EP0822987A2 - Polynucleotides and aminoacid sequences from staphylococcus aureus - Google Patents

Abstract

This invention relates to Staphylococcal polynucleotides, polypeptides encoded by such polynucleotides, the uses of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides and recombinant host cells transformed with the polynucleotides. This invention also relates to inhibiting the biosynthesis or action of such polynucleotides or polypeptides and to the use of such inhibitors in therapy.

Description

POLYNUCLEOTIDES AND AMINOACID SEQUENCES FROM STAPHYLOCOCCUS AUREUS FIELD OF THE INVENTION

This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such pol nucleotides and polypeptides and recombinant host cells transformed with the polynucleotides This invention also relates to inhibiting the biosynthesis or action of such polypeptides and to the use of inhibitors in therapy BACKGROUND OF THE INVENTION

The Staphylococci make up a medically important genera of microbes They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues Staphlococcυs aitreus is the second leading cause of bacteremia in cancer patients Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common There are at least three clinical conditions resulting from the toxi enic propeπies of Staphylococci The manifestation of these diseases result from the actions of exotoxms as opposed to tissue invasion and bacteremia These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome

While certain Staphylococcal proteins associated with pathogenicity have been identified, e.g., coaguiase, hemolysms, leucocidins and exo and enterotoxiπs, very little is known concerning the temporal expression of genes of bacterial pathogens during infection and disease progression in a mammalian host Discovering the sets of genes the bacterium is likely to be expressing at the different stages of infection, particularly when an infection is established, provides critical information for the screening and characterization of novel antibactenals which can interrupt pathogenesis, by identifying possible previously unrecognised targets

Recently several novel approaches have been described which purport to follow global gene expression during infection (Chuang, S. et al. [1993] Global Regulation of Gene Expression in Eschertchia colt J. Bacteπol. 175. 2026-2036, Mahan, M.J. et al [ 1993] Selection of Bacterial Virulence Genes That Are Specifically Induced in Host Tissues SCIENCE 259, 686-688. Hensel. M. et al. [1995] Simultaneous Identification of Bacterial Virulence Genes by Negative Selection SCIENCE 269. 400-403) These nev. techniques have so far been demonstrated with gram negative pathogen infections and not with infections with gram positives presumably due to the much slower development of global transposon mutagenesis and suitable vectors needed for these strategies in these organisms, and in the case of that process described by Chuang, S. et al [1993] the difficulty of isolating suitable quantities of bacterial RNA free of mammalian RNA derived from the infected tissue to furnish bacterial RNA labelled to sufficiently high specific activity The present invention employs a novel technology to determine gene expression in the pathogen at different stages of infection of the mammalian host DETAILED DESCRIPTION OF THE INVENTION

A novel aspect of this invention is the use of a suitably labelled o gonucleotide probe which anneals specifically to the bacterial nbosomal RNA in Northern blots of bacterial RNA preparations from infected tissue Using the more abundant nbosomal RNA as a hybridisation target greatly facilitates the optimisation of a protocol to purify bacterial RNA of a suitable size and quantity for RT-PCR from infected tissue Techniques reported in the scientific literature which are of use in purifying Staphylococcus aureus RNA from bacteria grown in vitro are unsuccessful when applied to infected tissue In a first aspect therefore, the invention provides a method of identifying genes transcribed in an organism in infected host tissue by identifying mRNA present using RT- PCR, characterised in that a bacterial mRNA preparation is obtained from total RNA from infected tissue by enriching for bacterial RNA by a suitable bacterial disruption technique in order to selectively damage mammalian RNA and at the same time give sufficient quantities of bacterial RNA for RT-PCR, and wherein the conditions for selectively enriching for bacterial RNA are determined by probing with an ohgonucleotide probe specific to bacterial nbosomal RNA

This process of optimisation preferably uses a unique labelled ohgonucleotide probe to bacterial nbosomal RNA which is used in Northern experiments against the experimental RNA preparations to determine those conditions which give optimal levels of bacterial RNA As bacterial nbosomal RNA is present at 2-4 orders of magnitude in amount to bacterial mRNA species this detection procedure provides a suitably sensitive indication to the existence and quantity of bacterial RNA in the presence of the vastly greater levels of mammalian RNA from the infected tissue This detection system may be used in conjunction with the visualisation of total RNA by ethidium bromide staining of 1% agarose gels on which it has been run out On these gels mammalian nbosomal RNA migrates at a different rate to bacterial nbosomal RNA and so can be identified Surprisingly, those disruption conditions which were found to just lead to the loss of 97/31114

mammalian RNA gave the best preparations of bacterial RNA as judged by the Northern experiment. A suitable ohgonucleotide useful for applying this method to genes expressed in Staphylococcus aureus is 5'-gctcctaaaaggttactccaccggc-3' [SEQ ID NO:91].

Use of the technology of the present invention enables identification of bacterial genes transcribed during infection, inhibitors of which would have utility in anti-bacterial therapy. Specific inhibitors of such gene transcription or of the subsequent translation of the resultant mRNA or of the function of the corresponding expressed proteins would have utility in anti-bacterial therapy

The present invention provides a polynucleotide having the DNA sequence given in any of sequences set forth in, or selected from the group consisting essentially of, SEQUENCE 1 [SEQ ID Nos: 1,4,7, 10,13, 16, 19,22,25,28,

31 ,34,37,40,43.46,49,52,55,58,61 ,64,67,70,73,76] of Table 1, or any combination of the sequences thereof. The invention further provides a polynucleotide encoding a protein from S. aureus WCUH 29 and characterized in that it comprises the DNA sequence given in any of sequences set forth in SEQUENCE 1 [SEQ ID Nos:

1 ,4,7, 10, 13, 16, 19,22,25,28,31 ,34,37,40,43,46,49,52,55,58,61 ,64, 67,70,73,76] of Table 1. The polynucleotides having the DNA sequence given in each sequence set forth in SEQUENCE 1 [SEQ ID Nos: 1,4,7,10,13,16,19,22,25,28, 31,34,37,40,43,46,49,52,55,58,61.64,67,70,73,76] of Table 1 were obtained from the sequencing of a library of clones of chromosomal DNA of S.aureus WCUH 29 in E.coli.

S. aureus WCUH 29 has been deposited at the National Collection of Industrial and Marine Bacteria Ltd. (NCIMB), Aberdeen, Scotland under number NCIMB 40771 on 1 1 September 1995.

The present invention also provides a novel protein from Staphylococcus. aureus WCUH29 obtainable by expression of a gene characterised in that it comprises the DNA sequence given in any of sequences set forth in SEQUENCE 1 [SEQ ID Nos: 1,4,7,10, 13,16,19,22,25,28,31 ,34,37,40,43,46,49,52,55,58,61,64,67,70,73,76] of Table 1, or a fragment, analogue or derivative thereof.

The present invention further relates to a novel protein from Staphylococcus. aureus WCUH29, characterised in that it comprises the amino acid sequence given in any of the sequences set forth in, or selected from the group consisting essentially of, SEQUENCE 2 [SEQ ID Nos: 79,80,81 ,82,83,84,85.86,87,88,89,90] of Table l, or a fragment, analogue or derivative thereof.

The invention also relates to a polypeptide fragment of the protein, having the amino acid sequence given in any of the sequences set forth in SEQUENCE 2 [SEQ ID Nos: 79,80,81 ,82,83,84,85,86,87,88,89,90] of Table 1, or a derivative thereof.

Hereinafter the term polypeptide(s) will be used to refer to the protein and its fragments, analogues or derivatives.

In accordance with another aspect of the present invention, there are provided polynucleotides (DNA or RNA) which encode such polypeptides. The invention also relates to novel oligonucleotides, including the sequences set forth in SEQUENCE 3 [SEQ ID Nos: 2,5,8,11 ,14,17,20,23,26,29,32,35,38,41 ,44,47, 50,53,56,59,62,65,68,71 ,74.77] and 4 [SEQ ID Nos: 3,6,9,12,15, 18,21,24,27,30, 33,36,39,42,45,48,51,54,57,60.63,66,69,72,75,78] ofTable 1 , derived from the sequences set forth in SEQUENCE 1 [SEQ ID Nos: 1 ,4,7,10,13,16,19.22,25,28,31,34, 37,40,43,46,49,52,55,58,61,64,67,70,73,76] of Table 1 which can act as PCR primers in the process herein described to determine whether or not the Staphylococcus aureus genes identified herein in whole or in part are transcribed in infected tissue. It is recognised that such sequences will also have utility in diagnosis of the stage of infection and type of infection the pathogen has attained. Each of the DNA sequences provided herein may be used in the discovery and development of antibacterial compounds. The encoded protein upon expression can be used as a target for the screening of antibacterial drugs. Additionally, the DNA sequences encoding regions of the encoded protein or Shine-Delgarno or other translation facilitating sequences of the respective mRNA can be used to construct antisense sequences to control the expression of the coding sequence of interest. Furthermore, many of the sequences disclosed herein also provide regions upstream and downstream from the encoding sequence. These sequences are useful as a source of regulatory elements for the control of bacterial gene expression. Such sequences are conveniently isolated by restriction enzyme action or synthesized chemically and introduced, for example, into promoter identification strains. These strains contain a reporter structural gene sequence located downstream from a restriction site such that if an active promoter is inserted, the reporter gene will be expressed. O 97/31114

Although each of the sequences may be employed as described above, this invention also provides several means for identifying particularly useful target genes. The first of these approaches entails searching appropriate databases for sequence matches. Thus, if a homoiogue exists, the Staphylococcal-like form of this gene would likely play an analogous role. For example, a Staphylococcal protein identified as homologous to a cell surface protein in another organism would be useful as a vaccine candidate. To the extent such homologies have been identified for the sequences disclosed herein they are reported along with the encoding sequence.

To obtain the polynucleotide encoding the protein using any DNA sequence given in a SEQ ID NO 1 typically a library of clones of chromosomal DNA of S.aureus WCUH 29 in E.coli or some other suitable host is probed with a radiolabelled ohgonucleotide, preferably a 17mer or longer, derived from the partial sequence. Clones carrying DNA identical to that of the probe can then be distinguished using high stringency washes. By sequencing the individual clones thus identified with sequencing primers designed from the original sequence it is then possible to extend the sequence in both directions to determine the full gene sequence. Conveniently such sequencing is performed using denatured double stranded DNA prepared from a plasmid clone. Suitable techniques are described by aniatis, T., Fritsch, E.F. and Sambrook, J. in MOLECULAR CLONING, A Laboratory Manual [2nd edition 1989 Cold Spring Harbor Laboratory, see Screening By Hybridization 1.90 and Sequencing Denatured Double-Stranded DNA Templates 13.70].

A polynucleotide of the present invention may be in the form of RNA or in the form of DNA, which DNA includes cDNA, genomic DNA, and synthetic DNA. The DNA may be double-stranded or single-stranded, and if single stranded may be the coding strand or non-coding (anti-sense) strand. The coding sequence which encodes the polypeptide may be identical to the coding sequence of any of the sequences of SEQUENCE I [SEQ ID Nos: 1 ,4,7, 10, 13, 16, 19,22,25,28,31 ,34,37,40,43,46,49,52,55,58,61 ,64,67,70,73,76] of Table 1 or may be a different coding sequence which coding sequence, as a result of the redundancy or degeneracy of the genetic code, encodes the same polypeptide. The present invention includes variants of the hereinabove described polynucleotides which encode fragments, analogues and derivatives of the polypeptides of the invention, and in particular polypeptides characterized by the deduced amino acid sequences set forth in each SEQUENCE 2 [SEQ ID Nos: 79,80,81,82,83,84, 85,86,87,88.89,90] ofTable 1. The variant of the polynucleotide may be a naturally occurring allelic variant of the polynucleotide or a non-naturally occurring variant of the polynucleotide.

Thus, the present invention includes polynucleotides encoding the same polypeptides of the invention, and in particular characterized by the deduced amino acid sequences set forth in each SEQUENCE 2 [SEQ ID Nos: 79,80,81 ,82,83,84,85,86,87, 88.89,90] of Table 1 as well as variants of such polynucleotides which variants encode for a fragment, derivative or analogue of the polypeptide. Such nucleotide variants include deletion variants, substitution variants and addition or insertion variants. The polynucleotide may have a coding sequence which is a naturally occurring allelic variant of the coding sequence characterized by the DNA sequence of any of the sequences set forth in Table 1 as SEQUENCE 1 [SEQ ID Nos: 1,4,7,10,13,16,19,22.25, 28,31,34,37,40,43,46,49,52,55,58,61,64,67,70,73,76]. As known in the art, an allelic variant is an alternate form of a polynucleotide sequence which may have a substitution, deletion or addition of one or more nucleotides, which does not substantially alter the function of the encoded polypeptide.

The polynucleotide which encodes for the mature polypeptide may include only the coding sequence for the mature polypeptide or the coding sequence for the mature polypeptide and additional coding sequence such as a leader or secretory sequence or a proprotein sequence.

Thus, the term "polynucleotide encoding a polypeptide" encompasses a polynucleotide which includes only coding sequence for the polypeptide as well as a polynucleotide which includes additional coding and/or non-coding sequence.

The present invention therefore includes polynucleotides, wherein the coding sequence for the mature polypeptide may be fused in the same reading frame to a polynucleotide sequence which aids in expression and secretion of a polypeptide from a host cell, for example, a leader sequence which functions as a secretory sequence for controlling transport of a polypeptide from the cell. The polypeptide having a leader sequence is a preprotein and may have the leader sequence cleaved by the host cell to form the mature form of the polypeptide. The polynucleotides may also encode for a proprotein which is the mature protein plus additional 5' amino acid residues. A mature protein having a prosequence is a proprotein and is an inactive form of the protein. Once the prosequence is cleaved an active mature protein remains. Thus, for example, the polynucleotide of the present invention may encode for a mature protein, or for a protein having a prosequence or for a protein having both a prosequence and a presequence (leader sequence). Further, the amino acid sequences provided herein show a methionine residue at the NH₂-terminus. It is appreciated, however, that during post-translational modification of the peptide, this residue may be deleted. Accordingly, this invention contemplates the use of both the sequences.

An expression vector is constructed so that the particular coding sequence is located in the vector with the appropriate regulatory sequences, the positioning and orientation of the coding sequence with respect to the control sequences being such that the coding sequence is transcribed under the "control" of the control sequences (i.e., RNA polymerase which binds to the DNA molecule at the control sequences transcribes the coding sequence). Modification of the coding sequences may be desirable to achieve this end. For example, in some cases it may be necessary to modify the sequence so that it may be attached to the control sequences with the appropriate orientation; i.e., to maintain the reading frame. The control sequences and other regulatory sequences may be ligated to the coding sequence prior to insertion into a vector, such as the cloning vectors described above. Alternatively, the coding sequence can be cloned directly into an expression vector which already contains the control sequences and an appropriate restriction site.

Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of E. coll and S. cerevisiae TRP1 gene, and a promoter derived from a highly- expressed gene to direct transcription of a downstream structural sequence. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the peripiasmic space or extracellular medium.

Optionally, the heterologous sequence can encode a fusion protein including an N-terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product.

The vector containing the appropriate DNA sequence as hereinabove described, as well as an appropriate promoter or control sequence, may be employed to transform an appropriate host to permit the host to express the protein.

