagtacaaac ttgtccccga gcgacgagag atcatccgcc agatctggtg 4980 ggagagactg cagggctgcc agcgtatcgt agaggactgg cagaaaatcc ttatggtgcg 5040 gtcccttgtg gtcagccctc atgaagacat gagaacctgg ctcaagtatg caagcctgtg 5100 cggcaagagt ggcaggctgg ctcttgctca taaaacttta gtgttgctcc tgggagttga 5160 tccgtctcgg caacttgacc atcctctgcc aacagttcac cctcaggtga cctatgccta 5220 catgaaaaac atgtggaaga gtgcccgcaa gatcgatgcc ttccagcaca tgcagcattt 5280 tgtccagacc atgcagcaac aggcccagca tgccatcgct actgaggacc agcagcataa 5340 gcaggaactg cacaagctca tggcccgatg cttcctgaaa cttggagagt ggcagctgaa 5400 tctacagggc atcaatgaga gcacaatccc caaagtgctg cagtactaca gcgccgccac 5460 agagcacgac cgcagctggt acaaggcctg gcatgcgtgg gcagtgatga acttcgaagc 5520 tgtgctacac tacaaacatc agaaccaagc ccgcgatgag aagaagaaac tgcgtcatgc 5580 cagcggggcc aacatcacca acgccaccac tgccgccacc acggccgcca ctgccaccac 5640 cactgccagc accgagggca gcaacagtga gagcgaggcc gagagcaccg agaacagccc 5700 caccccatcg ccgctgcaga agaaggtcac tgaggatctg tccaaaaccc tcctgatgta 5760 cacggtgcct gccgtccagg gcttcttccg ttccatctcc ttgtcacgag gcaacaacct 5820 ccaggataca ctcagagttc tcaccttatg gtttgattat ggtcactggc cagatgtcaa 5880 tgaggcctta gtggaggggg tgaaagccat ccagattgat acctggctac aggttatacc 5940 tcagctcatt gcaagaattg atacgcccag acccttggtg ggacgtctca ttcaccagct 6000 tctcacagac attggtcggt accaccccca ggccctcatc tacccactga cagtggcttc 6060 taagtctacc acgacagccc ggcacaatgc agccaacaag attctgaaga acatgtgtga 6120 gcacagcaac accctggtcc agcaggccat gatggtgagc gaggagctga tccgagtggc 6180 catcctctgg catgagatgt ggcatgaagg cctggaagag gcatctcgtt tgtactttgg 6240 ggaaaggaac gtgaaaggca tgtttgaggt gctggagccc ttgcatgcta tgatggaacg 6300 gggcccccag actctgaagg aaacatcctt taatcaggcc tatggtcgag atttaatgga 6360 ggcccaagag tggtgcagga agtacatgaa atcagggaat gtcaaggacc tcacccaagc 6420 ctgggacctc tattatcatg tgttccgacg aatctcaaag cagctgcctc agctcacatc 6480 cttagagctg caatatgttt ccccaaaact tctgatgtgc cgggaccttg aattggctgt 6540 gccaggaaca tatgacccca accagccaat cattcgcatt cagtccatag caccgtcttt 6600 gcaagtcatc acatccaagc agaggccccg gaaattgaca cttatgggca gcaacggaca 6660 tgagtttgtt ttccttctaa aaggccatga agatctgcgc caggatgagc gtgtgatgca 6720 gctcttcggc ctggttaaca cccttctggc caatgaccca acatctcttc ggaaaaacct 6780 cagcatccag agatacgctg tcatcccttt atcgaccaac tcgggcctca ttggctgggt 6840 tccccactgt gacacactgc acgccctcat ccgggactac agggagaaga agaagatcct 6900 tctcaacatc gagcatcgca tcatgttgcg gatggctccg gactatgacc acttgactct 6960 gatgcagaag gtggaggtgt ttgagcatgc cgtcaataat acagctgggg acgacctggc 7020 caagctgctg tggctgaaaa gccccagctc cgaggtgtgg tttgaccgaa gaaccaatta 7080 tacccgttct ttagcggtca tgtcaatggt tgggtatatt ttaggcctgg gagatagaca 7140 cccatccaac ctgatgctgg accgtctgag tgggaagatc ctgcacattg actttgggga 7200 ctgctttgag gttgctatga cccgagagaa gtttccagag aagattccat ttagactaac 7260 aagaatgttg accaatgcta tggaggttac aggcctggat ggcaactaca gaatcacatg 7320 ccacacagtg atggaggtgc tgcgagagca caaggacagt gtcatggccg tgctggaagc 7380 ctttgtctat gaccccttgc tgaactggag gctgatggac acaaatacca aaggcaacaa 7440 gcgatcccga acgaggacgg attcctactc tgctggccag tcagtcgaaa ttttggacgg 7500 tgtggaactt ggagagccag cccataagaa aacggggacc acagtgccag aatctattca 7560 ttctttcatt ggagacggtt tggtgaaacc agaggcccta aataagaaag ctatccagat 7620 tattaacagg gttcgagata agctcactgg tcgggacttc tctcatgatg acactttgga 7680 tgttccaacg caagttgagc tgctcatcaa acaagcgaca tcccatgaaa acctctgcca 7740 gtgctatatt ggctggtgcc ctttctggta actggaggcc cagatgtgcc catcacgttt 7800 tttctgaggc ttttgtactt tagtaaatgc ttccactaaa ctgaaaccat ggtgagaaag 7860 tttgactttg ttaaatattt tgaaatgtaa atgaaaagaa ctactgtata ttaaaagttg 7920 gtttgaacca actttctagc tgctgttgaa gaatatattg tcagaaacac aaggcttgat 7980 ttggttccca ggacagtgaa acatagtaat accacgtaaa tcaagccatt cattttgggg 8040 aacagaagat ccataacttt agaaatacgg gttttgactt aactcacaag agaactcatc 8100 ataagtactt gctgatggaa gaatgaccta gttgctcctc tcaacatggg tacagcaaac 8160 tcagcacagc caagaagcct caggtcgtgg agaacatgga ttaggatcct agactgtaaa 8220 gacacagaag atgctgacct cacccctgcc acctatccca agacctcact ggtctgtgga 8280 cagcagcaga aatgtttgca agataggcca aaatgagtac aaaaggtctg tcttccatca 8340 gacccagtga tgctgcgact cacacgcttc aattcaagac ctgaccgcta gtagggaggt 8400 ttattcagat cgctggcagc ctcggctgag cagatgcaca gaggggatca ctgtgcagtg 8460 ggaccaccct cactggcctt ctgcagcagg gttctgggat gttttcagtg gtcaaaatac 8520 tctgtttaga gcaagggctc agaaaacaga aatactgtca tggaggtgct gaacacaggg 8580 aaggtctggt acatattgga aattatgagc agaacaaata ctcaactaaa tgcacaaagt 8640 ataaagtgta gccatgtcta gacaccatgt tgtatcagaa taatttttgt gccaataaat 8700 gacatcagaa ttttaaacat atgtaaaaaa aaa 8733 <210> 99 <211> 2560 <212> DNA <213> Homo sapiens <400> 99 tgcggggagc cgagccgccg gcgctcgacg cgcgcgctct cgcgagaccc gcgggatcac 60 gtgacgcccg ggcgcggcgc agctcacgtg acaagcgctg ccggccgcgg tgtcttcttc 120 gtgccggcgt cgcagtggcc gggcctcttg cgtctggtaa cgccgctgtc tctaacgcca 180 gcccttggcg cccgcgcccc gccaccgcag cgcccggcag tccgcggccc aaccgccgcc 240 cgcgcccccg ctccccgcac cgtacccggc cgcctcgcgc catggcggcc cccggcagcg 300 cccggcgacc cctgctgctg ctactgctgt tgctgctgct cggcctcatg cattgtgcgt 360 cagcagcaat gtttatggtg aaaaatggca acgggaccgc gtgcataatg gccaacttct 420 ctgctgcctt ctcagtgaac tacgacacca agagtggccc taagaacatg acctttgacc 480 tgccatcaga tgccacagtg gtgctcaacc gcagctcctg tggaaaagag aacacttctg 540 accccagtct cgtgattgct tttggaagag gacatacact cactctcaat ttcacgagaa 600 atgcaacacg ttacagcgtc cagctcatga gttttgttta taacttgtca gacacacacc 660 ttttccccaa tgcgagctcc aaagaaatca agactgtgga atctataact gacatcaggg 720 cagatataga taaaaaatac agatgtgtta gtggcaccca ggtccacatg aacaacgtga 780 ccgtaacgct ccatgatgcc accatccagg cgtacctttc caacagcagc ttcagcaggg 840 gagagacacg ctgtgaacaa gacaggcctt ccccaaccac agcgccccct gcgccaccca 900 gcccctcgcc ctcacccgtg cccaagagcc cctctgtgga caagtacaac gtgagcggca 960 ccaacgggac ctgcctgctg gccagcatgg ggctgcagct gaacctcacc tatgagagga 1020 aggacaacac gacggtgaca aggcttctca acatcaaccc caacaagacc tcggccagcg 1080 ggagctgcgg cgcccacctg gtgactctgg agctgcacag cgagggcacc accgtcctgc 1140 tcttccagtt cgggatgaat gcaagttcta gccggttttt cctacaagga atccagttga 1200 atacaattct tcctgacgcc agagaccctg cctttaaagc tgccaacggc tccctgcgag 1260 cgctgcaggc cacagtcggc aattcctaca agtgcaacgc ggaggagcac gtccgtgtca 1320 cgaaggcgtt ttcagtcaat atattcaaag tgtgggtcca ggctttcaag gtggaaggtg 1380 gccagtttgg ctctgtggag gagtgtctgc tggacgagaa cagcatgctg atccccatcg 1440 ctgtgggtgg tgccctggcg gggctggtcc tcatcgtcct catcgcctac ctcgtcggca 1500 ggaagaggag tcacgcaggc taccagacta tctagcctgg tgcacgcagg cacagcagct 1560 gcaggggcct ctgttccttt ctctgggctt agggtcctgt cgaaggggag gcacactttc 1620 tggcaaacgt ttctcaaatc tgcttcatcc aatgtgaagt tcatcttgca gcatttacta 1680 tgcacaacag agtaactatc gaaatgacgg tgttaatttt gctaactggg ttaaatattt 1740 tgctaactgg ttaaacatta atatttacca aagtaggatt ttgagggtgg gggtgctctc 1800 tctgaggggg tgggggtgcc gctgtctctg aggggtgggg gtgccgctgt ctctgagggg 1860 tgggggtgcc gctctctctg agggggtggg ggtgccgctt tctctgaggg ggtgggggtg 1920 ccgctctctc tgagggggtg ggggtgctgc tctctccgag gggtggaatg ccgctgtctc 1980 tgaggggtgg gggtgccgct ctaaattggc tccatatcat ttgagtttag ggttctggtg 2040 tttggtttct tcattcttta ctgcactcag atttaagcct tacaaaggga aagcctctgg 2100 ccgtcacacg taggacgcat gaaggtcact cgtggtgagg ctgacatgct cacacattac 2160 aacagtagag agggaaaatc ctaagacaga ggaactccag agatgagtgt ctggagcgct 2220 tcagttcagc tttaaaggcc aggacgggcc acacgtggct ggcggcctcg ttccagtggc 2280 ggcacgtcct tgggcgtctc taatgtctgc agctcaaggg ctggcacttt tttaaatata 2340 aaaatgggtg ttatttttat ttttttttgt aaagtgattt ttggtcttct gttgacattc 2400 ggggtgatcc tgttctgcgc tgtgtacaat gtgagatcgg tgcgttctcc tgatgttttg 2460 ccgtggcttg gggattgtac acgggaccag ctcacgtaat gcattgcctg taacaatgta 2520 ataaaaagcc tctttctttt aaaaaaaaaa aaaaaaaaaa 2560 <210> 100 <211> 1030 <212> DNA <213> Homo sapiens <400> 100 accgggcgag ttacctcccg cagccgcagc cgccgtgctc agcgcgagcc ccggagccct 60 tgagcgcgag gcgcggagcc cccggagccc ccaaaccgca gacacatccc cgcgccccag 120 agccccggcc tgcgcgccca gccgggcccg cgcgatgccc tcagaccggc ctttcaagca 180 gcggcggagc ttcgccgacc gctgtaagga ggtacagcag atccgcgacc agcaccccag 240 caaaatcccg gtgatcatcg agcgctacaa gggtgagaag cagctgcccg tcctggacaa 300 gaccaagttt ttggtcccgg accatgtcaa catgagcgag ttggtcaaga tcatccggcg 360 ccgcctgcag ctgaacccca cgcaggcctt cttcctgctg gtgaaccagc acagcatggt 420 gagtgtgtcc acgcccatcg cggacatcta cgagcaggag aaagacgagg acggcttcct 480 ctatatggtc tacgcctccc aggaaacctt cggcttctga gccagcagta ggggggctcg 540 gcctgggagt cggggggccc cggtcaggcc ctgcccagag agctcctggt tcctgaactg 600 agctgcctct accgtggtgg gctgggcagg catgtgcccc cctagtcaga gggcaccaac 660 ccacctactc tgcccctggg tggatcctgg gccggtcgtg ttagggttgt ccctctgggt 720 gctggctggt gggatggggg agggtgggga gcagctccca gcacccctgc tgtgtggttc 780 atcttttttt taggcccctg cctgtctgcc catctgcccc tcacccaccc gaggctctgc 840 ccaccgcctg gacctgccca cccctgaaag actggcccct ggctccccgc ccctcggtct 900 ccacgtggtg tatggatctg tggtcattgt ccctctgcag aataaagatt gctcaggcct 960 gcctggcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1020 aaaaaaaaaa 1030 <210> 101 <211> 5085 <212> DNA <213> Homo sapiens <400> 101 agcgccatgc gcagactcag ttcctggaga aagatggcga cagccgagaa gcagaaacac 60 gacgggcggg tgaagatcgg ccactacatt ctgggtgaca cgctgggggt cggcaccttc 120 ggcaaagtga aggttggcaa acatgaattg actgggcata aagtagctgt gaagatactc 180 aatcgacaga agattcggag ccttgatgtg gtaggaaaaa tccgcagaga aattcagaac 240 ctcaagcttt tcaggcatcc tcatataatt aaactgtacc aggtcatcag tacaccatct 300 gatattttca tggtgatgga atatgtctca ggaggagagc tatttgatta tatctgtaag 360 aatggaaggc tggatgaaaa agaaagtcgg cgtctgttcc aacagatcct ttctggtgtg 420 gattattgtc acaggcatat ggtggtccat agagatttga aacctgaaaa tgtcctgctt 480 gatgcacaca tgaatgcaaa gatagctgat tttggtcttt caaacatgat gtcagatggt 540 gaatttttaa gaacaagttg tggctcaccc aactatgctg caccagaagt aatttcagga 600 agattgtatg caggcccaga ggtagatata tggagcagtg gggttattct ctatgcttta 660 ttatgtggaa cccttccatt tgatgatgac catgtgccaa ctctttttaa gaagatatgt 720 gatgggatct tctatacccc tcaatattta aatccttctg tgattagcct tttgaaacat 780 atgctgcagg tggatcccat gaagagggcc acaatcaaag atatcaggga acatgaatgg 840 tttaaacagg accttccaaa atatctcttt cctgaggatc catcatatag ttcaaccatg 900 attgatgatg aagccttaaa agaagtatgt gaaaagtttg agtgctcaga agaggaagtt 960 ctcagctgtc tttacaacag aaatcaccag gatcctttgg cagttgccta ccatctcata 1020 atagataaca ggagaataat gaatgaagcc aaagatttct atttggcgac aagcccacct 1080 gattcttttc ttgatgatca tcacctgact cggccccatc ctgaaagagt accattcttg 1140 gttgctgaaa caccaagggc acgccatacc cttgatgaat taaatccaca gaaatccaaa 1200 caccaaggtg taaggaaagc aaaatggcat ttaggaatta gaagtcaaag tcgaccaaat 1260 gatattatgg cagaagtatg tagagcaatc aaacaattgg attatgaatg gaaggttgta 1320 aacccatatt atttgcgtgt acgaaggaag aatcctgtga caagcactta ctccaaaatg 1380 agtctacagt tataccaagt ggatagtaga acttatctac tggatttccg tagtattgat 1440 gatgaaatta cagaagccaa atcagggact gctactccac agagatcggg atcagttagc 1500 aactatcgat cttgccaaag gagtgattca gatgctgagg ctcaaggaaa atcctcagaa 1560 gtttctctta cctcatctgt gacctcactt gactcttctc ctgttgacct aactccaaga 1620 cctggaagtc acacaataga attttttgag atgtgtgcaa atctaattaa aattcttgca 1680 caataaacag aaaactttgc ttatttcttt tgcagcaata agcatgcata ataagtcaca 1740 gccaaatgct tccatttgta atcaagttat acataattat aaccgagggc tggcgttttg 1800 gaatgcaatt tgcacaggga ttggaacatg atttatagtt aaaagcctaa tatgcagaaa 1860 tgaattaaga tcattttgtt gttcattgtg cagtatgtat atagcataat atacacagtg 1920 aattataggt ctcaggctta cttgattttt ggctatttta tatttagtgt acacagggct 1980 ttgaaatatt aatttacata aaggccttca tatattatta cgtgttatat attacgtgtt 2040 ataaatttat tcaataaata tttgcctaga attcccaaga cctttatagg tgattttgtt 2100 ttctgggctc cttaacttca taaatagcta gtatcttcca gcagtagtaa cagtctggat 2160 aacttcttcc atatccctcc ctctttgttt ttttgagaca gtgtcacttt gtcacccagg 2220 ctggagtgca atggtgtggt ctcggctcac tgcaacctcc acctcccggg ttcaagtgat 2280 tctcccgcct cagcttcctg agtagctgga actacaggcg tgtgccacca cacccggcta 2340 atttttcgta tttttagtgt agacggggtt tcactatgtt gcccaggctg gtctcgaact 2400 cctgaccgcg tgatccacca cctcagcttc ccaaagtggt gggattacag gcgtgagcca 2460 ccgcacccgg cctccatatc ccccttttaa aattctgtag tgtatggtaa gtcatatcag 2520 atatcagacc taatttaaat ttcattttag ctttacaagt ccaaaaacac agaatttata 2580 tattcagata ctctagcact aattttagtc ttaaaatatt cccacgatat tctgtacaca 2640 aaatgttctt tttgttacaa gagctgagtt gcatatactg tagataaatc atattatttt 2700 tgccaatttc acaaattcct ctggcccatc atgtcagtca ttattgagta tatgcacaca 2760 ttgctactta tttgattatg tatcttttaa attgattcag tgcatagaaa actatctctt 2820 acaaacttta agtgctctga tatgacttcc cccccaaatt ttattatgaa catttttaaa 2880 aacagaaaaa ttgaaaaact gtttggtaag cacatgtata tctaccattt agattcagca 2940 gttgttaatg ttttgtcatt tgttttctct atacctatat atgtatagat acagctagtt 3000 atgcatatat atgcatatat gtgtttgttt gtgtatgtat atatgctttt ttccccctga 3060 accatttgga tgttacagac atacttatca ccgtgaaaat acttcaagta tctcctacag 3120 ataatgacat tctcctaaaa atccgtaata ccattgtaaa agtaataatt ccccaatatc 3180 atctaatcaa gccatattta aatttctgaa gttaactcca aatttcttta tagctgatta 3240 tttcaaacta ggatccaatt aaagtttaca tatgacactt ggttataact ctttagttgg 3300 atataacatt attattattt tgataaaata tggaacaaat caattctatt aataagtggt 3360 cacatttgtt ttgggcttaa attacttttt aaagatactg gattttccta agatttctga 3420 tttacactga tatttttttt tgtcattctt aattgcatca cacaatagat gtaaatgaag 3480 atgtagtcac ctcagataaa attggtatcg tgtatgataa tattgtatca tttatatttg 3540 ccttatgtta actttaagaa attgattttt ttgtattaat cattttccca ttgcaacaga 3600 gctatatttt ttctatttta agaatcatat tttaggatta tttttggcaa atacagtgag 3660 cacttatgta accagatgat aatgaactca aatgtcatga tagcttgcat aaatggtgac 3720 tctagtagat ttgactcaag cacttctaga atcatgcact gaattcaaaa gaaaaatctt 3780 gctgcttttt gtccagggct tgttctattc aacttctaat ttgaaagctg tacaaagtaa 3840 tagaagttcc atttaaatat gagttcaaaa ctgtatttac tttttatgtg gccctctctt 3900 taggggattc taattttact tagggtctct aagtgcagca taatgttcct gatgttaaca 3960 gaagactgta tttttaaagt tacaaatttg tatatggaat taagtaatgg cgctatatac 4020 gctgttgtgg ggagggggga agaaaaggag gaaccaatta aataggacct tttaaaaatt 4080 gttaattttg taaactttgc ttctcttata agttattgtg attcatttta gttactgtgt 4140 tttattttga aaatatttaa atattgcact tctataaata gtatgataaa tgcacagaca 4200 attgcagtaa attctttttt aagctaggat atttgaaatg acaacctttg gttaagtgtg 4260 tcaaggttgc aacagaattt tcacaatttt tttgttgttt gcaaattgtt actaatattg 4320 aagaggtaag ggaggcaatg caaatgattt ttaatctttt tttattatct tttcagcagt 4380 ttatattttt tgtgacttta tgcaaccata tttttacttt gtcttgacaa ctgaaagatg 4440 tataaggttt tttgccagaa atgtactgta tacatagttt taagtataac agattttact 4500 gatatgtaaa aattttgcca ttaaaataaa tgatttctca ctgagaggaa cttttctacc 4560 aggttggggc atatgggagc ttaatatatc atatctaatt taaaataatt tcactgaaat 4620 aaactccatt gcttttacct aatttttttc ttgagatgct tttgtagttt ttcagagttt 4680 tagatgattt tatacaaaat cctctgccta gcactgctct ttttgatgtt gtagtgacac 4740 catttacatt gaattaatgc ttggtagcct ggggctagat gtggaactcc atggatctgt 4800 gttctgactg gcacctttgg aatgaaagaa aagtgtgtgc tgtccaaatt ttttcccctt 4860 aattctttcc ctcatcttct cacccataat agaaatttta tttccattgt gagttctgac 4920 aagaatgaaa ttccacatac aacataactg taaattgttg gtaggtagaa gttaatattt 4980 gtggttcatg tatattttga ccagagtata tttaagtata taatttcagc ttccttgatt 5040 tagaaatatg atataataaa gaaaaactcc atttatcatc tgtta 5085 <210> 102 <211> 5572 <212> DNA <213> Homo sapiens <400> 102 cctcccctcg cccggcgcgg tcccgtccgc ctctcgctcg cctcccgcct cccctcggtc 60 ttccgaggcg cccgggctcc cggcgcggcg gcggaggggg cgggcaggcc ggcgggcggt 120 gatgtggcgg gactctttat gcgctgcggc aggatacgcg ctcggcgctg ggacgcgact 180 gcgctcagtt ctctcctctc ggaagctgca gccatgatgg aagtttgaga gttgagccgc 240 tgtgaggcga ggccgggctc aggcgaggga gatgagagac ggcggcggcc gcggcccgga 300 gcccctctca gcgcctgtga gcagccgcgg gggcagcgcc ctcggggagc cggccggcct 360 gcggcggcgg cagcggcggc gtttctcgcc tcctcttcgt cttttctaac cgtgcagcct 420 cttcctcggc ttctcctgaa agggaaggtg gaagccgtgg gctcgggcgg gagccggctg 480 aggcgcggcg gcggcggcgg cacctcccgc tcctggagcg ggggggagaa gcggcggcgg 540 cggcggccgc ggcggctgca gctccaggga gggggtctga gtcgcctgtc accatttcca 600 gggctgggaa cgccggagag ttggtctctc cccttctact gcctccaaca cggcggcggc 660 ggcggcggca catccaggga cccgggccgg ttttaaacct cccgtccgcc gccgccgcac 720 cccccgtggc ccgggctccg gaggccgccg gcggaggcag ccgttcggag gattattcgt 780 cttctcccca ttccgctgcc gccgctgcca ggcctctggc tgctgaggag aagcaggccc 840 agtcgctgca accatccagc agccgccgca gcagccatta cccggctgcg gtccagagcc 900 aagcggcggc agagcgaggg gcatcagcta ccgccaagtc cagagccatt tccatcctgc 960 agaagaagcc ccgccaccag cagcttctgc catctctctc ctcctttttc ttcagccaca 1020 ggctcccaga catgacagcc atcatcaaag agatcgttag cagaaacaaa aggagatatc 1080 aagaggatgg attcgactta gacttgacct atatttatcc aaacattatt gctatgggat 1140 ttcctgcaga aagacttgaa ggcgtataca ggaacaatat tgatgatgta gtaaggtttt 1200 tggattcaaa gcataaaaac cattacaaga tatacaatct ttgtgctgaa agacattatg 1260 acaccgccaa atttaattgc agagttgcac aatatccttt tgaagaccat aacccaccac 1320 agctagaact tatcaaaccc ttttgtgaag atcttgacca atggctaagt gaagatgaca 1380 atcatgttgc agcaattcac tgtaaagctg gaaagggacg aactggtgta atgatatgtg 1440 catatttatt acatcggggc aaatttttaa aggcacaaga ggccctagat ttctatgggg 1500 aagtaaggac cagagacaaa aagggagtaa ctattcccag tcagaggcgc tatgtgtatt 1560 attatagcta cctgttaaag aatcatctgg attatagacc agtggcactg ttgtttcaca 1620 agatgatgtt tgaaactatt ccaatgttca gtggcggaac ttgcaatcct cagtttgtgg 1680 tctgccagct aaaggtgaag atatattcct ccaattcagg acccacacga cgggaagaca 1740 agttcatgta ctttgagttc cctcagccgt tacctgtgtg tggtgatatc aaagtagagt 1800 tcttccacaa acagaacaag atgctaaaaa aggacaaaat gtttcacttt tgggtaaata 1860 cattcttcat accaggacca gaggaaacct cagaaaaagt agaaaatgga agtctatgtg 1920 atcaagaaat cgatagcatt tgcagtatag agcgtgcaga taatgacaag gaatatctag 1980 tacttacttt aacaaaaaat gatcttgaca aagcaaataa agacaaagcc aaccgatact 2040 tttctccaaa ttttaaggtg aagctgtact tcacaaaaac agtagaggag ccgtcaaatc 2100 cagaggctag cagttcaact tctgtaacac cagatgttag tgacaatgaa cctgatcatt 2160 atagatattc tgacaccact gactctgatc cagagaatga accttttgat gaagatcagc 2220 atacacaaat tacaaaagtc tgaatttttt tttatcaaga gggataaaac accatgaaaa 2280 taaacttgaa taaactgaaa atggaccttt ttttttttaa tggcaatagg acattgtgtc 2340 agattaccag ttataggaac aattctcttt tcctgaccaa tcttgtttta ccctatacat 2400 ccacagggtt ttgacacttg ttgtccagtt gaaaaaaggt tgtgtagctg tgtcatgtat 2460 ataccttttt gtgtcaaaag gacatttaaa attcaattag gattaataaa gatggcactt 2520 tcccgtttta ttccagtttt ataaaaagtg gagacagact gatgtgtata cgtaggaatt 2580 ttttcctttt gtgttctgtc accaactgaa gtggctaaag agctttgtga tatactggtt 2640 cacatcctac ccctttgcac ttgtggcaac agataagttt gcagttggct aagagaggtt 2700 tccgaagggt tttgctacat tctaatgcat gtattcgggt taggggaatg gagggaatgc 2760 tcagaaagga aataatttta tgctggactc tggaccatat accatctcca gctatttaca 2820 cacacctttc tttagcatgc tacagttatt aatctggaca ttcgaggaat tggccgctgt 2880 cactgcttgt tgtttgcgca ttttttttta aagcatattg gtgctagaaa aggcagctaa 2940 aggaagtgaa tctgtattgg ggtacaggaa tgaaccttct gcaacatctt aagatccaca 3000 aatgaaggga tataaaaata atgtcatagg taagaaacac agcaacaatg acttaaccat 3060 ataaatgtgg aggctatcaa caaagaatgg gcttgaaaca ttataaaaat tgacaatgat 3120 ttattaaata tgttttctca attgtaacga cttctccatc tcctgtgtaa tcaaggccag 3180 tgctaaaatt cagatgctgt tagtacctac atcagtcaac aacttacact tattttacta 3240 gttttcaatc ataatacctg ctgtggatgc ttcatgtgct gcctgcaagc ttcttttttc 3300 tcattaaata taaaatattt tgtaatgctg cacagaaatt ttcaatttga gattctacag 3360 taagcgtttt ttttctttga agatttatga tgcacttatt caatagctgt cagccgttcc 3420 acccttttga ccttacacat tctattacaa tgaattttgc agttttgcac attttttaaa 3480 tgtcattaac tgttagggaa ttttacttga atactgaata catataatgt ttatattaaa 3540 aaggacattt gtgttaaaaa ggaaattaga gttgcagtaa actttcaatg ctgcacacaa 3600 aaaaaagaca tttgattttt cagtagaaat tgtcctacat gtgctttatt gatttgctat 3660 tgaaagaata gggttttttt tttttttttt tttttttttt ttaaatgtgc agtgttgaat 3720 catttcttca tagtgctccc ccgagttggg actagggctt caatttcact tcttaaaaaa 3780 aatcatcata tatttgatat gcccagactg catacgattt taagcggagt acaactacta 3840 ttgtaaagct aatgtgaaga tattattaaa aaggtttttt tttccagaaa tttggtgtct 3900 tcaaattata ccttcacctt gacatttgaa tatccagcca ttttgtttct taatggtata 3960 aaattccatt ttcaataact tattggtgct gaaattgttc actagctgtg gtctgaccta 4020 gttaatttac aaatacagat tgaataggac ctactagagc agcatttata gagtttgatg 4080 gcaaatagat taggcagaac ttcatctaaa atattcttag taaataatgt tgacacgttt 4140 tccatacctt gtcagtttca ttcaacaatt tttaaatttt taacaaagct cttaggattt 4200 acacatttat atttaaacat tgatatatag agtattgatt gattgctcat aagttaaatt 4260 ggtaaagtta gagacaacta ttctaacacc tcaccattga aatttatatg ccaccttgtc 4320 tttcataaaa gctgaaaatt gttacctaaa atgaaaatca acttcatgtt ttgaagatag 4380 ttataaatat tgttctttgt tacaatttcg ggcaccgcat attaaaacgt aactttattg 4440 ttccaatatg taacatggag ggccaggtca taaataatga cattataatg ggcttttgca 4500 ctgttattat ttttcctttg gaatgtgaag gtctgaatga gggttttgat tttgaatgtt 4560 tcaatgtttt tgagaagcct tgcttacatt ttatggtgta gtcattggaa atggaaaaat 4620 ggcattatat atattatata tataaatata tattatacat actctcctta ctttatttca 4680 gttaccatcc ccatagaatt tgacaagaat tgctatgact gaaaggtttt cgagtcctaa 4740 ttaaaacttt atttatggca gtattcataa ttagcctgaa atgcattctg taggtaatct 4800 ctgagtttct ggaatatttt cttagacttt ttggatgtgc agcagcttac atgtctgaag 4860 ttacttgaag gcatcacttt taagaaagct tacagttggg ccctgtacca tcccaagtcc 4920 tttgtagctc ctcttgaaca tgtttgccat acttttaaaa gggtagttga ataaatagca 4980 tcaccattct ttgctgtggc acaggttata aacttaagtg gagtttaccg gcagcatcaa 5040 atgtttcagc tttaaaaaat aaaagtaggg tacaagttta atgtttagtt ctagaaattt 5100 tgtgcaatat gttcataacg atggctgtgg ttgccacaaa gtgcctcgtt tacctttaaa 5160 tactgttaat gtgtcatgca tgcagatgga aggggtggaa ctgtgcacta aagtgggggc 5220 tttaactgta gtatttggca gagttgcctt ctacctgcca gttcaaaagt tcaacctgtt 5280 ttcatataga atatatatac taaaaaattt cagtctgtta aacagcctta ctctgattca 5340 gcctcttcag atactcttgt gctgtgcagc agtggctctg tgtgtaaatg ctatgcactg 5400 aggatacaca aaaataccaa tatgatgtgt acaggataat gcctcatccc aatcagatgt 5460 ccatttgtta ttgtgtttgt taacaaccct ttatctctta gtgttataaa ctccacttaa 5520 aactgattaa agtctcattc ttgtcaaaaa aaaaaaaaaa aaaaaaaaaa aa 5572 <210> 103 <211> 5239 <212> DNA <213> Homo sapiens <400> 103 ggatccggat tcggattagc agcccgggaa gagtgccgtg gcacaggcgc cggagggagc 60 gcgaccctcg gaccccgcct ggcccgcggg gctgggaccc ggccccggcc tgcccgatgg 120 ggcgcgcggc cccggagatg cgccctcgcc cggccccgcg cccccggccc cgcgcccccg 180 gcccgcccgc cccggcccgc gcctccgcct gagtcccccg cgccttggcc cgccaccccc 240 cgccccgcgc ccccggcccg cctgcgccat ggagcccggc cgcggcggca cagagaccgt 300 gggcaagttc gagttctccc gcaaggacct