More particularly, the present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above. The constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a forward or reverse orientation. In a preferred aspect of this embodiment, the construct further comprises regulatory sequences, including, for example, a promoter, operably linked to the sequence. Large numbers of suitable vectors and promoters are known to those of skill in the art, and are commercially available. The following vectors are provided by way of example. Bacterial: pET-3 vectors (Stratagene), pQE70, pQE60, pQE-9 (Qiagen), pbs, pDI O, phagescript, psiXI 74, pbluescript SK, pbsks, pNH8A, pNHlόa, pNH18A, pNH46A (Stratagene); ptrc99a, p K223-3, p K233-3, pDR540, pRIT5 (Pharmacia). Eukaryotic: pBlueBacIII (Invitrogen), pWLNEO, pSV2CAT, pOG44, pXTl , pSG (Stratagene) pSVK3, pBPV, pMSG, pSVL (Pharmacia). However, any other plasmid or vector may be used as long as they are replicable and viable in the host.

Examples of recombinant DNA vectors for cloning and host cells which they can transform include the bacteriophage λ (E. colt), pBR322 (E. coli), pACYCl 77 (£. coli), p T230 (gram-negative bacteria), pGVl 106 (gram-negative bacteria), pLAFRl (gram- negative bacteria), pME290 (non-£. coli gram-negative bacteria), pHV 14 (E. coli and Bacillus subtilis), pBD9 {Bacillus), pIJ61 Streptomyces), pUC6 (Streptomyces), YIp5 (Saccharomyces), a baculovirus insect cell system, YCpl9 (Saccharo yces). See, generally, "DNA Cloning": Vols. I & II, Glover et al. ed. IRL Press Oxford (1985) ( 1987) and; T. Maniatis et al. ("Molecular Cloning" Cold Spring Harbor Laboratory ( 1982). methionine-containing and the methionineiess amino terminal variants of each protein disclosed herein.

The polynucleotides of the present invention may also have the coding sequence fused in frame to a marker sequence at either the 5' or 3' terminus of the gene which allows for purification of the polypeptide of the present invention. The marker sequence may be a hexa-histidine tag supplied by the pQE series of vectors (supplied commercially by Quiagen Inc.) to provide for purification of the polypeptide fused to the marker in the case of a bacterial host.

The present invention further relates to polynucleotides which hybridize to the hereinabove-described sequences if there is at least 50% and preferably at least 70% identity between the sequences. The present invention particularly relates to Staphylococcal polynucleotides which hybridize under stringent conditions to the hereinabove-described polynucleotides . As herein used, the term "stringent conditions" means hybridization will occur only if there is at least 95% and preferably at least 97% identity between the sequences. The polynucleotides which hybridize to the hereinabove described polynucleotides in a preferred embodiment encode polypeptides which retain substantially the same biological function or activity as the polypeptide of the invention. A preferred embodiment of the invention is a polynucleotide having at least a 70%, 80%, 90% or 95% identity to a polynucleotide encoding a polypeptide comprising an amino acid sequence selected from the group consisting essentially of SEQ ID Nos: 79,80,81 ,82,83,84,85,86,87,88 and 89, or any combination of these amino acid sequences. The deposit referred to herein will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Micro-organisms for purposes of Patent Procedure. These deposits are provided merely as convenience to those of skill in the art and are not an admission that a deposit is required under 35 U.S.C. § 1 12. The sequence of the polynucleotides contained in the deposited material, as well as the amino acid sequence of the polypeptides encoded thereby, are incorporated herein by reference and are controlling in the event of any conflict with any description of sequences herein. A license may be required to make, use or sell the deposited material, and no such license is hereby granted.

The terms "fragment," "derivative" and "analogue" when referring to the polypeptide of the invention, means a polypeptide which retains essentially the same biological function or activity as such polypeptide. Thus, an analogue includes a proprotein which can be activated by cleavage of the proprotein portion to produce an active mature polypeptide.

The polypeptide of the present invention may be a recombinant polypeptide, a natural polypeptide or a synthetic polypeptide, preferably a recombinant polypeptide. The fragment, derivative or analogue of the polypeptide of the invention may be (i) one in which one or more of the amino acid residues are substituted with a conserved or non-conserved amino acid residue (preferably a conserved amino acid residue) and such substituted amino acid residue may or may not be one encoded by the genetic code, or (ii) one in which one or more of the amino acid residues includes a substituent group, or (iii) one in which the polypeptide is fused with another compound, such as a compound to increase the half-life of the polypeptide (for example, polyethylene glyeol), or (iv) one in which the additional amino acids are fused to the polypeptide, such as a leader or secretory sequence or a sequence which is employed for purification of the polypeptide or a proprotein sequence. Such fragments, derivatives and analogues are deemed to be within the scope of those skilled in the art from the teachings herein.

The polypeptides and polynucleotides of the present invention are preferably provided in an isolated form, and preferably are purified to homogeneity.

The term "isolated" means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment.

The present invention also relates to vectors which include polynucleotides of the present invention, host cells which are genetically engineered with vectors of the invention and the production of polypeptides of the invention by recombinant techniques. In accordance with yet a further aspect of the present invention, there is therefore provided a process for producing the polypeptide of the invention by recombinant techniques by expressing a polynucleotide encoding said polypeptide in a host and recovering the expressed product. Alternatively, the polypeptides of the invention can be synthetically produced by conventional peptide synthesizers. Host cells are genetically engineered (transduced or transformed or transfected) with the vectors of this invention which may be, for example, a cloning vector or an expression vector. The vector may be, for example, in the form of a plasmid, a cosmid, a phage, etc. The engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters, selecting transformants or amplifying the genes. The culture conditions, such as temperature, pH and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.

Suitable expression vectors include chromosomal, nonchromosomal and synthetic DNA sequences, e.g., bacterial plasmids; phage DNA; baculovirus; yeast plasmids; vectors derived from combinations of plasmids and phage DNA. However, any other vector may be used as long as it is replicable and viable in the host. The appropriate DNA sequence may be inserted into the vector by a variety of procedures. In general, the DNA sequence is inserted into an appropriate restriction endonuclease site(s) by procedures known in the art.

The DNA sequence in the expression vector is operativeiy linked to an appropriate expression control sequence(s) (promoter) to direct mRNA synthesis. As representative examples of such promoters, there may be mentioned: LTR or SV40 promoter, the E. coli. lac or trp, the phage lambda PL promoter and other promoters known to control expression of genes in eukaryotic or prokaryotic cells or their viruses. The expression vector also contains a ribosome binding site for translation initiation and a transcription terminator. The vector may also include appropriate sequences for amplifying expression.

In addition, the expression vectors preferably contain one or more selectable marker genes to provide a phenotypic trait for selection of transformed host cells such as dihydrofoiate reductase or neomycin resistance for eukaryotic cell culture, or such as tetracycline or ampicillin resistance in E. coli. The gene can be placed under the control of a promoter, ribosome binding site (for bacterial expression) and, optionally, an operator (collectively referred to herein as "control" elements), so that the DNA sequence encoding the desired protein is transcribed into RNA in the host cell transformed by a vector containing this expression construction. The coding sequence may or may not contain a signal peptide or leader sequence. The polypeptides of the present invention can be expressed using, for example, the E. coli tac promoter or the protein A gene (spa) promoter and signal sequence. Leader sequences can be removed by the bacterial host in post-translational processing. See, e.g., U.S. Patent Nos. 4,431,739; 4,425,437; 4,338,397. Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are PKK232-8 and PCM7. Particular named bacterial promoters include lad, lacZ, T3, T7, gpt, lambda PR, PL and trp. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art. In addition to control sequences, it may be desirable to add regulatory sequences which allow for regulation of the expression of the protein sequences relative to the growth of the host cell. Regulatory sequences are known to those of skill in the art, and examples include those which cause the expression of a gene to be turned on or off in response to a chemical or physical stimulus, including the presence of a regulatory compound. Other types of regulatory elements may also be present in the vector, for example, enhancer

In some cases, it may be desirable to add sequences which cause the secretion of the polypeptide from the host organism, with subsequent cleavage of the secretory signal. Polypeptides can be expressed in host cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described by Sambrook, et al., Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y., ( 1989), the disclosure of which is hereby incorporated by reference. Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, the selected promoter is induced by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification.

Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents, such methods are well known to those skilled in the art.

Depending on the expression system and host selected, the polypeptide of the present invention may be produced by growing host cells transformed by an expression vector described above under conditions whereby the polypeptide of interest is expressed. The polypeptide is then isolated from the host cells and purified. If the expression system secretes the polypeptide into growth media, the polypeptide can be purified directly from the media. If the polypeptide is not secreted, it is isolated from cell lysates or recovered from the ceil membrane fraction. Where the polypeptide is localized to the cell surface, whole cells or isolated membranes can be used as an assayable source of the desired gene product. Polypeptide expressed in bacterial hosts such as E. coli may require isolation from inclusion bodies and refolding. Where the mature protein has a very hydrophobic region which leads to an insoluble product of overexpression, it may be desirable to express a truncated protein in which the hydrophobic region has been deleted. The selection of the appropriate growth conditions and recovery methods are within the skill of the art.

The polypeptide can be recovered and purified from recombinant cell cultures by methods including ammonium sulphate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps.

Depending upon the host employed in a recombinant production procedure, the polypeptides of the present invention may be glycosylated or may be non-glycosylated. Polypeptides of the invention may also include an initial methionine amino acid residue. A "replicon" is any genetic element (e.g., plasmid, chromosome, virus) that functions as an autonomous unit of DNA replication in vivo; i.e.. capable of replication under its own control.

A "vector" is a replicon, such as a plasmid, phage, or cosmid, to which another DNA segment may be attached so as to bring about the replication of the attached segment. A "double-stranded DNA molecule" refers to the polymeric form of deoxyribonucleotides (bases adenine, guanine, thymine, or cytosine) in a double-stranded helix, both relaxed and supercoiled. This term refers only to the primary and secondary structure of the molecule, and does not limit it to any particular tertiary forms. Thus, this term includes double-stranded DNA found, inter alia, in linear DNA molecules (e.g., restriction fragments), viruses, plasmids, and chromosomes. In discussing the structure of particular double-stranded DNA molecules, sequences may be described herein according to the normal convention of giving only the sequence in the 5' to 3' direction along the nontranscribed strand of DNA (i.e., the strand having the sequence homologous to the mRNA).

A DNA "coding sequence of or a "nucleotide sequence encoding" a particular protein, is a DNA sequence which is transcribed and translated into a polypeptide when placed under the control of appropriate regulatory sequences.

A "promoter sequence" is a DNA regulatory region capable of binding RNA polymerase in a cell and initiating transcription of a downstream (3' direction) coding sequence. For purposes of defining the present invention, the promoter sequence is bound at the 3' terminus by a translation start codon (e.g., ATG) of a coding sequence and extends upstream (5' direction) to include the minimum number of bases or elements necessary to initiate transcription at levels detectable above background. Within the promoter sequence will be found a transcription initiation site (conveniently defined by mapping with nuclease S I ), as well as protein binding domains (consensus sequences) responsible for the binding of RNA polymerase. Eukaryotic promoters will often, but not always, contain "TATA" boxes and "CAT" boxes. Prokaryotic promoters contain Shine-Dalgarno sequences in addition to the - 10 and -35 consensus sequences. DNA "control sequences" refers collectively to promoter sequences, ribosome binding sites, polyadenylation signals, transcription termination sequences, upstream regulatory domains, enhancers, and the like, which collectively provide for the expression (i.e., the transcription and translation) of a coding sequence in a host cell.

A control sequence "directs the expression" of a coding sequence in a cell when RNA polymerase will bind the promoter sequence and transcribe the coding sequence into mRNA, which is then translated into the polypeptide encoded by the coding sequence.

A "host cell" is a cell which has been transformed or transfected, or is capable of transformation or transfection by an exogenous DNA sequence.

A cell has been "transformed" by exogenous DNA when such exogenous DNA has been introduced inside the cell membrane. Exogenous DNA may or may not be integrated (covalently linked) into chromosomal DNA making up the genome of the cell. In prokaryotes and yeasts, for example, the exogenous DNA may be maintained on an episomal element, such as a plasmid. With respect to eukaryotic cells, a stably transformed or transfected cell is one in which the exogenous DNA has become integrated into the chromosome so that it is inherited by daughter cells through chromosome replication. This stability is demonstrated by the ability of the eukaryotic cell to establish cell lines or clones comprised of a population of daughter cell containing the exogenous DNA.

A "clone" is a population of cells derived from a single cell or common ancestor by mitosis. A "cell line" is a clone of a primary cell that is capable of stable growth in vitro for many generations.

A "heterologous" region of a DNA construct is an identifiable segment of DNA within or attached to another DNA molecule that is not found in association with the other molecule in nature.

In accordance with yet a further aspect of the present invention, there is provided the use of a polypeptide of the invention for therapeutic or prophylactic purposes, for example, as an antibacterial agent or a vaccine. In accordance with another aspect of the present invention, there is provided the use of a polynucleotide of the invention for therapeutic or prophylactic purposes, in particular genetic immunisation.

In accordance with yet another aspect of the present invention, there are provided inhibitors to such polypeptides, useful as antibacterial agents. In particular, there are provided antibodies against such polypeptides.

Another aspect of the invention is a pharmaceutical composition comprising the above polypeptide, polynucleotide or inhibitor of the invention and a pharmaceutically acceptable carrier. In a particular aspect the invention provides the use of an inhibitor of the invention as an antibacterial agent.

The invention further relates to the manufacture of a medicament for such uses.

The polypeptide may be used as an antigen for vaccination of a host to produce specific antibodies which have anti-bacterial action. The polypeptides or ceils expressing them can be used as an immunogen to produce antibodies thereto. These antibodies can be, for example, polyclonal or monoclonal antibodies. The term antibodies also includes chimerie, single chain, and humanized antibodies, as well as Fab fragments, or the product of an Fab expression library. Various procedures known in the art may be used for the production of such antibodies and fragments.

Antibodies generated against the polypeptides of the present invention can be obtained by direct injection of the polypeptides into an animal or by administering the polypeptides to an animal, preferably a nonhuman. The antibody so obtained will then bind the polypeptides itself. In this manner, even a sequence encoding only a fragment of the polypeptides can be used to generate antibodies binding the whole native polypeptides. Such antibodies can then be used to isolate the polypeptide from tissue expressing that polypeptide.

Polypeptide derivatives include antigenically or immunologically equivalent derivatives which form a particular aspect of this invention. The term 'antigenically equivalent derivative' as used herein encompasses a polypeptide or its equivalent which will be specifically recognised by certain antibodies which, when raised to the protein or polypeptide according to the present invention, interfere with the interaction between pathogen and mammalian host. The term 'immunologically equivalent derivative' as used herein encompasses a peptide or its equivalent which when used in a suitable formulation to raise antibodies in a vertebrate, the antibodies act to interfere with the interaction between pathogen and mammalian host. In particular derivatives which are slightly longer or slightly shorter than the native protein or polypeptide fragment of the present invention may be used. In addition, polypeptides in which one or more of the amino acid residues are modified may be used. Such peptides may, for example, be prepared by substitution, addition, or rearrangement of amino acids or by chemical modification thereof. All such substitutions and modifications are generally well known to those skilled in the art of peptide chemistry.

The polypeptide, such as an antigenically or immunologically equivalent derivative or a fusion protein thereof is used as an antigen to immunize a mouse or other animal such as a rat or chicken. The fusion protein may provide stability to the polypeptide. The antigen may be associated, for example by conjugation , with an immunogenic carrier protein for example bovine serum albumin (BSA) or keyhole limpet haemocyanin (KLH). Alternatively a multiple antigenic peptide comprising multiple copies of the the protein or polypeptide, or an antigenically or immunologically equivalent polypeptide thereof may be sufficiently antigenic to improve immunogenicity so as to obviate the use of a carrier.

For preparation of monoclonal antibodies, any technique which provides antibodies produced by continuous cell line cultures can be used. Examples include the hybridoma technique (Kohler and Milstein, 1975, Nature, 256:495-497), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., 1983, Immunology Today 4:72), and the EBV-hybridoma technique to produce human monoclonal antibodies (Cole, et al., 1985, in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Techniques described for the production of single chain antibodies (U.S. Patent

4,946,778) can be adapted to produce single chain antibodies to immunogenic polypeptide products of this invention.