gatcggccac ggcgccttcg cggtggtctt 360 caagggccgc caccgcgaga agcacgattt ggaggtcgcc gtcaagtgca ttaacaagaa 420 gaacctcgcc aagtctcaga cgctgctggg gaaggaaatc aaaatcctga aggaactgaa 480 acatgaaaac atcgtggccc tgtacgactt ccaggaaatg gctaattctg tctacctggt 540 tatggagtac tgcaacggtg gggacctggc cgactacctg cacgccatgc gcacgctgag 600 cgaggacacc atcaggctct tcctgcagca gatcgcgggc gccatgcggc ttctgcacag 660 caaaggcatc atccaccgcg acctgaaacc gcagaacatc ctgctgtcca accccgccgg 720 ccgccgcgcc aaccccaaca gcatccgcgt caagatcgct gacttcggct tcgcgcggta 780 cctccagagc aacatgatgg cggccacact ctgcggctcc cccatgtaca tggcccccga 840 ggtcatcatg tcccagcact acgacgggaa ggcggacctg tggagcatcg gcaccatcgt 900 ctaccagtgc ctgacgggga aggcgccctt ccaggccagc agcccccagg acctgcgcct 960 gttctacgag aagaacaaga cgttggtccc caccatcccc cgggagacct cggccccgct 1020 gcggcagctg ctcctggccc tactgcaacg caaccacaag gaccgcatgg acttcgatga 1080 gttttttcat caccctttcc tcgatgccag cccctcggtc aggaaatccc cacccgtgcc 1140 tgtgccctcg tacccaagct cggggtccgg cagcagctcc agcagcagct ccacctccca 1200 cctggcctcc ccgccgtccc tgggcgagat gcagcagctg cagaagaccc tggcctcccc 1260 ggctgacacc gctggcttcc tgcacagctc ccgggactct ggtggcagca aggactcttc 1320 ctgtgacaca gacgacttcg tcatggtccc cgcgcagttt ccaggtgacc tggtggctga 1380 ggcgcccagt gccaaacccc cgccagacag cctgatgtgc agtgggagct cactggtggc 1440 ctctgcgggc ttggagagcc acggccggac cccatctcca tccccaccct gcagcagctc 1500 ccccagtccc tcaggccggg ctggcccgtt ctccagcagc aggtgcggcg cctctgtccc 1560 catcccagtc cccacgcagg tgcagaacta ccagcgcatt gagcgaaacc tgcagtcacc 1620 cacccagttc caaacacctc ggtcctctgc catccgcagg tcaggcagca ccagccccct 1680 gggctttgca agggccagcc cctcgccccc tgcccacgct gagcatggag gcgtcctggc 1740 caggaagatg tctctgggtg gaggccggcc ctacacgcca tctcctcaag ttggaaccat 1800 ccctgagcgg ccaggctgga gcgggacgcc ctccccacag ggagctgaga tgcggggtgg 1860 caggtcccct cgtccaggct cctctgcacc cgagcactct ccccgcactt ccgggctggg 1920 ctgccgcctg cacagcgccc ccaacctgtc tgacttgcac gtcgtccgcc ccaagctgcc 1980 caaacccccc acggaccccc tgggagctgt gttcagccca ccacaggcca gccctcccca 2040 gccgtcccac ggcctgcagt cctgccggaa cctgcggggc tcacccaagc tgcccgactt 2100 cctgcagcga aaccccctgc cccccatcct gggctccccc accaaggctg tgccctcctt 2160 tgacttcccg aagaccccca gctcccagaa cctgctggcc ctcctagccc ggcagggcgt 2220 ggtgatgacg ccccctcgaa accggacgct gcccgacctc tcggaggtgg gacccttcca 2280 tggtcagccg ttgggccctg gcctgcggcc aggcgaggac cccaagggcc cctttggccg 2340 gtctttcagc accagccgcc tcactgacct gctccttaag gcggcgtttg ggacacaagc 2400 cccggacccg ggcagcacgg agagcctgca ggagaagccc atggagatcg caccctcagc 2460 tggctttgga gggagcctgc acccaggagc ccgtgctggg ggcaccagca gcccttcccc 2520 ggtggtcttc accgtgggct ctcccccgag cgggagcacg cccccccagg gcccccgcac 2580 caggatgttc tcagcgggcc ccactggctc tgccagctct tctgcccgcc acctggtgcc 2640 tgggccctgc agcgaggccc cagcccctga gctccctgct ccaggacacg gctgcagctt 2700 tgccgacccc attgctgcga acctggaggg ggctgtgacc ttcgaggccc ccgacctccc 2760 tgaggagacc ctcatggagc aagagcacac ggagatcctg cgtggcctgc gcttcacgct 2820 gctgttcgtg cagcacgtcc tggagatcgc agccctgaag ggcagcgcca gtgaggcggc 2880 ggggggccct gagtaccagc tgcaggagag tgtggtggcc gaccagatca gcctgctgag 2940 ccgagaatgg ggcttcgcgg aacagctggt gctgtacctg aaggtggccg agctactgtc 3000 ctccggcctg caaagtgcca tcgaccagat ccgggccggc aagctctgcc tgtcgtccac 3060 tgtgaagcag gtggtgcgca ggctgaatga gctgtacaag gccagcgtgg tgtcctgcca 3120 gggcctgagc ctgcggctgc agcgcttctt cctggacaag cagcggctcc tggaccgcat 3180 tcacagcatc actgccgaga ggctcatctt cagccacgct gtgcagatgg tgcagtcggc 3240 tgccctggac gagatgttcc agcaccgtga gggctgcgtc ccacgctacc acaaggccct 3300 gctgctcctg gaggggctgc agcacatgct ctcggaccag gccgacatcg agaacgtcac 3360 caagtgcaag ctgtgcattg agcggagact ctcggcgctg ctgactggca tctgtgcctg 3420 acctttctgg cctggctggg ccccccgtcc tgccgagccc tgcagagtgg gctctgtgtg 3480 ctggctggac tcctcgggac aagcccatgg cgctgatcgc tggtgctgag ccctgccctg 3540 ggccccacgg acagtcagcc tgccggcctc cctgcagctc acggggcaga accagcacat 3600 ctggagccac acagcttggg gggtgtctcc catcttttac aggtggggat cacagaattt 3660 ctgcccctcc agctgcctgg ctcagcaggc gtgggtgcca ccaccctcta gccccagggc 3720 agccccggag gacaggcaag ggcctgagac cactgccgac tcaaagccaa agcgagctcc 3780 tgcttagggc aggtcagcag gcactgtgcc caggaagagc ctgcggcctc ggcgtccccc 3840 agtctccagg agcctctccc tccgagatac ccacccagct ttgtcaatca cccaagcact 3900 ttatgcatat agagacagaa cctggacctc accagggact gctgggcagc gattcctggc 3960 agtggcctgg tgtttgtaca tacacatatg cagacacatg ccagggcccc ccaagcccga 4020 gcaccggacc acgttgctgc ccaggtctgg acctcagcgg gagaactggc tccgggggga 4080 gtggggccct gcgctagagg cagaggcagt tctttgttca agcgttcctc tggggaccgg 4140 cagcagaggc accgtgttct ctcagccctg gatacgtctt gtaatctttc acactttatt 4200 cctaaaacgt gtcttatttt tatgcagctc attttttctt taaaggagaa aacttgtagg 4260 tgtttaagaa ttggttttgg gagggcgagg actgggccag gttagaggca gatggcacag 4320 gggcgtgtgg cgggcgggtg aggctgcttt gcacacctgt gttggtggct gtcccctgcc 4380 gcccctccct gtggcagcag caggacaggt gtgtgcccag caccctccct acctgggcct 4440 ggaagcagat gaggggaata cttcatgcaa agaaaaaagt aacatgtgca aaagctcccc 4500 gtccagcttt gacagtcagt tttgatgtca gctcctcggc agggtaggcc tgatgacagc 4560 cctgtccctc cctgcctctg ccttgcccaa ggccacggag ggcatctgca gagaggcctg 4620 ccttccggat tccaggcggg catgccctgc aaaccccgcc tgggcctccc ttggtctgcc 4680 cagccctcgg ttagccctgc ctgaatcagt agatacttga acgagtcccc agtctgcggg 4740 aggcagtggt ggggccatgg acccatgcgg ggggttccag ggtcacacgc cacataacag 4800 acaaaaatac acacacgtgt gtttttcttt gcaatacttg aaatattgcc actgtgcttg 4860 gacttagaag aagaaaatcc ccgtgacttc ttcctcatca ccttgatggc tttattctca 4920 ccttgtgggg catgtttgta tttattgctt catggccgac tggaatcctg agtcctggga 4980 agctggcact gcggggatct tgcccggtgt cctggtcctc ttgcttccgt cgcggccgca 5040 tgtgcgtgtg tccaagcagg tcctgggcgc ctcaactgct gcccctggtt gaatgttctc 5100 ttgatagtgc tggacccttt gtctatttta aagcgaattt tgtgtgattt cctgcccttt 5160 gcgttatatt gtataatacc aacgtaagga aataaacctt tggaattgtt gggctggtgt 5220 caaaaaaaaa aaaaaaaaa 5239 <210> 104 <211> 8413 <212> DNA <213> Homo sapiens <400> 104 tttccagatt ggggctcggg ccgcgcctcc tccgggaccc tccccttgga ccgagccgat 60 cgccgcgggg cagttcgggc cggctgtcct ggcgcgaaaa ggtggacaag tcctattttc 120 aagagaagat gacttttaac agttttgaag gatctaaaac ttgtgtacct gcagacatca 180 ataaggaaga agaatttgta gaagagttta atagattaaa aacttttgct aattttccaa 240 gtggtagtcc tgtttcagca tcaacactgg cacgagcagg gtttctttat actggtgaag 300 gagataccgt gcggtgcttt agttgtcatg cagctgtaga tagatggcaa tatggagact 360 cagcagttgg aagacacagg aaagtatccc caaattgcag atttatcaac ggcttttatc 420 ttgaaaatag tgccacgcag tctacaaatt ctggtatcca gaatggtcag tacaaagttg 480 aaaactatct gggaagcaga gatcattttg ccttagacag gccatctgag acacatgcag 540 actatctttt gagaactggg caggttgtag atatatcaga caccatatac ccgaggaacc 600 ctgccatgta tagtgaagaa gctagattaa agtcctttca gaactggcca gactatgctc 660 acctaacccc aagagagtta gcaagtgctg gactctacta cacaggtatt ggtgaccaag 720 tgcagtgctt ttgttgtggt ggaaaactga aaaattggga accttgtgat cgtgcctggt 780 cagaacacag gcgacacttt cctaattgct tctttgtttt gggccggaat cttaatattc 840 gaagtgaatc tgatgctgtg agttctgata ggaatttccc aaattcaaca aatcttccaa 900 gaaatccatc catggcagat tatgaagcac ggatctttac ttttgggaca tggatatact 960 cagttaacaa ggagcagctt gcaagagctg gattttatgc tttaggtgaa ggtgataaag 1020 taaagtgctt tcactgtgga ggagggctaa ctgattggaa gcccagtgaa gacccttggg 1080 aacaacatgc taaatggtat ccagggtgca aatatctgtt agaacagaag ggacaagaat 1140 atataaacaa tattcattta actcattcac ttgaggagtg tctggtaaga actactgaga 1200 aaacaccatc actaactaga agaattgatg ataccatctt ccaaaatcct atggtacaag 1260 aagctatacg aatggggttc agtttcaagg acattaagaa aataatggag gaaaaaattc 1320 agatatctgg gagcaactat aaatcacttg aggttctggt tgcagatcta gtgaatgctc 1380 agaaagacag tatgcaagat gagtcaagtc agacttcatt acagaaagag attagtactg 1440 aagagcagct aaggcgcctg caagaggaga agctttgcaa aatctgtatg gatagaaata 1500 ttgctatcgt ttttgttcct tgtggacatc tagtcacttg taaacaatgt gctgaagcag 1560 ttgacaagtg tcccatgtgc tacacagtca ttactttcaa gcaaaaaatt tttatgtctt 1620 aatctaactc tatagtaggc atgttatgtt gttcttatta ccctgattga atgtgtgatg 1680 tgaactgact ttaagtaatc aggattgaat tccattagca tttgctacca agtaggaaaa 1740 aaaatgtaca tggcagtgtt ttagttggca atataatctt tgaatttctt gatttttcag 1800 ggtattagct gtattatcca ttttttttac tgttatttaa ttgaaaccat agactaagaa 1860 taagaagcat catactataa ctgaacacaa tgtgtattca tagtatactg atttaatttc 1920 taagtgtaag tgaattaatc atctggattt tttattcttt tcagataggc ttaacaaatg 1980 gagctttctg tatataaatg tggagattag agttaatctc cccaatcaca taatttgttt 2040 tgtgtgaaaa aggaataaat tgttccatgc tggtggaaag atagagattg tttttagagg 2100 ttggttgttg tgttttagga ttctgtccat tttcttttaa agttataaac acgtacttgt 2160 gcgaattatt tttttaaagt gatttgccat ttttgaaagc gtatttaatg atagaatact 2220 atcgagccaa catgtactga catggaaaga tgtcaaagat atgttaagtg taaaatgcaa 2280 gtggcaaaac actatgtata gtctgagcca gatcaaagta tgtatgtttt taatatgcat 2340 agaacaaaag atttggaaag atatacacca aactgttaaa tgtggtttct cttcggggag 2400 ggggggattg ggggaggggc cccagagggg ttttataggg gccttttcac tttctacttt 2460 tttcattttg ttctgttcga attttttata agtatgtatt acttttgtaa tcagaatttt 2520 tagaaagtat tttgctgatt taaaggctta ggcatgttca aacgcctgca aaactactta 2580 tcactcagct ttagtttttc taatccaaga aggcagggca gttaaccttt ttggtgccaa 2640 tgtgaaatgt aaatgatttt atgtttttcc tgctttgtgg atgaaaaata tttctgagtg 2700 gtagtttttt gacaggtaga ccatgtctta tcttgtttca aaataagtat ttctgatttt 2760 gtaaaatgaa atataaaata tgtctcagat cttccaatta attagtaagg attcatcctt 2820 aatccttgct agtttaagcc tgcctaagtc actttactaa aagatctttg ttaactcagt 2880 attttaaaca tctgtcagct tatgtaggta aaagtagaag catgtttgta cactgcttgt 2940 agttatagtg acagctttcc atgttgagat tctcatatca tcttgtatct taaagtttca 3000 tgtgagtttt taccgttagg atgattaaga tgtatatagg acaaaatgtt aagtctttcc 3060 tctacctaca tttgttttct tggctagtaa tagtagtaga tacttctgaa ataaatgttc 3120 tctcaagatc cttaaaacct cttggaaatt ataaaaatat tggcaagaaa agaagaatag 3180 ttgtttaaat attttttaaa aaacacttga ataagaatca gtagggtata aactagaagt 3240 ttaaaaatgc ttcatagaac gtccagggtt tacattacaa gattctcaca acaaacctat 3300 tgtagaggtg agtaaggcat gttactacag aggaaagttt gagagtaaaa ctgtaaaaaa 3360 ttatattttt gttgtacttt ctaagagaaa gagtattgtt atgttctcct aacttctgtt 3420 gattactact ttaagtgata ttcatttaaa acattgcaaa tttattttat ttatttaatt 3480 ttctttttga gatggagtct tgcttgtcac ccaggctgga gtgcagtgga gtgatctctg 3540 ctcactgcaa cctccgcctt ctgggttcaa gcgattctcg tgcctcagct tcctgagtag 3600 ctggaattac aggcaggtgc caccatgccc gactaatttt tttttatttt tagtagagac 3660 ggggtttcac catgttggcc aggctggtat caaactcctg acctcaagag atccactcgc 3720 cttgccctcc caaagtgctg ggattacagg cttgagccac cacgcccggc taaaacattg 3780 caaatttaaa tgagagtttt aaaaattaaa taatgactgc cctgtttctg ttttagtatg 3840 taaatcctca gttcttcacc tttgcactgt ctgccactta gtttggttat atagtcatta 3900 acttgaattt ggtctgtata gtctagactt taaatttaaa gttttctaca aggggagaaa 3960 agtgttaaaa tttttaaaat atgttttcca ggacacttca cttccaagtc aggtaggtag 4020 ttcaatctag ttgttagcca aggactcaag gactgaattg ttttaacata aggcttttcc 4080 tgttctggga gccgcacttc attaaaattc ttctaaaact tgtatgttta gagttaagca 4140 agactttttt tcttcctctc catgagttgt gaaatttaat gcacaacgct gatgtggcta 4200 acaagtttat tttaagaatt gtttagaaat gctgttgctt caggttctta aaatcactca 4260 gcactccaac ttctaatcaa atttttggag acttaacagc atttgtctgt gtttgaacta 4320 taaaaagcac cggatctttt ccatctaatt ccgcaaaaat tgatcatttg caaagtcaaa 4380 actatagcca tatccaaatc ttttccccct cccaagagtt ctcagtgtct acatgtagac 4440 tattcctttt ctgtataaag ttcactctag gatttcaagt caccacttat tttacatttt 4500 agtcatgcaa agattcaagt agttttgcaa taagtactta tctttatttg taataattta 4560 gtctgctgat caaaagcatt gtcttaattt ttgagaactg gttttagcat ttacaaacta 4620 aattccagtt aattaattaa tagctttata ttgcctttcc tgctacattt ggttttttcc 4680 cctgtccctt tgattacggg ctaaggtagg gtagagtggg tgtagtgagt gtatataatg 4740 tgatttggcc ctgtgtatta tgatattttg ttatttttgt tgttatatta tttacatttc 4800 agtagttgtt ttttgtgttt ccattttagt ggataaaatt tgtattttga actatgaatg 4860 gagactaccg ccccagcatt agtttcacat gatataccct ttaaacccga atcattgttt 4920 tatttcctga ttacacaggt gttgaatggg gaaaggggct agtatatcag taggatatac 4980 tatgggatgt atatatatca ttgctgttag agaaatgaaa taaaatgggg ctgggctcag 5040 tggctcacgc ctgtaatccc agcactttgg gaggctgagg caggtggatc acgaggtcag 5100 gagatcgaga ccatcctggc taacacggtg aaaccccgtc tctactaaaa aacagaaaat 5160 tagccgggcg tggtggcggg cgcctgtagt cccagctact cgggaggctg aggcaggaga 5220 atggtgtgaa cccgggaggc agagcttgca gtgagccgag atctcgccac tgcactccag 5280 cctgggcaac agagcaagac tctgtctcaa aaaaaaaaaa aaaagaaata agaaaatggg 5340 aagcaatatt tgacatagtt ctttttagtc aaatctactt gttaaaaaaa gggtagcagt 5400 ttattcatct gtgaaaggaa aataatactt atcttacaag gttgcaagag ctcaaggaga 5460 ccatgtatgt aaagttcctg ctgtaaatat gaactcccat cctaataccc ttttacctct 5520 ctgtgggttt gtcttgacct ggaaatttgg gctaaaactt agaaaaaatt cttacatgat 5580 aactcagtga tgcttactca tagtttttgg tgtttctcat agataagata taaatcagct 5640 gggcgcggtg gctcatgcct gtaatcccag cactttggga ggccgaggcg ggcagatcac 5700 ctgaggtcgg gaggtcgaga ccagcctgac caacatggag aaaccccgtc tctactaaaa 5760 atacaaaatt agctgggcgt ggtggctcat gcctgtaatc ccagctactt gggaggctga 5820 ggcaggagaa tcgcttgaac ccaggaggcg gaggttgtgg tgagcgaaga tcgtgccatt 5880 gcactccagc ctgggcaaca agagcaaaac tctgtctcaa aaaaaaaaaa agatataaat 5940 cacaataaat aaataggtca atacaaatgt tagccaggcg tggtggcaca tgcccatagt 6000 cgcagctact ctggaggcag aggcaggagg atcacttgag cccatgaatt tgaggcagca 6060 gtgagctatg attgtgccac tgtactccag tctgggtgac agagtgagac cccatctcta 6120 aataaatagg tcaaaccctt aaaaatattt aaattcttaa aaaattgaaa agattattct 6180 tctcaaattt agttgagctt tctaagagaa gcaattggct ttttcccact tcaataatca 6240 ttttcagttt gactcataca gttaacacaa tgtgaatttc ttcctcagca taacagagtt 6300 atagaatgac agggctggaa gtgaccttag agagtatcca gttctttcat tttacaggtg 6360 aggcaactga gactcaaagg tgatgtaatt tgtgcaaaga ttatagctaa ttagtagcag 6420 agccctgact gggacatagt ttgaaggtga aaaacttcac caagctacct ttcttgaaag 6480 gtccaaatgt ttatgttttc aactactctt tccactgtac cataactttc actacatatt 6540 aaatgacact ttataactaa tataatagga caatcatcaa tgcatatata gccagccctt 6600 catatctgtg ggttttgcat ccatggattc aaccaaggag gaattgaaaa cactgagaaa 6660 aaaaaaaaag accacacaat aaaaaaaaaa aatacaaaat aatacaaaga aaaagccaaa 6720 attgtcatac tgttgttaag caacagtata acaactattt acatagcatt aaggttggtg 6780 caaaaatgca aaaaaaaaaa aagcaattat ttttaaacca acctaatata ttgtattagg 6840 tattaaagtc atctggacat gaattaaagt atatgatgcc agcctggaca aaaggcaaaa 6900 ccctgtctct acaaaaaata caaaaattag ctgggcatgg tggtgtgtgc ctgtagtcct 6960 ggctactccg gagcctgagg tgggaggatc gcttgagtct gggaggcaga ggctgcattg 7020 agctatgatc atggcactgc attccagcct gggtgacagt gcaagacctt gtctcagaat 7080 aaataaagta tgtgatgaag atgtgcatac attatatgca aatactgttt tttttttttt 7140 taatttaaac agtctcactg tgttgcccag gatggagtgc aatggcacaa tcttggctca 7200 tggcaaactc tgcctcgcaa gcagctggga ctacaggcat gctccacggt gcccagttaa 7260 ttttttttgt attcttagta gagacagggt ttcaccatgt tggccaggct agtcttgaat 7320 ttctgacctc aagtgattca tctcccaaag tgctgggatt acaggcgtga gccaccacgg 7380 ccggctaatt tttgtatttt ttagtagtga ctggtttcgc ggtgttgacc aggctggtct 7440 cgaactcctg atctcaggtg atctgcctgc ctcggcctca caaagtgctg ggattacagg 7500 tgtgaaccac tgctcccggc cttgtgtgat tttatctaag ggacttaagc gtcctcaggt 7560 cctagggggt cgtgaaacca aaaccccagg gatagcaagg gacaattgta tcttcaaagt 7620 agacaaatgg cgccgggcac ggtggctcac gcctgtaatc ccagcagttt ccgaggctga 7680 ggcaggcggc tcacctgagg tcaggagttg gagaccagcc tggccaacat gctgaaaccc 7740 tgtctgtaca aaaatacaaa aatagctggg catggtggcg catgcctgta gtcccagcta 7800 ctagagcgac tgaggcagga gaattgcttg aacctgggag gcggaggttg cagggagcca 7860 agatggcgcc accgcactcc agcctaggtg atagagtgag actccctctc aaaaacaaaa 7920 caaaacaaaa aaattagaca aatgctacat taatgtttgg gtggtcagat tctactttga 7980 atctgaagtt tgcagatatg cctatagatt tttggagttt accactttct tattctgtat 8040 cattaatgta atattttaaa ttactatata tgttaccatt tttctggatt tagtaagaaa 8100 tttgcagttt tggtttgatg taacaagggt tttaatgtaa tttatgttag attttgcatt 8160 tttttcatta ctgttatatt ttaacctgac tgactgatct aattgtatta gtattgtgaa 8220 taatcatgtg aaatgttttg agacagagta ctatatttgt gaatataatt ttatggtttt 8280 tttcacttag aacctttctg tgtggaaaac taagaaaatt gctttctgct gtataatctg 8340 gcattcattg tagattaaag cttatttttc tgtgaataaa acgtattcaa taaaatacta 8400 ttctttaaaa tta 8413 <110> CBSBIOSCIENCE, CO., LTD <120> MARKERS FOR LIVER CANCER PROGNOSIS <130> Y09KP-027 <160> 104 <170> KopatentIn 1.71 <210> 1 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CBS forward primer <400> 1 gttggcaaag tcatctacaa gca 23 <210> 2 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> CBS reverse primer <400> 2 gggcgaagtg gtccatctc 19 <210> 3 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> CBS probe <400> 3 acgctgggca ggctctcgca c 21 <210> 4 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NNMT forward primer <400> 4 ttgaggtgat ctcgcaaagt tatt 24 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> 223 NNMT reverse primer <400> 5 ctcgccacca gggagaaa 18 <210> 6 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NNMT probe <400> 6 ccaccatggc caacaacgaa ggac 24 <210> 7 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TKT forward primer <400> 7 gaggctgtgt ccagtgcagt ag 22 <210> 8 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TKT reverse primer <400> 8 ccacttcttg gtacccggtt aa 22 <210> 9 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> TKT probe <400> 9 cctggcatca ctgtcaccca cctg 24 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> BCL2 forward primer <400> 10 catgtgtgtg gagagcgtca a 21 <210> 11 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> BCL2 reverse primer <400> 11 gccggttcag gtactcagtc a 21 <210> 12 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BCL2 probe <400> 12 cctggtggac aacatcgccc tgt 23 <210> 13 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> FAS forward primer <400> 13 aatggtgtca atgaagccaa aat 23 <210> 14 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> FAS reverse primer <400> 14 gtcatacgct tctttctttc catga 25 <210> 15 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> FAS probe <400> 15 tgacaatgtc caagacacag cagaacagaa 30 <210> 16 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAX forward primer <400> 16 ggttgtcgcc cttttctact ttg 23 <210> 17 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> BAX reverse primer <400> 17 cagttccggc accttggt 18 <210> 18 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BAX probe <400> 18 cagcaaactg gtgctcaagg ccct 24 <210> 19 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BCL2L1 forward primer <400> 19 gattgccttt gttttgatgt ttgt 24 <210> 20 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BCL2L1 reverse primer <400> 20 ggaaagggaa cccaggttag tg 22 <210> 21 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> BCL2L1 probe <400> 21 cagaattgat cattttcccc ccactctcc 29 <210> 22 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> AIFM1 forward primer <400> 22 tgaagatctc aatgaagtag ccaaactat 29 <210> 23 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> AIFM1 reverse primer <400> 23 ctgcagtggg tttgccaat 19 <210> 24 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> AIFM1 probe <400> 24 caacattcat gaagactgaa gccccaca 28 <210> 25 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CASP8 forward primer <400> 25 ccttctgatt gatggtgcta ttttg 25 <210> 26 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> CASP8 reverse primer <400> 26 gcggtgagcc gagatcac 18 <210> 27 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> CASP8 probe <400> 27 cagaatctcg ctctgtcgcc cagg 24 <210> 28 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CSE1L forward primer <400> 28 gcatgatcct gtaggtcaaa tgg 23 <210> 29 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CSE1L reverse primer <400> 29 caggcggtag acaacttgtg aa 22 <210> 30 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> CSE1L probe <400> 30 aataacccca aaattcacct ggcacagtca 30 <210> 31 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> XIAP forward primer <400> 31 gacaggccat ctgagacaca tg 22 <210> 32 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> XIAP reverse primer <400> 32 agcatagtct ggccagttct gaa 23 <210> 33 <211> 28 <212> DNA <213> Artificial Sequence <220> 223 XIAP probe <400> 33 agacaccata tacccgagga accctgcc 28 <210> 34 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> DIABLO forward primer <400> 34 aatcacattc agctggtgaa actg 24 <210> 35 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> DIABLO reverse primer <400> 35 tgccagcttg gtttctgctt 20 <210> 36 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> DIABLO probe <400> 36 aagaggtgca ccagctctcc cgg 23 <210> 37 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> AKT1 forward primer <400> 37 tctcgggtgc atttgagaga a 21 <210> 38 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> AKT1 reverse primer <400> 38 acagcacaaa aacgtctttc ca 22 <210> 39 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> AKT1 probe <400> 39 ccacgctgtc ctctcgagcc ca 22 <210> 40 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> PTEN forward primer <400> 40 tggcggaact tgcaatcc 18 <210> 41 <211> 24 <212> DNA <213> Artificial Sequence <220> P223 reverse primer <400> 41 gctgagggaa ctcaaagtac atga 24 <210> 42 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> PTEN probe <400> 42 atattcctcc aattcaggac ccacacgac 29 <210> 43 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> FRAP1 forward primer <400> 43 aggccgcatt gtctctatca a 21 <210> 44 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> FRAP1 reverse primer <400> 44 gcagtaaatg caggtagtca tcca 24 <210> 45 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> FRAP1 probe <400> 45 tgcaatccag ctgtttggcg cc 22 <210> 46 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> PRKAA1 forward primer <400> 46 ggcagttgcc taccatctca taa 23 <210> 47 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PRKAA1 reverse primer <400> 47 gccgagtcag gtgatgatca 20 <210> 48 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> PRKAA1 probe <400> 48 tctatttggc gacaagccca cctgatt 27 <210> 49 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ATG3 forward primer <400> 49 ccattgaaaa tcaccctcat ctg 23 <210> 50 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> ATG3 reverse primer <400> 50 cacctcagca tgcctgcat 19 <210> 51 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ATG3 probe <400> 51 caccacctcc catgtgttca gttcacc 27 <210> 52 