Using the procedure of Kohler and Milstein (supra ( 1975), antibody-containing cells from the immunised mammal are fused with myeloma cells to create hybridoma cells secreting monoclonal antibodies.

The hybridomas are screened to select a cell line with high binding affinity and favorable cross reaction with other staphylococcal species using one or more of the original polypeptide and/or the fusion protein. The selected cell line is cultured to ob_tain the desired Mab.

Hybridoma cell lines secreting the monoclonal antibody are another aspect of this invention.

Alternatively phage display technology could be utilised to select antibody genes with binding activities towards the polypeptide either from repertoires of PCR amplified v- genes of lymphocytes from humans screened for possessing anti-Fbp or from naive libraries (McCafferty, J. et al., (1990), Nature 348, 552-554; Marks, J. et al., (,992) Biotechnology 10, 779-783). The affinity of these antibodies can also be improved by chain shuffling (Clackson, T. et al., (1991) Nature 352, 624-628).

The antibody should be screened again for high affinity to the polypeptide and/or fusion protein.

As mentioned above, a fragment of the final antibody may be prepared.

The antibody may be either intact antibody of M_r approx 150,000 or a derivative of ⁱt, for example a Fab fragment or a Fv fragment as described in Skerra, A and Pluckthun A (1988) Science 240 1038-1040. If two antigen binding domains are present each domain' may be directed against a different epitope - termed 'bispecific' antibodies.

The antibody of the invention may be prepared by conven_tional means for example by established monoclonal antibody technology (Kohler, G. and Milstein, C. supra (1975)) or using recombinant means e.g. combinatorial libraries, for example as described in Huse W.D. et al., (1989) Science 246,1275- 1281.

Preferably the antibody is prepared by expression of a DNA polymer encoding said antⁱbody in an appropriate expression system such as described above for the expression of polypeptides of the invention. The choice of vector for the expression system will be determined in part by the host, which may be a prokaryotic cell, such as E. coli (preferably straⁱn B) or Streptomyces s_P. or a eukaryotic cell, such as a mouse C127, mouse myeloma human HeLa, Chinese hamster ovary, filamentous or unicellular fungi or insect cell. The ' host may also be a transgenic animal or a transgenic plant [for example as described in H-*A « αt.(19W) Nature 34, 76-78]. Suitable vectors include plasmids, bacteriophages cosm,ds and recombinant viruses, derived from, f_or example, baculoviruses and vaccinia.

The Fab fragment may also be prepared from its parent monoclonal antibody by enzyme treatment, for example using papain to cleave the Fab portion from the Fc portion Preferably the antibody or derivative thereof is modified to make it less immunogenic in the patient. For example, if the patient is human the antibody may most preferably be 'humanised'; where the complimentarity determining region(s) of the hybridoma-derived antibody has been transplanted into a human monoclonal antibody , for example as described in Jones, P. et al (1986), Nature 321, 522-525 or Tempest et α/.,( 1991 ) Biotechnology 9, 266-273.

The modification need not be restricted to one of 'humanisation' ; other primate sequences (for example Newman, R. et al . 1992, Biotechnology,10, 1455- 1460) may also be used. The humanised monoclonal antibody, or its fragment having binding activity, form a particular aspect of this invention.

This invention provides a method of screening drugs to identify those which interfere with the proteins herein, which method comprises measuring the interference of the protein activity by test drug. For example, if the protein has enzymatic activity, after suitable purification and formulation the activity of the enzyme can be followed by its ability to convert its natural substrates. By incorporating different chemically synthesised test compounds or natural products into such an assay of enzymatic activity one is able to detect those additives which compete with the natural substrate or otherwise inhibit enzymatic activity. The invention also relates to inhibitors identified thereby.

The use of a polynucleotide of the invention in genetic immunisation will preferably employ a suitable delivery method such as direct injection of plasmid DNA into muscles (Wolff et al., Hum Mol Genet 1992, 1 :363, Manthorpe et al., Hum. Gene Ther. 1963:4, 419), delivery of DNA complexed with specific protein carriers ( Wu et al., J Biol Chem 1989:264, 16985), coprecipitation of DNA with calcium phosphate (Benvenisty & Reshef, PNAS,1986:83,9551), encapsulation of DNA in various forms of liposomes (Kaneda e/ α/., Science 1989:243,375), particle bombardment (Tang et al.. Nature 1992, 356: 152, Eisenbraun et al., DNA Cell Biol 1993, 12:791 ) and in vivo infection using cloned retroviral vectors (Seeger et al, PNAS 1984:81,5849). Suitable promoters for muscle transfection include CMV, RSV, SRa, actin, MCK, alpha globin, adenovirus and dihydrofolate reductase. In therapy or as a prophylactic, the active agent i.e the polypeptide, polynucleotide or inhibitor of the invention, may be administered to a patient as an injectable composition, for example as a sterile aqueous dispersion, preferably isotonic.

Alternatively the composition may be formulated for topical application for example in the form of ointments, creams, lotions, eye ointments, eye drops, ear drops, mouthwash, impregnated dressings and sutures and aerosols, and may contain appropriate conventional additives, including, for example, preservatives, solvents to assist drug penetration, and emollients in ointments and creams. Such topical formulations may also contain compatible conventional carriers, for example cream or ointment bases, and ethanol or oleyl alcohol for lotions. Such carriers may constitute from about 1% to about 98% by weight of the formulation; more usually they will constitute up to about 80% by weight of the formulation.

For administration to human patients, it is expected that the daily dosage level of the active agent will be from 0.01 to 10 mg/kg, typically around 1 mg/kg. The physician in any event will determine the actual dosage which will be most suitable for an individual patient and will vary with the age, weight and response of the particular patient. The above dosages are exemplary of the average case. There can, of course, be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. A vaccine composition is conveniently in injectable form. Conventional adjuvants may be employed to enhance the immune response.

A suitable unit dose for vaccination is 0.5-5ug/kg of antigen, and such dose is preferably administered 1-3 times and with an interval of 1-3 weeks.

Within the indicated dosage range, no adverse toxicologicals effects are expected with the compounds of the invention which would preclude their administration to suitable patients. EXAMPLES

In order to facilitate understanding of the following examples certain frequently occurring methods and/or terms will be described. "Plasmids" are designated by a lower case p preceded and/or followed by capital letters and/or numbers. The starting plasmids herein are either commercially available, publicly available on an unrestricted basis, or can be constructed from available plasmids in accord with published procedures. In addition, equivalent plasmids to those described are known in the art and will be apparent to the ordinarily skilled artisan.

"Digestion" of DNA refers to catalytic cleavage of the DNA with a restriction enzyme that acts only at certain sequences in the DNA. The various restriction enzymes used herein are commercially available and their reaction conditions, cofactors and other requirements were used as would be known to the ordinarily skilled artisan. For analytical purposes, typically 1 μg of plasmid or DNA fragment is used with about 2 units of enzyme in about 20 μl of buffer solution. For the purpose of isolating DNA fragments for plasmid construction, typically 5 to 50 μg of DNA are digested with 20 to 250 units of enzyme in a larger volume. Appropriate buffers and substrate amounts for particular restriction enzymes are specified by the manufacturer. Incubation times of about 1 hour at 37 C are ordinarily used, but may vary in accordance with the supplier's instructions. After digestion the reaction is electrophoresed directly on a polyacrylamide gel to isolate the desired fragment. Size separation of the cleaved fragments is performed using 8 percent polyacrylamide gel described by Goeddel, D. et al., (1980) Nucleic Acids Res., 8:4057. "Oligonucleotides" refers to either a single stranded polydeoxynucleotide or two complementary polydeoxynucleotide strands which may be chemically synthesized. Such synthetic oligonucleotides have no 5' phosphate and thus will not ligate to another ohgonucleotide without adding a phosphate with an ATP in the presence of a kinase. A synthetic ohgonucleotide will ligate to a fragment that has not been dephosphorylated. "Ligation" refers to the process of forming phosphodiester bonds between two double stranded nucleic acid fragments (Maniatis, T., et al., Id., p. 146). Unless otherwise provided, ligation may be accomplished using known buffers and conditions with 10 units to T4 DNA ligase ("ligase") per 0.5 μg of approximately equimoiar amounts of the DNA fragments to be ligated. Example 1 Isolation of DNA from S. Aureus WCUH 29

The polynucleotide having the DNA sequence given in SEQ ID NO 1 was obtained from a library of clones of chromosomal DNA of S.aureus WCUH 29 in E.coli. In some cases the sequencing data from two or more clones containing overlapping S.aureus WCUH 29 DNA was used to construct the contiguous DNA sequence in Sequences set forth in SEQUENCE 1 [SEQ ID Nos: l,4,7,10,13, 16, 19,22.25,28,31 ,34,37,40,43,46, 49,52,55,58,61,64,67,70,73,76] of Table 1. Libraries may be prepared by routine methods, for example:

Methods 1 and 2

Total cellular DNA is isolated from Staphylococcus aureus strain WCUH29 (NCIMB 40771 ) according to standard procedures and size-fractionated by either of two methods.

Method I.

Total cellular DNA is mechanically sheared by passage through a needle in order to size-fractionate according to standard procedures. DNA fragments of up to 1 1 kbp in size are rendered blunt by treatment with exonuclease and DNA polymerase, and EcoRI linkers added. Fragments are ligated into the vector Lambda ZapII that has been cut with EcoRI, the library packaged by standard procedures and E.coli infected with the packaged library.

The library is amplified by standard procedures.

Method 2. Total cellular DNA is partially hydrolysed with a combination of four restriction enzymes (Rsal, Pall, AIuI and Bshl235I) and size- fractionated according to standard procedures. EcoRI linkers are ligated to the DNA and the fragments then ligated into the vector Lambda ZapII that have been cut with EcoRI, the library packaged by standard procedures, and E.coli infected with the packaged library. The library is amplified by standard procedures.

Example 2

The determination of expression during infection of a gene from Staphylococcus aureus WCUH29

Necrotic fatty tissue from a four day groin infection of Staphylococcus aureus WCUH29 in the mouse is efficiently disrupted and processed in the presence of chaotropic agents and RNAase inhibitor to provide a mixture of animal and bacterial RNA. The optimal conditions for disruption and processing to give stable preparations and high yields of bacterial RNA are followed by the use of hybridisation to a radiolabelled ohgonucleotide specific to Staphylococcus aureus 16S RNA on Northern blots. The RNAase free, DNAase free, DNA and protein free preparations of RNA obtained are suitable for Reverse

Transcription PCR (RT-PCR) using unique primer pairs designed from the sequence of each gene of Staphylococcus aureus WCUH29. a) Isolation of tissue infected with Staphylococcus aureus WCUH29 from a mouse animal model of infection

10 mi. volumes of sterile nutrient broth (No.2 Oxoid) are seeded with isolated, individual colonies of Staphylococcus aureus WCUH29 from an agar culture plate. The cultures are incubated aerobicaliy (static culture) at 37 degrees C for 16-20 hours . 4 week old mice (female, 18g-22g, strain MF1) are each infected by subcutaneous injection of 0.5ml. of this broth culture of Staphylococcus aureus WCUH29 (diluted in broth to approximately 10 cfu/ml.) into the anterior , right lower quadrant (groin area). Mice should be monitored regularly during the first 24 hours after infection, then daily until termination of study. Animals with signs of systemic infection, i.e. lethargy, ruffled appearance, isolation from group, should be monitored closely and if signs progress to moribundancy, the animal should be culled immediately.

Visible external signs of lesion development will be seen 24-48h after infection. Examination of the abdomen of the animal will show the raised outline of the abscess beneath the skin. The localised lesion should remain in the right lower quadrant, but may occasionally spread to the left lower quadrant, and superiorly to the thorax. On occasions, the abscess may rupture through the overlying skin layers. In such cases the affected animal should be culled immediately and the tissues sampled if possible. Failure to cull the animal may result in the necrotic skin tissue overlying the abscess being sloughed off, exposing the abdominal muscle wall.

Approximately 96h after infection, animals are killed using carbon dioxide asphyxiation. To minimise delay between death and tissue processing /storage, mice should be killed individually rather than in groups.The dead animal is placed onto its back and the fur swabbed liberally with 70% alcohol. An initial incision using scissors is made through the skin of the abdominal left lower quadrant, travelling superiorly up to, then across the thorax. The incision is completed by cutting inferiorly to the abdominal lower right quadrant. Care should be taken not to penetrate the abdominal wall. Holding the skin flap with forceps, the skin is gently pulled way from the abdomen. The exposed abscess, which covers the peritoneal wall but generally does not penetrate the muscle sheet completely, is excised, taking care not to puncture the viscera

The abscess/muscle sheet and other infected tissue may require cutting in sections, prior to flash-freezing in liquid nitrogen, thereby allowing easier storage in plastic collecting vials. b) Isolation of Staphylococcus aureus WCUH29 RNA from infected tissue samples

4-6 infected tissue samples(each approx 0.5-0.7g) in 2ml screw-cap tubes are removed from -80°C.storage into a dry ice ethanol bath In a microbiological safety cabinet the samples are disrupted individually whilst the remaining samples are kept cold in the dry ice ethanol bath. To disrupt the bacteria within the tissue sample 1ml of TRIzol Reagent (Gibco BRL, Life Technologies) is added followed by enough 0.1mm zirconia/silica beads to almost fill the tube, the lid is replaced taking care not to get any beads into the screw thread so as to ensure a good seal and eliminate aerosol generation. The sample is then homogenised in a Mini-BeadBeater Type BX-4 (Biospec Products). Necrotic fatty tissue is treated for 100 seconds at 5000 rpm in order to achieve bacterial lysis. In vivo grown bacteria require longer treatment than in vitro grown S.aureus WCUH29 which are disrupted by a 30 second bead-beat.

After bead-beating the tubes are chilled on ice before opening in a fume-hood as heat generated during disruption may degrade the TRIzol and release cyanide. 200 microlitres of chloroform is then added and the tubes shaken by hand for 15 seconds to ensure complete mixing. After 2-3 minutes at room temperature the tubes are spun down at 12,000 x g, 4 °C for 15minutes and RNA extraction is then continued according to the method given by the manufacturers of TRIzol Reagent i.e.:- The aqueous phase, approx 0.6 ml, is transferred to a sterile eppendorf tube and 0.5 ml of isopropanol is added. After 10 minutes at room temperature the samples are spun at 12,000 x g, 4 °C for 10 minutes. The supernatant is removed and discarded then the RNA pellet is washed with 1 ml 75% ethanol. A brief vortex is used to mix the sample before centrifuging at 7,500 x g, 4 °C for 5 minutes. The ethanol is removed and the RNA pellet dried under vacuum for no more than 5 minutes. Samples are then resuspended by repeated pipetting in 100 microlitres of DEPC treated water, followed by 5-10 minutes at 55 °C. Finally, after at least 1 minute on ice, 200 units of Rnasin (Promega) is added.