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ATG12 forward primer <400> 52 cgacagcttc gatttgaatg ac 22 <210> 53 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> ATG12 reverse primer <400> 53 gggagcgtcg caaagga 17 <210> 54 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ATG12 probe <400> 54 tgtaattgcg tccccctact ccggc 25 <210> 55 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ATG5 forward primer <400> 55 tttcctccac tgccatcatt aa 22 <210> 56 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ATG5 reverse primer <400> 56 ggccaaaggt ttcagcttca 20 <210> 57 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ATG5 probe <400> 57 cctcagctgt gacatgaaag acttaccgg 29 <210> 58 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> ATG7 forward primer <400> 58 cggatgaatg agcctccaa 19 <210> 59 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ATG7 reverse primer <400> 59 ggacattatc aaaccgtgaa agaa 24 <210> 60 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ATG7 probe <400> 60 tcttgggctt gtgcctcacc agatc 25 <210> 61 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BNIP3 forward primer <400> 61 ttccccccaa ggagttcct 19 <210> 62 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BNIP3 reverse primer <400> 62 cgctcgtgtt cctcatgct 19 <210> 63 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BNIP3 probe <400> 63 acccgaagcg cacggccac 19 <210> 64 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> DRAM forward primer <400> 64 cagccgcctt cattatctcc ta 22 <210> 65 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> DRAM reverse primer <400> 65 tggaggtgtt gttcccgtat c 21 <210> 66 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> DRAM probe <400> 66 tgctctccgg gcacgtcaac c 21 <210> 67 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> LAMP1 forward primer <400> 67 tgcactcaga tttaagcctt acaaa 25 <210> 68 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> LAMP1 reverse primer <400> 68 tcaccacgag tgaccttcat g 21 <210> 69 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LAMP1 probe <400> 69 aagcctctgg ccgtcacacg tagg 24 <210> 70 <211> 21 <212> DNA <213> Artificial Sequence <220> LC223 forward primer <400> 70 aaccagcaca gcatggtgag t 21 <210> 71 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LC3 reverse primer <400> 71 cctcgtcttt ctcctgctcg ta 22 <210> 72 <211> 19 <212> DNA <213> Artificial Sequence <220> LC223 probe <400> 72 tccacgccca tcgcggaca 19 <210> 73 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> ULK1 forward primer <400> 73 tcgcggccgc atgt 14 <210> 74 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ULK1 reverse primer <400> 74 aagggtccag cactatcaag aga 23 <210> 75 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ULK1 probe <400> 75 agcaggtcct gggcgcctca ac 22 <210> 76 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> E2F1 forward primer <400> 76 ctggaccacc tgatgaatat ctgt 24 <210> 77 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> E2F1 reverse primer <400> 77 caatgctacg aaggtcctga ca 22 <210> 78 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> E2F1 probe <400> 78 cagctgcgcc tgctctccga 20 <210> 79 <211> 2609 <212> DNA <213> Homo sapiens <400> 79 acattggccg gcgccggcct ccgcccccgc ctctccgcca atcaccgccc gcctgctccc 60 ctcgccgtgg gtccccgcga ggccgccacc ccggggtcgc cgtctccgcc tcgccgcagt 120 cggggcagcc gctcgcccct cttttccatg tatccgtcca ggatcccatg acagattctg 180 ttgtcacgtc tccttacaga gtttgagcgg tgctgaactg tcagcaccat ctgtccggtc 240 ccagcatgcc ttctgagacc ccccaggcag aagtggggcc cacaggctgc ccccaccgct 300 cagggccaca ctcggcgaag gggagcctgg agaaggggtc cccagaggat aaggaagcca 360 aggagcccct gtggatccgg cccgatgctc cgagcaggtg cacctggcag ctgggccggc 420 ctgcctccga gtccccacat caccacactg ccccggcaaa atctccaaaa atcttgccag 480 atattctgaa gaaaatcggg gacaccccta tggtcagaat caacaagatt gggaagaagt 540 tcggcctgaa gtgtgagctc ttggccaagt gtgagttctt caacgcgggc gggagcgtga 600 aggaccgcat cagcctgcgg atgattgagg atgctgagcg cgacgggacg ctgaagcccg 660 gggacacgat tatcgagccg acatccggga acaccgggat cgggctggcc ctggctgcgg 720 cagtgagggg ctatcgctgc atcatcgtga tgccagagaa gatgagctcc gagaaggtgg 780 acgtgctgcg ggcactgggg gctgagattg tgaggacgcc caccaatgcc aggttcgact 840 ccccggagtc acacgtgggg gtggcctggc ggctgaagaa cgaaatcccc aattctcaca 900 tcctagacca gtaccgcaac gccagcaacc ccctggctca ctacgacacc accgctgatg 960 agatcctgca gcagtgtgat gggaagctgg acatgctggt ggcttcagtg ggcacgggcg 1020 gcaccatcac gggcattgcc aggaagctga aggagaagtg tcctggatgc aggatcattg 1080 gggtggatcc cgaagggtcc atcctcgcag agccggagga gctgaaccag acggagcaga 1140 caacctacga ggtggaaggg atcggctacg acttcatccc cacggtgctg gacaggacgg 1200 tggtggacaa gtggttcaag agcaacgatg aggaggcgtt cacctttgcc cgcatgctga 1260 tcgcgcaaga ggggctgctg tgcggtggca gtgctggcag cacggtggcg gtggccgtga 1320 aggccgcgca ggagctgcag gagggccagc gctgcgtggt cattctgccc gactcagtgc 1380 ggaactacat gaccaagttc ctgagcgaca ggtggatgct gcagaagggc tttctgaagg 1440 aggaggacct cacggagaag aagccctggt ggtggcacct ccgtgttcag gagctgggcc 1500 tgtcagcccc gctgaccgtg ctcccgacca tcacctgtgg gcacaccatc gagatcctcc 1560 gggagaaggg cttcgaccag gcgcccgtgg tggatgaggc gggggtaatc ctgggaatgg 1620 tgacgcttgg gaacatgctc tcgtccctgc ttgccgggaa ggtgcagccg tcagaccaag 1680 ttggcaaagt catctacaag cagttcaaac agatccgcct cacggacacg ctgggcaggc 1740 tctcgcacat cctggagatg gaccacttcg ccctggtggt gcacgagcag atccagtacc 1800 acagcaccgg gaagtccagt cagcggcaga tggtgttcgg ggtggtcacc gccattgact 1860 tgctgaactt cgtggccgcc caggagcggg accagaagtg aagtccggag cgctgggcgg 1920 tgcggagcgg gcccgccacc cttgcccact tctccttcgc tttcctgagc cctaaacaca 1980 cgcgtgattg gtaactgcct ggcctggcac cgttatccct gcacacggca cagagcatcc 2040 gtctcccctc gttaacacat ggcttcctaa atggccctgt ttacggccta tgagatgaaa 2100 tatgtgattt tctctaatgt aacttcctct taggatgttt caccaaggaa atattgagag 2160 agaagtcggc caggtaggat gaacacaggc aatgactgcg cagagtggat taaaggcaaa 2220 agagagaaga gtccaggaag gggcggggag aagcctgggt ggctcagcat cctccacggg 2280 ctgcgccgtc tgctcggggc tgagctggcg ggagcagttt gcgtgtttgg gttttttaat 2340 tgagatgaaa ttcaaataac ctaaaaatca atcacttgaa agtgaacaat cagcggcatt 2400 tagtacatcc agaaagttgt gtaggcacca cctctgtcac gttctggaac attctgtcat 2460 caccccgtga agcaatcatt tcccctcccg tcttcctcct cccctggcaa ctgctgatcg 2520 actttgtgtc tctgttgtct aaaataggtt ttccctgttc tggacatttc atataaatgg 2580 aatcacacaa aaaaaaaaaa aaaaaaaaa 2609 <210> 80 <211> 1579 <212> DNA <213> Homo sapiens <400> 80 gaggaggtgc ttgccagaca ctgggtcatg gcagtggtcg gtgaagctgc agttgcctag 60 ggcagggatg gagagagagt ctgggcatga ggagagggtc tcgggatgtt tggctggact 120 agattttaca gaaagcctta tccaggcttt taaaattact ctttccagac ttcatctgag 180 actccttctt cagccaacat tccttagccc tgaatacatt tcctatcctc atctttccct 240 tctttttttt cctttctttt acatgtttaa atttaaacca ttcttcgtga ccccttttct 300 tgggagattc atggcaagaa cgagaagaat gatggtgctt gttaggggat gtcctgtctc 360 tctgaacttt ggggtcctat gcattaaata attttcctga cgagctcaag tgctccctct 420 ggtctacaat ccctggcggc tggccttcat cccttgggca agcattgcat acagctcatg 480 gccctccctc taccataccc tccacccccg ttcgcctaag ctcccttctc cgggaatttc 540 atcatttcct agaacagcca gaacatttgt ggtctatttc tctgttagtg tttaaccaac 600 catctgttct aaaagaaggg ctgaactgat ggaaggaatg ctgttagcct gagactcagg 660 aagacaactt ctgcagggtc actccctggc ttctggagga aagagaagga gggcagtgct 720 ccagtggtac agaagtgaga cataatggaa tcaggcttca cctccaagga cacctatcta 780 agccatttta accctcggga ttacctagaa aaatattaca agtttggttc taggcactct 840 gcagaaagcc agattcttaa gcaccttctg aaaaatcttt tcaagatatt ctgcctagac 900 ggtgtgaagg gagacctgct gattgacatc ggctctggcc ccactatcta tcagctcctc 960 tctgcttgtg aatcctttaa ggagatcgtc gtcactgact actcagacca gaacctgcag 1020 gagctggaga agtggctgaa gaaagagcca gaggcctttg actggtcccc agtggtgacc 1080 tatgtgtgtg atcttgaagg gaacagagtc aagggtccag agaaggagga gaagttgaga 1140 caggcggtca agcaggtgct gaagtgtgat gtgactcaga gccagccact gggggccgtc 1200 cccttacccc cggctgactg cgtgctcagc acactgtgtc tggatgccgc ctgcccagac 1260 ctccccacct actgcagggc gctcaggaac ctcggcagcc tactgaagcc agggggcttc 1320 ctggtgatca tggatgcgct caagagcagc tactacatga ttggtgagca gaagttctcc 1380 agcctccccc tgggccggga ggcagtagag gctgctgtga aagaggctgg ctacacaatc 1440 gaatggtttg aggtgatctc gcaaagttat tcttccacca tggccaacaa cgaaggactt 1500 ttctccctgg tggcgaggaa gctgagcaga cccctgtgat gcctgtgacc tcaattaaag 1560 caattccttt gacctgtca 1579 <210> 81 <211> 2117 <212> DNA <213> Homo sapiens <400> 81 gacttaacgc gcccccgccc cgcgcccggc ctcggcagcc gcctgtcgcc gcgggagcag 60 ccgctatctc tgtgtgtccg cgtgtgcgcc cggtccccgc ctgccgcacc atggagagct 120 accacaagcc tgaccagcag aagctgcagg ccttgaagga cacggccaac cgcctacgta 180 tcagctccat ccaggccacc actgcggcgg gctctggcca ccccacgtca tgctgcagcg 240 ccgcagagat catggctgtc ctctttttcc acaccatgcg ctacaagtcc caggaccccc 300 ggaatccgca caatgaccgc tttgtgctct ccaagggcca tgcagctccc atcctctacg 360 cggtctgggc tgaagctggt ttcctggccg aggcggagct gctgaacctg aggaagatca 420 gctccgactt ggacgggcac ccggtcccga aacaagcttt caccgacgtg gccactggct 480 ccctgggcca gggcctcggg gccgcttgtg ggatggccta caccggcaaa tacttcgaca 540 aggccagcta ccgagtctat tgcttgctgg gagacgggga gctgtcagag ggctctgtat 600 gggaggccat ggccttcgcc agcatctata agctggacaa ccttgtggcc attctagaca 660 tcaatcgcct gggccagagt gacccggccc cactgcagca ccagatggac atctaccaga 720 agcggtgcga ggccttcggt tggcatgcca tcatcgtgga tggacacagc gtggaggagc 780 tgtgcaaggc ctttggccag gccaagcacc agccaacagc catcattgcc aagaccttca 840 agggccgagg gatcacgggg gtagaagata aggagtcttg gcatgggaag cccctcccca 900 aaaacatggc tgagcagatc atccaggaga tctacagcca gatccagagc aaaaagaaga 960 tcctggcaac ccctccacag gaggacgcac cctcagtgga cattgccaac atccgcatgc 1020 ccagcctgcc cagctacaaa gttggggaca agatagccac ccgcaaggcc tacgggcagg 1080 cactggccaa gctgggccat gccagtgacc gcatcatcgc cctggatggg gacaccaaaa 1140 attccacctt ctcggagatc ttcaaaaagg agcacccgga ccgcttcatc gagtgctaca 1200 ttgctgagca gaacatggtg agcatcgcgg tgggctgtgc cacccgcaac aggacggtgc 1260 ccttctgcag cacttttgca gccttcttca cgcgggcctt tgaccagatt cgcatggccg 1320 ccatctccga gagcaacatc aacctctgcg gctcccactg cggcgtttcc atcggggaag 1380 acgggccctc ccagatggcc ctagaagatc tggctatgtt tcggtcagtc cccacatcaa 1440 ctgtctttta cccaagtgat ggcgttgcta cagagaaggc agtggaacta gccgccaata 1500 caaagggtat ctgcttcatc cggaccagcc gcccagaaaa tgccatcatc tataacaaca 1560 atgaggactt ccaggtcgga caagccaagg tggtcctgaa gagcaaggat gaccaggtga 1620 ccgttatcgg ggctggggtg accctgcacg aggccttggc cgctgccgaa ctgctgaaga 1680 aagaaaagat caacatccgc gtgctggacc ccttcaccat caagcccctg gacagaaaac 1740 tcattctcga cagcgctcgt gccaccaagg gcaggatcct caccgtggag gaccattatt 1800 atgaaggtgg cattggtgag gctgtgtcca gtgcagtagt gggcgagcct ggcatcactg 1860 tcacccacct ggcagttaac cgggtaccaa gaagtgggaa gccggctgag ctgctgaaga 1920 tgtttggtat cgacagggat gccattgcac aagctgtgag gggcctcatc accaaggcct 1980 agggcgggta tgaagtgtgg ggcgggggtc tatacattcc tgagattctg ggaaaggtgc 2040 tcaaagatgt actgagagga ggggtaaata tatgttttga gaaaaatgaa ttggccctga 2100 aaaaaaaaaa aaaaaaa 2117 <210> 82 <211> 2215 <212> DNA <213> Homo sapiens <400> 82 ttccccggct ctagcaggcc ggcttctctg tccaatgccc acccggagct gggaggagga 60 gtctgcgtaa tgtgcgtgtg aagagactgg gggagctggc cggggctcac ggtgtttgac 120 ccgtcggtcg tgcgtgagag gaaagggaag gaggaggtcc cgaatagcgg tcgccgaaat 180 gttccggtgt ggaggcctgg cggcgggtgc tttgaagcag aagctggtgc ccttggtgcg 240 gaccgtgtgc gtccgaagcc cgaggcagag gaaccggctc ccaggcaact tgttccagcg 300 atggcatgtt cctctagaac tccagatgac aagacaaatg gctagctctg gtgcatcagg 360 gggcaaaatc gataattctg tgttagtcct tattgtgggc ttatcaacag taggagctgg 420 tgcctatgcc tacaagacta tgaaagagga tgaaaaaaga tacaatgaaa gaatttcagg 480 gttagggctg acaccagaac agaaacagaa aaaggccgcg ttatctgctt cagaaggaga 540 ggaagttcct caagacaagg cgccaagtca tgttcctttc ctgctaattg gtggaggcac 600 agctgctttt gctgcagcca gatccatccg ggctcgggat cctggggcca gggtactgat 660 tgtatctgaa gatcctgagc tgccgtacat gcgacctcct ctttcaaaag aactgtggtt 720 ttcagatgac ccaaatgtca caaagacact gcgattcaaa cagtggaatg gaaaagagag 780 aagcatatat ttccagccac cttctttcta tgtctctgct caggacctgc ctcatattga 840 gaatggtggt gtggctgtcc tcactgggaa gaaggtagta cagctggatg tgagagacaa 900 catggtgaaa cttaatgatg gctctcaaat aacctatgaa aagtgcttga ttgcaacagg 960 aggtactcca agaagtctgt ctgccattga tagggctgga gcagaggtga agagtagaac 1020 aacgcttttc agaaagattg gagactttag aagcttggag aagatttcac gggaagtcaa 1080 atcaattacg attatcggtg ggggcttcct tggtagcgaa ctggcctgtg ctcttggcag 1140 aaaggctcga gccttgggca cagaagtgat tcaactcttc cccgagaaag gaaatatggg 1200 aaagatcctc cccgaatacc tcagcaactg gaccatggaa aaagtcagac gagagggggt 1260 taaggtgatg cccaatgcta ttgtgcaatc cgttggagtc agcagtggca agttacttat 1320 caagctgaaa gacggcagga aggtagaaac tgaccacata gtggcagctg tgggcctgga 1380 gcccaatgtt gagttggcca agactggtgg cctggaaata gactcagatt ttggtggctt 1440 ccgggtaaat gcagagctac aagcacgctc taacatctgg gtggcaggag atgctgcatg 1500 cttctacgat ataaagttgg gaaggaggcg ggtagagcac catgatcacg ctgttgtgag 1560 tggaagattg gctggagaaa atatgactgg agctgctaag ccgtactggc atcagtcaat 1620 gttctggagt gatttgggcc ccgatgttgg ctatgaagct attggtcttg tggacagtag 1680 tttgcccaca gttggtgttt ttgcaaaagc aactgcacaa gacaacccca aatctgccac 1740 agagcagtca ggaactggta tccgatcaga gagtgagaca gagtccgagg cctcagaaat 1800 tactattcct cccagcaccc cggcagttcc acaggctccc gtccaggggg aggactacgg 1860 caaaggtgtc atcttctacc tcagggacaa agtggtcgtg gggattgtgc tatggaacat 1920 ctttaaccga atgccaatag caaggaagat cattaaggac ggtgagcagc atgaagatct 1980 caatgaagta gccaaactat tcaacattca tgaagactga agccccacag tggaattggc 2040 aaacccactg cagcccctga gaggaggtcg aatgggtaaa ggagcatttt tttattcagc 2100 agactttctc tgtgtatgag tgtgaatgat caagtccttt gtgaatattt tcaactatgt 2160 aggtaaattc ttaatgttca catagtgaaa taaattctga ttcttctaaa ttaaa 2215 <210> 83 <211> 3008 <212> DNA <213> Homo sapiens <400> 83 taattatggg tctgtaacca ccctggactg ggtgctcctc actgacggac ttgtctgaac 60 ctctctttgt ctccagcgcc cagcactggg cctggcaaaa cctgagacgc ccggtacatg 120 ttggccaaat gaatgaacca gattcagacc ggcaggggcg ctgtggttta ggaggggcct 180 ggggtttctc ccaggaggtt tttgggcttg cgctggaggg ctctggactc ccgtttgcgc 240 cagtggcctg catcctggtc ctgtcttcct catgtttgaa tttctttgct ttcctagtct 300 ggggagcagg gaggagccct gtgccctgtc ccaggatcca tgggtaggaa caccatggac 360 agggagagca aacggggcca tctgtcacca ggggcttagg gaaggccgag ccagcctggg 420 tcaaagaagt caaaggggct gcctggagga ggcagcctgt cagctggtgc atcagaggct 480 gtggccaggc cagctgggct cggggagcgc cagcctgaga ggagcgcgtg agcgtcgcgg 540 gagcctcggg caccatgagc gacgtggcta ttgtgaagga gggttggctg cacaaacgag 600 gggagtacat caagacctgg cggccacgct acttcctcct caagaatgat ggcaccttca 660 ttggctacaa ggagcggccg caggatgtgg accaacgtga ggctcccctc aacaacttct 720 ctgtggcgca gtgccagctg atgaagacgg agcggccccg gcccaacacc ttcatcatcc 780 gctgcctgca gtggaccact gtcatcgaac gcaccttcca tgtggagact cctgaggagc 840 gggaggagtg gacaaccgcc atccagactg tggctgacgg cctcaagaag caggaggagg 900 aggagatgga cttccggtcg ggctcaccca gtgacaactc aggggctgaa gagatggagg 960 tgtccctggc caagcccaag caccgcgtga ccatgaacga gtttgagtac ctgaagctgc 1020 tgggcaaggg cactttcggc aaggtgatcc tggtgaagga gaaggccaca ggccgctact 1080 acgccatgaa gatcctcaag aaggaagtca tcgtggccaa ggacgaggtg gcccacacac 1140 tcaccgagaa ccgcgtcctg cagaactcca ggcacccctt cctcacagcc ctgaagtact 1200 ctttccagac ccacgaccgc ctctgctttg tcatggagta cgccaacggg ggcgagctgt 1260 tcttccacct gtcccgggag cgtgtgttct ccgaggaccg ggcccgcttc tatggcgctg 1320 agattgtgtc agccctggac tacctgcact cggagaagaa cgtggtgtac cgggacctca 1380 agctggagaa cctcatgctg gacaaggacg ggcacattaa gatcacagac ttcgggctgt 1440 gcaaggaggg gatcaaggac ggtgccacca tgaagacctt ttgcggcaca cctgagtacc 1500 tggcccccga ggtgctggag gacaatgact acggccgtgc agtggactgg tgggggctgg 1560 gcgtggtcat gtacgagatg atgtgcggtc gcctgccctt ctacaaccag gaccatgaga 1620 agctttttga gctcatcctc atggaggaga tccgcttccc gcgcacgctt ggtcccgagg 1680 ccaagtcctt gctttcaggg ctgctcaaga aggaccccaa gcagaggctt ggcgggggct 1740 ccgaggacgc caaggagatc atgcagcatc gcttctttgc cggtatcgtg tggcagcacg 1800 tgtacgagaa gaagctcagc ccacccttca agccccaggt cacgtcggag actgacacca 1860 ggtattttga tgaggagttc acggcccaga tgatcaccat cacaccacct gaccaagatg 1920 acagcatgga gtgtgtggac agcgagcgca ggccccactt cccccagttc tcctactcgg 1980 ccagcggcac ggcctgaggc ggcggtggac tgcgctggac gatagcttgg agggatggag 2040 aggcggcctc gtgccatgat ctgtatttaa tggtttttat ttctcgggtg catttgagag 2100 aagccacgct gtcctctcga gcccagatgg aaagacgttt ttgtgctgtg ggcagcaccc 2160 tcccccgcag cggggtaggg aagaaaacta tcctgcgggt tttaatttat ttcatccagt 2220 ttgttctccg ggtgtggcct cagccctcag aacaatccga ttcacgtagg gaaatgttaa 2280 ggacttctgc agctatgcgc aatgtggcat tggggggccg ggcaggtcct gcccatgtgt 2340 cccctcactc tgtcagccag ccgccctggg ctgtctgtca ccagctatct gtcatctctc 2400 tggggccctg ggcctcagtt caacctggtg gcaccagatg caacctcact atggtatgct 2460 ggccagcacc ctctcctggg ggtggcaggc acacagcagc cccccagcac taaggccgtg 2520 tctctgagga cgtcatcgga ggctgggccc ctgggatggg accagggatg ggggatgggc 2580 cagggtttac ccagtgggac agaggagcaa ggtttaaatt tgttattgtg tattatgttg 2640 ttcaaatgca ttttgggggt ttttaatctt tgtgacagga aagccctccc ccttcccctt 2700 ctgtgtcaca gttcttggtg actgtcccac cgggagcctc cccctcagat gatctctcca 2760 cggtagcact tgaccttttc gacgcttaac ctttccgctg tcgccccagg ccctccctga 2820 ctccctgtgg gggtggccat ccctgggccc ctccacgcct cctggccaga cgctgccgct 2880 gccgctgcac cacggcgttt ttttacaaca ttcaacttta gtatttttac tattataata 2940 taatatggaa ccttccctcc aaattcttca ataaaagttg cttttcaaaa aaaaaaaaaa 3000 aaaaaaaa 3008 <210> 84 <211> 1372 <212> DNA <213> Homo sapiens <400> 84 cgggtgctga tgcgagtcgg tggcagcgag gacattttct gactccctgg cccctgacac 60 ggctgcactt tccatcccgt cgcggggccg gccgctactc cggccccagg atgcagaatg 120 tgattaatac tgtgaaggga aaggcactgg aagtggctga gtacctgacc ccggtcctca 180 aggaatcaaa gtttaaggaa acaggtgtaa ttaccccaga agagtttgtg gcagctggag 240 atcacctagt ccaccactgt ccaacatggc aatgggctac aggggaagaa ttgaaagtga 300 aggcatacct accaacaggc aaacaatttt tggtaaccaa aaatgtgccg tgctataagc 360 ggtgcaaaca gatggaatat tcagatgaat tggaagctat cattgaagaa gatgatggtg 420 atggcggatg ggtagataca tatcacaaca caggtattac aggaataacg gaagccgtta 480 aagagatcac actggaaaat aaggacaata taaggcttca agattgctca gcactatgtg 540 aagaggaaga agatgaagat gaaggagaag ctgcagatat ggaagaatat gaagagagtg 600 gattgttgga aacagatgag gctaccctag atacaaggaa aatagtagaa gcttgtaaag 660 ccaaaactga tgctggcggt gaagatgcta ttttgcaaac cagaacttat gacctttaca 720 tcacttatga taaatattac cagactccac gattatggtt gtttggctat gatgagcaac 780 ggcagccttt aacagttgag cacatgtatg aagacatcag tcaggatcat gtgaagaaaa 840 cagtgaccat tgaaaatcac cctcatctgc caccacctcc catgtgttca gttcacccat 900 gcaggcatgc tgaggtgatg aagaaaatca ttgagactgt tgcagaagga gggggagaac 960 ttggagttca tatgtatctt cttattttct tgaaatttgt acaagctgtc attccaacaa 1020 tagaatatga ctacacaaga cacttcacaa tgtaatgaag agagcataaa atctatccta 1080 attattggtt ctgattttta aagaattaac ccatagatgt gaccattgac catattcatc 1140 aatatataca gtttctctaa taagggactt atatgtttat gcattaaata aaaatatgtt 1200 ccactaccag ccttacttgt ttaataaaaa tcagtgcaaa gaaaaaaaaa aaaaaaaaaa 1260 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1320 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 1372 <210> 85 <211> 3244 <212> DNA <213> Homo sapiens <400> 85 gtgacgtcat ctccgggcgc cgagggtgac tggacttgtg gtgcgctgcc agggctccgc 60 agcgttgccg gttgtattcg ctggatacca gagggcggaa gtgcagcagg gttcagctcc 120 gacctccgcg ccggtgcttt ttgcggctgc gcgggcttcc tggagtcctg ctaccgcgtc 180 cccgcaggac agtgtgtcag gcgggcagct tgccccgccg ccccaccgga gcgcggaatc 240 tgggcgtccc caccagtgcg gggagccgga aggaggagcc atagcttgga gtaggtttgg 300 ctttggttga aataagaatt tagcctgtat gtactgcttt aactcctgga agaatgacag 360 atgacaaaga tgtgcttcga gatgtgtggt ttggacgaat tccaacttgt ttcacgctat 420 atcaggatga gataactgaa agggaagcag aaccatacta tttgcttttg ccaagagtaa 480 gttatttgac gttggtaact gacaaagtga aaaagcactt tcagaaggtt atgagacaag 540 aagacattag tgagatatgg tttgaatatg aaggcacacc actgaaatgg cattatccaa 600 ttggtttgct atttgatctt cttgcatcaa gttcagctct tccttggaac atcacagtac 660 attttaagag ttttccagaa aaagaccttc tgcactgtcc atctaaggat gcaattgaag 720 ctcattttat gtcatgtatg aaagaagctg atgctttaaa acataaaagt caagtaatca 780 atgaaatgca gaaaaaagat cacaagcaac tctggatggg attgcaaaat gacagatttg 840 accagttttg ggccatcaat cggaaactca tggaatatcc tgcagaagaa aatggatttc 900 gttatatccc ctttagaata tatcagacaa cgactgaaag acctttcatt cagaagctgt 960 ttcgtcctgt ggctgcagat ggacagttttc acacactagg agatctcctc aaagaagttt 1020 gtccttctgc tattgatcct gaagatgggg aaaaaaagaa tcaagtgatg attcatggaa 1080 ttgagccaat gttggaaaca cctctgcagt ggctgagtga acatctgagc tacccggata 1140 attttcttca tattagtatc atcccacagc caacagattg aaggatcaac tatttgcctg 1200 aacagaatca tccttaaatg ggatttatca gagcatgtca cccttttgct tcaatcaggt 1260 ttggtggagg caacctgacc agaaacactt cgctgctgca agccagacag gaaaaagatt 1320 ccatgtcaga taaggcaact gggctggtct tactttgcat cacctctgct ttcctccact 1380 gccatcatta aacctcagct gtgacatgaa agacttaccg gaccactgaa ggtcttctgt 1440 aaaatataat gaagctgaaa cctttggcct aagaagaaaa tggaagtatg tgccactcga 1500 tttgtatttc tgattaacaa ataaacaggg gtatttccta aggtgaccat ggttgaactt 1560 tagctcatga aagtggaaac attggtttaa ttttcaagag aattaagaaa gtaaaagaga 1620 aattctgtta tcaataactt gcaagtaatt ttttgtaaaa gattgaatta cagtaaaccc 1680 atctttcctt aacgaaaatt tcctatgttt acagtctgtc tattggtatg caatcttgta 1740 actttgataa tgaacagtga gagattttta aataaagcct ctaaatatgt tttgtcattt 1800 aataacatac agttttgtca cttttcaagt actttctgac tcacatacag tagatcactt 1860 tttactctgt gttaccattt tgactggtcg tcattggcat ggggtggata tagggcatag 1920 gattacttgt ctcagaagct gtcatagaat ttcttgctgc caattaaaaa acctgtgttc 1980 tttacacact acacgtataa atattgtaac tgttcatctt tgttgtttta tcactgtaag 2040 cctgtcaaat catagtatcc taagcatctg taaatgctaa ttttgcattt ttggaaaaac 2100 ccattccttc caagctagtg tttttcattg gctccaggtc taatttttca ctgtggtccc 2160 tggcagccag tcttttgaag tttaaagatt acctgtctct tgactgcagt accttttctt 2220 taatttttac caaaaatatc cagaggttac tggagttctt attcaatata aggaaagttt 2280 gctgcacttt attaccaagc ctctgggatt ttaccagtca aacatatttg tgcattacat 2340 ttcatttctt gtgagctagc tggctgtcca tattgaatgt tgacccattt gagtacgcta 2400 aaaggcttac agtatcagac acgatcatgg ttttagatcc cataataaaa atgaatgttt 2460 ttcttataaa aaattataca aatgctgaag tgagattcta ctattgttca ttgcttcctt 2520 ttctttttcc ttttgcgatt ttcactgatt aatagcacat ttcttcacaa aattagataa 2580 agttggtcaa agaccagata ttctggaatg gaaattgtaa agcttaatca aaaagaatag 2640 ccagtacagc atacaatctc agaaacttag aagcaagtag aaaataattg gttgatgtaa 2700 acgaaagtgc cattttagta aaggcaggaa aaaaatagca atatttgagt tatgtaagga 2760 taaaaaatcc actgacttgt atttttgcac aagaggctgg tctgaatatg attgttcaca 2820 ttaagagtgt ttattcgtcg gttcattttg gggattttcc cccttgatgt tttgacagat 2880 tgaagtgagc tttagtgagc aaaaggatca gaatgcaggg aacactaagc tgtgatgaag 2940 aaagtgtggt aaaaagccag agtagtttta tacagacaaa accagtgtca ggcctttgca 3000 gtaggcttga gtgaacttct gatctagatt tgaaagtaaa ttttatgaag acattgccca 3060 tttttacttc ctcattcatt attgtaccag catcatagct ttattactct aatcccaggt 3120 aagtcaagcc tacaatgccc tagaggaaga gtaaaaccag aaattcatgc tggcttaaat 3180 aatctatttt tgtttctttt catttgaata tttaaatttt atggtttatt aaaaaattaa 3240 ataa 3244 <210> 86 <211> 5059 <212> DNA <213> Homo sapiens <400> 86 ctttgcgcac gcgcgccgct tcccagtggc aagcgcgggc aggaccgcgt tgcgtcatcg 60 gggcgcgcgc ctcagagaga gctgtggttg ccggaagttg agcggcggca agaaataatg 120 gcggcagcta cgggggatcc tggactctct aaactgcagt ttgccccttt tagtagtgcc 180 ttggatgttg ggttttggca tgagttgacc cagaagaagc tgaacgagta tcggctggat 240 gaagctccca aggacattaa gggttattac tacaatggtg actctgctgg gctgccagct 300 cgcttaacat tggagttcag tgcttttgac atgagtgctc ccaccccagc ccgttgctgc 360 ccagctattg gaacactgta taacaccaac acactcgagt ctttcaagac tgcagataag 420 aagctccttt tggaacaagc agcaaatgag atatgggaat ccataaaatc aggcactgct 480 cttgaaaacc ctgtactcct caacaagttc ctcctcttga catttgcaga tctaaagaag 540 taccacttct actattggtt ttgctatcct gccctctgtc ttccagagag tttacctctc 600 attcaggggc cagtgggttt ggatcaaagg ttttcactaa aacagattga agcactagag 660 tgtgcatatg ataatctttg tcaaacagaa ggagtcacag ctcttcctta cttcttaatc 720 aagtatgatg agaacatggt gctggtttcc ttgcttaaac actacagtga tttcttccaa 780 ggtcaaagga cgaagataac aattggtgta tatgatccct gtaacttagc ccagtaccct 840 ggatggcctt tgaggaattt tttggtccta gcagcccaca gatggagtag cagtttccag 900 tctgttgaag ttgtttgctt ccgtgaccgt accatgcagg gggcgagaga cgttgcccac 960 agcatcatct tcgaagtgaa gcttccagaa atggcattta gcccagattg tcctaaagca 1020 gttggatggg aaaagaacca gaaaggaggc atgggaccaa ggatggtgaa cctcagtgaa 1080 tgtatggacc ctaaaaggtt agctgagtca tcagtggatc taaatctcaa actgatgtgt 1140 tggagattgg ttcctacttt agacttggac aaggttgtgt ctgtcaaatg tctgctgctt 1200 ggagccggca ccttgggttg caatgtagct aggacgttga tgggttgggg cgtgagacac 1260 atcacatttg tggacaatgc caagatctcc tactccaatc ctgtgaggca gcctctctat 1320 gagtttgaag attgcctagg gggtggtaag cccaaggctc tggcagcagc ggaccggctc 1380 cagaaaatat tccccggtgt gaatgccaga ggattcaaca tgagcatacc tatgcctggg 1440 catccagtga acttctccag tgtcactctg gagcaagccc gcagagatgt ggagcaactg 1500 gagcagctca tcgaaagcca tgatgtcgtc ttcctattga tggacaccag ggagagccgg 1560 tggcttcctg ccgtcattgc tgcaagcaag agaaagctgg tcatcaatgc tgctttggga 1620 tttgacacat ttgttgtcat gagacatggt ctgaagaaac caaagcagca aggagctggg 1680 gacttgtgtc caaaccaccc tgtggcatct gctgacctcc tgggctcatc gctttttgcc 1740 aacatccctg gttacaagct tggctgctac ttctgcaatg atgtggtggc cccaggagat 1800 tcaaccagag accggacctt ggaccagcag tgcactgtga gtcgtccagg actggccgtg 1860 attgcaggag ccctggccgt ggaattgatg gtatctgttt tgcagcatcc agaagggggc 1920 tatgccattg ccagcagcag tgacgatcgg atgaatgagc ctccaacctc tcttgggctt 1980 gtgcctcacc agatccgggg atttctttca cggtttgata atgtccttcc cgtcagcctg 2040 gcatttgaca aatgtacagc ttgttcttcc aaagttcttg atcaatatga acgagaagga 2100 tttaacttcc tagccaaggt gtttaattct tcacattcct tcttagaaga cttgactggt 2160 cttacattgc tgcatcaaga aacccaagct gctgagatct gggacatgag cgatgatgag 2220 accatctgag atggccccgc tgtggggctg acttctcccc ggccgcctgc tgaggagctc 2280 tccatcgcca gagcaggact gctgacccca ggcctggtga ttctgggccc ctcctccata 2340 ccccgaggtc tgggattccc ccctctgctg cccaggagtg gccagtgttc ggcgttgctc 2400 gggattcaag ataccaccag ttcagagcta aataataacc ttggccttgg ccttgctatt 2460 gacctgggac ttggtcctcc atgcagtttt tatttcttgt cacagtgact gatagccatc 2520 ccccaggatc ctttcccctt ggccctgagg gggtgaccca acacagacca aatggggaaa 2580 tgagcaacca gctcctgccc agagccactg cgggaggtgg caccctcatc cccggaatgt 2640 gctgcccacc gcaccgcagg ctcctcctgt gggggccctg ggcatgggtg agggtgggac 2700 cccgtgagcg cactgcaccc tggccctggt ggagcgggag gaggaggaga gccgagctgg 2760 gtacgagact aaagggccca catgacccag tgacgccaga tttccaccaa ggactgagtg 2820 agctgctcag acatggcttt ctgcctccca gcctgtcctc cactgtgggc atagcatctg 2880 tgcctgcctg cctgcttgag ggagaggagt ttctgctgct gccttgagct ggggggaaga 2940 gcccaggggc agatcctggc agctgcctgg atggggctcc tccctgccct tatgagcagg 3000 ccaggcccag aaaggccgag cctgggctgc cttcctgccc cagccgaggg aggggtcaga 3060 cggctctacc atgggtaact caggcaagag ctggttttcc tctttattct gggtgtgtgc 3120 agctgtgagg ccccaaccca ggagaggcca tggcctaggt acctgtgacc accctgcccc 3180 cgtgtagagg gcatcgtctt tcctgctatt ttattctttc agcttttgtc ttaggcccag 3240 aatcaaagtg aaaattgagt cgagctgacc cttacaacag taggatttag tagggtagat 3300 ttcaaatgag gcttcgcttc tcccaaagta gccagtccaa gttccagtgg ctgtcgttca 3360 gctcatggga gcttcatggg gacacagccg gcacaggtgc agggcccgag tccgcccacc 3420 cagcctggcg ctgaaactgc acacgtacac tatgtggttt aagagcactt tattattgtt 3480 cttaaggcta cttttaagta caaaaaaaga tggcctgcca aacctttttt tttcttcttc 3540 caggaaaaac aggccacaga gaatggtata ttacagattt acacacatga agagaaggtc 3600 agagcgcact gcaggcagcg cggctctggg aagaacttca cggagcccct tcttagagca 3660 gggagggggc tttctcagtg aaatgtttgg ttttctgctg cctcctctgc cccaggcccc 3720 cctccagggt actgcctatc ccagataggt cagtgcacca gggacccggc cgccagcacc 3780 gccgacccct cccagagtga cgcccttgtt cactgacaaa gagacctgtc ccaggagtgt 3840 cctccaccga gccggtcagc tgtgggtggt tttcctgtta cgacgctcag tagcctgtag 3900 caataacaaa ctcgtggcta tgaatgcaga tgcagtgttc tcatagaata actgttcctg 3960 cacttttaca gacaaatcta cgacaaaaaa aaagatcaac tttttttttc cgaacaacaa 4020 aaaaaatgaa tgattacaat aggaaaggga aaaattaaat agctacatat cattaacaaa 4080 ttaatgttct tcaaaaaata cctacaaatt tctctgtaca ttctttacgc acagcgtaac 4140 gatggtctca aaatcaccca tatagaaaag tgttctcaac gatttttcct acagaaaata 4200 taggggcctg aatgccaaag cttggaagcc cagtacagtg ggagtgaaat gtgtgcgggg 4260 caaggagaag ggcttttctt tcctccactt ttcaaaggcc tgcagccact ctgtgactac 4320 aagagccagt cctccgacct tttcacccag tgccaatttc caaaattcaa cagctaaaaa 4380 ctgtaaaacc gggggtcata cggtgtgcag agtccacaaa gccttgcagg tgaggtgacc 4440 acgcccacgt cacctggtca ggtgccatcg tcgtgagcct ctggtgggcc aggtgggaca 4500 cagcacaccc cagggggagg ggatagaaac gctcattgac caaaaaggag cagctgtgac 4560 ctccacagct gtgtctgtca tgcttgcttc atctaatttc tagttagtag ctattaatat 4620 agcaaataat aaatgcagta ataacagtat aaagtcagag gaatgtatac tgccttggcc 4680 ccagcgtacg aggaagcgta taaaacacca tatcacagat tgtctgtcag taatctgctg 4740 ttcagccaag agagttcaaa gggagcagtt tctgcatgta gggaagttgg aagacacaaa 4800 ccccacctcc cctgggagct tgtaacaaag cagacaggga tgcaaaaata aatgatgtca 4860 gcctgcagcc aaactccagc atcccacacc gcagctgacc cactgctcat cgcgagggcc 4920 tgccaggagc tggcctcccg cactacttgt gagtaaagtg aatatcaaat accaatctta 4980 gagtacaact gtaccagcag taagtatatc taggactgta actgacaaaa ataaactaat 5040 tctgaaaaga aaaaaaaaa 5059 <210> 87 <211> 2359 <212> DNA <213> Homo sapiens <400> 87 cgaccgagca cagacacgtt gcccaccgct cctctcccga ggtctgtagt cgcggagaaa 60 cacatgttgc gttactaacg ttcagaggtc tgcgacagct tcgatttgaa tgactagccg 120 ggaacaccaa gtttcactgt gtaattgcgt ccccctactc cggcgcctcc tttgcgacgc 180 tccctggaga aaagcacgcc cactgcacgc gctcagtcgc tacttccgct ctcgagtgtc 240 tccaagcaag atggcggagg agccgcagtc tgtgttgcag cttcctactt caattgctgc 300 tggaggggaa ggacttacgg atgtctcccc agaaacaacc accccggagc ccccgtcttc 360 cgctgcagtt tccccgggaa cagaggaacc tgctggcgac accaagaaaa aaattgacat 420 tttgctaaag gctgtgggag acactcctat tatgaaaaca aagaagtggg cagtagagcg 480 aacacgaacc atccaaggac tcattgactt catcaaaaag tttcttaaac ttgtggcctc 540 agaacagttg tttatttatg tgaatcagtc ctttgctcct tccccagacc aagaagttgg 600 aactctctat gagtgttttg gcagtgatgg taaactggtt ttacattact gcaagtctca 660 ggcgtgggga tgaaccacaa agaaaatcaa cttgctacta catgaaatgg attttcacgg 720 aagagacagc tctgaaaagt tttgatgctt gtggcaagag acttaacaga tgtgatctat 780 ttagtatgtg tctactctat gtttatgcat aagaaaacat ccatagcatg aatggactca 840 gaaaaatgtg atttgtatta atgcaccagt catcataaaa gatggtcatg atagtacacc 900 cattgctcct acttgttact attattgctg cagatctgcc tccaaggttg aaaaggagac 960 taagactgta taaacatctt cattgtcagt tctcaaaatg actgaaattg ttttcatggt 1020 aaaagttaat atactaaagg gttccttttt ttttaatgtt tacatttatc tctatgttta 1080 cctttttagt cacattgacc tgctggctga atacctcaaa tagtccagta gagggcagtc 1140 caccaggcag aaaaggttag gcgttttggt ttcacatctt tgctggggaa taatagggga 1200 aatggctgtt tttgctaatt tttagctaat atctagccag gagagcaagc acataggaca 1260 gactgaaaga ctgtaatttt acacaataca catggcttaa ttattttatt gggatacaga 1320 aaaatataaa ttctggacaa ataagtcata tacctgtttt cagtcctaac atttaaggat 1380 tcttgagtcc caatcacata actgtggtgt tactctgtca tttatatggt gtcaaaagca 1440 cttgatgagt aaacccagta gcatcttttt gagtgtttca taatgcattt tccaacttga 1500 aaacaataat tgaaaaatag ccttattgta tattttatgc catgactaaa agtgccattt 1560 ttactgatgc tattagactg ataatttctt gaagtgaaat ttaacctttt tttctcttta 1620 gtattatgtt tataatgcca tatttttaga aagcattcca gatcaggcat ggtggcttac 1680 acctgtaatc ccagcacttt ggaaggctga ggtgtgggga ttgcgtgaag ccacaagttt 1740 gagaccagcc tggttagcaa ggcaagatcc ccaactctac aaaaaaataa aaattaaaaa 1800 aaaattatta ggctgcagag gcaagaggat cccctgagcc cagaagttca agggtatagt 1860 gagtcgtgat tgtaccactg cattcctgct gagcaacaga gtgagacccc atctcaaaaa 1920 agaaaaaaaa aggcattcta gtaaatcgaa tgtaatgtga atggaatttc aaaacaggat 1980 ctaagatggt atgtagtaga attcaaagta atatcatttt aaagttaaat gagtatggaa 2040 aaggtctgtt ctctagtttt gtccagttca gtttactgaa ggaatatatt taattatatt 2100 catatattta acaaataaaa atatgttgaa ttttcgtatt gtttgccact gagggttcag 2160 atgatagacc tcaaaaaatc gaaaatactg gttgaaattt gtagcatcca tttagttatt 2220 ctttttgacc taaataactt aatagtttat taaatctaag gttagctaaa tatgtagcta 2280 accttatttg ttttctttcc taacaactct gaagaataca taggactttg cacttttttt 2340 tttttttttt ttttttaaa 2359 <210> 88 <211> 891 <212> DNA <213> Homo sapiens <400> 88 tcacgtgacc cgggcgcgct gcggccgccc gcgcggaccc ggcgagaggc ggcggcggga 60 gcggcggtga tggacgggtc cggggagcag cccagaggcg gggggcccac cagctctgag 120 cagatcatga agacaggggc ccttttgctt cagggtttca tccaggatcg agcagggcga 180 atgggggggg aggcacccga gctggccctg gacccggtgc ctcaggatgc gtccaccaag 240 aagctgagcg agtgtctcaa gcgcatcggg gacgaactgg acagtaacat ggagctgcag 300 aggatgattg ccgccgtgga cacagactcc ccccgagagg tctttttccg agtggcagct 360 gacatgtttt ctgacggcaa cttcaactgg ggccgggttg tcgccctttt ctactttgcc 420 agcaaactgg tgctcaaggc cctgtgcacc aaggtgccgg aactgatcag aaccatcatg 480 ggctggacat tggacttcct ccgggagcgg ctgttgggct ggatccaaga ccagggtggt 540 tgggtgagac tcctcaagcc tcctcacccc caccaccgcg ccctcaccac cgcccctgcc 600 ccaccgtccc tgccccccgc cactcctctg ggaccctggg ccttctggag caggtcacag 660 tggtgccctc tccccatctt cagatcatca gatgtggtct ataatgcgtt ttccttacgt 720 gtctgatcaa tccccgattc atctaccctg ctgacctccc agtgacccct gacctcactg 780 tgaccttgac ttgattagtg ccttctgccc tccctggagc ctccactgcc tctggaattg 840 ctcaagttca ttgatgaccc tctgacccta gctctttcct tttttttttt t 891 <210> 89 <211> 6492 <212> DNA <213> Homo sapiens <400> 89 tttctgtgaa gcagaagtct gggaatcgat ctggaaatcc tcctaatttt tactccctct 60 ccccgcgact cctgattcat tgggaagttt caaatcagct ataactggag agtgctgaag 120 attgatggga tcgttgcctt atgcatttgt tttggtttta caaaaaggaa acttgacaga 180 ggatcatgct gtacttaaaa aatacaacat cacagaggaa gtagactgat attaacaata 240 cttactaata ataacgtgcc tcatgaaata aagatccgaa aggaattgga ataaaaattt 300 cctgcatctc atgccaaggg ggaaacacca gaatcaagtg ttccgcgtga ttgaagacac 360 cccctcgtcc aagaatgcaa agcacatcca ataaaatagc tggattataa ctcctcttct 420 ttctctgggg gccgtggggt gggagctggg gcgagaggtg ccgttggccc ccgttgcttt 480 tcctctggga aggatggcgc acgctgggag aacagggtac gataaccggg agatagtgat 540 gaagtacatc cattataagc tgtcgcagag gggctacgag tgggatgcgg gagatgtggg 600 cgccgcgccc ccgggggccg cccccgcacc gggcatcttc tcctcccagc ccgggcacac 660 gccccatcca gccgcatccc gggacccggt cgccaggacc tcgccgctgc agaccccggc 720 tgcccccggc gccgccgcgg ggcctgcgct cagcccggtg ccacctgtgg tccacctgac 780 cctccgccag gccggcgacg acttctcccg ccgctaccgc cgcgacttcg ccgagatgtc 840 cagccagctg cacctgacgc ccttcaccgc gcggggacgc tttgccacgg tggtggagga 900 gctcttcagg gacggggtga actgggggag gattgtggcc ttctttgagt tcggtggggt 960 catgtgtgtg gagagcgtca accgggagat gtcgcccctg gtggacaaca tcgccctgtg 1020 gatgactgag tacctgaacc ggcacctgca cacctggatc caggataacg gaggctggga 1080 tgcctttgtg gaactgtacg gccccagcat gcggcctctg tttgatttct cctggctgtc 1140 tctgaagact ctgctcagtt tggccctggt gggagcttgc atcaccctgg gtgcctatct 1200 gggccacaag tgaagtcaac atgcctgccc caaacaaata tgcaaaaggt tcactaaagc 1260 agtagaaata atatgcattg tcagtgatgt accatgaaac aaagctgcag gctgtttaag 1320 aaaaaataac acacatataa acatcacaca cacagacaga cacacacaca cacaacaatt 1380 aacagtcttc aggcaaaacg tcgaatcagc tatttactgc caaagggaaa tatcatttat 1440 tttttacatt attaagaaaa aaagatttat ttatttaaga cagtcccatc aaaactcctg 1500 tctttggaaa tccgaccact aattgccaag caccgcttcg tgtggctcca cctggatgtt 1560 ctgtgcctgt aaacatagat tcgctttcca tgttgttggc cggatcacca tctgaagagc 1620 agacggatgg aaaaaggacc tgatcattgg ggaagctggc tttctggctg ctggaggctg 1680 gggagaaggt gttcattcac ttgcatttct ttgccctggg ggctgtgata ttaacagagg 1740 gagggttcct gtggggggaa gtccatgcct ccctggcctg aagaagagac tctttgcata 1800 tgactcacat gatgcatacc tggtgggagg aaaagagttg ggaacttcag atggacctag 1860 tacccactga gatttccacg ccgaaggaca gcgatgggaa aaatgccctt aaatcatagg 1920 aaagtatttt tttaagctac caattgtgcc gagaaaagca ttttagcaat ttatacaata 1980 tcatccagta ccttaagccc tgattgtgta tattcatata ttttggatac gcacccccca 2040 actcccaata ctggctctgt ctgagtaaga aacagaatcc tctggaactt gaggaagtga 2100 acatttcggt gacttccgca tcaggaaggc tagagttacc cagagcatca ggccgccaca 2160 agtgcctgct tttaggagac cgaagtccgc agaacctgcc tgtgtcccag cttggaggcc 2220 tggtcctgga actgagccgg ggccctcact ggcctcctcc agggatgatc aacagggcag 2280 tgtggtctcc gaatgtctgg aagctgatgg agctcagaat tccactgtca agaaagagca 2340 gtagaggggt gtggctgggc ctgtcaccct ggggccctcc aggtaggccc gttttcacgt 2400 ggagcatggg agccacgacc cttcttaaga catgtatcac tgtagaggga aggaacagag 2460 gccctgggcc cttcctatca gaaggacatg gtgaaggctg ggaacgtgag gagaggcaat 2520 ggccacggcc cattttggct gtagcacatg gcacgttggc tgtgtggcct tggcccacct 2580 gtgagtttaa agcaaggctt taaatgactt tggagagggt cacaaatcct aaaagaagca 2640 ttgaagtgag gtgtcatgga ttaattgacc cctgtctatg gaattacatg taaaacatta 2700 tcttgtcact gtagtttggt tttatttgaa aacctgacaa aaaaaaagtt ccaggtgtgg 2760 aatatggggg ttatctgtac atcctggggc attaaaaaaa aaatcaatgg tggggaacta 2820 taaagaagta acaaaagaag tgacatcttc agcaaataaa ctaggaaatt tttttttctt 2880 ccagtttaga atcagccttg aaacattgat ggaataactc tgtggcatta ttgcattata 2940 taccatttat ctgtattaac tttggaatgt actctgttca atgtttaatg ctgtggttga 3000 tatttcgaaa gctgctttaa aaaaatacat gcatctcagc gtttttttgt ttttaattgt 3060 atttagttat ggcctataca ctatttgtga gcaaaggtga tcgttttctg tttgagattt 3120 ttatctcttg attcttcaaa agcattctga gaaggtgaga taagccctga gtctcagcta 3180 cctaagaaaa acctggatgt cactggccac tgaggagctt tgtttcaacc aagtcatgtg 3240 catttccacg tcaacagaat tgtttattgt gacagttata tctgttgtcc ctttgacctt 3300 gtttcttgaa ggtttcctcg tccctgggca attccgcatt taattcatgg tattcaggat 3360 tacatgcatg tttggttaaa cccatgagat tcattcagtt aaaaatccag atggcaaatg 3420 accagcagat tcaaatctat ggtggtttga cctttagaga gttgctttac gtggcctgtt 3480 tcaacacaga cccacccaga gccctcctgc cctccttccg cgggggcttt ctcatggctg 3540 tccttcaggg tcttcctgaa atgcagtggt gcttacgctc caccaagaaa gcaggaaacc 3600 tgtggtatga agccagacct ccccggcggg cctcagggaa cagaatgatc agacctttga 3660 atgattctaa tttttaagca aaatattatt ttatgaaagg tttacattgt caaagtgatg 3720 aatatggaat atccaatcct gtgctgctat cctgccaaaa tcattttaat ggagtcagtt 3780 tgcagtatgc tccacgtggt aagatcctcc aagctgcttt agaagtaaca atgaagaacg 3840 tggacgtttt taatataaag cctgttttgt cttttgttgt tgttcaaacg ggattcacag 3900 agtatttgaa aaatgtatat atattaagag gtcacggggg ctaattgctg gctggctgcc 3960 ttttgctgtg gggttttgtt acctggtttt aataacagta aatgtgccca gcctcttggc 4020 cccagaactg tacagtattg tggctgcact tgctctaaga gtagttgatg ttgcattttc 4080 cttattgtta aaaacatgtt agaagcaatg aatgtatata aaagcctcaa ctagtcattt 4140 ttttctcctc ttcttttttt tcattatatc taattatttt gcagttgggc aacagagaac 4200 catccctatt ttgtattgaa gagggattca catctgcatc ttaactgctc tttatgaatg 4260 aaaaaacagt cctctgtatg tactcctctt tacactggcc agggtcagag ttaaatagag 4320 tatatgcact ttccaaattg gggacaaggg ctctaaaaaa agccccaaaa ggagaagaac 4380 atctgagaac ctcctcggcc ctcccagtcc ctcgctgcac aaatactccg caagagaggc 4440 cagaatgaca gctgacaggg tctatggcca tcgggtcgtc tccgaagatt tggcaggggc 4500 agaaaactct ggcaggctta agatttggaa taaagtcaca gaattaagga agcacctcaa 4560 tttagttcaa acaagacgcc aacattctct ccacagctca cttacctctc tgtgttcaga 4620 tgtggccttc catttatatg tgatctttgt tttattagta aatgcttatc atctaaagat 4680 gtagctctgg cccagtggga aaaattagga agtgattata aatcgagagg agttataata 4740 atcaagatta aatgtaaata atcagggcaa tcccaacaca tgtctagctt tcacctccag 4800 gatctattga gtgaacagaa ttgcaaatag tctctatttg taattgaact tatcctaaaa 4860 caaatagttt ataaatgtga acttaaactc taattaattc caactgtact tttaaggcag 4920 tggctgtttt tagactttct tatcacttat agttagtaat gtacacctac tctatcagag 4980 aaaaacagga aaggctcgaa atacaagcca ttctaaggaa attagggagt cagttgaaat 5040 tctattctga tcttattctg tggtgtcttt tgcagcccag acaaatgtgg ttacacactt 5100 tttaagaaat acaattctac attgtcaagc ttatgaaggt tccaatcaga tctttattgt 5160 tattcaattt ggatctttca gggatttttt ttttaaatta ttatgggaca aaggacattt 5220 gttggagggg tgggagggag gaagaatttt taaatgtaaa acattcccaa gtttggatca 5280 gggagttgga agttttcaga ataaccagaa ctaagggtat gaaggacctg tattggggtc 5340 gatgtgatgc ctctgcgaag aaccttgtgt gacaaatgag aaacattttg aagtttgtgg 5400 tacgaccttt agattccaga gacatcagca tggctcaaag tgcagctccg tttggcagtg 5460 caatggtata aatttcaagc tggatatgtc taatgggtat ttaaacaata aatgtgcagt 5520 tttaactaac aggatattta atgacaacct tctggttggt agggacatct gtttctaaat 5580 gtttattatg tacaatacag aaaaaaattt tataaaatta agcaatgtga aactgaattg 5640 gagagtgata atacaagtcc tttagtctta cccagtgaat cattctgttc catgtctttg 5700 gacaaccatg accttggaca atcatgaaat atgcatctca ctggatgcaa agaaaatcag 5760 atggagcatg aatggtactg taccggttca tctggactgc cccagaaaaa taacttcaag 5820 caaacatcct atcaacaaca aggttgttct gcataccaag ctgagcacag aagatgggaa 5880 cactggtgga ggatggaaag gctcgctcaa tcaagaaaat tctgagacta ttaataaata 5940 agactgtagt gtagatactg agtaaatcca tgcacctaaa ccttttggaa aatctgccgt 6000 gggccctcca gatagctcat ttcattaagt ttttccctcc aaggtagaat ttgcaagagt 6060 gacagtggat tgcatttctt ttggggaagc tttcttttgg tggttttgtt tattatacct 6120 tcttaagttt tcaaccaagg tttgcttttg ttttgagtta ctggggttat ttttgtttta 6180 aataaaaata agtgtacaat aagtgttttt gtattgaaag cttttgttat caagattttc 6240 atacttttac cttccatggc tctttttaag attgatactt ttaagaggtg gctgatattc 6300 tgcaacactg tacacataaa aaatacggta aggatacttt acatggttaa ggtaaagtaa 6360 gtctccagtt ggccaccatt agctataatg gcactttgtt tgtgttgttg gaaaaagtca 6420 cattgccatt aaactttcct tgtctgtcta gttaatattg tgaagaaaaa taaagtacag 6480 tgtgagatac tg 6492 <210> 90 <211> 2386 <212> DNA <213> Homo sapiens <400> 90 ggaggaggaa gcaagcgagg gggctggttc ctgagcttcg caattcctgt gtcgccttct 60 gggctcccag cctgccgggt cgcatgatcc ctccggccgg agctggtttt tttgccagcc 120 accgcgaggc cggctgagtt accggcatcc ccgcagccac ctcctctccc gacctgtgat 180 acaaaagatc ttccgggggc tgcacctgcc tgcctttgcc taaggcggat ttgaatctct 240 ttctctccct tcagaatctt atcttggctt tggatcttag aagagaatca ctaaccagag 300 acgagactca gtgagtgagc aggtgttttg gacaatggac tggttgagcc catccctatt 360 ataaaaatgt ctcagagcaa ccgggagctg gtggttgact ttctctccta caagctttcc 420 cagaaaggat acagctggag tcagtttagt gatgtggaag agaacaggac tgaggcccca 480 gaagggactg aatcggagat ggagaccccc agtgccatca atggcaaccc atcctggcac 540 ctggcagaca gccccgcggt gaatggagcc actggccaca gcagcagttt ggatgcccgg 600 gaggtgatcc ccatggcagc agtaaagcaa gcgctgaggg aggcaggcga cgagtttgaa 660 ctgcggtacc ggcgggcatt cagtgacctg acatcccagc tccacatcac cccagggaca 720 gcatatcaga gctttgaaca ggatactttt gtggaactct atgggaacaa tgcagcagcc 780 gagagccgaa agggccagga acgcttcaac cgctggttcc tgacgggcat gactgtggcc 840 ggcgtggttc tgctgggctc actcttcagt cggaaatgac cagacactga ccatccactc 900 taccctccca cccccttctc tgctccacca catcctccgt ccagccgcca ttgccaccag 960 gagaaccact acatgcagcc catgcccacc tgcccatcac agggttgggc ccagatctgg 1020 tcccttgcag ctagttttct agaatttatc acacttctgt gagaccccca cacctcagtt 1080 cccttggcct cagaattcac aaaatttcca caaaatctgt ccaaaggagg ctggcaggta 1140 tggaagggtt tgtggctggg ggcaggaggg ccctacctga ttggtgcaac ccttacccct 1200 tagcctccct gaaaatgttt ttctgccagg gagcttgaaa gttttcagaa cctcttcccc 1260 agaaaggaga ctagattgcc tttgttttga tgtttgtggc ctcagaattg atcattttcc 1320 ccccactctc cccacactaa cctgggttcc ctttccttcc atccctaccc cctaagagcc 1380 atttaggggc cacttttgac tagggattca ggctgcttgg gataaagatg caaggaccag 1440 gactccctcc tcacctctgg actggctaga gtcctcactc ccagtccaaa tgtcctccag 1500 aagcctctgg ctagaggcca gccccaccca ggagggaggg ggctatagct acaggaagca 1560 ccccatgcca aagctagggt ggcccttgca gttcagcacc accctagtcc cttcccctcc 1620 ctggctccca tgaccatact gagggaccaa ctgggcccaa gacagatgcc ccagagctgt 1680 ttatggcctc agctgcctca cttcctacaa gagcagcctg tggcatcttt gccttgggct 1740 gctcctcatg gtgggttcag gggactcagc cctgaggtga aagggagcta tcaggaacag 1800 ctatgggagc cccagggtct tccctacctc aggcaggaag ggcaggaagg agagcctgct 1860 gcatggggtg gggtagggct gactagaagg gccagtcctg cctggccagg cagatctgtg 1920 ccccatgcct gtccagcctg ggcagccagg ctgccaaggc cagagtggcc tggccaggag 1980 ctcttcaggc ctccctctct cttctgctcc acccttggcc tgtctcatcc ccaggggtcc 2040 cagccacccc gggctctctg ctgtacatat ttgagactag tttttattcc ttgtgaagat 2100 gatatactat ttttgttaag cgtgtctgta tttatgtgtg aggagctgct ggcttgcagt 2160 gcgcgtgcac gtggagagct ggtgcccgga gattggacgg cctgatgctc cctcccctgc 2220 cctggtccag ggaagctggc cgagggtcct ggctcctgag gggcatctgc ccctccccca 2280 acccccaccc cacacttgtt ccagctcttt gaaatagtct gtgtgaaggt gaaagtgcag 2340 ttcagtaata aactgtgttt actcagtgaa aaaaaaaaaa aaaaaa 2386 <210> 91 <211> 1535 <212> DNA <213> Homo sapiens <400> 91 cctccgctca gtccgggagc gcacgtgggc cgcggcgctc cgacctccgc tttcccaccg 60 cccgcagctg aagcacatcc cgcagcccgg cgcggactcc gatcgccgca gttgccctct 120 ggcgccatgt cgcagaacgg agcgcccggg atgcaggagg agagcctgca gggctcctgg 180 gtagaactgc acttcagcaa taatgggaac gggggcagcg ttccagcctc ggtttctatt 240 tataatggag acatggaaaa aatactgctg gacgcacagc atgagtctgg acggagtagc 300 tccaagagct ctcactgtga cagcccacct cgctcgcaga caccacaaga taccaacagg 360 gcttctgaaa cagataccca tagcattgga gagaaaaaca gctcacagtc tgaggaagat 420 gatattgaaa gaaggaaaga agttgaaagc atcttgaaga aaaactcaga ttggatatgg 480 gattggtcaa gtcggccgga aaatattccc cccaaggagt tcctctttaa acacccgaag 540 cgcacggcca ccctcagcat gaggaacacg agcgtcatga agaaaggggg catattctct 600 gcagaatttc tgaaagtttt ccttccatct ctgctgctct ctcatttgct ggccatcgga 660 ttggggatct atattggaag gcgtctgaca acctccacca gcaccttttg atgaagaact 