RNA preparations are stored at -80 °C for up to one month. For longer term storage the RNA precipitate can be stored at the wash stage of the protocol in 75% ethanol for at least one year at -20 °C. Quality of the RNA isolated is assessed by running samples on 1% agarose gels. 1 x TBE gels stained with ethidium bromide are used to visualise total RNA yields. To demonstrate the isolation of bacterial RNA from the infected tissue 1 x MOPS, 2.2M formaldehyde gels are run and vacuum blotted to Hybond-N (Amersham). The blot is then hybridised with a ³² P labelled oligonucletide probe specific to 16s rRNA of S.aureus ( K.Greisen, M. Loeffelholz, A. Purohit and D. Leong. J.CIin. ( 1994) Microbiol. 32 335-351 ). An ohgonucleotide of the sequence:-

5'-gctcctaaaaggttactccaccggc-3' [SEQ ID NO:91] is used as a probe. The size of the hybridising band is compared to that of control RNA isolated from in vitro grown S.aureus WCUH29 in the Northern blot. Correct sized bacterial 16s rRNA bands can be detected in total RNA samples which show extensive degradation of the mammalian RNA when visualised on TBE gels. c) The removal of DNA from Staphylococcus aureus WCUH29 derived RNA DNA was removed from 73 microlitre samples of RNA by a 15 minute treatment on ice with 3 units of DNAasel, amplification grade (Gibco BRL, Life Technologies) in the buffer supplied with the addition of 200 units of Rnasin (Promega) in a final volume of 90 microlitres.

The DNAase was inactivated and removed by treatment with TRIzol LS Reagent (Gibco BRL, Life Technologies) according to the manufacturers protocol.

DNAase treated RNA was resuspended in 73 microlitres of DEPC treated water with the addition of Rnasin as described in Method 1. d) The preparation of cDNA from RNA samples derived from infected tissue

10 microlitre samples of DNAase treated RNA are reverse transcribed using.a Superscript Preamplification System for First Strand cDNA Synthesis kit (Gibco BRL, Life Technologies) according to the manufacturers instructions. 1 nanogram of random hexamers is used to prime each reaction. Controls without the addition of SuperScriptll reverse transcriptase are also run. Both +/-RT samples are treated with RNaseH before proceeding to the PCR reaction e) The use of PCR to determine the presence of a bacterial cDNA species PCR reactions are set up on ice in 0.2ml tubes by adding the following components:

45 microlitres PCR SUPERMIX (Gibco BRL, Life Technologies).

1 microlitre 50mM MgCl₂ , to adjust final concentration to 2.5mM. 1 microlitre PCR primers(optimally 18-25 basepairs in length and designed to possess similar annealing temperatures), each primer at lOmM initial concentration.

2 microlitres cDNA. PCR reactions are run on a Perkin Elmer GeneAmp PCR System 9600 as follows: 5 minutes at 95 °C, then 50 cycles of 30 seconds each at 94 °C, 42 °C and 72 °C followed by 3 minutes at 72 °C and then a hold temperature of 4 °C. (the number of cycles is optimally 30-50 to determine the appearance or lack of a PCR product and optimally 8-30 cycles if an estimation of the starting quantity of cDNA from the RT reaction is to be made).

10 microlitre aliquots are then run out on 1% 1 x TBE gels stained with ethidium bromide with PCR product, if present, sizes estimated by comparison to a 100 bp DNA Ladder (Gibco BRL, Life Technologies). Alternatively if the PCR products are conveniently labelled by the use of a labelled PCR primer (e.g. labelled at the 5'end with a dye) a suitable aliquot of the PCR product is run out on a polyacrylamide sequencing gel and its presence and quantity detected using a suitable gel scanning system (e.g. ABI Prism 377 Sequencer using GeneScan software as supplied by Perkin Elmer) RT PCR controls may include +/- reverse transcriptase reactions, 16s rRNA primers or DNA specific primer pairs designed to produce PCR products from non- transcribed S.aureus WCUH29 genomic sequences.

To test the efficiency of the primer pairs they are used in DNA PCR with WCUH29 total DNA. PCR reactions are set up and run as described above using approx. 1 microgram of DNA in place of the cDNA and 35 cycles of PCR. Primer pairs which fail to give the predicted sized product in either DNA PCR or

RT PCR are PCR failures and as such are uniπformative. Of those which give the correct size product with DNA PCR two classes are distinguished in RT/PCR:

1.Genes which are not transcribed in vivo reproducibly fail to give a product in RT/PCR. 2.Genes which are transcribed in vivo reproducibly give the correct size product in

RT PCR and show a stronger signal in the +RT samples than the signal (if at all present) in -RT controls.

The following nucleotide sequences (sequences set forth in SEQUENCE 1 [SEQ ID Nos: 1 ,4,7, 10, 13, 16, 19,22,25,28,31 ,34,37,40,43,46,49,52,55,58,61 ,64,67,70,73 ,76] of Table 1 ) were identified in the above test as transcribed in vivo. Each set of sequences relates to a separate gene (Gene #). Deduced amino acid sequences are given where available as the sequences set forth in each SEQUENCE 2 [SEQ ID Nos: 79,80,81,82,83,84,85,86,87,88,89,90] of Table 1. The pair of PCR primers used to identify the gene are given as the sequences set forth in SEQUENCE 3 [SEQ ID Nos: 2,5,8,1 1 ,14,

17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71 ,74,77] and 4 [SEQ ID

Nos: 3,6,9, 12, 15, 18,21 ,24,27,30,33,36,39,42,45,48,51 ,54,57,60.63,66,69,72,75,78] of Table 1. Homologies to known genes are given where determined and represent the putative identification of gene function for each gene in Table 1.

TABLE 1

Gene # 1

E.coli pts system 5'end ptfB

SEQUENCE 1 [SEQ ID NO: 1]

1 CTAGGAGTAG TATTTGGTTC ATGATTGCCT AATTCAATCA CATCTTTACT

51 TTGCTCTAAG TGCAAATCAC GCAATTGACC ATNTGGATCT CGTCTATCAT

101 AGTCATAAAT ACGGTATGTC GTATCGGATG ATTGTTGTGT CTCTAAAATT

151 AAAATACCCG AACCAATGGC ATGGACAGTG CCAGCAGGAA CATAATAAAA 201 GTCACCGGGC TTAACAGGTA TACGTTTGAA AAGACTGCCA AATTCATGAT

251 TATCAATCAT GTCGATTAAC GCCTGTTTAT TATGTGCATG GACGCCATAA

301 TATAATTTCA GCACCTGGGC TGCATCTAAA TATACCAACA TTCTGTTTTA

351 CCTAGTTCGC CTTCGTGTTT TAAAGCGTAG TCATCATCTG GATGAACTTG

401 AACAGATAAT TTATCATTGG CATCTAATAC TTTAGTTAGC AGAGGGAAAC 451 TATCTCGTGA ATCATTATCG AATAATTCAC GATGTTGTGA CCAAAGTTGA

501 TCTAGGGTCA TATCCTTGTA TGGACCATTG ATAATTGTAT TAGGACCATT

551 TGGATGTGCA GAAATTGCCC AGCATTCACC AGTTGTTTCA TTAGGGATAT

601 CATAGTTAAA TGCTTTTAAT GCATGACCGC CCCAAATTCT GTCTTTAAAA

651 ACGGGTTGTA AAAATAATGC CATAGTTAAA ACTCCTCTAT ATTTTCATTA 701 AT AGTTATA AATTTCTGTA GTACTGTTGG CATTAATTAG TGATTGGCGT

751 GTCTCATCAT TCATTAACGC TTTAGATAAG CGCTGAAGTA TTTTTAAATG

801 TGTATCCTGA CTGTTGTTTG GTACGGCAAT TAAGAATATC AATTGAGGTA

851 GACTACCATC TAGACTGTCC CATTTAACAC CATGATTATT TTTCATAACA

901 GCTACAATCG GTTGTTTTAC AACATCAGAC TTTGCATGTG GAATGGCCAC 951 GTTCATGCCA ATAGCTGTCG TAGACTCCAT TTCACGTTCT AGTATTGCAT 1001 TTTTTAAATG CGATGTGTGC TCTACATAAC GGCAAATTTT AAGTTTATGA

1051 ATCAACATAT CAATTGCTTC GTTTCGAGAC ATGTCGTGAT CAGTAATTAT

1101 CATAGTTTGT TGATCAAAAA CATGAGAAGG TTTATTGAGA TGTGAATGTT

1151 TCGCTCGTGC CATCNACATT GTCAACCTCT GTATCATGTT GTGTAATATC 1201 TGTATCATGA AGTTGCGTGT GTTGCGCTGG TGCATCTACT GCTATAACTG

1251 GTGTATTGCG TNTTAATAAT AGTACAGTAG GCATTGTGAC AAGACTACCT

1301 ACTATCNCTC CAAAGATAAA CCATAATACA TGATCAATAC CACCTAATAC

1351 AGCCACGATT GGACCTCCAT GTGCGACTCT ATCGCCGACA CCACCAATGN

1401 CTGCAATGAC TGATGCAATC ATTGCACCAA TGATGTTTGC AGGTATAATG 1451 CGCAATGGAT CTTGGGCTGC GAAAGGAATA GCACCTTCAG TAATNCCAAA

1501 TAGTCCCATA GTGAAGGNAG CCTTACCCAT TTCTCTTTCG GAATGATTGA

1551 ATTTATACTT NTGAACANAC GTTGCTAAAC CTAAACCGAT TGGTGGTGTA

1601 CATACANCAA CTGCGACCAT ACCCATAACG GCGTAATTAC CTTCAGCAAT

1651 AAGTGCTGAG CCAAATAAAA ATGCTACCTT GTTTAATTGG ACCGCCCATA 1701 TCGAAGGCGA TCATCGCACC TATAATCATC GACAAGTATA ATAATATTAG

1751 CACCTTGCAT ACTTTTTAAC CAGGGTTGTT AGGAATGCCG CAAAAATATT

1801 AGAAATCGTG CACCGATTAA AAATATAAAT ATCAATCCTA ACAACGACCG

1851 ATGAAATAAT GGGAATAATA ATGATAGGCA TAATTGGTGC CATTGCTTTT

1901 GGAACTTTAA TATCTTTAAT CCACTTTGCG ATATAACCTG CTAAGAAACC 1951 AGCAACAATA CCACCTAAAA ATCCTGCGCC TGCATCACTG CCATAAAAAC

2001 TACCGTCAGC AGCGATAGCG CCGCCAATCA TACCAGGAAC AAGACCGGGC

2051 TTGTCAGCGA TACTAACAGC GATATATCCA GCTCGTGCCG AATTCGGCAC

2101 GAGCTCGTGC C

SEQUENCE 2 (STOPS SHORT) [SEQ ID NO:79]

1 MGMVAVXVCT PPIGLGLATX VXKYKFNHSE REMGKAXFTM GLFGITEGAI

51 PFAAQDPLRI IPANIIGAMI ASVIAXIGGV GDRVAHGGPI VAVLGGIDHV 101 LWFIFGXIVG SLVTMPTVLL LXRNTPVIAV DAPAQHTQLH DTDITQHDTE 151 VDNVDGTSET FTSQ* SEQUENCE 3 [SEQ ID NO: 2] accctctgta tcatgttg

SEQUENCE 4 [SEQ ID NO: 3] gtgcgatgat cgccttgg

Gene #2 E.coli RelA

SEQUENCE 1 [SEQ ID NO: 4]

1 CGGCTCTTCG TAATATTGAT AATGTGCAAT ATTTNAAGAA TAATCAATTT

51 ATTGAAGAAG AAACCGTAGT GACCGTGAGC GAATATCGAA NCGGCTATTG

101 ATAGAATACG TACTGAAATG GACCCGAATG AATATCGAAG NCGATATAAA

151 TGGTAGACCT AAACATATTT ACAGTATTTA TCGGNAAATG ATGAAGCAGA 201 AAAAACAATT TGATCAAATT TTTGATTTGT TGGCGATACG TGTTATTGTC

251 AATTCTATTA ATGATTGTTA TGCGATACTT GGGTTGGTGC ATACGTTATG

301 GAAACCGATG CCAGGACGTT TTAAAGATTA TATTGCAATG CCTAAACAAA

351 ATTTGTATCA GTCATTGCAT ACTACAGTAG TAGGTCCAAA TGGAGACCCG

401 CTCGAAATCC AAATACGAAC GTTTGATATG CACGAAATTG CTGAGCATGG

451 TGTTGCAGCA CACTGGGCTT ACAAAGAAGG TAAAAAAGTA AGTGAAAAAG

501 ATCAAACTTA TCAAAATAAG TTAAATTGGT TAAAAGAATT AGCTGAAGCG

551 GATCATACAT CGTCTGACGC TCAAGAATTT ATGGAAACCT TATAATATGA

601 CTTACAGAGT GACAAAGTAT ACGCATTTAC CCCAGGGAGT GATGTTATTG

651 AGTNGGCATA TGGTGCTGTG CCGATTGGAT TTTGGCTTAT GCGAATCACA 701 GGGAANGTAG GTAATAAGAT GATTGGCGCC CAGGTGGAAT GGCAAAATTG

751 TACCANATTG ACTTATNTTT TCACAAAACA GGCGGATATT GTTGGAAATA

801 CCGTTCTAG

SEQUENCE 2 [SEQ ID NO: 80]

1 MNIEXDINGR PKHIYSIYRX MMKQKKQFDQ IFDLLAIRVI VNSINDCYAI

51 LGLVHTLWKP MPGRFKDYIA MPKQNLYQSL HTTVVGPNGD PLEIQIRTFD

101 MHEIAEHGVA AHWAYKEGKK VSEKDQTYQN KLNWLKELAE ADHTSSDAQE

151 FMETL* SEQUENCE 3 [SEQ ID NO:5] agatacgtac tgaaatgg

SEQUENCE 4 [SEQ ID NO: 6] cctgtgattc gcataagc

Gene #3 Staph FemB SEQUENCE 1 [SEQ ID NO:7]

1 GTGATGTGGC TAAACGCTTA AATGCAAATA TATATGTGTC TGGCGAAGGT

51 GAAGATGCAT TAGGGTATAA AAATATGCCA TCAAAAACAC AATTTGTTAA 101 ACATGGAGAT ATCATTCAAG TAGGCAATGT TAAATTAGAA GTTCTGCATA

151 CTCCAGGACA CACGCCTGAA AGTATTAGCT TTTTACTCAC TGATTTAGGT

201 GGTGGNTCAN GTGTTCCGAT GGGATTATTT AGTGGTGACT TTATTTNTGN

251 TGGTGATATA GGTAGACCTG ATTTATTAGA AAAATCTTGT TCAAATAAAG

301 GGTTCGGCAC GAAATTAGCG CGAAACAAAT GTATGAGTCC GATCAAAATA 351 TTAAAAATTT ACCAGACTAT GTTCAAATCT GGCCGGGTCA TGGTGCTGGA

401 AGCCCTTGTG GTAAAGCATT AGGTGCCATA CCTATATCTA CAATAGGTTA

451 TGAGAAAATT AATAACTGGG CATTTAATGA AATTGATGAG ACTAAATTTA

501 TTGNNTCATT AACATCAAAT CAACCAGCAC CACCNCATCA TTGTGCACAA

551 ATGAAACAAG TTANTCAGTG TGGCATGAAT TTATNTCAAT CATATGATGT 601 TTATCCNAGC TTAGATNATA AGAGAGTAGC ATTTGATCTT CGCGTAGCAA

651 AGAGGGCTTT CACGGGTGGC CACACAAAAG GAACAATCAA TATACCATAC

701 AACAAAAACT TTATTANTCA ANTTGGGTGG GTACTTAGAT TNTGAAAAAG

751 ATATAGATTT AATTGGAGAT AAATCTACTG TTGAGAAAAG CGAAACACAC

801 TTTACAATTA ATTGGGTTTG ATAAGGTAGC AGGCTATCGT NTGCCAAAAT 851 CAGGCATTTC ACCCCAGTCC GNTCATAGCG CTGATATGAC AGGTAAAGAA

901 GAACATGTAT TAGACGTACG TAATGATGAA GAGTGGAATA ATGGACACTT

951 AGNTCAAGCA GTTAATATTC CACATGGTAA ATTATTAAAT GAAAATATTC

1001 CTTTTAATAA AGAGGATAAA ATATATGTAC ATTGTCAGTC AGGTGTTAGA

1051 AGNTCAATTG CAGTGGGGTA TATTGGGAAA GCAAAGGCTT SEQUENCE 2 [SEQ ID NO: 81]

1 DVAKRLNANI YVSGEGEDAL GYKNMPSKTQ FVKHGDIIQV GNVKLEVLHT

51 PGHTPESISF LLTDLGGGSX VPMGLFSGDF IXXGDIGRPD LLEKSCSNKG

101 FGTKLARNKC MSPIKILKIY QTMFKSGRVM VLEALWKH*

SEQUENCE 3 [SEQ ID NO:8] ttcgggtgtt ttaccttc

SEQUENCE 4 [SEQ ID NO: 9] tgcagcaagc cttttctc

Gene #4

DiCitrate Binding Protein

SEQUENCE 1 [SEQ ID NO: 10]