720 ggagtctgac ttggttcgtt agtggattac ttctgagctt gcaacatagc tcactgaaga 780 gctgttagat cctggggtgg ccacgtcact tgtgtttatt tgttctgtaa atgctgcgtt 840 cctaatttag taaaataaaa gaatagacac taaaatcatg ttgatctata attacaccta 900 tgggatcaat aagcatgtca gactgattaa tgtctactgt gaaaatttgg tagtaaattt 960 tcatttgata ttagatataa atatctgaat ataaataatt ttaatatact agtcatgatg 1020 tgtgttgtat tttaaaaatt atctgcaacc ttaattcagc tgaagtactt tatatttcaa 1080 aagaatgaat aacattgata ataaaatcgc tactttaagg ggtttgtcca aaataaatat 1140 tgtggcctta tatatcacac tattgtagaa agtattattt aatttaaatg gatgcaggtt 1200 gtctactaaa gaaagattat atataactat gctaattgtt cataatcaac agaaaccaag 1260 atagagctac aaactcagct gtacagttcg tacactaaac tcttcttgct tttgcattat 1320 aaggaattaa gtctccgatt attaggtgat caccctggat gatcagtttt ctgctgaagg 1380 cacctactca gtatcttttc ctctttatca ctctgcattg gtgaatttaa tcctctcctt 1440 tgtgttcaac ttttgtgtgc ttttaaaatc agctttattc taagcaaatc tgtgtctact 1500 ttaaaaaact ggaaatggaa aaaaaaataa atctt 1535 <210> 92 <211> 2914 <212> DNA <213> Homo sapiens <400> 92 gtgctctgag tttttggttt ctgtttcacc ttgtgtctga gctggtctga aggctggttg 60 ttcagactga gcttcctgcc tgcctgtacc ccgccaacag cttcagaaga aggtgactgg 120 tggctgcctg aggaatacca gtgggcaaga gaattagcat ttctggagca tctgctgtct 180 gagcagcccc tgggtgcgtc cactttctgg gcacgtgagg ttgggccttg gccgcctgag 240 cccttgagtt ggtcacttga accttgggaa tattgagatt atattctcct gccttttaaa 300 aagatggact tcagcagaaa tctttatgat attggggaac aactggacag tgaagatctg 360 gcctccctca agttcctgag cctggactac attccgcaaa ggaagcaaga acccatcaag 420 gatgccttga tgttattcca gagactccag gaaaagagaa tgttggagga aagcaatctg 480 tccttcctga aggagctgct cttccgaatt aatagactgg atttgctgat tacctaccta 540 aacactagaa aggaggagat ggaaagggaa cttcagacac caggcagggc tcaaatttct 600 gcctacaggt tccacttctg ccgcatgagc tgggctgaag caaacagcca gtgccagaca 660 cagtctgtac ctttctggcg gagggtcgat catctattaa taagggtcat gctctatcag 720 atttcagaag aagtgagcag atcagaattg aggtctttta agtttctttt gcaagaggaa 780 atctccaaat gcaaactgga tgatgacatg aacctgctgg atattttcat agagatggag 840 aagagggtca tcctgggaga aggaaagttg gacatcctga aaagagtctg tgcccaaatc 900 aacaagagcc tgctgaagat aatcaacgac tatgaagaat tcagcaaagg ggaggagttg 960 tgtggggtaa tgacaatctc ggactctcca agagaacagg atagtgaatc acagactttg 1020 gacaaagttt accaaatgaa aagcaaacct cggggatact gtctgatcat caacaatcac 1080 aattttgcaa aagcacggga gaaagtgccc aaacttcaca gcattaggga caggaatgga 1140 acacacttgg atgcaggggc tttgaccacg acctttgaag agcttcattt tgagatcaag 1200 ccccacgatg actgcacagt agagcaaatc tatgagattt tgaaaatcta ccaactcatg 1260 gaccacagta acatggactg cttcatctgc tgtatcctct cccatggaga caagggcatc 1320 atctatggca ctgatggaca ggaggccccc atctatgagc tgacatctca gttcactggt 1380 ttgaagtgcc cttcccttgc tggaaaaccc aaagtgtttt ttattcaggc ttgtcagggg 1440 gataactacc agaaaggtat acctgttgag actgattcag aggagcaacc ctatttagaa 1500 atggatttat catcacctca aacgagatat atcccggatg aggctgactt tctgctgggg 1560 atggccactg tgaataactg tgtttcctac cgaaaccctg cagagggaac ctggtacatc 1620 cagtcacttt gccagagcct gagagagcga tgtcctcgag gcgatgatat tctcaccatc 1680 ctgactgaag tgaactatga agtaagcaac aaggatgaca agaaaaacat ggggaaacag 1740 atgcctcagc ctactttcac actaagaaaa aaacttgtct tcccttctga ttgatggtgc 1800 tattttgttt gttttgtttt gttttgtttt tttgagacag aatctcgctc tgtcgcccag 1860 gctggagtgc agtggcgtga tctcggctca ccgcaagctc cgcctcccgg gttcaggcca 1920 ttctcctgcc tcagcctccc gagtagctgg gactacaggg gcccgccacc acacctggct 1980 aattttttaa aaatattttt agtagagaca gggtttcact gtgttagcca gggtggtctt 2040 gatctcctga cctcgtgatc cacccacctc ggcctcccaa agtgctggga ttacaggcgt 2100 gagccaccgc gcctggccga tggtactatt tagatataac actatgttta tttactaatt 2160 ttctagattt tctactttat taattgtttt gcactttttt ataagagcta aagttaaata 2220 ggatattaac aacaataaca ctgtctcctt tctcttatgc ttaaggcttt gggaatgttt 2280 ttagctggtg gcaataaata ccagacacgt acaaaatcca gctatgaata tagagggctt 2340 atgattcaga ttgttatcta tcaactataa gcccactgtt aatattctat taactttaat 2400 tctctttcaa agctaaattc cacactacca cattaaaaaa attagaaagt agccacgtat 2460 ggtggctcat gtctataatc ccagcacttt gggaggttga ggtgggagga ttgcttgaac 2520 ccaagaggtc aaggctgcag tgagccatgt tcacaccgct gcactcaagc ttgggtgaca 2580 gaacaagacc ccgtctcaaa aaaaattttt tttttaataa aacaaaattt gtttgaaatc 2640 ttttaaaaat tcaaatgatt tttacaagtt ttaaataagc tctccccaaa cttgctttat 2700 gccttcttat tgcttttatg atatatatat gcttggctaa ctatatttgc tttttgctaa 2760 caatgctctg gggtcttttt atgcatttgc atttgctctt tcatctctgc ttggattatt 2820 ttaaatcatt aggaattaag ttatctttaa aatttaagta tcttttttca aaaacatttt 2880 ttaatagaat aaaatataat ttgatcttat taaa 2914 <210> 93 <211> 3579 <212> DNA <213> Homo sapiens <400> 93 tcaggctcgc tgtcgcgcca ttttgccggg gtttgaatgt gaggcggagc ggcggcagga 60 gcgggtagtg ccagctacgg tccgcggctg gggttccctc ctccgtttct gtatccccac 120 gagatcctat agcaatggaa ctcagcgatg caaatctgca aacactaaca gaatatttaa 180 agaaaacact tgatcctgat cctgccatcc gacgtccagc tgagaaattt cttgaatctg 240 ttgaaggaaa tcagaattat ccactgttgc ttttgacatt actggagaag tcccaggata 300 atgttatcaa agtatgtgct tcagtaacat tcaaaaacta tattaaaagg aactggagaa 360 ttgttgaaga tgaaccaaac aaaatttgtg aagccgatcg agtggccatt aaagccaaca 420 tagtgcactt gatgcttagc agcccagagc aaattcagaa gcagttaagt gatgcaatta 480 gcattattgg cagagaagat tttccacaga aatggcctga cttgctgaca gaaatggtga 540 atcgctttca gagtggagat ttccatgtta ttaatggagt cctccgtaca gcacattcat 600 tatttaaaag ataccgtcat gaatttaagt caaacgagtt atggactgaa attaagcttg 660 ttctggatgc ctttgctttg cctttgacta atctttttaa ggccactatt gaactctgca 720 gtacccatgc aaatgatgcc tctgccctga ggattctgtt ttcttccctg atcctgatct 780 caaaattgtt ctatagttta aactttcagg atctccctga attttttgaa gataatatgg 840 aaacttggat gaataatttt catactctct taacattgga taataagctt ttacaaactg 900 atgatgaaga ggaagccggc ttattggagc tcttaaaatc ccagatttgt gataatgccg 960 cactctatgc acaaaagtac gatgaagaat tccagcgata cctgcctcgt tttgttacag 1020 ccatctggaa tttactagtt acaacgggtc aagaggttaa atatgatttg ttggtaagta 1080 atgcaattca atttctggct tcagtttgtg agagacctca ttataagaat ctatttgagg 1140 accagaacac gctgacaagt atctgtgaaa aggttattgt gcctaacatg gaatttagag 1200 ctgctgatga agaagcattt gaagataatt ctgaggagta cataaggaga gatttggaag 1260 gatctgatat tgatactaga cgcagggctg cttgtgatct ggtacgagga ttatgcaagt 1320 tttttgaggg acctgtgaca ggaatcttct ctggttatgt taattccatg ctgcaggaat 1380 acgcaaaaaa tccatctgtc aactggaaac acaaagatgc agccatctac ctagtgacat 1440 ctttggcatc aaaagcccaa acacagaagc atggaattac acaagcaaat gaacttgtaa 1500 acctaactga gttctttgtg aatcacatcc tccctgattt aaaatcagct aatgtgaatg 1560 aatttcctgt ccttaaagct gacggtatca aatatattat gatttttaga aatcaagtgc 1620 caaaagaaca tcttttagtc tcgattcctc tcttgattaa tcatcttcaa gctgaaagta 1680 ttgttgttca tacttacgca gctcatgctc ttgaacggct ctttactatg cgagggccta 1740 acaatgccac tctctttaca gctgcagaaa tcgcaccgtt tgttgagatt ctgctaacaa 1800 accttttcaa agctctcaca cttcctggct cttcagaaaa tgaatatatt atgaaagcta 1860 tcatgagaag tttttctctc ctacaagaag ccataatccc ctacatccct actctcatca 1920 ctcagcttac acagaagcta ttagctgtta gtaagaaccc aagcaaacct cactttaatc 1980 actacatgtt tgaagcaata tgtttatcca taagaataac ttgcaaagct aaccctgctg 2040 ctgttgtaaa ttttgaggag gctttgtttt tggtgtttac tgaaatctta caaaatgatg 2100 tgcaagaatt tattccatac gtctttcaag tgatgtcttt gcttctggaa acacacaaaa 2160 atgacatccc gtcttcctat atggccttat ttcctcatct ccttcagcca gtgctttggg 2220 aaagaacagg aaatattcct gctctagtga ggcttcttca agcattctta gaacgcggtt 2280 caaacacaat agcaagtgct gcagctgaca aaattcctgg gttactaggt gtctttcaga 2340 agctgattgc atccaaagca aatgaccacc aaggttttta tcttctaaac agtataatag 2400 agcacatgcc tcctgaatca gttgaccaat ataggaaaca aatcttcatt ctgctattcc 2460 agagacttca gaattccaaa acaaccaagt ttatcaagag ttttttagtc tttattaatt 2520 tgtattgcat aaaatatggg gcactagcac tacaagaaat atttgatggt atacaaccaa 2580 aaatgtttgg aatggttttg gaaaaaatta ttattcctga aattcagaag gtatctggaa 2640 atgtagagaa aaagatctgt gcggttggca taaccaaatt actaacagaa tgtcccccaa 2700 tgatggacac tgagtatacc aaactgtgga ctccattatt acagtctttg attggtcttt 2760 ttgagttacc cgaagatgat accattcctg atgaggaaca ttttattgac atagaagata 2820 caccaggata tcagactgcc ttctcacagt tggcatttgc tgggaaaaaa gagcatgatc 2880 ctgtaggtca aatggtgaat aaccccaaaa ttcacctggc acagtcactt cacaagttgt 2940 ctaccgcctg tccaggaagg gttccatcaa tggtgagcac cagcctgaat gcagaagcgc 3000 tccagtatct ccaagggtac cttcaggcag ccagtgtgac actgctttaa actgcatttt 3060 tctaatgggc taaacccaga tggtttccta ggaaatcaca ggcttctgag cacagctgca 3120 ttaaaacaaa ggaagttctc cttttgaact tgtcacgaat tccatcttgt aaaggatatt 3180 aaatgttgct ttaacctgaa ccttgagcaa attagttggt ttgtgtgatc atacagttat 3240 gtgggtggct tctagtttgc aacttcaagg gacaagtatt aatagttcag tgtatggcgt 3300 tggtttgtgt tgagcgtttg cacggtttgg ataatcttaa attttgacgg acactgtgga 3360 gactttctgt tactaaatcc ttttgttttg aagctgttgc tatttgtatt tctcttgtcc 3420 tttatatttt ttgtctgttt atttacgctt ttattggaaa tgtgaataag taaagaatta 3480 cttgtgttac ttgccaagca gtgcacattt catagtttca aatctgtaat cagcaataaa 3540 aatcctaaaa tatgtaccta aaaaaaaaaa aaaaaaaaa 3579 <210> 94 <211> 2265 <212> DNA <213> Homo sapiens <400> 94 acgcggaggt tgtaattggt ctctagacca cacctagttg ttgagtgccg ctgcttgaaa 60 atctcagttc tgccgagatc gcagaataca cacaagctac ctttgggcac cagagcagac 120 agaaccgcgg agcttcaggg tggaagattc gtggaaactt tgccaaggcc aggacctcgt 180 gtgttcccgt ccgcccctct gggacggcgc cagcccggca ggccgccgac cgtcctgggg 240 ctcccgcgca gcgcgatgcc ggcctcgtcc accgtccacg tgctgcagct gctgcgggag 300 ctgctcgcct tcgtgctcct cagctacacg gtgctcatcg gggcgctgct gctggccggc 360 tggaccactt acttcctggt gctgaagtga cagcgccgtc gccgcgcccg gccccgcctc 420 ccgcccggcc ccgcctcccg cccggccccg cctccctaac tcaccaggaa attcccttca 480 agccctggcc cgaactgagt ccccgcccac ccgccagcgt cacggcgccc gactcagctc 540 cgcgccggac ccacctccgc gccctcaggc cctgcatatg ccccgccccg cgcggaagtt 600 ccggcggttg gttgccttgc gcggccgtta cagcctttgc cctaagcctc gccccctttc 660 cccctgcctg cccaatcccg actgcttcct tgggtggggg cgtggctatg gggcgaggcg 720 ctctcaggtg gaggccgtgc cccgctccgc gctcacgaag ctgcgtcact tccggcgtgt 780 gcgtctggcg tccgcgcgct gcacaatggc ggctctgaag agttggctgt cgcgcagcgt 840 aacttcattc ttcaggtaca gacagtgttt gtgtgttcct gttgtggcta actttaagaa 900 gcggtgtttc tcagaattga taagaccatg gcacaaaact gtgacgattg gctttggagt 960 aaccctgtgt gcggttccta ttgcacagaa atcagagcct cattccctta gtagtgaagc 1020 attgatgagg agagcagtgt ctttggtaac agatagcacc tctacctttc tctctcagac 1080 cacatatgcg ttgattgaag ctattactga atatactaag gctgtttata ccttaacttc 1140 tctttaccga caatatacaa gtttacttgg gaaaatgaat tcagaggagg aagatgaagt 1200 gtggcaggtg atcataggag ccagagctga gatgacttca aaacaccaag agtacttgaa 1260 gctggaaacc acttggatga ctgcagttgg tctttcagag atggcagcag aagctgcata 1320 tcaaactggc gcagatcagg cctctataac cgccaggaat cacattcagc tggtgaaact 1380 gcaggtggaa gaggtgcacc agctctcccg gaaagcagaa accaagctgg cagaagcaca 1440 gatagaagag ctccgtcaga aaacacagga ggaaggggag gagcgggctg agtcggagca 1500 ggaggcctac ctgcgtgagg attgagggcc tgagcacact gccctgtctc cccactcagt 1560 ggggaaagca ggggcagatg ccaccctgcc cagggttggc atgactgtct gtgcaccgag 1620 aagaggcggc agatcctgcc ctggccaatc aggcgagacg cctttgtgag ctgtgagtgc 1680 ctcctgtggt ctcaggcttg cgctggacct ggttcttagc ccttgggcac tgcaccctgt 1740 ttaacatttc accccactct gtacagctgc tcttacccat tttttttacc tcacacccaa 1800 agcattttgc ctacctgggt cagagagagg agtccttttt gtcatgccct taagttcagc 1860 aactgtttaa cctgttttca gtcttattta cgtcgtcaaa aatgatttag tacttgttcc 1920 ctctgttggg atgccagttg tggcaggggg aggggaacct gtccagtttg tacgatttct 1980 ttgtatgtat ttctgatgtg ttctctgatc tgcccccact gtcctgtgag gacagctgag 2040 gccaaggagt gaaaaaccta ttactactaa gagaaggggt gcagagtgtt tacctggtgc 2100 tctcaacagg acttaacatc aacaggactt aacacaggcc tcttgttcct tcctttcttt 2160 ccgtttctct attgtatcca aaggagaaga gtgtaagatt ttgtttgcat ctgaaagaga 2220 aaatgcgtct ctcctggggt cctaaaaaaa aaaaaaaaaa aaaaa 2265 <210> 95 <211> 3553 <212> DNA <213> Homo sapiens <400> 95 gagccagcgc ggtagggcca gagtgggaag gccagagcgg gcgtccccgc cagtgacccc 60 acgccgcccg tccgcgccca acccggcctc cgccgagtgt ccaaaccaaa agcgaaagga 120 acccgacccc gcgtcccctc cggcggctcc gtagtcgcgt ccgcttggag ctcgccgggc 180 gcctccgacc ctgccgggcc gctttgtgac ttcactcgtt tcgcaacaag cccgggcagc 240 ccgcgcccca cccactctgg cccggcagcc tcgccgcccg cagcctcgct ccgctcctcg 300 cgcttcccct ccctccgggg ctgggcctgc cccggccgtc gcggagcctc ccctcccacc 360 gtccgtgagt gtacgcgccc ggccgccgcc tccaggcagc ccggagcaac ccggcgcccg 420 gccccgctgg gcgcagcact ccgtcggcgg cggcggcggc gcgatgctgt gcttcctgag 480 gggaatggct ttcgtcccct tcctcttggt gacctggtcg tcagccgcct tcattatctc 540 ctacgtggtc gccgtgctct ccgggcacgt caaccccttc ctcccgtata tcagtgatac 600 gggaacaaca cctccagaga gtggtatttt tggatttatg ataaacttct ctgcatttct 660 tggtgcagcc acgatgtata caagatacaa aatagtacag aagcaaaatc aaacctgcta 720 tttcagcact cctgttttta acttggtgtc tttagtgctt ggattggtgg gatgtttcgg 780 aatgggcatt gtcgccaatt ttcaggagtt agctgtgcca gtggttcatg acgggggcgc 840 tcttttggcc tttgtctgtg gtgtcgtgta cacgctccta cagtccatca tctcttacaa 900 atcatgtccc cagtggaaca gtctctcgac atgccacata cggatggtca tctctgccgt 960 ttcttgcgca gctgtcatcc ccatgattgt ctgtgcttca ctaatttcca taaccaagct 1020 ggagtggaat ccaagagaaa aggattatgt atatcacgta gtgagtgcga tctgtgaatg 1080 gacagtggcc tttggtttta ttttctactt cctaactttc atccaagatt tccagagtgt 1140 caccctaagg atatccacag aaatcaatgg tgatatttga agaaagaaga attcagtctc 1200 actcagtgaa tgtcgcaggc catttctaaa agtgctacag aggacagaca gggttttgag 1260 gccaccctga ttattgggat gcatctgcag cacatccagg acttgaattt cattacgagt 1320 tcctaatagt tgtatttcta aagatgtgtt tcctagagaa tgtacagcct tatgacactg 1380 tagtgatgtt tttataattt tctaagtaga tttttttata ttaacaaatt catatacaga 1440 aaaaataagg tgttacaaaa aatggagagc tcttattttt gtacagattc tgtcgttttt 1500 gttttatttg tgtgagattt atggaaatac actaaatgag taattcaggt tcagtacatt 1560 tattacaaag tgaaatcagg ggatattcat ttgtaaattt tattcttagt gaatgaactg 1620 tataattttt tttatcagga gagcacttat aaaattcaat ttataaagat catataccca 1680 aatcataaag atttagttga tacattaaca ctaagatact ctgattttta gccgaactaa 1740 acaaagtgct tctactgaga ggcctttata ccaccatgta cagtaactct aagtgaatac 1800 ggaagacctt ggttttgaaa ttctgccacc ttgtttctcc ctgctcatga ggtcgcacct 1860 tttgctcttg ctgctaattg cccattcgta gtgggtgtaa tgccaggtgg aatggtttca 1920 acaagtcagg tgaaaaccat cctttattgt tgctggcaca acttgatata tagtctgact 1980 cagaactgaa gctcacatct caaattcatt tcatgccagt aaatgtggca aagagaagaa 2040 aggcccaaga gcgagacaag aagaatggag aagggggcag ccaagaagaa cttctgggtt 2100 cagggtactg tttatttgct ccttctcttc atgcctgtgg ctggatgtcc cacaacacta 2160 taagaaatat aagtcaagcc ctttgtgtta agcaagaact acagactcca tcttttcacc 2220 caaatcatga atgaccaata aaaagcaagt tattccagag gaagaagcag cccttgaaat 2280 gttaaggctt aggcttgaaa ggtgaagagc aggaattctc tctttcaaat cctagagcat 2340 aaacccatgt gtggccaagt gagatcagcc ctcaagggca catgccaagg gcagagcagc 2400 ccatgtagac agcttcggag ggcatggggg tgtagggagt tcggggtagc tcctcattaa 2460 ctatttgttg ggtgagtaaa ggggtgaggc tcagtggcag gtacctctgc aatgacaagc 2520 tgcctcccct ctatgtgttt agcatatgtt attagaacat gtccgacacc cctaccgctg 2580 ccatttgggc cctttaataa agccaagtag agaaatctgg caataaaagg caaatgtaag 2640 catgctttct ttaagacgca tcataaatgg ttttctttaa gtgaatggaa gagtttgaca 2700 gagatacacc tttgtaagaa aacattaaga atgctggctg gctgtggtgg ctcacacctg 2760 tattcccagc actttgggag gcctaggcag gaggattgct tgagcctggg acttcgagac 2820 cagactggga aacatggcaa aatcccatct ctacaacaaa aatacaaaaa ttagccaagt 2880 gcggtggtgt gcctgtagtc ctagttactt gggaggctga ggtgggagaa tcacctgagc 2940 ccaggaggtg gaggctgcag tgagccatgc caatgcactc cagtctgggc aacagagtga 3000 gaccctgtct caaaaataaa taaataaata aatgaataaa gagaatgcta atcatttctg 3060 ggttcactgc gactcactgt agtgctgggg atcccccttg taacactgga actgaaagac 3120 agtgatgaaa gctatgtcaa gcattcatta ttctgaagag gaggagaaat gccacatacc 3180 tttcccatgg gacctgtggt ggaatgaatc catacttctg cctcacttcg agcagacttt 3240 tgttctcggc gctcctcacg atggagtttc atgcttcatt ttcacatctc tctgcacaat 3300 tagattggga gctccttgag ggcagagtac gtgccttaat ctttatcttt gtaatgccac 3360 aatgaacaga gtgcctcctg gtacactgta ggagcttaag aaatactcac tgaatgcatg 3420 aatgaatgaa tgaacaaatg aaggaatgac taaggatgtt tgtagtgcta taatatagaa 3480 tgggatttac tctgctttac cagttagttt cataataaac aaatagtctg tatcgcctgg 3540 taaaaaaaaa aaa 3553 <210> 96 <211> 2722 <212> DNA <213> Homo sapiens <400> 96 ttggcgcgta aaagtggccg ggactttgca ggcagcggcg gccgggggcg gagcgggatc 60 gagccctcgc cgaggcctgc cgccatgggc ccgcgccgcc gccgccgcct gtcacccggg 120 ccgcgcgggc cgtgagcgtc atggccttgg ccggggcccc tgcgggcggc ccatgcgcgc 180 cggcgctgga ggccctgctc ggggccggcg cgctgcggct gctcgactcc tcgcagatcg 240 tcatcatctc cgccgcgcag gacgccagcg ccccgccggc tcccaccggc cccgcggcgc 300 ccgccgccgg cccctgcgac cctgacctgc tgctcttcgc cacaccgcag gcgccccggc 360 ccacacccag tgcgccgcgg cccgcgctcg gccgcccgcc ggtgaagcgg aggctggacc 420 tggaaactga ccatcagtac ctggccgaga gcagtgggcc agctcggggc agaggccgcc 480 atccaggaaa aggtgtgaaa tccccggggg agaagtcacg ctatgagacc tcactgaatc 540 tgaccaccaa gcgcttcctg gagctgctga gccactcggc tgacggtgtc gtcgacctga 600 actgggctgc cgaggtgctg aaggtgcaga agcggcgcat ctatgacatc accaacgtcc 660 ttgagggcat ccagctcatt gccaagaagt ccaagaacca catccagtgg ctgggcagcc 720 acaccacagt gggcgtcggc ggacggcttg aggggttgac ccaggacctc cgacagctgc 780 aggagagcga gcagcagctg gaccacctga tgaatatctg tactacgcag ctgcgcctgc 840 tctccgagga cactgacagc cagcgcctgg cctacgtgac gtgtcaggac cttcgtagca 900 ttgcagaccc tgcagagcag atggttatgg tgatcaaagc ccctcctgag acccagctcc 960 aagccgtgga ctcttcggag aactttcaga tctcccttaa gagcaaacaa ggcccgatcg 1020 atgttttcct gtgccctgag gagaccgtag gtgggatcag ccctgggaag accccatccc 1080 aggaggtcac ttctgaggag gagaacaggg ccactgactc tgccaccata gtgtcaccac 1140 caccatcatc tcccccctca tccctcacca cagatcccag ccagtctcta ctcagcctgg 1200 agcaagaacc gctgttgtcc cggatgggca gcctgcgggc tcccgtggac gaggaccgcc 1260 tgtccccgct ggtggcggcc gactcgctcc tggagcatgt gcgggaggac ttctccggcc 1320 tcctccctga ggagttcatc agcctttccc caccccacga ggccctcgac taccacttcg 1380 gcctcgagga gggcgagggc atcagagacc tcttcgactg tgactttggg gacctcaccc 1440 ccctggattt ctgacagggc ttggagggac cagggtttcc agagatgctc accttgtctc 1500 tgcagccctg gagccccctg tccctggccg tcctcccagc ctgtttggaa acatttaatt 1560 tatacccctc tcctctgtct ccagaagctt ctagctctgg ggtctggcta ccgctaggag 1620 gctgagcaag ccaggaaggg aaggagtctg tgtggtgtgt atgtgcatgc agcctacacc 1680 cacacgtgtg taccgggggt gaatgtgtgt gagcatgtgt gtgtgcatgt accggggaat 1740 gaaggtgaac atacacctct gtgtgtgcac tgcagacacg ccccagtgtg tccacatgtg 1800 tgtgcatgag tccatgtgtg cgcgtggggg ggctctaact gcactttcgg cccttttgct 1860 ctgggggtcc cacaaggccc agggcagtgc ctgctcccag aatctggtgc tctgaccagg 1920 ccaggtgggg aggctttggc tggctgggcg tgtaggacgg tgagagcact tctgtcttaa 1980 aggttttttc tgattgaagc tttaatggag cgttatttat ttatcgaggc ctctttggtg 2040 agcctgggga atcagcaaag gggaggaggg gtgtggggtt gataccccaa ctccctctac 2100 ccttgagcaa gggcaggggt ccctgagctg ttcttctgcc ccatactgaa ggaactgagg 2160 cctgggtgat ttatttattg ggaaagtgag ggagggagac agactgactg acagccatgg 2220 gtggtcagat ggtggggtgg gccctctcca gggggccagt tcagggcccc agctgccccc 2280 caggatggat atgagatggg agaggtgagt gggggacctt cactgatgtg ggcaggaggg 2340 gtggtgaagg cctcccccag cccagaccct gtggtccctc ctgcagtgtc tgaagcgcct 2400 gcctccccac tgctctgccc caccctccaa tctgcacttt gatttgcttc ctaacagctc 2460 tgttccctcc tgctttggtt ttaataaata ttttgatgac gtttgggccg ggttttggga 2520 ctctgttggg aacatttcgg ggcgggagag gccaaggttg ctggggaaat gcccattctc 2580 cacttccctt ctccctgtcc gtgcccgatt tgatttgagc ctcataactc gaagaaaggt 2640 cagcttcctc gctgttttgg tcctaactca aaagcagatc cagtaaaggt ttttgttgta 2700 aaaaaaaaaa aaaaaaaaaa aa 2722 <210> 97 <211> 2755 <212> DNA <213> Homo sapiens <400> 97 cctacccgcg cgcaggccaa gttgctgaat caatggagcc ctccccaacc cgggcgttcc 60 ccagcgaggc ttccttccca tcctcctgac caccggggct tttcgtgagc tcgtctctga 120 tctcgcgcaa gagtgacaca caggtgttca aagacgcttc tggggagtga gggaagcggt 180 ttacgagtga cttggctgga gcctcagggg cgggcactgg cacggaacac accctgaggc 240 cagccctggc tgcccaggcg gagctgcctc ttctcccgcg ggttggtgga cccgctcagt 300 acggagttgg ggaagctctt tcacttcgga ggattgctca acaaccatgc tgggcatctg 360 gaccctccta cctctggttc ttacgtctgt tgctagatta tcgtccaaaa gtgttaatgc 420 ccaagtgact gacatcaact ccaagggatt ggaattgagg aagactgtta ctacagttga 480 gactcagaac ttggaaggcc tgcatcatga tggccaattc tgccataagc cctgtcctcc 540 aggtgaaagg aaagctaggg actgcacagt caatggggat gaaccagact gcgtgccctg 600 ccaagaaggg aaggagtaca cagacaaagc ccatttttct tccaaatgca gaagatgtag 660 attgtgtgat gaaggacatg gcttagaagt ggaaataaac tgcacccgga cccagaatac 720 caagtgcaga tgtaaaccaa actttttttg taactctact gtatgtgaac actgtgaccc 780 ttgcaccaaa tgtgaacatg gaatcatcaa ggaatgcaca ctcaccagca acaccaagtg 840 caaagaggaa ggatccagat ctaacttggg gtggctttgt cttcttcttt tgccaattcc 900 actaattgtt tgggtgaaga gaaaggaagt acagaaaaca tgcagaaagc acagaaagga 960 aaaccaaggt tctcatgaat ctccaacctt aaatcctgaa acagtggcaa taaatttatc 1020 tgatgttgac ttgagtaaat atatcaccac tattgctgga gtcatgacac taagtcaagt 1080 taaaggcttt gttcgaaaga atggtgtcaa tgaagccaaa atagatgaga tcaagaatga 1140 caatgtccaa gacacagcag aacagaaagt tcaactgctt cgtaattggc atcaacttca 1200 tggaaagaaa gaagcgtatg acacattgat taaagatctc aaaaaagcca atctttgtac 1260 tcttgcagag aaaattcaga ctatcatcct caaggacatt actagtgact cagaaaattc 1320 aaacttcaga aatgaaatcc aaagcttggt ctagagtgaa aaacaacaaa ttcagttctg 1380 agtatatgca attagtgttt gaaaagattc ttaatagctg gctgtaaata ctgcttggtt 1440 ttttactggg tacattttat catttattag cgctgaagag ccaacatatt tgtagatttt 1500 taatatctca tgattctgcc tccaaggatg tttaaaatct agttgggaaa acaaacttca 1560 tcaagagtaa atgcagtggc atgctaagta cccaaatagg agtgtatgca gaggatgaaa 1620 gattaagatt atgctctggc atctaacata tgattctgta gtatgaatgt aatcagtgta 1680 tgttagtaca aatgtctatc cacaggctaa ccccactcta tgaatcaata gaagaagcta 1740 tgaccttttg ctgaaatatc agttactgaa caggcaggcc actttgcctc taaattacct 1800 ctgataattc tagagatttt accatatttc taaactttgt ttataactct gagaagatca 1860 tatttatgta aagtatatgt atttgagtgc agaatttaaa taaggctcta cctcaaagac 1920 ctttgcacag tttattggtg tcatattata caatatttca attgtgaatt cacatagaaa 1980 acattaaatt ataatgtttg actattatat atgtgtatgc attttactgg ctcaaaacta 2040 cctacttctt tctcaggcat caaaagcatt ttgagcagga gagtattact agagctttgc 2100 cacctctcca tttttgcctt ggtgctcatc ttaatggcct aatgcacccc caaacatgga 2160 aatatcacca aaaaatactt aatagtccac caaaaggcaa gactgccctt agaaattcta 2220 gcctggtttg gagatactaa ctgctctcag agaaagtagc tttgtgacat gtcatgaacc 2280 catgtttgca atcaaagatg ataaaataga ttcttatttt tcccccaccc ccgaaaatgt 2340 tcaataatgt cccatgtaaa acctgctaca aatggcagct tatacatagc aatggtaaaa 2400 tcatcatctg gatttaggaa ttgctcttgt cataccccca agtttctaag atttaagatt 2460 ctccttacta ctatcctacg tttaaatatc tttgaaagtt tgtattaaat gtgaatttta 2520 agaaataata tttatatttc tgtaaatgta aactgtgaag atagttataa actgaagcag 2580 atacctggaa ccacctaaag aacttccatt tatggaggat ttttttgccc cttgtgtttg 2640 gaattataaa atataggtaa aagtacgtaa ttaaataatg tttttggtaa aaaaaaaaaa 2700 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2755 <210> 98 <211> 8733 <212> DNA <213> Homo sapiens <400> 98 gctcccggct tagaggacag cggggaaggc gggcggtggg gcagggggcc tgaagcggcg 60 gtaccggtgc tggcggcggc agctgaggcc ttggccgaag ccgcgcgaac ctcagggcaa 120 gatgcttgga accggacctg ccgccgccac caccgctgcc accacatcta gcaatgtgag 180 cgtcctgcag cagtttgcca gtggcctaaa gagccggaat gaggaaacca gggccaaagc 240 cgccaaggag ctccagcact atgtcaccat ggaactccga gagatgagtc aagaggagtc 300 tactcgcttc tatgaccaac tgaaccatca catttttgaa ttggtttcca gctcagatgc 360 caatgagagg aaaggtggca tcttggccat agctagcctc ataggagtgg aaggtgggaa 420 tgccacccga attggcagat ttgccaacta tcttcggaac ctcctcccct ccaatgaccc 480 agttgtcatg gaaatggcat ccaaggccat tggccgtctt gccatggcag gggacacttt 540 taccgctgag tacgtggaat ttgaggtgaa gcgagccctg gaatggctgg gtgctgaccg 600 caatgagggc cggagacatg cagctgtcct ggttctccgt gagctggcca tcagcgtccc 660 taccttcttc ttccagcaag tgcaaccctt ctttgacaac atttttgtgg ccgtgtggga 720 ccccaaacag gccatccgtg agggagctgt agccgccctt cgtgcctgtc tgattctcac 780 aacccagcgt gagccgaagg agatgcagaa gcctcagtgg tacaggcaca catttgaaga 840 agcagagaag ggatttgatg agaccttggc caaagagaag ggcatgaatc gggatgatcg 900 gatccatgga gccttgttga tccttaacga gctggtccga atcagcagca tggagggaga 960 gcgtctgaga gaagaaatgg aagaaatcac acagcagcag ctggtacacg acaagtactg 1020 caaagatctc atgggcttcg gaacaaaacc tcgtcacatt acccccttca ccagtttcca 1080 ggctgtacag ccccagcagt caaatgcctt ggtggggctg ctggggtaca gctctcacca 1140 aggcctcatg ggatttggga cctcccccag tccagctaag tccaccctgg tggagagccg 1200 gtgttgcaga gacttgatgg aggagaaatt tgatcaggtg tgccagtggg tgctgaaatg 1260 caggaatagc aagaactcgc tgatccaaat gacaatcctt aatttgttgc cccgcttggc 1320 tgcattccga ccttctgcct tcacagatac ccagtatctc caagatacca tgaaccatgt 1380 cctaagctgt gtcaagaagg agaaggaacg tacagcggcc ttccaagccc tggggctact 1440 ttctgtggct gtgaggtctg agtttaaggt ctatttgcct cgcgtgctgg acatcatccg 1500 agcggccctg cccccaaagg acttcgccca taagaggcag aaggcaatgc aggtggatgc 1560 cacagtcttc acttgcatca gcatgctggc tcgagcaatg gggccaggca tccagcagga 1620 tatcaaggag ctgctggagc ccatgctggc agtgggacta agccctgccc tcactgcagt 1680 gctctacgac ctgagccgtc agattccaca gctaaagaag gacattcaag atgggctact 1740 gaaaatgctg tccctggtcc ttatgcacaa accccttcgc cacccaggca tgcccaaggg 1800 cctggcccat cagctggcct ctcctggcct cacgaccctc cctgaggcca gcgatgtggg 1860 cagcatcact cttgccctcc gaacgcttgg cagctttgaa tttgaaggcc actctctgac 1920 ccaatttgtt cgccactgtg cggatcattt cctgaacagt gagcacaagg agatccgcat 1980 ggaggctgcc cgcacctgct cccgcctgct cacaccctcc atccacctca tcagtggcca 2040 tgctcatgtg gttagccaga ccgcagtgca agtggtggca gatgtgctta gcaaactgct 2100 cgtagttggg ataacagatc ctgaccctga cattcgctac tgtgtcttgg cgtccctgga 2160 cgagcgcttt gatgcacacc tggcccaggc ggagaacttg caggccttgt ttgtggctct 2220 gaatgaccag gtgtttgaga tccgggagct ggccatctgc actgtgggcc gactcagtag 2280 catgaaccct gcctttgtca tgcctttcct gcgcaagatg ctcatccaga ttttgacaga 2340 gttggagcac agtgggattg gaagaatcaa agagcagagt gcccgcatgc tggggcacct 2400 ggtctccaat gccccccgac tcatccgccc ctacatggag cctattctga aggcattaat 2460 tttgaaactg aaagatccag accctgatcc aaacccaggt gtgatcaata atgtcctggc 2520 aacaatagga gaattggcac aggttagtgg cctggaaatg aggaaatggg ttgatgaact 2580 ttttattatc atcatggaca tgctccagga ttcctctttg ttggccaaaa ggcaggtggc 2640 tctgtggacc ctgggacagt tggtggccag cactggctat gtagtagagc cctacaggaa 2700 gtaccctact ttgcttgagg tgctactgaa ttttctgaag actgagcaga accagggtac 2760 acgcagagag gccatccgtg tgttagggct tttaggggct ttggatcctt acaagcacaa 2820 agtgaacatt ggcatgatag accagtcccg ggatgcctct gctgtcagcc tgtcagaatc 2880 caagtcaagt caggattcct ctgactatag cactagtgaa atgctggtca acatgggaaa 2940 cttgcctctg gatgagttct acccagctgt gtccatggtg gccctgatgc ggatcttccg 3000 agaccagtca ctctctcatc atcacaccat ggttgtccag gccatcacct tcatcttcaa 3060 gtccctggga ctcaaatgtg tgcagttcct gccccaggtc atgcccacgt tccttaacgt 3120 cattcgagtc tgtgatgggg ccatccggga atttttgttc cagcagctgg gaatgttggt 3180 gtcctttgtg aagagccaca tcagacctta tatggatgaa atagtcaccc tcatgagaga 3240 attctgggtc atgaacacct caattcagag cacgatcatt cttctcattg agcaaattgt 3300 ggtagctctt gggggtgaat ttaagctcta cctgccccag ctgatcccac acatgctgcg 3360 tgtcttcatg catgacaaca gcccaggccg cattgtctct atcaagttac tggctgcaat 3420 ccagctgttt ggcgccaacc tggatgacta cctgcattta ctgctgcctc ctattgttaa 3480 gttgtttgat gcccctgaag ctccactgcc atctcgaaag gcagcgctag agactgtgga 3540 ccgcctgacg gagtccctgg atttcactga ctatgcctcc cggatcattc accctattgt 3600 tcgaacactg gaccagagcc cagaactgcg ctccacagcc atggacacgc tgtcttcact 3660 tgtttttcag ctggggaaga agtaccaaat tttcattcca atggtgaata aagttctggt 3720 gcgacaccga atcaatcatc agcgctatga tgtgctcatc tgcagaattg tcaagggata 3780 cacacttgct gatgaagagg aggatccttt gatttaccag catcggatgc ttaggagtgg 3840 ccaaggggat gcattggcta gtggaccagt ggaaacagga cccatgaaga aactgcacgt 3900 cagcaccatc aacctccaaa aggcctgggg cgctgccagg agggtctcca aagatgactg 3960 gctggaatgg ctgagacggc tgagcctgga gctgctgaag gactcatcat cgccctccct 4020 gcgctcctgc tgggccctgg cacaggccta caacccgatg gccagggatc tcttcaatgc 4080 tgcatttgtg tcctgctggt ctgaactgaa tgaagatcaa caggatgagc tcatcagaag 4140 catcgagttg gccctcacct cacaagacat cgctgaagtc acacagaccc tcttaaactt 4200 ggctgaattc atggaacaca gtgacaaggg ccccctgcca ctgagagatg acaatggcat 4260 tgttctgctg ggtgagagag ctgccaagtg ccgagcatat gccaaagcac tacactacaa 4320 agaactggag ttccagaaag gccccacccc tgccattcta gaatctctca tcagcattaa 4380 taataagcta cagcagccgg aggcagcggc cggagtgtta gaatatgcca tgaaacactt 4440 tggagagctg gagatccagg ctacctggta tgagaaactg cacgagtggg aggatgccct 4500 tgtggcctat gacaagaaaa tggacaccaa caaggacgac ccagagctga tgctgggccg 4560 catgcgctgc ctcgaggcct tgggggaatg gggtcaactc caccagcagt gctgtgaaaa 4620 gtggaccctg gttaatgatg agacccaagc caagatggcc cggatggctg ctgcagctgc 4680 atggggttta ggtcagtggg acagcatgga agaatacacc tgtatgatcc ctcgggacac 4740 ccatgatggg gcattttata gagctgtgct ggcactgcat caggacctct tctccttggc 4800 acaacagtgc attgacaagg ccagggacct gctggatgct gaattaactg cgatggcagg 4860 agagagttac agtcgggcat atggggccat ggtttcttgc cacatgctgt ccgagctgga 4920 ggaggttatc cagtacaaac ttgtccccga gcgacgagag atcatccgcc agatctggtg 4980 ggagagactg cagggctgcc agcgtatcgt agaggactgg cagaaaatcc ttatggtgcg 5040 gtcccttgtg gtcagccctc atgaagacat gagaacctgg ctcaagtatg caagcctgtg 5100 cggcaagagt ggcaggctgg ctcttgctca taaaacttta gtgttgctcc tgggagttga 5160 tccgtctcgg caacttgacc atcctctgcc aacagttcac cctcaggtga cctatgccta 5220 catgaaaaac atgtggaaga gtgcccgcaa gatcgatgcc ttccagcaca tgcagcattt 5280 tgtccagacc atgcagcaac aggcccagca tgccatcgct actgaggacc agcagcataa 5340 gcaggaactg cacaagctca tggcccgatg cttcctgaaa cttggagagt ggcagctgaa 5400 tctacagggc atcaatgaga gcacaatccc caaagtgctg cagtactaca gcgccgccac 5460 agagcacgac cgcagctggt acaaggcctg gcatgcgtgg gcagtgatga acttcgaagc 5520 tgtgctacac tacaaacatc agaaccaagc ccgcgatgag aagaagaaac tgcgtcatgc 5580 cagcggggcc aacatcacca acgccaccac tgccgccacc acggccgcca ctgccaccac 5640 cactgccagc accgagggca gcaacagtga gagcgaggcc gagagcaccg agaacagccc 5700 caccccatcg ccgctgcaga agaaggtcac tgaggatctg tccaaaaccc tcctgatgta 5760 cacggtgcct gccgtccagg gcttcttccg ttccatctcc ttgtcacgag gcaacaacct 5820 ccaggataca ctcagagttc tcaccttatg gtttgattat ggtcactggc cagatgtcaa 5880 tgaggcctta gtggaggggg tgaaagccat ccagattgat acctggctac aggttatacc 5940 tcagctcatt gcaagaattg atacgcccag acccttggtg ggacgtctca ttcaccagct 6000 tctcacagac attggtcggt accaccccca ggccctcatc tacccactga cagtggcttc 6060 taagtctacc acgacagccc ggcacaatgc agccaacaag attctgaaga acatgtgtga 6120 gcacagcaac accctggtcc agcaggccat gatggtgagc gaggagctga tccgagtggc 6180 catcctctgg catgagatgt ggcatgaagg cctggaagag gcatctcgtt tgtactttgg 6240 ggaaaggaac gtgaaaggca tgtttgaggt gctggagccc ttgcatgcta tgatggaacg 6300 gggcccccag actctgaagg aaacatcctt taatcaggcc tatggtcgag atttaatgga 6360 ggcccaagag tggtgcagga agtacatgaa atcagggaat gtcaaggacc tcacccaagc 6420 ctgggacctc tattatcatg tgttccgacg aatctcaaag cagctgcctc agctcacatc 6480 cttagagctg caatatgttt ccccaaaact tctgatgtgc cgggaccttg aattggctgt 6540 gccaggaaca tatgacccca accagccaat cattcgcatt cagtccatag caccgtcttt 6600 gcaagtcatc acatccaagc agaggccccg gaaattgaca cttatgggca gcaacggaca 6660 tgagtttgtt ttccttctaa aaggccatga agatctgcgc caggatgagc gtgtgatgca 6720 gctcttcggc ctggttaaca cccttctggc caatgaccca acatctcttc ggaaaaacct 6780 cagcatccag agatacgctg tcatcccttt atcgaccaac tcgggcctca ttggctgggt 6840 tccccactgt gacacactgc acgccctcat ccgggactac agggagaaga agaagatcct 6900 tctcaacatc gagcatcgca tcatgttgcg gatggctccg gactatgacc acttgactct 6960 gatgcagaag gtggaggtgt ttgagcatgc cgtcaataat acagctgggg acgacctggc 7020 caagctgctg tggctgaaaa gccccagctc cgaggtgtgg tttgaccgaa gaaccaatta 7080 tacccgttct ttagcggtca tgtcaatggt tgggtatatt ttaggcctgg gagatagaca 7140 cccatccaac ctgatgctgg accgtctgag tgggaagatc ctgcacattg actttgggga 7200 ctgctttgag gttgctatga cccgagagaa gtttccagag aagattccat ttagactaac 7260 aagaatgttg accaatgcta tggaggttac aggcctggat ggcaactaca gaatcacatg 7320 ccacacagtg atggaggtgc tgcgagagca caaggacagt gtcatggccg tgctggaagc 7380 ctttgtctat gaccccttgc tgaactggag gctgatggac acaaatacca aaggcaacaa 7440 gcgatcccga acgaggacgg attcctactc tgctggccag tcagtcgaaa ttttggacgg 7500 tgtggaactt ggagagccag cccataagaa aacggggacc acagtgccag aatctattca 7560 ttctttcatt ggagacggtt tggtgaaacc agaggcccta aataagaaag ctatccagat 7620 tattaacagg gttcgagata agctcactgg tcgggacttc tctcatgatg acactttgga 7680 tgttccaacg caagttgagc tgctcatcaa acaagcgaca tcccatgaaa acctctgcca 7740 gtgctatatt ggctggtgcc ctttctggta actggaggcc cagatgtgcc catcacgttt 7800 tttctgaggc ttttgtactt tagtaaatgc ttccactaaa ctgaaaccat ggtgagaaag 7860 tttgactttg ttaaatattt tgaaatgtaa atgaaaagaa ctactgtata ttaaaagttg 7920 gtttgaacca actttctagc tgctgttgaa gaatatattg tcagaaacac aaggcttgat 7980 ttggttccca ggacagtgaa acatagtaat accacgtaaa tcaagccatt cattttgggg 8040 aacagaagat ccataacttt agaaatacgg gttttgactt aactcacaag agaactcatc 8100 ataagtactt gctgatggaa gaatgaccta gttgctcctc tcaacatggg tacagcaaac 8160 tcagcacagc caagaagcct caggtcgtgg agaacatgga ttaggatcct agactgtaaa 8220 gacacagaag atgctgacct cacccctgcc acctatccca agacctcact ggtctgtgga 8280 cagcagcaga aatgtttgca agataggcca aaatgagtac aaaaggtctg tcttccatca 8340 gacccagtga tgctgcgact cacacgcttc aattcaagac ctgaccgcta gtagggaggt 8400 ttattcagat cgctggcagc ctcggctgag cagatgcaca gaggggatca ctgtgcagtg 8460 ggaccaccct cactggcctt ctgcagcagg gttctgggat gttttcagtg gtcaaaatac 8520 tctgtttaga gcaagggctc agaaaacaga aatactgtca tggaggtgct gaacacaggg 8580 aaggtctggt acatattgga aattatgagc agaacaaata ctcaactaaa tgcacaaagt 8640 ataaagtgta gccatgtcta gacaccatgt tgtatcagaa taatttttgt gccaataaat 8700 gacatcagaa ttttaaacat atgtaaaaaa aaa 8733 <210> 99 <211> 2560 <212> DNA <213> Homo sapiens <400> 99 tgcggggagc cgagccgccg gcgctcgacg cgcgcgctct cgcgagaccc gcgggatcac 60 gtgacgcccg ggcgcggcgc agctcacgtg acaagcgctg ccggccgcgg tgtcttcttc 120 gtgccggcgt cgcagtggcc gggcctcttg cgtctggtaa cgccgctgtc tctaacgcca 180 gcccttggcg cccgcgcccc gccaccgcag cgcccggcag tccgcggccc aaccgccgcc 240 cgcgcccccg ctccccgcac cgtacccggc cgcctcgcgc catggcggcc cccggcagcg 300 cccggcgacc cctgctgctg ctactgctgt tgctgctgct cggcctcatg cattgtgcgt 360 cagcagcaat gtttatggtg aaaaatggca acgggaccgc gtgcataatg gccaacttct 420 ctgctgcctt ctcagtgaac tacgacacca agagtggccc taagaacatg acctttgacc 480 tgccatcaga tgccacagtg gtgctcaacc gcagctcctg tggaaaagag aacacttctg 540 accccagtct cgtgattgct tttggaagag gacatacact cactctcaat ttcacgagaa 600 atgcaacacg ttacagcgtc cagctcatga gttttgttta taacttgtca gacacacacc 660 ttttccccaa tgcgagctcc aaagaaatca agactgtgga atctataact gacatcaggg 720 cagatataga taaaaaatac agatgtgtta gtggcaccca ggtccacatg aacaacgtga 780 ccgtaacgct ccatgatgcc accatccagg cgtacctttc caacagcagc ttcagcaggg 840 gagagacacg ctgtgaacaa gacaggcctt ccccaaccac agcgccccct gcgccaccca 900 gcccctcgcc ctcacccgtg cccaagagcc cctctgtgga caagtacaac gtgagcggca 960 ccaacgggac ctgcctgctg gccagcatgg ggctgcagct gaacctcacc tatgagagga 1020 aggacaacac gacggtgaca aggcttctca acatcaaccc caacaagacc tcggccagcg 1080 ggagctgcgg cgcccacctg gtgactctgg agctgcacag cgagggcacc accgtcctgc 1140 tcttccagtt cgggatgaat gcaagttcta gccggttttt cctacaagga atccagttga 1200 atacaattct tcctgacgcc agagaccctg cctttaaagc tgccaacggc tccctgcgag 1260 cgctgcaggc cacagtcggc aattcctaca agtgcaacgc ggaggagcac gtccgtgtca 1320 cgaaggcgtt ttcagtcaat atattcaaag tgtgggtcca ggctttcaag gtggaaggtg 1380 gccagtttgg ctctgtggag gagtgtctgc tggacgagaa cagcatgctg atccccatcg 1440 ctgtgggtgg tgccctggcg gggctggtcc tcatcgtcct catcgcctac ctcgtcggca 1500 ggaagaggag tcacgcaggc taccagacta tctagcctgg tgcacgcagg cacagcagct 1560 gcaggggcct ctgttccttt ctctgggctt agggtcctgt cgaaggggag gcacactttc 1620 tggcaaacgt ttctcaaatc tgcttcatcc aatgtgaagt tcatcttgca gcatttacta 1680 tgcacaacag agtaactatc gaaatgacgg tgttaatttt gctaactggg ttaaatattt 1740 tgctaactgg ttaaacatta atatttacca aagtaggatt ttgagggtgg gggtgctctc 1800 tctgaggggg tgggggtgcc gctgtctctg aggggtgggg gtgccgctgt ctctgagggg 1860 tgggggtgcc gctctctctg agggggtggg ggtgccgctt tctctgaggg ggtgggggtg 1920 ccgctctctc tgagggggtg ggggtgctgc tctctccgag gggtggaatg ccgctgtctc 1980 tgaggggtgg gggtgccgct ctaaattggc tccatatcat ttgagtttag ggttctggtg 2040 tttggtttct tcattcttta ctgcactcag atttaagcct tacaaaggga aagcctctgg 2100 ccgtcacacg taggacgcat gaaggtcact cgtggtgagg ctgacatgct cacacattac 2160 aacagtagag agggaaaatc ctaagacaga ggaactccag agatgagtgt ctggagcgct 2220 tcagttcagc tttaaaggcc aggacgggcc acacgtggct ggcggcctcg ttccagtggc 2280 ggcacgtcct tgggcgtctc taatgtctgc agctcaaggg ctggcacttt tttaaatata 2340 aaaatgggtg ttatttttat ttttttttgt aaagtgattt ttggtcttct gttgacattc 2400 ggggtgatcc tgttctgcgc tgtgtacaat gtgagatcgg tgcgttctcc tgatgttttg 2460 ccgtggcttg gggattgtac acgggaccag ctcacgtaat gcattgcctg taacaatgta 2520 ataaaaagcc tctttctttt aaaaaaaaaa aaaaaaaaaa 2560 <210> 100 <211> 1030 <212> DNA <213> Homo sapiens <400> 100 accgggcgag ttacctcccg cagccgcagc cgccgtgctc agcgcgagcc ccggagccct 60 tgagcgcgag gcgcggagcc cccggagccc ccaaaccgca gacacatccc cgcgccccag 120 agccccggcc tgcgcgccca gccgggcccg cgcgatgccc tcagaccggc ctttcaagca 180 gcggcggagc ttcgccgacc gctgtaagga ggtacagcag atccgcgacc agcaccccag 240 caaaatcccg gtgatcatcg agcgctacaa gggtgagaag cagctgcccg tcctggacaa 300 gaccaagttt ttggtcccgg accatgtcaa catgagcgag ttggtcaaga tcatccggcg 360 ccgcctgcag ctgaacccca cgcaggcctt cttcctgctg gtgaaccagc acagcatggt 420 gagtgtgtcc acgcccatcg cggacatcta cgagcaggag aaagacgagg acggcttcct 480 ctatatggtc tacgcctccc aggaaacctt cggcttctga gccagcagta ggggggctcg 540 gcctgggagt cggggggccc cggtcaggcc ctgcccagag agctcctggt tcctgaactg 600 agctgcctct accgtggtgg gctgggcagg catgtgcccc cctagtcaga gggcaccaac 660 ccacctactc tgcccctggg tggatcctgg gccggtcgtg ttagggttgt ccctctgggt 720 gctggctggt gggatggggg agggtgggga gcagctccca gcacccctgc tgtgtggttc 780 atcttttttt taggcccctg cctgtctgcc catctgcccc tcacccaccc gaggctctgc 840 ccaccgcctg gacctgccca cccctgaaag actggcccct ggctccccgc ccctcggtct 900 ccacgtggtg tatggatctg tggtcattgt ccctctgcag aataaagatt gctcaggcct 960 gcctggcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1020 aaaaaaaaaa 1030 <210> 101 <211> 5085 <212> DNA <213> Homo sapiens <400> 101 agcgccatgc gcagactcag ttcctggaga aagatggcga cagccgagaa gcagaaacac 60 gacgggcggg tgaagatcgg ccactacatt ctgggtgaca cgctgggggt cggcaccttc 120 ggcaaagtga aggttggcaa acatgaattg actgggcata aagtagctgt gaagatactc 180 aatcgacaga agattcggag ccttgatgtg gtaggaaaaa tccgcagaga aattcagaac 240 ctcaagcttt tcaggcatcc tcatataatt aaactgtacc aggtcatcag tacaccatct 300 gatattttca tggtgatgga atatgtctca ggaggagagc tatttgatta tatctgtaag 360 aatggaaggc tggatgaaaa agaaagtcgg cgtctgttcc aacagatcct ttctggtgtg 420 gattattgtc acaggcatat ggtggtccat agagatttga aacctgaaaa tgtcctgctt 480 gatgcacaca tgaatgcaaa gatagctgat tttggtcttt caaacatgat gtcagatggt 540 gaatttttaa gaacaagttg tggctcaccc aactatgctg caccagaagt aatttcagga 600 agattgtatg caggcccaga ggtagatata tggagcagtg gggttattct ctatgcttta 660 ttatgtggaa cccttccatt tgatgatgac catgtgccaa ctctttttaa gaagatatgt 720 gatgggatct tctatacccc tcaatattta aatccttctg tgattagcct tttgaaacat 780 atgctgcagg tggatcccat gaagagggcc acaatcaaag atatcaggga acatgaatgg 840 tttaaacagg accttccaaa atatctcttt cctgaggatc catcatatag ttcaaccatg 900 attgatgatg aagccttaaa agaagtatgt gaaaagtttg agtgctcaga agaggaagtt 960 ctcagctgtc tttacaacag aaatcaccag gatcctttgg cagttgccta ccatctcata 1020 atagataaca ggagaataat gaatgaagcc aaagatttct atttggcgac aagcccacct 1080 gattcttttc ttgatgatca tcacctgact cggccccatc ctgaaagagt accattcttg 1140 gttgctgaaa caccaagggc acgccatacc cttgatgaat taaatccaca gaaatccaaa 1200 caccaaggtg taaggaaagc aaaatggcat ttaggaatta gaagtcaaag tcgaccaaat 1260 gatattatgg cagaagtatg tagagcaatc aaacaattgg attatgaatg gaaggttgta 1320 aacccatatt atttgcgtgt acgaaggaag aatcctgtga caagcactta ctccaaaatg 1380 agtctacagt tataccaagt ggatagtaga acttatctac tggatttccg tagtattgat 1440 gatgaaatta cagaagccaa atcagggact gctactccac agagatcggg atcagttagc 1500 aactatcgat cttgccaaag gagtgattca gatgctgagg ctcaaggaaa atcctcagaa 1560 gtttctctta cctcatctgt gacctcactt gactcttctc ctgttgacct aactccaaga 1620 cctggaagtc acacaataga attttttgag atgtgtgcaa atctaattaa aattcttgca 1680 caataaacag aaaactttgc ttatttcttt tgcagcaata agcatgcata ataagtcaca 1740 gccaaatgct tccatttgta atcaagttat acataattat aaccgagggc tggcgttttg 1800 gaatgcaatt tgcacaggga ttggaacatg atttatagtt aaaagcctaa tatgcagaaa 1860 tgaattaaga tcattttgtt gttcattgtg cagtatgtat atagcataat atacacagtg 1920 aattataggt ctcaggctta cttgattttt ggctatttta tatttagtgt acacagggct 1980 ttgaaatatt aatttacata aaggccttca tatattatta cgtgttatat attacgtgtt 2040 ataaatttat tcaataaata tttgcctaga attcccaaga cctttatagg tgattttgtt 2100 ttctgggctc cttaacttca taaatagcta gtatcttcca gcagtagtaa cagtctggat 2160 aacttcttcc atatccctcc ctctttgttt ttttgagaca gtgtcacttt gtcacccagg 2220 ctggagtgca atggtgtggt ctcggctcac tgcaacctcc acctcccggg ttcaagtgat 2280 tctcccgcct cagcttcctg agtagctgga actacaggcg tgtgccacca cacccggcta 2340 atttttcgta tttttagtgt agacggggtt tcactatgtt gcccaggctg gtctcgaact 2400 cctgaccgcg tgatccacca cctcagcttc ccaaagtggt gggattacag gcgtgagcca 2460 ccgcacccgg cctccatatc ccccttttaa aattctgtag tgtatggtaa gtcatatcag 2520 atatcagacc taatttaaat ttcattttag ctttacaagt ccaaaaacac agaatttata 2580 tattcagata ctctagcact aattttagtc ttaaaatatt cccacgatat tctgtacaca 2640 aaatgttctt tttgttacaa gagctgagtt gcatatactg tagataaatc atattatttt 2700 tgccaatttc acaaattcct ctggcccatc atgtcagtca ttattgagta tatgcacaca 2760 ttgctactta tttgattatg tatcttttaa attgattcag tgcatagaaa actatctctt 2820 acaaacttta agtgctctga tatgacttcc cccccaaatt ttattatgaa catttttaaa 2880 aacagaaaaa ttgaaaaact gtttggtaag cacatgtata tctaccattt agattcagca 2940 gttgttaatg ttttgtcatt tgttttctct atacctatat atgtatagat acagctagtt 3000 atgcatatat atgcatatat gtgtttgttt gtgtatgtat atatgctttt ttccccctga 3060 accatttgga tgttacagac atacttatca ccgtgaaaat acttcaagta tctcctacag 3120 ataatgacat tctcctaaaa atccgtaata ccattgtaaa agtaataatt ccccaatatc 3180 atctaatcaa gccatattta aatttctgaa gttaactcca aatttcttta tagctgatta 3240 tttcaaacta ggatccaatt aaagtttaca tatgacactt ggttataact ctttagttgg 3300 atataacatt attattattt tgataaaata tggaacaaat caattctatt aataagtggt 3360 cacatttgtt ttgggcttaa attacttttt aaagatactg gattttccta agatttctga 3420 tttacactga tatttttttt tgtcattctt aattgcatca cacaatagat gtaaatgaag 3480 atgtagtcac ctcagataaa attggtatcg tgtatgataa tattgtatca tttatatttg 3540 ccttatgtta actttaagaa attgattttt ttgtattaat cattttccca ttgcaacaga 3600 gctatatttt ttctatttta agaatcatat tttaggatta tttttggcaa atacagtgag 3660 cacttatgta accagatgat aatgaactca aatgtcatga tagcttgcat aaatggtgac 3720 tctagtagat ttgactcaag cacttctaga atcatgcact gaattcaaaa gaaaaatctt 3780 gctgcttttt gtccagggct tgttctattc aacttctaat ttgaaagctg tacaaagtaa 3840 tagaagttcc atttaaatat gagttcaaaa ctgtatttac tttttatgtg gccctctctt 3900 taggggattc taattttact tagggtctct aagtgcagca taatgttcct gatgttaaca 3960 gaagactgta tttttaaagt tacaaatttg tatatggaat taagtaatgg cgctatatac 4020 gctgttgtgg ggagggggga agaaaaggag gaaccaatta aataggacct tttaaaaatt 4080 gttaattttg taaactttgc ttctcttata agttattgtg attcatttta gttactgtgt 4140 tttattttga aaatatttaa atattgcact tctataaata gtatgataaa tgcacagaca 4200 attgcagtaa attctttttt aagctaggat atttgaaatg acaacctttg gttaagtgtg 4260 tcaaggttgc aacagaattt tcacaatttt tttgttgttt gcaaattgtt actaatattg 4320 aagaggtaag ggaggcaatg caaatgattt ttaatctttt tttattatct tttcagcagt 4380 ttatattttt tgtgacttta tgcaaccata tttttacttt gtcttgacaa ctgaaagatg 4440 tataaggttt tttgccagaa atgtactgta tacatagttt taagtataac agattttact 4500 gatatgtaaa aattttgcca ttaaaataaa tgatttctca ctgagaggaa cttttctacc 4560 aggttggggc atatgggagc ttaatatatc atatctaatt taaaataatt tcactgaaat 4620 aaactccatt gcttttacct aatttttttc ttgagatgct tttgtagttt ttcagagttt 4680 tagatgattt tatacaaaat cctctgccta gcactgctct ttttgatgtt gtagtgacac 4740 catttacatt gaattaatgc ttggtagcct ggggctagat gtggaactcc atggatctgt 4800 gttctgactg gcacctttgg aatgaaagaa aagtgtgtgc tgtccaaatt ttttcccctt 4860 aattctttcc ctcatcttct cacccataat agaaatttta tttccattgt gagttctgac 4920 aagaatgaaa ttccacatac aacataactg taaattgttg gtaggtagaa gttaatattt 4980 gtggttcatg tatattttga ccagagtata tttaagtata taatttcagc ttccttgatt 5040 tagaaatatg atataataaa gaaaaactcc atttatcatc tgtta 5085 <210> 102 <211> 5572 <212> DNA <213> Homo sapiens <400> 102 cctcccctcg cccggcgcgg tcccgtccgc ctctcgctcg cctcccgcct cccctcggtc 60 ttccgaggcg cccgggctcc cggcgcggcg gcggaggggg cgggcaggcc ggcgggcggt 120 gatgtggcgg gactctttat gcgctgcggc aggatacgcg ctcggcgctg ggacgcgact 180 gcgctcagtt ctctcctctc ggaagctgca gccatgatgg aagtttgaga gttgagccgc 240 tgtgaggcga ggccgggctc aggcgaggga gatgagagac ggcggcggcc gcggcccgga 300 gcccctctca gcgcctgtga gcagccgcgg gggcagcgcc ctcggggagc cggccggcct 360 gcggcggcgg cagcggcggc gtttctcgcc tcctcttcgt cttttctaac cgtgcagcct 420 cttcctcggc ttctcctgaa agggaaggtg gaagccgtgg gctcgggcgg gagccggctg 480 aggcgcggcg gcggcggcgg cacctcccgc tcctggagcg ggggggagaa gcggcggcgg 540 cggcggccgc ggcggctgca gctccaggga gggggtctga gtcgcctgtc accatttcca 600 gggctgggaa cgccggagag ttggtctctc cccttctact gcctccaaca cggcggcggc 660 ggcggcggca catccaggga cccgggccgg ttttaaacct cccgtccgcc gccgccgcac 720 cccccgtggc