1 AGCAGAATCT TTTTTAGCAT GATCTGTCAT AATGATCATA CGCTCTGGAT

51 TTAAATCAGC TAAATGTTCA GTGTCTAATT GTAAGTAAGG TCCTTTCAAA

101 TATTTACTTA AACCTTGTGT TACATCGTCA CTTAATGCAT TTTTAAATCC 151 TAGNTCGTTT AAAAATTGTC CAACATATGA ATAGTGTGGA TGTGCTAATA

201 AACCAGCTTT AGCAACTACT GCTGGAAGCA CTTTGTGATT TCTATCAAAT

251 TTAATTTCAT CTTTATACTT ATTGATTAAT TTATCATGCT CAGCAAGACG

301 TTTNNCGCCT TCTTTNTCTT TATTTAAAGC TTTAGCAATT GTTGTTGAAC

351 GAATTAATAT TGTGGGTGTA GTCTCCATCA AAACTCTTTA ATGATAATGT 401 GGTGCAATGT GGGCTAATTC TTTATTAATA CCCTTATGTC TACTGCTATC

451 AGNGATAATT AATCCCGGNT TTAATTTACT AATNTCTCTT AAGTTNGCTT

501 GTTACGTGTA CCTACAGAAG TATTACCCCC AATTTTTCTC TTACTGGGTT

551 ATGATACGTT TTTTCTTACC ATCATCAGCA ATACCAACTT GGTNTAACGG

601 CTATATGCTG NTAATGCAAC CTTGCAAATG AGTACTCTAA TACAACGATA 651 CGTTGTGCAT CTTTAGGTAC TTTTACTGTA CCATTTTCAT CTTTTACCCG

701 AAATAGTATC TTTAGTTGAT GATTCTTCTT TTACTTGAAT TATCCGTATT

751 ACCACAAGCT GCAACTAAAA GTAAGGCAAC TATTAATCCC AATATACTAA

801 AAGTTTTTAG ACCTCTCATC NGTCCCACTC CTTAATATGT ATANCTTCAT

851 TTATTATTTT ATTGATAACA ATTATCATTG TCAAGTAGCG TTCAATCTTT 901 TTTATATTTC TAAAATGTAT GACTATATAT TTCCTCTAAT AATTATGACT 951 ACAATTAGCA CATTTCCTTA GACAAAATAC TGATAATGTA TCATTGCTAT

1001 ATCATCTTTG CATTAATACA ATTGACACCA CTTAGCATGA CCGNTATCCC

1051 TGTAATTCAG CTGATATTAT CTGTTGCAAT TTTATGTGAC GAACTGTTGC

1101 ACTTAATTTG ATAANTCAAC AANTACAANA NATCTAAGTT GAACAATTAT 1151 GATACAACCG TGCAAACGAT ATGTAGTATA ACTTGTCAAC TTAGAATTAT

1201 TGATAAATAT ATTAATATTG GTTTACCATA GCAGGAGATT TCACATCAAA

1251 ATTTTGAAGT AGCGTATCAA TCTTTGAATC ATCAATATAT ACCTTATGTA

1301 AATTTTTCAT ATACATCGAA TGAGAAAGTG CTTCATAATT TAATGAAAAA

1351 GATATATGAT CTCCAACTTG ATAGTGTCCT TGACCATTTA AATCAAGCAT 1401 TAAATGATCA CTCGAAGCGC CTAAAATATT GATATGCTGA TCCATAGGTG

1451 AAATATTATC GACTTGTGTA TCTNAAATAA CCAATATCTA CAATAGCTTG

1501 TAAGAATGAT TCATGCGTGT GTGTATTAAC TCGAGGTTTA ATTTCTAAAA

1551 TCTCAGCCTC CAATGTAATC GCATCTTGAT ATAACATAGC GAATCGCTTG

1601 ATTTGCGTTG TTTCAACAAC TCTAAACAAC GTNTCANCTA TTCGGAANTC 1651 AATTTATTTT TACCCAAATC AATATATAAA AGGTGGGGGG NAACATGCTC

1701 CGAATTACCA CCCGGAAATA ATTTNCANTC GATATCCTAT TTCTCTTNCA

1751 ACAGCTGAGA CGAATCGATT AATCATAAAG ATATCANCAC CACTTGGCGC

1801 ATCAGATTTA AAACACATAA AATTGAATGC TAAACCTACA AAATGGATAT

1851 TTTNCAAGTG AATAATCTCT TTANTATAAT CTAAAACATC ATAAGTCAGA 1901 ACACCTTCAC GGACATCTTT CCAATCTACC ATTAATAAAA TCTTATGTTT

1951 TTTTCCTAAA ACTTCTGCTA CTTCATTTAT NTGATGTATG GTAGATAATT

2001 CTGTGTGGAT ACTCATATCA ACTTTCCTCT ATCATATCTG AAATCTCTTT

2051 TGNGGGAGGC GTACGCAATA ACGTATATGT TAAATCCTGA TCTGCAATAC

2101 TAATTATGTT ATCCAATCTG GATTCTGCAA CATGATTGAT ACCTAACGCT 2151 TTTAAGCTTN CTACAATGGT ACGGGCANCA GCTATACACT TAATTACTGG

2201 TGTGANTNGN ATATTTTTAC TTTGAAAACT NNGTGGAGGT ACTTGGG

SEQUENCE 3 [SEQ ID NO: 11] tgtaagtaag gtcctttc SEQUENCE 4 [SEQ ID NO: 12] taatacttct gtaggtac

Gene #5

Staph enterotoxin etxA

SEQUENCE 1 [SEQ ID NO: 13] 1 GGCACGAGCG GCACGAGCGT GTTGTATCAA GATTTTGTAG GCAGTTTTAC

51 AACGTCCGAT TCAGCAAGTT ATGCACAAGA TTTTAAATCT GAGGAAAACG

101 CTAAAAAGAT TGCTGAAACT TTAAATCTTT TATATCAATT AACAGGCAAT

151 CAAAACGGTG TGAAAGTTGT GAAAGAAGTT GTGGATAGAA CTGACTTGTC

201 ATCTGATAAA TCAGTTGATA GCGAAACAAT GTAACTATAC TAAGTTATGA 251 GCATTACGCT CATAGCTTTC TTAGAAAGTA GGTGTAGTTT TGGATGATAT

301 TCAGAAAATA AAAAAAGAGC TTTCTGAATT AGTTGAACGT GTTGATGATG

351 TTGAAATACT AGCAAACGAA ACAGCTGATC ATGTGCTTGA ACTTAGAGAG

401 GAACATAAGC AACATCATAA TGAACTAAGA GAATCTCATA AAGAACTTAA

451 AGATAAGCAA GATAAAGTTG TAGATGAGAA TTTAGAGCAA ACAAAGATAT 501 TAAACAGAAT TGAAGAAAGA TATCANACGC AAGTAGNTGT TGNGCAAAAA

551 AATGAAGAAA AGACACTCGC CCAAAATAAA TGGCTCGTAG GTGCCATATG

601 GGCGCTTGTA ACAATTGTTA TGATTGCAGT CATTACTGCA TCAATTNCTG

651 CGTTATTACC TTAAGGGAGG TGGACATAAT GAGTTGGGCA AGATGGTTAT

701 CATGTTATTT GTNTGGTCGT AAATGTAAAT AATGTTTTTG GTCAGTGCAT 751 CGGCACTGGC TTTTTATTTT GATTGAAAAG AGGTACGTAC ATGGTATTAC

801 ACAGCTCACA AGACAGGAAG CATACTCCAA GTGAAGTTGG GAAGTGTTGT

851 TAATACCAAG TAAGTAGGAT ATCTGANATG TATAATAGAG TAAAAATGAA

901 ATCTTTTTAT TATAGACACA TATAAAAAGT GTATAGTAAT ATATGTATGT

951 ATAATTAAAT GATAATCATT TCATAATTAT TGTATATAAC TAAATAACTA 1001 CTTAACANAA ATAATTATGC TTTAGAGNTG ACCANNATGA NNNANNCCAG

1051 CATTTACATT ACTTTTATTC ATTGCCCTNA CGTTGACNAC AAGTCCCANT

1101 TGTAAATGGT AGCGAGAAAA GCGNAGNAAT AAATGCGAAA GATTTGCGAA 1151 AAAAGTCTGA ATTCCAGGGN ACAGCTTTAG NCAATCTTAN NCANATCTAT

1201 TATTACNATG NNANAGCTAN AACTGAAAAT AAAGAGAGTC CNCGACCACA

1251 TTTTTACAGC ATACTATATT GTTTANAGGC TTTTTTACAG ATCATTCGTG

1301 GTATANCGAT TTATTAGTAG ATTNTGATTC NNAGGATATT GTTNATAAAA

1351 ATAAAGGGNA AANAGTAGAC TTGTATGGTG CTTATTATGG TTATCAATGT

1401 GCGGGTGGTA CACCACACAA AACAGCTTGT ATGTATGGTG GTGTAACGTT

1451 ACATGATAAT AATCGATTGA CCGAAGAGAA AAAAGTGCCG ATCAATTTAT 1501 GGCTAGACGG TAAACANAAT ACAGTACCTT TGGAAACGGT TAAAACGAAT

1551 AAGAAAAATG TAACTGTTCA GGAGTTGGAT CTTCAAGCAA GACGTTATTT

1601 ACAGGAAAAA TATAATTTAT ATAACTCTGA TGTTTTTGAT GGGAAGGTTC

1651 AGAGGGGATT AATCGTGTTT CATACTTCTA CAGAACCTTC GGTTAATTAC

1701 GATTAATTTG GTGCTCAAGG ACAGTATTCA NATACACTAT TAAGAATNTA 1751 TAGAGATAAT AAAACGATTA ACTCTGAAAA CNTGCGTAG

SEQUENCE 2 (Short) [SEQ ID NO: 82]

1 MYGGVTLHDN NRLTEEKKVP INLWLDGKXN TVPLETVKTN KKNVTVQELD 51 QARRYLQEK YNLYNSDVFD G VQRGLIVF HTSTEPSVNY D*

SEQUENCE 3 [SEQ ID NO: 14] atcccctctg aaccttcc SEQUENCE 4 [SEQ ID NO: 15] aaatggtagc gagaaaag

Gene #6 Staph Lipase Precursor

SEQUENCE 1 [SEQ ID NO: 16]

1 TCAAATGCAG TCAGGGAAGC AATAGGACGA TATGCATAAA GGAGATGGTA 51 AAGTGGAACA GTGACAGAAG GTAAAGACAC GCTTCAATCA TCGGAGNCAT

101 CAATCAANCA CAAAATAGTA AAACAATCAG GAACGCAAAA TGATAATCAA

151 GTAAAGCAAG ATTCTGGAAC GACAAGGTTC TAAACAGTCA CACCAAAATA

201 ATGCGACTAA TAATACTGAA CGTCAAAATG ATCAGGTTCA AAATACCCAT

251 CATGCTGAAC GTAATGGATC ACAATCGACA ACGTCACAAT CGAATGATGT 301 TGATAAATCA CAACCATCCA TTCCGGCACA AAAGGTATTA CCCAATCATG 351 ATAAAGCAGC ACCAACTTCA ACTACACCCC CGTCTAATGA TAAAACTGCA