ccgggctccg gaggccgccg gcggaggcag ccgttcggag gattattcgt 780 cttctcccca ttccgctgcc gccgctgcca ggcctctggc tgctgaggag aagcaggccc 840 agtcgctgca accatccagc agccgccgca gcagccatta cccggctgcg gtccagagcc 900 aagcggcggc agagcgaggg gcatcagcta ccgccaagtc cagagccatt tccatcctgc 960 agaagaagcc ccgccaccag cagcttctgc catctctctc ctcctttttc ttcagccaca 1020 ggctcccaga catgacagcc atcatcaaag agatcgttag cagaaacaaa aggagatatc 1080 aagaggatgg attcgactta gacttgacct atatttatcc aaacattatt gctatgggat 1140 ttcctgcaga aagacttgaa ggcgtataca ggaacaatat tgatgatgta gtaaggtttt 1200 tggattcaaa gcataaaaac cattacaaga tatacaatct ttgtgctgaa agacattatg 1260 acaccgccaa atttaattgc agagttgcac aatatccttt tgaagaccat aacccaccac 1320 agctagaact tatcaaaccc ttttgtgaag atcttgacca atggctaagt gaagatgaca 1380 atcatgttgc agcaattcac tgtaaagctg gaaagggacg aactggtgta atgatatgtg 1440 catatttatt acatcggggc aaatttttaa aggcacaaga ggccctagat ttctatgggg 1500 aagtaaggac cagagacaaa aagggagtaa ctattcccag tcagaggcgc tatgtgtatt 1560 attatagcta cctgttaaag aatcatctgg attatagacc agtggcactg ttgtttcaca 1620 agatgatgtt tgaaactatt ccaatgttca gtggcggaac ttgcaatcct cagtttgtgg 1680 tctgccagct aaaggtgaag atatattcct ccaattcagg acccacacga cgggaagaca 1740 agttcatgta ctttgagttc cctcagccgt tacctgtgtg tggtgatatc aaagtagagt 1800 tcttccacaa acagaacaag atgctaaaaa aggacaaaat gtttcacttt tgggtaaata 1860 cattcttcat accaggacca gaggaaacct cagaaaaagt agaaaatgga agtctatgtg 1920 atcaagaaat cgatagcatt tgcagtatag agcgtgcaga taatgacaag gaatatctag 1980 tacttacttt aacaaaaaat gatcttgaca aagcaaataa agacaaagcc aaccgatact 2040 tttctccaaa ttttaaggtg aagctgtact tcacaaaaac agtagaggag ccgtcaaatc 2100 cagaggctag cagttcaact tctgtaacac cagatgttag tgacaatgaa cctgatcatt 2160 atagatattc tgacaccact gactctgatc cagagaatga accttttgat gaagatcagc 2220 atacacaaat tacaaaagtc tgaatttttt tttatcaaga gggataaaac accatgaaaa 2280 taaacttgaa taaactgaaa atggaccttt ttttttttaa tggcaatagg acattgtgtc 2340 agattaccag ttataggaac aattctcttt tcctgaccaa tcttgtttta ccctatacat 2400 ccacagggtt ttgacacttg ttgtccagtt gaaaaaaggt tgtgtagctg tgtcatgtat 2460 ataccttttt gtgtcaaaag gacatttaaa attcaattag gattaataaa gatggcactt 2520 tcccgtttta ttccagtttt ataaaaagtg gagacagact gatgtgtata cgtaggaatt 2580 ttttcctttt gtgttctgtc accaactgaa gtggctaaag agctttgtga tatactggtt 2640 cacatcctac ccctttgcac ttgtggcaac agataagttt gcagttggct aagagaggtt 2700 tccgaagggt tttgctacat tctaatgcat gtattcgggt taggggaatg gagggaatgc 2760 tcagaaagga aataatttta tgctggactc tggaccatat accatctcca gctatttaca 2820 cacacctttc tttagcatgc tacagttatt aatctggaca ttcgaggaat tggccgctgt 2880 cactgcttgt tgtttgcgca ttttttttta aagcatattg gtgctagaaa aggcagctaa 2940 aggaagtgaa tctgtattgg ggtacaggaa tgaaccttct gcaacatctt aagatccaca 3000 aatgaaggga tataaaaata atgtcatagg taagaaacac agcaacaatg acttaaccat 3060 ataaatgtgg aggctatcaa caaagaatgg gcttgaaaca ttataaaaat tgacaatgat 3120 ttattaaata tgttttctca attgtaacga cttctccatc tcctgtgtaa tcaaggccag 3180 tgctaaaatt cagatgctgt tagtacctac atcagtcaac aacttacact tattttacta 3240 gttttcaatc ataatacctg ctgtggatgc ttcatgtgct gcctgcaagc ttcttttttc 3300 tcattaaata taaaatattt tgtaatgctg cacagaaatt ttcaatttga gattctacag 3360 taagcgtttt ttttctttga agatttatga tgcacttatt caatagctgt cagccgttcc 3420 acccttttga ccttacacat tctattacaa tgaattttgc agttttgcac attttttaaa 3480 tgtcattaac tgttagggaa ttttacttga atactgaata catataatgt ttatattaaa 3540 aaggacattt gtgttaaaaa ggaaattaga gttgcagtaa actttcaatg ctgcacacaa 3600 aaaaaagaca tttgattttt cagtagaaat tgtcctacat gtgctttatt gatttgctat 3660 tgaaagaata gggttttttt tttttttttt tttttttttt ttaaatgtgc agtgttgaat 3720 catttcttca tagtgctccc ccgagttggg actagggctt caatttcact tcttaaaaaa 3780 aatcatcata tatttgatat gcccagactg catacgattt taagcggagt acaactacta 3840 ttgtaaagct aatgtgaaga tattattaaa aaggtttttt tttccagaaa tttggtgtct 3900 tcaaattata ccttcacctt gacatttgaa tatccagcca ttttgtttct taatggtata 3960 aaattccatt ttcaataact tattggtgct gaaattgttc actagctgtg gtctgaccta 4020 gttaatttac aaatacagat tgaataggac ctactagagc agcatttata gagtttgatg 4080 gcaaatagat taggcagaac ttcatctaaa atattcttag taaataatgt tgacacgttt 4140 tccatacctt gtcagtttca ttcaacaatt tttaaatttt taacaaagct cttaggattt 4200 acacatttat atttaaacat tgatatatag agtattgatt gattgctcat aagttaaatt 4260 ggtaaagtta gagacaacta ttctaacacc tcaccattga aatttatatg ccaccttgtc 4320 tttcataaaa gctgaaaatt gttacctaaa atgaaaatca acttcatgtt ttgaagatag 4380 ttataaatat tgttctttgt tacaatttcg ggcaccgcat attaaaacgt aactttattg 4440 ttccaatatg taacatggag ggccaggtca taaataatga cattataatg ggcttttgca 4500 ctgttattat ttttcctttg gaatgtgaag gtctgaatga gggttttgat tttgaatgtt 4560 tcaatgtttt tgagaagcct tgcttacatt ttatggtgta gtcattggaa atggaaaaat 4620 ggcattatat atattatata tataaatata tattatacat actctcctta ctttatttca 4680 gttaccatcc ccatagaatt tgacaagaat tgctatgact gaaaggtttt cgagtcctaa 4740 ttaaaacttt atttatggca gtattcataa ttagcctgaa atgcattctg taggtaatct 4800 ctgagtttct ggaatatttt cttagacttt ttggatgtgc agcagcttac atgtctgaag 4860 ttacttgaag gcatcacttt taagaaagct tacagttggg ccctgtacca tcccaagtcc 4920 tttgtagctc ctcttgaaca tgtttgccat acttttaaaa gggtagttga ataaatagca 4980 tcaccattct ttgctgtggc acaggttata aacttaagtg gagtttaccg gcagcatcaa 5040 atgtttcagc tttaaaaaat aaaagtaggg tacaagttta atgtttagtt ctagaaattt 5100 tgtgcaatat gttcataacg atggctgtgg ttgccacaaa gtgcctcgtt tacctttaaa 5160 tactgttaat gtgtcatgca tgcagatgga aggggtggaa ctgtgcacta aagtgggggc 5220 tttaactgta gtatttggca gagttgcctt ctacctgcca gttcaaaagt tcaacctgtt 5280 ttcatataga atatatatac taaaaaattt cagtctgtta aacagcctta ctctgattca 5340 gcctcttcag atactcttgt gctgtgcagc agtggctctg tgtgtaaatg ctatgcactg 5400 aggatacaca aaaataccaa tatgatgtgt acaggataat gcctcatccc aatcagatgt 5460 ccatttgtta ttgtgtttgt taacaaccct ttatctctta gtgttataaa ctccacttaa 5520 aactgattaa agtctcattc ttgtcaaaaa aaaaaaaaaa aaaaaaaaaa aa 5572 <210> 103 <211> 5239 <212> DNA <213> Homo sapiens <400> 103 ggatccggat tcggattagc agcccgggaa gagtgccgtg gcacaggcgc cggagggagc 60 gcgaccctcg gaccccgcct ggcccgcggg gctgggaccc ggccccggcc tgcccgatgg 120 ggcgcgcggc cccggagatg cgccctcgcc cggccccgcg cccccggccc cgcgcccccg 180 gcccgcccgc cccggcccgc gcctccgcct gagtcccccg cgccttggcc cgccaccccc 240 cgccccgcgc ccccggcccg cctgcgccat ggagcccggc cgcggcggca cagagaccgt 300 gggcaagttc gagttctccc gcaaggacct gatcggccac ggcgccttcg cggtggtctt 360 caagggccgc caccgcgaga agcacgattt ggaggtcgcc gtcaagtgca ttaacaagaa 420 gaacctcgcc aagtctcaga cgctgctggg gaaggaaatc aaaatcctga aggaactgaa 480 acatgaaaac atcgtggccc tgtacgactt ccaggaaatg gctaattctg tctacctggt 540 tatggagtac tgcaacggtg gggacctggc cgactacctg cacgccatgc gcacgctgag 600 cgaggacacc atcaggctct tcctgcagca gatcgcgggc gccatgcggc ttctgcacag 660 caaaggcatc atccaccgcg acctgaaacc gcagaacatc ctgctgtcca accccgccgg 720 ccgccgcgcc aaccccaaca gcatccgcgt caagatcgct gacttcggct tcgcgcggta 780 cctccagagc aacatgatgg cggccacact ctgcggctcc cccatgtaca tggcccccga 840 ggtcatcatg tcccagcact acgacgggaa ggcggacctg tggagcatcg gcaccatcgt 900 ctaccagtgc ctgacgggga aggcgccctt ccaggccagc agcccccagg acctgcgcct 960 gttctacgag aagaacaaga cgttggtccc caccatcccc cgggagacct cggccccgct 1020 gcggcagctg ctcctggccc tactgcaacg caaccacaag gaccgcatgg acttcgatga 1080 gttttttcat caccctttcc tcgatgccag cccctcggtc aggaaatccc cacccgtgcc 1140 tgtgccctcg tacccaagct cggggtccgg cagcagctcc agcagcagct ccacctccca 1200 cctggcctcc ccgccgtccc tgggcgagat gcagcagctg cagaagaccc tggcctcccc 1260 ggctgacacc gctggcttcc tgcacagctc ccgggactct ggtggcagca aggactcttc 1320 ctgtgacaca gacgacttcg tcatggtccc cgcgcagttt ccaggtgacc tggtggctga 1380 ggcgcccagt gccaaacccc cgccagacag cctgatgtgc agtgggagct cactggtggc 1440 ctctgcgggc ttggagagcc acggccggac cccatctcca tccccaccct gcagcagctc 1500 ccccagtccc tcaggccggg ctggcccgtt ctccagcagc aggtgcggcg cctctgtccc 1560 catcccagtc cccacgcagg tgcagaacta ccagcgcatt gagcgaaacc tgcagtcacc 1620 cacccagttc caaacacctc ggtcctctgc catccgcagg tcaggcagca ccagccccct 1680 gggctttgca agggccagcc cctcgccccc tgcccacgct gagcatggag gcgtcctggc 1740 caggaagatg tctctgggtg gaggccggcc ctacacgcca tctcctcaag ttggaaccat 1800 ccctgagcgg ccaggctgga gcgggacgcc ctccccacag ggagctgaga tgcggggtgg 1860 caggtcccct cgtccaggct cctctgcacc cgagcactct ccccgcactt ccgggctggg 1920 ctgccgcctg cacagcgccc ccaacctgtc tgacttgcac gtcgtccgcc ccaagctgcc 1980 caaacccccc acggaccccc tgggagctgt gttcagccca ccacaggcca gccctcccca 2040 gccgtcccac ggcctgcagt cctgccggaa cctgcggggc tcacccaagc tgcccgactt 2100 cctgcagcga aaccccctgc cccccatcct gggctccccc accaaggctg tgccctcctt 2160 tgacttcccg aagaccccca gctcccagaa cctgctggcc ctcctagccc ggcagggcgt 2220 ggtgatgacg ccccctcgaa accggacgct gcccgacctc tcggaggtgg gacccttcca 2280 tggtcagccg ttgggccctg gcctgcggcc aggcgaggac cccaagggcc cctttggccg 2340 gtctttcagc accagccgcc tcactgacct gctccttaag gcggcgtttg ggacacaagc 2400 cccggacccg ggcagcacgg agagcctgca ggagaagccc atggagatcg caccctcagc 2460 tggctttgga gggagcctgc acccaggagc ccgtgctggg ggcaccagca gcccttcccc 2520 ggtggtcttc accgtgggct ctcccccgag cgggagcacg cccccccagg gcccccgcac 2580 caggatgttc tcagcgggcc ccactggctc tgccagctct tctgcccgcc acctggtgcc 2640 tgggccctgc agcgaggccc cagcccctga gctccctgct ccaggacacg gctgcagctt 2700 tgccgacccc attgctgcga acctggaggg ggctgtgacc ttcgaggccc ccgacctccc 2760 tgaggagacc ctcatggagc aagagcacac ggagatcctg cgtggcctgc gcttcacgct 2820 gctgttcgtg cagcacgtcc tggagatcgc agccctgaag ggcagcgcca gtgaggcggc 2880 ggggggccct gagtaccagc tgcaggagag tgtggtggcc gaccagatca gcctgctgag 2940 ccgagaatgg ggcttcgcgg aacagctggt gctgtacctg aaggtggccg agctactgtc 3000 ctccggcctg caaagtgcca tcgaccagat ccgggccggc aagctctgcc tgtcgtccac 3060 tgtgaagcag gtggtgcgca ggctgaatga gctgtacaag gccagcgtgg tgtcctgcca 3120 gggcctgagc ctgcggctgc agcgcttctt cctggacaag cagcggctcc tggaccgcat 3180 tcacagcatc actgccgaga ggctcatctt cagccacgct gtgcagatgg tgcagtcggc 3240 tgccctggac gagatgttcc agcaccgtga gggctgcgtc ccacgctacc acaaggccct 3300 gctgctcctg gaggggctgc agcacatgct ctcggaccag gccgacatcg agaacgtcac 3360 caagtgcaag ctgtgcattg agcggagact ctcggcgctg ctgactggca tctgtgcctg 3420 acctttctgg cctggctggg ccccccgtcc tgccgagccc tgcagagtgg gctctgtgtg 3480 ctggctggac tcctcgggac aagcccatgg cgctgatcgc tggtgctgag ccctgccctg 3540 ggccccacgg acagtcagcc tgccggcctc cctgcagctc acggggcaga accagcacat 3600 ctggagccac acagcttggg gggtgtctcc catcttttac aggtggggat cacagaattt 3660 ctgcccctcc agctgcctgg ctcagcaggc gtgggtgcca ccaccctcta gccccagggc 3720 agccccggag gacaggcaag ggcctgagac cactgccgac tcaaagccaa agcgagctcc 3780 tgcttagggc aggtcagcag gcactgtgcc caggaagagc ctgcggcctc ggcgtccccc 3840 agtctccagg agcctctccc tccgagatac ccacccagct ttgtcaatca cccaagcact 3900 ttatgcatat agagacagaa cctggacctc accagggact gctgggcagc gattcctggc 3960 agtggcctgg tgtttgtaca tacacatatg cagacacatg ccagggcccc ccaagcccga 4020 gcaccggacc acgttgctgc ccaggtctgg acctcagcgg gagaactggc tccgggggga 4080 gtggggccct gcgctagagg cagaggcagt tctttgttca agcgttcctc tggggaccgg 4140 cagcagaggc accgtgttct ctcagccctg gatacgtctt gtaatctttc acactttatt 4200 cctaaaacgt gtcttatttt tatgcagctc attttttctt taaaggagaa aacttgtagg 4260 tgtttaagaa ttggttttgg gagggcgagg actgggccag gttagaggca gatggcacag 4320 gggcgtgtgg cgggcgggtg aggctgcttt gcacacctgt gttggtggct gtcccctgcc 4380 gcccctccct gtggcagcag caggacaggt gtgtgcccag caccctccct acctgggcct 4440 ggaagcagat gaggggaata cttcatgcaa agaaaaaagt aacatgtgca aaagctcccc 4500 gtccagcttt gacagtcagt tttgatgtca gctcctcggc agggtaggcc tgatgacagc 4560 cctgtccctc cctgcctctg ccttgcccaa ggccacggag ggcatctgca gagaggcctg 4620 ccttccggat tccaggcggg catgccctgc aaaccccgcc tgggcctccc ttggtctgcc 4680 cagccctcgg ttagccctgc ctgaatcagt agatacttga acgagtcccc agtctgcggg 4740 aggcagtggt ggggccatgg acccatgcgg ggggttccag ggtcacacgc cacataacag 4800 acaaaaatac acacacgtgt gtttttcttt gcaatacttg aaatattgcc actgtgcttg 4860 gacttagaag aagaaaatcc ccgtgacttc ttcctcatca ccttgatggc tttattctca 4920 ccttgtgggg catgtttgta tttattgctt catggccgac tggaatcctg agtcctggga 4980 agctggcact gcggggatct tgcccggtgt cctggtcctc ttgcttccgt cgcggccgca 5040 tgtgcgtgtg tccaagcagg tcctgggcgc ctcaactgct gcccctggtt gaatgttctc 5100 ttgatagtgc tggacccttt gtctatttta aagcgaattt tgtgtgattt cctgcccttt 5160 gcgttatatt gtataatacc aacgtaagga aataaacctt tggaattgtt gggctggtgt 5220 caaaaaaaaa aaaaaaaaa 5239 <210> 104 <211> 8413 <212> DNA <213> Homo sapiens <400> 104 tttccagatt ggggctcggg ccgcgcctcc tccgggaccc tccccttgga ccgagccgat 60 cgccgcgggg cagttcgggc cggctgtcct ggcgcgaaaa ggtggacaag tcctattttc 120 aagagaagat gacttttaac agttttgaag gatctaaaac ttgtgtacct gcagacatca 180 ataaggaaga agaatttgta gaagagttta atagattaaa aacttttgct aattttccaa 240 gtggtagtcc tgtttcagca tcaacactgg cacgagcagg gtttctttat actggtgaag 300 gagataccgt gcggtgcttt agttgtcatg cagctgtaga tagatggcaa tatggagact 360 cagcagttgg aagacacagg aaagtatccc caaattgcag atttatcaac ggcttttatc 420 ttgaaaatag tgccacgcag tctacaaatt ctggtatcca gaatggtcag tacaaagttg 480 aaaactatct gggaagcaga gatcattttg ccttagacag gccatctgag acacatgcag 540 actatctttt gagaactggg caggttgtag atatatcaga caccatatac ccgaggaacc 600 ctgccatgta tagtgaagaa gctagattaa agtcctttca gaactggcca gactatgctc 660 acctaacccc aagagagtta gcaagtgctg gactctacta cacaggtatt ggtgaccaag 720 tgcagtgctt ttgttgtggt ggaaaactga aaaattggga accttgtgat cgtgcctggt 780 cagaacacag gcgacacttt cctaattgct tctttgtttt gggccggaat cttaatattc 840 gaagtgaatc tgatgctgtg agttctgata ggaatttccc aaattcaaca aatcttccaa 900 gaaatccatc catggcagat tatgaagcac ggatctttac ttttgggaca tggatatact 960 cagttaacaa ggagcagctt gcaagagctg gattttatgc tttaggtgaa ggtgataaag 1020 taaagtgctt tcactgtgga ggagggctaa ctgattggaa gcccagtgaa gacccttggg 1080 aacaacatgc taaatggtat ccagggtgca aatatctgtt agaacagaag ggacaagaat 1140 atataaacaa tattcattta actcattcac ttgaggagtg tctggtaaga actactgaga 1200 aaacaccatc actaactaga agaattgatg ataccatctt ccaaaatcct atggtacaag 1260 aagctatacg aatggggttc agtttcaagg acattaagaa aataatggag gaaaaaattc 1320 agatatctgg gagcaactat aaatcacttg aggttctggt tgcagatcta gtgaatgctc 1380 agaaagacag tatgcaagat gagtcaagtc agacttcatt acagaaagag attagtactg 1440 aagagcagct aaggcgcctg caagaggaga agctttgcaa aatctgtatg gatagaaata 1500 ttgctatcgt ttttgttcct tgtggacatc tagtcacttg taaacaatgt gctgaagcag 1560 ttgacaagtg tcccatgtgc tacacagtca ttactttcaa gcaaaaaatt tttatgtctt 1620 aatctaactc tatagtaggc atgttatgtt gttcttatta ccctgattga atgtgtgatg 1680 tgaactgact ttaagtaatc aggattgaat tccattagca tttgctacca agtaggaaaa 1740 aaaatgtaca tggcagtgtt ttagttggca atataatctt tgaatttctt gatttttcag 1800 ggtattagct gtattatcca ttttttttac tgttatttaa ttgaaaccat agactaagaa 1860 taagaagcat catactataa ctgaacacaa tgtgtattca tagtatactg atttaatttc 1920 taagtgtaag tgaattaatc atctggattt tttattcttt tcagataggc ttaacaaatg 1980 gagctttctg tatataaatg tggagattag agttaatctc cccaatcaca taatttgttt 2040 tgtgtgaaaa aggaataaat tgttccatgc tggtggaaag atagagattg tttttagagg 2100 ttggttgttg tgttttagga ttctgtccat tttcttttaa agttataaac acgtacttgt 2160 gcgaattatt tttttaaagt gatttgccat ttttgaaagc gtatttaatg atagaatact 2220 atcgagccaa catgtactga catggaaaga tgtcaaagat atgttaagtg taaaatgcaa 2280 gtggcaaaac actatgtata gtctgagcca gatcaaagta tgtatgtttt taatatgcat 2340 agaacaaaag atttggaaag atatacacca aactgttaaa tgtggtttct cttcggggag 2400 ggggggattg ggggaggggc cccagagggg ttttataggg gccttttcac tttctacttt 2460 tttcattttg ttctgttcga attttttata agtatgtatt acttttgtaa tcagaatttt 2520 tagaaagtat tttgctgatt taaaggctta ggcatgttca aacgcctgca aaactactta 2580 tcactcagct ttagtttttc taatccaaga aggcagggca gttaaccttt ttggtgccaa 2640 tgtgaaatgt aaatgatttt atgtttttcc tgctttgtgg atgaaaaata tttctgagtg 2700 gtagtttttt gacaggtaga ccatgtctta tcttgtttca aaataagtat ttctgatttt 2760 gtaaaatgaa atataaaata tgtctcagat cttccaatta attagtaagg attcatcctt 2820 aatccttgct agtttaagcc tgcctaagtc actttactaa aagatctttg ttaactcagt 2880 attttaaaca tctgtcagct tatgtaggta aaagtagaag catgtttgta cactgcttgt 2940 agttatagtg acagctttcc atgttgagat tctcatatca tcttgtatct taaagtttca 3000 tgtgagtttt taccgttagg atgattaaga tgtatatagg acaaaatgtt aagtctttcc 3060 tctacctaca tttgttttct tggctagtaa tagtagtaga tacttctgaa ataaatgttc 3120 tctcaagatc cttaaaacct cttggaaatt ataaaaatat tggcaagaaa agaagaatag 3180 ttgtttaaat attttttaaa aaacacttga ataagaatca gtagggtata aactagaagt 3240 ttaaaaatgc ttcatagaac gtccagggtt tacattacaa gattctcaca acaaacctat 3300 tgtagaggtg agtaaggcat gttactacag aggaaagttt gagagtaaaa ctgtaaaaaa 3360 ttatattttt gttgtacttt ctaagagaaa gagtattgtt atgttctcct aacttctgtt 3420 gattactact ttaagtgata ttcatttaaa acattgcaaa tttattttat ttatttaatt 3480 ttctttttga gatggagtct tgcttgtcac ccaggctgga gtgcagtgga gtgatctctg 3540 ctcactgcaa cctccgcctt ctgggttcaa gcgattctcg tgcctcagct tcctgagtag 3600 ctggaattac aggcaggtgc caccatgccc gactaatttt tttttatttt tagtagagac 3660 ggggtttcac catgttggcc aggctggtat caaactcctg acctcaagag atccactcgc 3720 cttgccctcc caaagtgctg ggattacagg cttgagccac cacgcccggc taaaacattg 3780 caaatttaaa tgagagtttt aaaaattaaa taatgactgc cctgtttctg ttttagtatg 3840 taaatcctca gttcttcacc tttgcactgt ctgccactta gtttggttat atagtcatta 3900 acttgaattt ggtctgtata gtctagactt taaatttaaa gttttctaca aggggagaaa 3960 agtgttaaaa tttttaaaat atgttttcca ggacacttca cttccaagtc aggtaggtag 4020 ttcaatctag ttgttagcca aggactcaag gactgaattg ttttaacata aggcttttcc 4080 tgttctggga gccgcacttc attaaaattc ttctaaaact tgtatgttta gagttaagca 4140 agactttttt tcttcctctc catgagttgt gaaatttaat gcacaacgct gatgtggcta 4200 acaagtttat tttaagaatt gtttagaaat gctgttgctt caggttctta aaatcactca 4260 gcactccaac ttctaatcaa atttttggag acttaacagc atttgtctgt gtttgaacta 4320 taaaaagcac cggatctttt ccatctaatt ccgcaaaaat tgatcatttg caaagtcaaa 4380 actatagcca tatccaaatc ttttccccct cccaagagtt ctcagtgtct acatgtagac 4440 tattcctttt ctgtataaag ttcactctag gatttcaagt caccacttat tttacatttt 4500 agtcatgcaa agattcaagt agttttgcaa taagtactta tctttatttg taataattta 4560 gtctgctgat caaaagcatt gtcttaattt ttgagaactg gttttagcat ttacaaacta 4620 aattccagtt aattaattaa tagctttata ttgcctttcc tgctacattt ggttttttcc 4680 cctgtccctt tgattacggg ctaaggtagg gtagagtggg tgtagtgagt gtatataatg 4740 tgatttggcc ctgtgtatta tgatattttg ttatttttgt tgttatatta tttacatttc 4800 agtagttgtt ttttgtgttt ccattttagt ggataaaatt tgtattttga actatgaatg 4860 gagactaccg ccccagcatt agtttcacat gatataccct ttaaacccga atcattgttt 4920 tatttcctga ttacacaggt gttgaatggg gaaaggggct agtatatcag taggatatac 4980 tatgggatgt atatatatca ttgctgttag agaaatgaaa taaaatgggg ctgggctcag 5040 tggctcacgc ctgtaatccc agcactttgg gaggctgagg caggtggatc acgaggtcag 5100 gagatcgaga ccatcctggc taacacggtg aaaccccgtc tctactaaaa aacagaaaat 5160 tagccgggcg tggtggcggg cgcctgtagt cccagctact cgggaggctg aggcaggaga 5220 atggtgtgaa cccgggaggc agagcttgca gtgagccgag atctcgccac tgcactccag 5280 cctgggcaac agagcaagac tctgtctcaa aaaaaaaaaa aaaagaaata agaaaatggg 5340 aagcaatatt tgacatagtt ctttttagtc aaatctactt gttaaaaaaa gggtagcagt 5400 ttattcatct gtgaaaggaa aataatactt atcttacaag gttgcaagag ctcaaggaga 5460 ccatgtatgt aaagttcctg ctgtaaatat gaactcccat cctaataccc ttttacctct 5520 ctgtgggttt gtcttgacct ggaaatttgg gctaaaactt agaaaaaatt cttacatgat 5580 aactcagtga tgcttactca tagtttttgg tgtttctcat agataagata taaatcagct 5640 gggcgcggtg gctcatgcct gtaatcccag cactttggga ggccgaggcg ggcagatcac 5700 ctgaggtcgg gaggtcgaga ccagcctgac caacatggag aaaccccgtc tctactaaaa 5760 atacaaaatt agctgggcgt ggtggctcat gcctgtaatc ccagctactt gggaggctga 5820 ggcaggagaa tcgcttgaac ccaggaggcg gaggttgtgg tgagcgaaga tcgtgccatt 5880 gcactccagc ctgggcaaca agagcaaaac tctgtctcaa aaaaaaaaaa agatataaat 5940 cacaataaat aaataggtca atacaaatgt tagccaggcg tggtggcaca tgcccatagt 6000 cgcagctact ctggaggcag aggcaggagg atcacttgag cccatgaatt tgaggcagca 6060 gtgagctatg attgtgccac tgtactccag tctgggtgac agagtgagac cccatctcta 6120 aataaatagg tcaaaccctt aaaaatattt aaattcttaa aaaattgaaa agattattct 6180 tctcaaattt agttgagctt tctaagagaa gcaattggct ttttcccact tcaataatca 6240 ttttcagttt gactcataca gttaacacaa tgtgaatttc ttcctcagca taacagagtt 6300 atagaatgac agggctggaa gtgaccttag agagtatcca gttctttcat tttacaggtg 6360 aggcaactga gactcaaagg tgatgtaatt tgtgcaaaga ttatagctaa ttagtagcag 6420 agccctgact gggacatagt ttgaaggtga aaaacttcac caagctacct ttcttgaaag 6480 gtccaaatgt ttatgttttc aactactctt tccactgtac cataactttc actacatatt 6540 aaatgacact ttataactaa tataatagga caatcatcaa tgcatatata gccagccctt 6600 catatctgtg ggttttgcat ccatggattc aaccaaggag gaattgaaaa cactgagaaa 6660 aaaaaaaaag accacacaat aaaaaaaaaa aatacaaaat aatacaaaga aaaagccaaa 6720 attgtcatac tgttgttaag caacagtata acaactattt acatagcatt aaggttggtg 6780 caaaaatgca aaaaaaaaaa aagcaattat ttttaaacca acctaatata ttgtattagg 6840 tattaaagtc atctggacat gaattaaagt atatgatgcc agcctggaca aaaggcaaaa 6900 ccctgtctct acaaaaaata caaaaattag ctgggcatgg tggtgtgtgc ctgtagtcct 6960 ggctactccg gagcctgagg tgggaggatc gcttgagtct gggaggcaga ggctgcattg 7020 agctatgatc atggcactgc attccagcct gggtgacagt gcaagacctt gtctcagaat 7080 aaataaagta tgtgatgaag atgtgcatac attatatgca aatactgttt tttttttttt 7140 taatttaaac agtctcactg tgttgcccag gatggagtgc aatggcacaa tcttggctca 7200 tggcaaactc tgcctcgcaa gcagctggga ctacaggcat gctccacggt gcccagttaa 7260 ttttttttgt attcttagta gagacagggt ttcaccatgt tggccaggct agtcttgaat 7320 ttctgacctc aagtgattca tctcccaaag tgctgggatt acaggcgtga gccaccacgg 7380 ccggctaatt tttgtatttt ttagtagtga ctggtttcgc ggtgttgacc aggctggtct 7440 cgaactcctg atctcaggtg atctgcctgc ctcggcctca caaagtgctg ggattacagg 7500 tgtgaaccac tgctcccggc cttgtgtgat tttatctaag ggacttaagc gtcctcaggt 7560 cctagggggt cgtgaaacca aaaccccagg gatagcaagg gacaattgta tcttcaaagt 7620 agacaaatgg cgccgggcac ggtggctcac gcctgtaatc ccagcagttt ccgaggctga 7680 ggcaggcggc tcacctgagg tcaggagttg gagaccagcc tggccaacat gctgaaaccc 7740 tgtctgtaca aaaatacaaa aatagctggg catggtggcg catgcctgta gtcccagcta 7800 ctagagcgac tgaggcagga gaattgcttg aacctgggag gcggaggttg cagggagcca 7860 agatggcgcc accgcactcc agcctaggtg atagagtgag actccctctc aaaaacaaaa 7920 caaaacaaaa aaattagaca aatgctacat taatgtttgg gtggtcagat tctactttga 7980 atctgaagtt tgcagatatg cctatagatt tttggagttt accactttct tattctgtat 8040 cattaatgta atattttaaa ttactatata tgttaccatt tttctggatt tagtaagaaa 8100 tttgcagttt tggtttgatg taacaagggt tttaatgtaa tttatgttag attttgcatt 8160 tttttcatta ctgttatatt ttaacctgac tgactgatct aattgtatta gtattgtgaa 8220 taatcatgtg aaatgttttg agacagagta ctatatttgt gaatataatt ttatggtttt 8280 tttcacttag aacctttctg tgtggaaaac taagaaaatt gctttctgct gtataatctg 8340 gcattcattg tagattaaag cttatttttc tgtgaataaa acgtattcaa taaaatacta 8400 ttctttaaaa tta 8413