401 CCTAAATCAA CAAAAGCACA AGATGCAACC ACGGACAAAC ATCCAAATCA

451 ACAAGATACA CATCAACCCG CGTGCCTCAA ATCATAGATG CAAAGCAAGA

501 TGATACTGTT CGCCAAAGTG AACAGAAACC ACAAGTTGGC GATTTAAGTA

551 AACATATCGA TGGTCAAAAT TCCCCAGAGA AACCGACAGA TAAAAATACT

601 GATAATAAAC AACTAATCAA AGATGCGCTT CAAGCGCCTA AAACACGTTC

651 GACTACAAAT GCAGCAGCAG ATGCTAAAAA GGTTCGACCA CTTAAAGCGA

701 ATCAAGTACA ACCACTTAAC AAATATCCAG TTGTTTTTGT ACATGGATTT

751 TTAGGATTAG TAGGCGATAA TGCACCTGCT TTATATCCAA ATTATTGGGG 801 TGGAAATAAA TTTAAAGTTA TCGAGGGAAT TGAGAAAGCA AGGCTATAAT

851 GTACATCAAG CAAGTGTAAG TGCATTTGGT AGTAACTATG ATCGCGCTGT

901 AGAACTTTAT TATTACATTA AAGGTGGTCA CGAGCGTAGA TTATGGCGCA

951 GCACATGCAG CTAAATACGG ACATGAGCGC TATGGTAAGA CTTATAAAGG

1001 AATCATGCCT AATTGGGAAC CTGGTAAAAA GGTACATCTT GTAGGGCATA 1051 GTATGGGTGG TCAAACAATT CGTTTAATGG AAGAGTTTTT AAGAAATGGT

1101 AACAAAGAAG AAATTGCCTA TCATAAAGCG CATGGTGGAG AAATATCACC

1151 ATTATTCACT GGTGGTCATA ACAATATGGT TGCATCAATC ACAACATTAG

1201 CAACACCACA TAATGGTTCA CAAGCAGCTG ATAAGTTTGG AAATACAGAA

1251 GCTGTTAGAA AAATCATGTT CGCTTTAAAT CGATTTATGG GTAACAAGTA 1301 TTCCGAATAT CGATTTAGGA TTAACGCAAT GGGGCTTTAA ACAATTACCA

1351 AATGAGAGTT ACATTGACTA TATTAAAACG CGTTAGTAAA AGCAAAATTT

1401 GGACATCAGA CGATAATGCT GCCTATGATT TAACGTTAGA TGGCTCTGCA

1451 AAATTGAACA ACATGACAAG TATGAATCCT AATATTACGT ATACGACTTA

1501 TACAGGTGTG TCTTCACATA CTGGTCCATT AGGGCACGAA AATCCTGCCG 1551 AATTAGGCAC GAGACATTTT TCTTAATGGA TACAACGAGT AGAATTATTG

1601 GTCATGATGC AAGAGAAGAA TGGCGTAAAA ATGATGGTGT CGTACCAGTG

1651 ATTTCGTCGT TACATCCATC CAATCAACCA TTTATTAATG TTACGAATGA 1701 TGAACCTGCC ACACGCAGAG GTATCTGGCA AGTTAAACCA ATCATACAAG

1751 GATGGGATCA TGTCGATTTT ATCGGTGTGG ACTTCCTGGA TTTCAACACC

1801 GTAAGGTGCA GAACTTGCCA ACTTCTATAC AGGTATAATA AATGACTTGT

1851 TGCGTGTGGA AGCGNCTGAA AGTAAAGGAA CACAATTGAA AGCAAGTTAA

1901 ATTCATCTTC TGAATTTAAT AGGCTATGTA AATCGTGCTG TTATCATGGC

1951 ACATCAGATA TAAGTAGCAT CACAGTGTTG AATCTCAAAA TAGTAAAGTG

2001 AAATAAAGCG CCTGTCTCAT TAGCGAAAAC TAAAGGGACA GGCGTATCTG 2051 TTTATGAGCT TAATAAATTG TATGAATAAT ATGGTTGATC GAATAACTGT

2101 TTATCATTGA TGATAAATTT GAGTTTTTTA AAAATAATTG ATATATTACA

2151 CCATTGTTAT AGCGTTTAAA GAAATCAACC CAACTTTACG ATAAATAGTG

2201 ATTGCTTCGT CATTAGGTCT ACGATCAAAA TCATGCTCGT TTTTATTCAC

2251 GCGTTCAAAT GTTGAATGTG GAACATGATT CATGATATGT TCGCTTTCCT 2301 CAACGGGAAC ATCATAATCG CCATTACAAT GCGCAATGAA AACAGGTGGA

2351 AGTGTTTTAA GNTCATCTGG TGCAATATTA TATTTTGAAT CAGTATAATC

2401 ANCAATGTTA ATCATATTTA TCCATTTACC TGTGCCACGT GCATAAACGT

2451 AGAGTAAAAA ACGTGTGCGA TTTGATCTTG ANCAACCGGT GTTGGTGAAG

2501 TGAGTTGTCC AATCATTGTT TCGTTTATGC TTTGAGCTAT TTTTGCGTAA 2551 TACCTATTAG TTGTTTTAAA AGGGTTCAGT GTTGATGCGA CTATAACCAT

2601 AAAAATCAAT AACACCATCA ATATCTCTGT CTCGTGCAAT TAATAAGACT

2651 TAAATATGCA CCTGATGATC TGCCAAAGGT AAAAATAGGG CAATTAGAAT

2701 ATTGTGATTG AATCGCATCG AATGATGCGT AGACATCCTC AATAATGCAA

2751 TCGAGACTTA CTTCTGGTAA TAAACGATAA CTTAGTTGAA TTAAATCGTA 2801 ATGTTCCGTA AGGATATCGA TATACTGTGG GGATAAATCG TTAGCTTTAC

2851 CGAACATTAA TCCACCACCG TGGATGTAGA CAATAACGCC TTTTGTTGGT

2901 TGATTTTTTG CTTTAATAAT TGTGTAAGGT AATGCAAATG CATCTTTAGT

2951 AATTACTTTA TATTTAATTT CAGTCACGAT TTAATAGGCT CCTTAGGAAT

3001 CCGATATTGA TGTCATTATA ACACTGTCNT NAATTTCCAT GNAAAATAGT 3051 CTTAAGACGA TGAGTCATGA TAATTCTGTT CCAATTGACG TAAAGCGTCN 3101 CGGGTATGCT TCTTTAGACC TTCCCCATAA TCCATCATTT TAACAATATC

3151 TTTAAAAGCA GCATGTGGNA TGGCTAAATC TTCTAAATCT GCCATAGAAA

3201 ATTCAAGATT GATATCATGT GGTCGCTGTT CAGCAAGTTT ATGCACAAAG

3251 TCAGGTTCTG TGACCAAAGG CGAAGACATG CCGACCATAT CTGCATGTTG 3301 TAAAGCATCT AAAGCAGACT CTGGAGAATT AATCCCGCCA CTTGCAATTA

3351 AAGGGATACG ACCTGCTAAA TGTTCATAGA CAATTTGGTT AACTGGTCGA

3401 CCGAAATGAT CACCTGGTGT ACGAGACGTA TTTTGATAAA TATGTCGACC

3451 CCAGCTAGCG ATTGCTAAGT ATTGGATGTT TGAAACGTCC ATGACCCAAT

3501 CGATTAATTG GTTGAACTCG TCAATGGTAT ATCCTAAATC ACTGCCTCTG 3551 GTTTCTTCTG GCGTTGCTCG AAATCCTAAA ATAAAATTGT CAGGTGCTTC

3601 TTTATCAATC ACTTCTTGTA CCGCACGCAT AACTTCTAAA CATAATCTTG

3651 CACGATTTTT TAATGAGTCG GCACCGTAAT GGTCTGTACG TCTATTTGAA

3701 AAAGTTGAGA AAAATGTTTG AATCAGCAAA CGTTGTGCAA TCGAAATTTC

3751 CACACCATCA AAACCTGCTT TAATCGCGCG TGCATCGAGC TCGTGCC SEQUENCE 3 [SEQ ID NO: 17] gactaataat actgaacg

SEQUENCE 4 [SEQ ID NO: 18] tctgtcggtt tctctggg

Gene #7

Fatty Acid Oxidation Complex Subunit SEQUENCE 1 [SEQ ID NO: 19]

1 CAGGCGTTTC CTCNGGTACN TGTTGCNNGC CTTTAATTAC CGACNCTGCA

51 ATANCCAAAC CGACCAGGTC GGATAGGGNA TATGTACCTG TTTTAGGACG 101 ACCAATCGCT TGCCCAGTTA AAGCATCCAC ATCTACNATG CTTANCTTGT

151 GTTGCTCGGC GCGATACAGA ATATCATTCA TTGTGTGCGT GCCGACTCTA

201 TTTGCGACAA AGCCAGGCAC ATCATTGACG ACAATGACAC CTTTACCTAA

251 TACATTGTGC GCGAAATTTT TTACATCTAA TATGATAGAT TCCTTCGTGT

301 GTGACGTAGG TATTAACTCC ACTAATTNCA TAATACGTGG TGGGTTAAAG 351 AAATGTAGAC CAAAGAATCG CTCTTGATCC TTCTCGTTAA ATGCTTGAGC 401 AATCGCATTA ATTGGGATTA CCTGATGTAT TTGTAGCAAA TAAAGCATCT

451 TCTNTAGCAT GTTGTAGAAC TTGTTGCCAA ACAGCATGCT TAATTTCAAT

501 ATCTTCTTTG ACTGCTTCGA TATATAAATC AGNATCATCA TTTACCAAGT

551 CATCATCAAA ATTACCATAT GTTAAATGAC TCACTAGATT TAAGTCGAAT 601 AGTAGCGGCC GTTTCTTATC TGTAATTTTA TCGTAAGATT TTTTCGCAAT

651 GAGATTTGGA TCGTTTGTGT CCACTACAAT ATCTAATAGT TTTACTTTAA

701 GTCCAGCATN CACAAAGAGT GCTGCCAGTT GAGCGCCCAT CGTGCCTGCG

751 CCAAGAACGG TTACTTTATT AATTGTCATA GTGATTCCTC CAATTTAGGT

801 GAGGATAAGA TAACCATTAA GATAATTGGA ATAACGNTGC TATTTTATNA 851 AATTAATTAA GTATCTTTGA CAAGACATCT CAGNCTCTTT ATTTTAAGGA

901 AAAAGCTTTA TGCTTAAAAT AAGTCTTTTT TAGTGAAATT AATGCATCTC

951 ATATAATTAT TTGCTATTTA TACGAAAGCA GAATCTCCAG TCAAAGCGCG

1001 TCCAATTACT AAGGCATTAA TTTCATGTGT ACCTTCGTAC GTGTAAATCG

1051 CTTCTGCATC AGAGAAGAAA CGTGCAATAT CATAATCGTC AGCTAGTATG 1101 CCATTACCAC CTGTAATACC GCGGCCCATA GCTACTGTCT CACGCAAACG

1151 TAAGGCATTC ATCATCTTCG CCGGTGAAGT TGCAACCTCG TCATATTCAC

1201 CATGTGCTTG CATATTAGCT AATTGAGCAC ATGTTGCCAT TGCTTGAGCT

1251 AAATTACCTT GCATCATTGC TAGCTTNTCT TGTATTAACT GATATTTACT

1301 AATTGGGTNT GCCGAATTGC TTACGCTCAA GTGACATAAT CTAATGTGGC 1351 ACGTAAAGCG CCAGCCATAC CACCTGTAGC CATATAAGCA ACGCCTGCTC

1401 TCCGGTGGAA TAAAGAATTT TG

SEQUENCE 2 [SEQ ID NO:83] 1 MLXKMLYLLQ IHQVIPINAI AQAFNEKDQE RFFGLHFFNP PRIMXLVELI

51 PTSHTKESII LDVKNFAHNV LGKGVIVVND VPGFVANRVG THTMNDILYR

101 AEQHKXSXVD VDALTGQAIG RPKTGTYXLS DLVG XIAXS VIKGXQXVPE

151 ETP

SEQUENCE 3 [SEQ ID NO:20; atgtacctgt tttaggac SEQUENCE 4 [SEQ ID NO:2i; gagtcattta acatatgg

Gene #8

ATP DEPENDENT RNA HELICASE DEAD

SEQUENCE 1 [SEQ ID NO:22]

1 ATACTTTGAT TTTAGATGAA GCTGATGAAA TGATGAATAT GGGATTCATC

51 GATGATATGA GATTTATTAT GGATAAAATT CCAGCAGTAC AACGTCAAAC

101 AATGTTGTTC TCAGCTACAA TGCCTAAAGC AATCCAAGCT TTAGTACAAC 151 AATTTATGAA ATCACCAAAA ATCATTAAGA CAATGAATAA TGAAATGTCT

201 GATCCACAAA TCGAAGAATT CTATACAATT GTTAAAGAAT TAGAGAAATT

251 TGATACATTT ACAAATTTCC TAGATGTTCA TCAACCTGAA TTAGCAATCG

301 TATTCGGACG TACAAAACGT CGTGTTGATG AATTAACAAG TGCTTTGATT

351 TCTAAAGGAT ATAAAGCTGA AGGCTTACAT GGTGATATTA CACAAGCGAA 401 ACGTTTAGAA GTATTAAAGA AATTTAAAAA TGACCAAATT AATATTTTAG

451 TCGCTACTGA TGTAGCAGCA AGAGGACTAG ATATTTCTGG TGTGAGTCAT

501 GTTTATAACT TTGATATACC TCAAGATACT GAAAGCTATA CACACCGTAT

551 TGGTCGTACG GGTCGGTGCT GGTAAAGAAG GTATCGCTTG TAACGTTTGG

601 TTAATCCAAT CGAAATGGAT TATATCAAGA CAAATTGAAG ATGCAAACGG 651 GTAGAAAAAT GAGTGACTCC GCCACCTCAT CGGTAAGAAG TACTTCCAAG

701 CACGTGAGGA TGACATCAAA GGAAAAGGTG GAAACTGGAT GTCTTTAAGA

751 GTCAAGAATC ACGCTGGAAA CGCATTCTTC AGAGGTGGGT AAATTGAATT

801 TTACGATGTG G

SEQUENCE 3 [SEQ ID NO:23] gatgaagctg atgaaatg

SEQUENCE 4 [SEQ ID NO: 24] tatctagtcc tcttgctg

Gene #9

PHOSPHORIBOSYLAMINE GLYCINE LIGASE

SEQUENCE 1 [SEQ ID NO: 25]

1 TAATTCGCAA TAGGAGTGAT GAATATCATA AATTTTACCC TCCAAATGAA 51 GCTAATGAAG TCCTGGACCC GAGTAAGACG CATGTAGCCA AGCTAAAATA

101 ATCCACTCTA CCTTATCTTT AGTTAATAAT GTTACTAAAT GTTGTTCATA

151 CGCTGCTTTT GAATCAAATT GTTTTGGTTC ATTAATATAA ACAGGAATAT

201 CGTGCTTGTT TGCTCTATCT ATACAAAACG CATTTTGATG ATCCGTATAT

251 AGCNCCGTAA CTTCAATATT TTCAAGTTTT CCTGATTCAA CATGCTCAAC

301 TATATTTTCA AAGTTACTTC CTGAACCTGA TGCAAAAATC GCAATTTTAA

351 CCATTGTTAT ACCCCCAACA ATTCAATTGC AGTTGACTCA TTTTTCACAA 401 TATGACCAAT TTGATAAGCT TCCACATTTT GTTCTGCTAA AATCTTCAAA

451 GCGCGTCGAT GCATCTTTTT CATCAACGAT AACCGTATAG CCAATACCCA

501 TGTTAAAAAT GTTATACATT TCATTTGTGT CTATATTGCC TTGTTGTTGT

551 AACCAATCAA ATATTTTTGG CGTTGGAAAT GATGTAGTAT CAATTCTAGC

601 AGCATATCCG GCTGGCAATG CACGTGGAAT ATTTTCATAA AAACCTCCAC 651 CAGTAATATG ATTCATTGCC TTAATAGAAA CTTCTTTTTT TAAAGCAAGT

701 ACAGGTNTGA CATATAATTT AGTTGGCTCT AAAAAGACAT CTATAAATGG

751 ACGATTATCG NAGGGTGATG CCAAATCAAT GNCTGATTCA NTAATTAATN

801 TGCGCACTAA ACTGTNTCCA TTNGANTGAA TGNCACTTGG ACGCAAGTCC

851 TATAACAACT TGGCCCTCTT NCAATTCTTG AACCATCTTA CAATAGNCAA

901 CCTTTTTCAA CTGCTCCAAC AGCAAATCCG GCTACATCAT ATTCACCTTC

951 GTGATACATT

SEQUENCE 3 [SEQ ID NO: 26] ataagcttcc acattttg

SEQUENCE 4 [SEQ ID NO: 27] gataatcgtc catttata

Gene #10

Methanobacteria formate dehydrogenase

SEQUENCE 1 [SEQ ID NO: 28]

1 GGCACGAGCG CTAAATAATT AATATTTAGT TTTTAAGTTA TTAATAACGT

51 AGGGATATTA ATTTTAAAAG AAGCAGACAA AATGGTGTTT GCTTCTTTTT

101 TATGTCGTAT AAGTAATAAA TAAAACAGTT TGATTTTAAA ATGAAAGCGT 151 AAAAATGGTA AAATATCCCA AAATTGATTG TGATATAATT ATAAGGAAAA

201 TGAGCAATTT ATGAAAAAAG TTTACGNACA AATCGGAGAA TTAAAACTAA

251 ATAATTATCA AAACAACGTC AATATTTAGT TGAATACTCA GACTTTAGCC

301 CATGGCCAAG TGGGGAAGAC AGCATATATT AGTAAAGGTG AATGATTTGT

351 TATTACTCAC TCGAAAATAG AAAGACAAGA TTTTAACGAT TAAAATAAAC

401 TATTTTACAA ATAAAGTAAA ATTAATTTAT TANGCTAATA ATGCAAAAAA

451 TTAAAAAGTA ATGGACAAAG AGATAATGAT ATGGCTCAAG AGGTAATAAA 501 ATAGAGGTGG ACGCACACTA AATGGGGAAG TTAATACAAG G

SEQUENCE 3 [SEQ ID NO: 29] gcacgagcgc taaatttg SEQUENCE 4 [SEQ ID NO: 30] CTTCCCCATT TAGTGTGC

Gene #11 E.coli Nitrate Reductase

SEQUENCE 1 [SEQ ID NO: 31]

1 CCACCCANCT GATTATAATG TTTTAGCANG AGCTAGACTT GGTTGGTTAC 51 CATCATATCC ACAATTTAAT AAAAATAGTT TGTTGTTTGC AGAAGAAGCT

1C1 AAAGATGAAG GCATTGAGTC GAATGAGGCA ATTTTAAAAC GAGCGATAAA

151 TGGAAGTTAA GTCAAAACAA ACGCAATTTG CGATAGAAGA TCCGGATTTG

201 AAAAAGAATC ATCCGGAAAT CACTGTTTAT ATGGCGCTCA AATCTAATCT

251 CAAGTTCTGC AAAAGGTCAA GAATACTTTA TGAAGCATTT ACTTGGCACA 301 AAATCAGGGT TATTAGCTAC ACCAAATGAA GATGAAAAGC CAGAAGAAAT

351 TACGTGGCGT GAGGAAACAA CAGGGAAATT AGATTTAGTC GTTTCTTTAG

401 ATTTCAGAAT GACAGCAACA CCTTTATATT CTGACATTGT TTTGCCAGCA

451 GCGACTTGGT ATGAGAAGCA TGATTTGTCA TCTACAGATA TGCATCCATA

501 TGTACATCCT TTTAATCCAG CTATTGATCC ATTATGGGAA TCGCGTTCAG 551 ACTGGGATAT TTATAAAACG TTGGCAAAAG CATTTTCAGA AATGGCAAAA

601 GACTATTTAC CTGGAACGTT TAAAGATGTT GTGACAACTC CACTTAGTCA

651 TGATACAAAG CAAGAAATTT CAACACCATA CGGCGTAGTG AAAGATTGGT 701 CGAAGGGTGA AATTGAAGCG GTACCTGGAC GTACAATGCC TAACTTTGCA

751 ATTGTAGAAC GCGACTACAC TAAAATTTAC GACAAATATG TCACGCTTGG 801 TCCTGTACTT GAAAAAGGGA AAGTTGGAGC ACATGGTGTA AGTTTCGGTG

851 TCAGTGAACA ATATGAAGAA TTAAAAAGTA TGTTAGGTAC GTGGAGTGAT 901 ACAAATGATG ATTCTGTGAG AGCGAATCGT CCGCGTATTG ATACAGCACG 951 TAATGTAGCA GATGCAATAC TAAGTATTTC ATCTGCTACG AATGGTAAAT

1001 TATCACAAAA ATCATATGAA GATCTTGAAG AACAAACTGG AATGCCGTTA 1051 AAAGATATTT CTAGCGAACG TGCTGCTGAG AAAATTCGTT TTTAAATATA

1101 ACTTCACAAC CACGAGAAGT AATACCGACA GCAGTATTCC CAGGTTCAAA

1151 TAAACAAGGT CGACGATATT CACCATTTAC AACGAATATA GAACGTCTAG

1201 TACCTTTTAG AACATTAACA GGACGTCAAA GTTATTATGT GGATCACGAA

1251 GTTTTCCAAC AATTTGGGGA GAGCTTACCA GTATATAAAC CGACATTGCC 1301 GCCAATGGTA TTTGGGAATA GAGATAAGAA AATTAANGGT GGTACAGATG

1351 CTTTGGTACT GCGTTATTTA ACGCCTCATG GANAATGGAA TATACACTCA

1401 ATGTATCAAG ATAATAAGCA TATGTTGACA CTATTTAGAG GTGTCCACCG

1451 GTTTGGATAT CANATGAAGA TGCTGNAAAA CACGATATCC AAGATAATGA

1501 TTGGCTAGAA GTGTATANCC GTAATGGTGT TGTAACGGCA AGAGCAGTTA 1551 TTTCGCATCG TATGCCTAAA GGTACAATGT TTATGTATCA TGCACAAGAT

1601 AAACATATTC AAACGCCTGG GTCAGAAATT ACAGATACAC GTGGTGGTTC

1651 ACACAACGCG CCGACTAGAA TCCATTTGAA ACCAACACAA CTAGTCGGAG

1701 GATACGCACA AATTAGTTAT CACTTTAATT ATTATGGACC AATTGGGAAC

1751 CAAAGGGATT TATATGTAGC AGTTAGAAAG ATGAAGGAGG TTAATTGGCT 1801 TGAAGATTAA AGCGCAAGTT GCGATGGTAT TAAATTTAGA TAAATGCATA

1851 GGATGCCATA CGTGTAGTGT GACATGTAAA AACACTTGGA CAAATCGTCC

1901 AGGTGCTGAG TAACATGTGG TTCAATAACG TAGAAACGAA GCCAGGTGTA

1951 GGGTATCCGA AACGTTGGGA AGACCAAGAA CACTACAAAG GTGGTTGGGT

2001 ACTAAANTCG TAAAGGGAAA CTTGAATTAA AATCTGGAAG TAGAATTTCA 2051 CAAATTGCTT TAGGTAAAAT TTTTTATAAC CCAGATATNC CATTAATAAA 2101 AGATTATTAT GANCCATGGA NCTATAATTA TGAACATTTA ACAACTGCGA

2151 AATCAGGGAA GCATTCGCCA GTTGCTAGAG CGTATTCAGA AATTACAGGG

2201 GATAACATTG AAATTGAATG GGGACCTAAC TGGGAAGATG ACTTAGCAGG

2251 TGGTCATGTT ACAGGCCCAA AAGATCCTAA CATACACAAA ATAGAAGAAG 2301 AGATTAAATT CCAATTTGAC GAAACTTTTA TGAG

SEQUENCE 2 [SEQ ID NO:84]

1 MKHLLGTKSG LLATPNEDEK PEEIT REET TGKLDLWSL DFRMTATPLY 51 SDIVLPAATW YEKHDLSSTD MHPYVHPFNP AIDPL ESRS DWDIYKTLAK

101 AFSEMAKDYL PGTFKDWTT PLSHDTKQEI STPYGW DW SKGEIEAVPG

151 RTMPNFAIVE RDYTKIYDKY VTLGPVLEKG KVGAHGVSFG VSEQYEELKS

201 MLGT SDTND DSVRANRPRI DTARNVADAI LSISSATNGK LSQKSYEDLE

251 EQTGMPLKDI SSERAAEKIR F*

SEQUENCE 3 [SEQ ID NO: 32] attgatccat tatgggaa

SEQUENCE 4 [SEQ ID NO: 33] catattgttc actgacac

Gene #12

E.coli ftsE (abc transporter)

SEQUENCE 1 [SEQ ID NO: 34]

1 AGTTATTGTA TTTAAAAATG TTTCATTTCA ATATCAAAGT GATGCATCCT

51 TCACATTGAA AGATGTTTCT TTTAATATAC CTAAAGGTCA GTGGACATCT

101 ATTGTTGGTC ATAACGGTTC TGGAAAATCT ACAATTGNCA AGTTAATGAT

151 TGGCATAGAG AAAGTTAAAT CTGGAGAAAT TTTTTATAAT AATCAAGCTA 201 TAACTGATGA TAATTNTGAA AAGTTAAGAA AAGACATAGG AATTGTATNT

251 CAGAATCCGG ATAATCAATN TGTTGGNTCA ATTGTAAAAT ACGATGTGGC

301 ATTTGGACTC GAAAATCATG CGGNTCCACA TGACGAAATG CATAGAAGAG

351 TCAGCGAAGC ACTTAAACAA GTTGATATGT TAGAACGTGC AGATTATGAC

401 CCTAATGCAT TATCGGGGGG ACAGAAGCAG CGTGTGGCTA TAGCAAGTGT 451 ATTAGCACTT AACCCTCTGT CATTATATAG ATGAGGCGAC TCTATGTTAG 501 GATCCCTGAT GCACGTCAAA TTTATGGGAT TTAGNGAGAA AGTAANTCAG

551 ACATTATATA CAATCATTCT ATACGCATGA TTTATCTGAG GCGATGAGNA

601 GATCAAGTAT CCGTATGATA AGGACTTNCT TTTAAGGC

SEQUENCE 3 [SEQ ID NO: 35] gtttcatttc aatatcaa

SEQUENCE 4 [SEQ ID NO: 36] atctatataa tgacagag

Gene #13

B.subtilis secA

SEQUENCE 1 [SEQ ID NO: 37]

1 GTTAATCAAG TATCGAAGCG GAACAATCAT ACTTTAATGT TGAAGATTTA

51 TATNGCGAAC AAGCGATGGT CCTAGTGCGT AATATTAATT TAGCACTGCG

101 CGCACAATAT TTGTTNGNAT CTNATGTCGA TTACTTTGTA TATNNTGGTG 151 ATATTGTTTT AACTGACCNC ATTACAGGTC GTNTGTTACC GGNAACTAAG

201 TTGCAAGCTG GACTTCACCA NGCTATTGAA GCGAAAGAAG GTATGGAGGT

251 TTCAACAGAT AAAAGTGTTA TGCCAACCAA TTACCCTTCC AGAATTTATT

301 TAAACTTTTT GAATCAATTT TCAGGTATGA CAAGCTACAG GAAAATTAGG

351 CGAATCAGAG TTCTTTGATT TGTATTCANA AATAGTCGTA CAAGCACCCA 401 ACTGATAAAG CGATTCAACG TATCGATGAA CCAGATAAAG TGTTTCGTTC

451 AGTTGATGAG AAAAACATCG CGATGATTCA TTGATATAGT TGAACTTCAT

501 GANNCGGGGC CGACCGGTTT TACCTCATAA CCGAGNACTG CTGAAGCGGC

551 TTGAATACTT TTCNGAAGTA TTATTCCAAA TGGATATTCC TAATAATTTA

601 CTCATTGCGC AAAATGTTCC AAAAGAAGCG CAGATGATAG CTGAAGCAGG 651 CCAAATTGGT TCCATGACTG TTGCGACTAG TATGGCAGGT CGAGGCACAG

701 ATATTAAACT TGGTGAAGGT GTCGAAGCAT TAGCTGGATT AGCTGTTATT

751 ATTCATGAAC ATATGGAAAA TAGCCGTGTA GACAGGCAAT TACGTGGTCG

801 TTCTGGTAGA CAAGGGGATC CGGGATCATC TTGTATATAT ATTTCACTAG

851 ATGATTATTT AGNTAAGCGA TGGAGCGATA GTAATTTAGC GGAAAATAAT 901 CAATTATATT CANTAGATGC ACAACGATTA TCGCAAAGTA ATTTGTTTAA 951 TCGNAAAGTT AAGCAAATTG TAGTTAAAGC GCAGCGTATC TCGGAAAGAA

1001 CAAGGGGTTA AAGCTCGGTG AAATGGCTTA ATTGAATTTG NNAAAAAGCA

1051 TNAGTATTCA GCGAAGATCT TNGTATTTAC GANGGAACGC AAATCCGAGT

1101 TTTTAGAAAT TAGATTGATG CTGAGAATCC NAGATTTTTA ANGCGGTTAG 1151 CTTAAAGATT GTATTTGAAA TNGTTTGGGG NAATGANGGA AANGGTGCTA

1201 ACAAAATCGC GNGTTGGGCG AGTATATTTT ATCAAAAATT TAAGTTNCCA

1251 ATTTAATAAA GATGTGGCTT GTGTTAATTT TAAAGATAAG CAAGCAGNAG

1301 TGACATTTTT ATTAGAGCAA TTTGAAAAGC AATTAGCTTT GGANTCCGTA

1351 AAAACATGCA ANGNGCATAT TATTATAATA TTNCCGGCCA AAANGTCTTT 1401 NGGGAAAGCA ATTGATNCAA GTTGGGGTTA GGAACAAGTC GGCTTTTNAC

1451 AACAANTTAA NAGCAAGCGN TAATCAAACG ACAAAANTGG CAACCT

SEQUENCE 2 [SEQ ID NO: 85] 1 MDIPNNLLIA QNVPKEAQMI AEAGQIGSMT VATSMAGRGT DIKLGEGVEA

51 LAGLAVIIHE HMENSRVDRQ LRGRSGRQGD PGSSCIYISL DDYLXKRWSD

101 SNLAENNQLY SXDAQRLSQS NLFNRKVKQI WKAQRISER TRG*

SEQUENCE 3 [SEQ ID NO: 38] ccgctaaatt actatcgc

SEQUENCE 4 [SEQ ID NO: 39] ctgaagcggc ttgaatac

Gene #14

E.coli choline dehydrogenase

SEQUENCE 1 [SEQ ID NO: 40]

1 ATATAAATTA TTTAAGCGTA TGGTTTTACT TCGATTGCAC CCTTCATTTT

51 CATCATTGAA CACCATGCTT AATATAATCC ATATATTTGT GGCTCTAAAG

101 NCTTTCCTCC CACCGTATAA TGTCTGCTGC TTTTTCAGCT AACATTAAAA

151 CAGGTGCGTG TATATTGCCA TTTGTCGTAC GTGGCATAGC GGATGCATCA 201 ACTACACGTA AATTTTCCAT ACCGTGGACT TTCATTGTTA ACGGGTCAAC

251 TACTGCCATT GGATNCTGAA GCAGGACCCA TTTTAGCACN ACAAGATGGG

301 TGTAATNCTG TTTCACCATC TCNACGGAAN NCAATCAAGN ATTTCTTCGT 351 CTGTTTGCAC TTCTGGGTCC TGGGTGAAAT TTCTCCACCA TTGAATGGAT

401 CCATTGCTTT TTGAGATAAG ATATTTCTTG CTACACGAAT TGCTTCTACC

451 CATTCTNTTT TATCTTCTTC TGTTGATAAA TAATTAAAGC GGATACTTGG

501 TTTTTCGAAT GGATCTTTAG ATTTGATTGG CACGAGCTAC CACGAGAGTT

551 TGAATACATT GGTCCTACGT GAACTTGATA ACCATGTGCG ACCGCTGCCT

601 TTTGACCATC ATATCTTACA NCTATTGGTA AGAAATGGAA CATTAAGTTA

651 GGATAATCAA CTTCGTTATT TGAACGTACA AATCCGCCAC CTTCAAAATG 701 GTTAGATGCT GCTGCACCTG TACGTGTGAA AATCCAGTGG TAAACCAATT

751 AAATGGCATG CGCCTTGATA TCTAAGCTTG GCTGTAATGA TACAGGTTTC

801 CTTACATTTA TGTTGAATGT ATACCTCTAA GTGATCTTCC AAAGTTTTCA

851 CCCACACCTG GTAAATGAAC ACGTGGCTCA ATGCCTTTTG ATTTTAGGAA

901 CTCTGAATCA CCGATACCAG ATAATTGTAG TAATTGTGGC GTTATTGAAT 951 GCCCC

SEQUENCE 3 [SEQ ID NO: 41] gaagcaggac ccatttta SEQUENCE 4 [SEQ ID NO: 42] gattttcaca cgtacagg

Gene #15 S.aureus DNA Gyrase

SEQUENCE 1 [SEQ ID NO: 43]

1 GAATTCCTAC ATAATACTTT TGTTTACCTT GTGTCAGTTT ATACAACGGT 51 GGCTGTGCAA TATACACATA GCCTGCTTCA ATTAACGGTC TCATAAATCG

101 ATAGAAGAAT GTTAATAACA ATGTTCTAAT ATGCGCTCCA TCCACATCGG

151 CATCAGTCAT AATGACGATT TTGTGATATC TTGCTTTCGC TAGATCAAAG

201 TCGCCACCGA TTCCTGTACC AAATGCTGTG ATCATTTGAC GAATTTCATT

251 GTTATTCAAA ATTCTATCTA ATCGTGCTTT NTCAACATTT AATATCTTAC 301 CTCGTAATGG TAAAATCGCC TGCGTTCTAG AGTCACGACA GATTTTGGTG

351 GACCCCCNGC AGAGTCCCCT TCGACTAAGA AAATCTCACA TTCTTCAGGA

401 CTTTTACTAG AGCAATCGGC TAATTTACTG GAAGACTGCT ACATCTACGC 451 TGATTTACGA GGTGTTACTT CAGGGCTTTN TCGAGACACG TGCANGT

SEQUENCE 3 [SEQ ID NO: 44] cataatactt ttgtttacc

SEQUENCE 4 [SEQ ID NO: 45] agtaacacct cgtaaatc

Gene #16

E.coli pts system ptkC

SEQUENCE 1 [SEQ ID NO: 46]