Claims

하기 유전자로 이루어진 군으로부터 선택되는 하나 또는 둘 이상의 조합을 포함하는 간암 예후 마커:Liver cancer prognostic markers comprising one or more combinations selected from the group consisting of:

제 1 항의 간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두를 특이적으로 검출하는 물질을 포함하는 간암 예후 추정용 조성물.A composition for estimating hepatic cancer prognosis comprising a substance that specifically detects the expression level, expression pattern, or both of the liver cancer prognostic markers of claim 1.

제 1 항의 간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두를 특이적으로 검출하는 물질을 포함하는 간암 예후 추정용 조성물.A composition for estimating hepatic cancer prognosis comprising a substance that specifically detects an amount of a protein encoded by the liver cancer prognostic marker of claim 1, a presence pattern, or both.

제 2 항 또는 제 3 항의 간암 예후 추정용 조성물을 포함하는 간암 예후 추정용 키트.A liver cancer prognosis kit comprising the composition for estimating hepatic cancer prognosis of claim 2.

제 2 항의 간암 예후 추정용 조성물을 대상 간암 환자에게서 채취한 생물학적 시료에 처리하는 제 1 단계; 및A first step of treating the liver cancer prognostic composition of claim 2 with a biological sample collected from a target liver cancer patient; And

제 1 단계의 처리 결과를 기준치와 대비하여 제 1 항의 간암 예후 마커의 발현량, 발현 패턴, 또는 양자 모두의 차이를 검출하는 제 2 단계;A second step of detecting a difference in expression level, expression pattern, or both of the liver cancer prognostic marker of claim 1 based on the treatment result of the first step against a reference value;

를 포함하는 간암 예후 추정 방법.Liver cancer prognosis estimation method comprising a.

제 3 항의 간암 예후 추정용 조성물을 간암 환자에게서 채취한 생물학적 시료에 처리하는 제 1 단계; 및A first step of treating the liver cancer prognosis composition of claim 3 to a biological sample collected from a liver cancer patient; And

제 1 단계의 처리 결과를 기준치와 대비하여 제 1 항의 간암 예후 마커가 코딩하는 단백질의 존재량, 존재 패턴, 또는 양자 모두의 차이를 검출하는 제 2 단계;A second step of detecting a difference in the amount of abundance, the pattern of presence, or both of the proteins encoded by the liver cancer prognostic marker of claim 1 against the treatment result of the first step against a reference value;

시험 화합물이 제 1 항의 간암 예후 마커의 발현을 촉진 또는 억제하는지 여부를 확인하는 단계;Identifying whether the test compound promotes or inhibits the expression of the hepatic cancer prognostic marker of claim 1;

를 포함하는 간암 치료제의 스크리닝 방법.Screening method for a liver cancer therapeutic agent comprising a.

제 1 항의 간암 예후 마커가 코딩하는 단백질에 시험 화합물을 결합시키는 제 1 단계; 및A first step of binding the test compound to the protein encoded by the liver cancer prognostic marker of claim 1; And

시험 화합물이 상기 단백질의 생리학적 활성을 촉진 또는 억제하는지 여부를 확인하는 제 2 단계;A second step of determining whether the test compound promotes or inhibits the physiological activity of the protein;

제 1 항의 간암 예후 마커가 코딩하는 단백질을 특이적으로 인식하는 항체.An antibody that specifically recognizes a protein encoded by the liver cancer prognostic marker of claim 1.