1 CTANCNAANG GAANTTCAGC ATCCTTAAAA ATACCTATTT GACTGTAGAA

51 ACCTTTTGNT GCGTACAATA TCTAAACCTT GTCGTGCTGC TGGAACTGCA

101 CCTGAACATT CAACAACAAC ATCTGCACCG TAACCGTCTG TAATTCCATT 151 GATATACGTT TTTAAGTCTG TGTGTTGTAA ATTGACTACA TAATCCATGT

201 GCAATGCTTC TGCTTTATCT AATCTGACTT NGTGGCANTG TCCAATCCAG

251 TTACCACAAC AGGTGCGCCT TTACTTTTCA ACACTTGTGC TACAAGTAAT

301 CCGATTGGCC CAGGTCCCAT TACAACTGCT ACATCGCCAG AGTTCACTTG

351 AATCTTAGAA ACGCCATGAT GTGCACATGC TAATGGTTCT TGTCATAGCT 401 GCAGACTGAT ACGATACTTC CGCTTCTGGA ATATGATNCA AACTTTCTTC

451 ACGTGCAATG ACATAATTAG TAAATGCGCC ATCAACTTGT GTTCCAATAC

501 CTTTTCGATG GTTGCATAAA TGATAGTTTT TTGATTTACA GGAATCACAC

551 TCATTACANA CCATAGAATG TAGTTTCAGA AGTGACNCGG TCACCAACTT

601 TAAAATCNTT AACGTCTGCT CCCAACTTCA ACGATNTCAC CAGAAAATTC 651 ATGACCTAAT GTCACTGGAA AATTAACTTN ATAATGCCCT TCATAAGTAT

701 GAAGGTCTGT GCCACAAATT CCTGCATAAT GTACTTTAAT CTTTACTTTA

751 TCATCTAGCG GTGTTGCAAC TTCTTTATCA AGAAGTTCTA AGTTGCCATG

801 TCCTTCTCTT GTTTTTACTA AAGCTTCCAC CACAAACACN TCGANTTTTT

851 ANTTGNAATA GACTNNATAG NTTNAAGATA AGATAGTTAN CGATATTNCC 901 ACCTTGATCA ATACTTGANA TTTCAGATGA ACCTTTTGNC ATTTGTACAT

951 TCGTACCTTT CGCCATATCT GTGAAAATGG GTGCTACGTC TGTTGCAATA

1001 TATAATGAAA TTGCAATCAT AATCGTACCC ACAATGACAG AATGAATAAT 1051 GTTTCCTCTT GCTGCACCAA CAATAAACGC GACAACAAAT GGTATAGTTG

1101 CTAAGTCACC AAAAGGTAGT ACTTGGTTTC CTGGTAAAAT AACGGCTAAT

1151 AAAACAGTGA TAGGTACTAA AATTAATGCT GTCGAAATAA CCGCTGGATG

1201 ACCTAATGCT ACAGCCGCAT CCAATCCAAT ATAAATTTCA CGTTCGCCAA

1251 AACGTTTATT TAGCCATGTT CTTGCAGACT CTGAAACTGG CATTAAACCT

1301 TCCATTAAGA TTTTTACCAT TCTAGGCATT AAGACCATTA CTGCAGCCAT

1351 TGACATTCCT AAATTAATGA TGTCTCCAGG TTTGTAACCT GCTAACACAC 1401 CAATACCTAA ACCTAAAATT AAGCCGACAA ATATAGACTC TCC

SEQUENCE 2 [SEQ ID NO:86]

1 GESIFVGLIL GLGIGVLAGY KPGDIINLGM SMAAVMVLMP RMVKILMEGL 51 MPVSESART LNKRFGEREI YIGLDAAVAL GHPAVISTAL ILVPITVLLA

101 VILPGNQVLP FGDLATIPFV VAFIVGAARG NIIHSVIVGT IMIAISLYIA

151 TDVAPIFTDM AKGTNVQMXK GSSEXSSIDQ GGNIXNYLIX XLXSLXQXKX

201 RXVCGGSFSK NKRRT QLRT S*

SEQUENCE 3 [ SEQ I D NO : 47 ] gttctaagtt gccatgtc

SEQUENCE 4 [SEQ ID NO: 481 cctagaatgg taaaaatc

Gene #17

S.typhimurium adenine glycosylase

SEQUENCE 1 [SEQ ID NO: 49] 1 CCATTTAAAA GTATTGTAAA ATCATCCACN TTNTATAAAC CAACCACNTT

51 AACNTTTTTG ACATTTGTTA TCCGATGAGA TTAAAAGATA TCAATNAATA

101 CAATTTTTAN AATTAATGTC ACTATGTTTT CCGATAATAT NACCCAATCA

151 TCGNAATGTT ACCCATTTAT AAAATGANAA ATCNTTGACA TAGGTANAGG

201 GAATGTATAT TGGTCNCGGA TCACTTAAAT TAAACCCANA TCATGTCATC 251 TGGTAATGTN TCAATGTTAA TTGCTCCTGA AGCGGCGTAN ACTTTAATCT

301 TCCATGTTAA ATGAGTAAAT TGATGCGTCA ACTCNAAAAT AGGTGTTTCT

351 NCTGGNTGAA TGTCATGACC GATTTTTTCA NTCATTTTAC GTCTANCATG 401 CTCACTATCN AACATAGGAN ATTGCCACAT ACCATACNAT AATTNTTCCC

451 TACGCTTTTG CAACAGATAT TGACCTTGAT TATTTCTAAT TAANAAGACG

501 GATTGCTCAA TTACNTTTTT ACTTACATTT TTAGATTTAA CAGGTAACTT

551 TTCAAATGGA CCTTTATCAA ATGCCTCACA GTTTTCTTGN ACTGGACNAA

601 ATAAGCATAA TGGATTTTTT GGTGNACAAA TTAATGCCCC TAATTCCATC

651 ATAGCTTGAT TAAACGTTCC AGCTTCTGTA GTAACATACG GTAACAATTC

701 TTGTTCGTAC GATTTCCTCG TCGATTGTAA TTTAATATCT CGATAGTCAT 751 CATTCAATCT AGACCATACG CGAAAAACAT TTCCGTCTAC AGTTGCTAGT

801 GGTACATTAT ATGCAATGCT CATTACTGCA GCTTGTGTGT ATGGGCCAAC

851 ACCTTTTAAC GCTTTAAATT GATCAGGATC TTTGGGAACT AAGCCTTCAT

901 ATTTATCANA AACTTCTTTA ATCGCCGTAT GAAAATTTCG AGCTCTACTA

951 TAATATCCTA AGCCTTCCCA ATACTTTAAC ACTTCATCTT CCGAAGCTTG 1001 ACTCAAAACT TCCACAGTTG GAAATCGGNC ACCAAAACGA TGATAATAGT

1051 CAATAACTGT TTTAACTTGT GTCTGTTGTA ACATGACCTC ACTTAACCAA

1101 ATATAGTACG GATTGGTCGT TTGTCGCCAT GGCATTTCTC TTTGATTTTC

1151 ATCAAACCAG TGTATCAAAT TTTCTTTAAA ACTAGACTGC TGATACATTT

1201 ATAAAACCCT TTCCTCACCA AAATTAATTG TCTTTACTCA TAATGTTTTT 1251 ATTGTACATT AAAATCATGG TTAGTATGTA AGTTAATTTA GTTATNTGCG

1301 AAATTGGATT ATAATAGTAT ATATAATATT ATGAAATGAG TGAACTGATA

1351 TGGACACTGC AACACATATC GCAATTGGGG TGGGCCTTAC AGCACTTGCA

1401 ACTCAAGATC CAGCAATGGC TTCTACGTTT GGTGCAACAG CTACAACCCT

1451 TATCGTTGGT TCATTAATTC CTGATGGGGA TANTGTNCTT AAATTANAGG 1501 ACANTGCAAC ATATATTTCG NATCATAGAG GNATNACGTC ATNCCATCCC

1551 CTCCCACAAN NNTATGNCCA GTCNCNTTTA CANTTTNTAT NTNTTCACGT

1601 CACTNTNGCT GGTANGCATC CCNCCTCACG TATGGCTTGT GG

SEQUENCE 2 [SEQ ID NO: 87]

1 MYQQSSFKEN LIH FDENQR EMPWRQTTNP YYIWLSEVML QQTQVKTVID

51 YYHRFGXRFP TVEVLSQASE DEVLKYWEGL GYYSRARNFH TAIKEVXDKY 101 EGLVPKDPDQ FKAL GVGPY TQAAVMSIAY NVPLATVDGN VFRVWSRLND

151 DYRDIKLQST RKSYEQELLP YVTTEAGTFN QAMMELGALI CXPKNPLCLF

201 XPVQENCEAF DKGPFEKLPV KSKNVSKXVI EQSVXLIRNN QGQYLLQKRR

251 EXLXYGMWQX PMXDSEHXRR KMXEKIGHDI XPXETPIXEL THQFTHLTWK

301 IKVYAASGAI NIXTLPDDMX WV*

SEQUENCE 3 [SEQ ID NO: 50] tcctgaagcg gcgtatac

SEQUENCE 4 [SEQ ID NO: 51] tatgaaggct tagttccc

Gene #18

S .aureus femA

SEQUENCE 1 [SEQ ID NO: 52]

1 GGGAAAAAAA GAAAACCTTC CAAAATACGG GAAATTGAAA TTAATTANCC

51 GGAGAGACCA NATAGGAAGT AATTGATAAT GGAAGTTTCC CCANAATTTA

101 ACAAGCTAAA AGAGTTTGGG TGCCTTTTAC AAGATAAGCA TGCCAATACA

151 GTCATTTCAC GCACACTGTT GNCCACTATG AGTTAAAGCT TGCTGAAGGT 201 TATGAAACAC ATTTAGTGGG AATAAAAAAC AATAATAACG AGGTCATTGC

251 AGCTTGCTTA CTTACTGCTG TACCTGTTAT GAAAGTGTTC AAGTATTTTT

301 ATTCAAATCG CGGTCCAGTG ATCGATTATG AAAATCAAGA ACTCGTACAC

351 TTTTTCTTTA ATGAATTATC ANAATATGTT AAAAAACATC GTTGTCTATA

401 CCTACATATC GATCCATATT TACCATATCA ATACTTGAAT CATGATGGCG 451 AGATTACAGG TAAGGCTGGT AATGATTGGT TCTTTGATAA AATGAGTAAC

501 TTAGGATTTG AACG

SEQUENCE 3 [SEQ ID NO: 53] gaggtcattg cagcttgc

SEQUENCE 4 [SEQ ID NO: 54] CAAATCCTAA GTTACTCATT

Gene #19

Parsley S-adenosyl methionine synthetase

SEQUENCE 1 [SEQ ID NO: 55] 1 CGCACATAAC GTGCAGCATA TGCAGCTGAG CGGTCTACTT TTTGTAGGAT 51 CCTTACCACT GAAGCATCCG CCACCATGAC GTGCATAGCC ACCATACGTA

101 TCAACAATGA TTTTACGTCC TGTTAATCCT GCATCACCTT GAGGTCCACC

151 GATTACAAAG CGTCCTGTAG GATTGATGTA GAATTTAGTT TGTTCATTAA

201 TCAAGTTTTC TGGAACAGTT GGATAAATGA CATGCGCTTT GATGTCTTCT 251 TGAATTTGTT CAAGTGTCAC ATCATCAGCA TGTTGTGTTG ATACGACAAT

301 CGTATCAATA CGTACTGGGT TATCATTTTC ATCATATTCA ACAGTGACCT

351 GAACTTTACC GTCTGGTCGT AAATAATTCA ACGTCTCGNG CCATCTTTTA

401 CGCACATCAG ATTAAACGTT TGGGGCAATT GGGTGTGATA AATTAAATTG

451 CTAGAGGGAT GTACGTTTCT TGTTTCAAT SEQUENCE 3 [SEQ ID NO: 56] acgtgcatag ccaccata

SEQUENCE 4 [SEQ ID NO: 57] acaagaaacg tacatccc

Gene #20

E.coli dipeptide permease Sequence 1 [SEQ ID NO: 58]

1 ACAACCCTNC AGTGCTTGGC CAATTAGGTA GAGAATTTNA CCTAGGTAAN

51 TTAATGCGAT AAAGCCCAAG TTTGTAAAAT GTCCNTTGTG CGCCAATTTG 101 TTCCTGTACN TANTGGGANC TATTTTAGGA TTCTTATCAG GGATATTTCC

151 CAAGGGTTTT GTTGACNCCT TAATCATGCG TGCGTGTGAT GTTATGTTGG

201 CAATTCCCCA AGTTATGTTG TAACGTTAGC ATTAATTTGC ATTGTTTGGA

251 ATGGGTGCCG AAAATATTAT CATGGCATTT ATTTTGACGC GTTGGGCATG

301 GTTCTGTCGT GTTATACGTA CAAGTGTTAT GCAGTACACT GCTTCTGACC 351 ATGTCAGATT TGCTAAAACA ATCGGTATGA ATGATATGAA AATTATTCAC

401 AAACATATTA TGCCGTTAAC ATTAGCAGAT ATTGCTATCA TCTCTAGTAG

451 TTCGATGTGT TCAATGATCT TGCAAATATC TGGCTTTTCA TTTTTAGGAT

501 TAGGTGTCAA AGCGCCTACT GCAGAGTGGG GCATGATGCT TAACGAAGCT

551 AGAAAAGTGA TGTTTACACA TCCTGAAATG ATGTTTGNGC CAGGTATTGC 601 CATAGGGATT ATAGTGATGG CATTTAACTT CTTATCCGAT GCTTTACAAA 651 ATTGNTATTG GATCCCCCGC ATCTCTTTCT TAAAGATAAA CTTCCGCNCC

701 TTGTGAAAAA AGGGAGTGGN GCAATCATGA CATTGTTAAC AAGCTAAGCA

751 TTTGGCGATT ACAGATACCT GGACAGATCA ACCACCGTGA GTGATGTGAN

801 TTTNNCAATT AACTAAGGGG TGAAACTCTA GGCNTTATTG GGGAAAGTGG 851 TAGCGGT

SEQUENCE 2 [SEQ ID NO:88]

1 MGAENIIMAF ILTRWAWFCR VIRTSVMQYT ASDHVRFAKT IGMNDMKIIH 51 KHIMPLTLAD IAIISSSSMC SMILQISGFS FLGLGVKAPT AEWGMMLNEA

101 RKVMFTHPEM MFXPGIAIGI IVMAFNFLSD ALQNXYWIPR ISFLKINFRX

151 L*

SEQUENCE 3 [SEQ ID NO: 59] atattatcat ggcattta

SEQUENCE 4 [SEQ ID NO: 60] atctttaaga aagagatg

Gene #21

S.carnosus pts mannitol permease

SEQUENCE 1 [SEQ ID NO: 61]

1 GAATTCTTGC ACATGTTGCT CGGTGTCTTC CTTGCTGCAC TTGTATCATT

51 CGTTGTAGCT GCTTTAATTA TGAAGTTCAC TAGAGAACCA AAGCAGGATT

101 TAGAAGCTGC GACAGCTCAA ATGGAAAATA CTAAAGGGAA AAAATCAAGC

151 GTTGCTTCTA AGTTAGTATC TTCTGATAAA AATGTTAATA CAGAAGAAAA 201 TGCTAGTGGT AATGTTAGTG AAACATCTTC ATCAGATGAT GATCCTGAAG

251 CGCTATTGGA TAATTACAAC ACTGAAGATG TTGATGCACA CAATTACAAT

301 AATATAAATC ATGTTATTTT TGGCTGCGAT GCGGGTATGG GTTCTTNGGT

351 GCAAATGGGG TGCAAGCATT GTTACNGTNA TTAAATTTTA AAAAGGCGGC

401 AATTAATGAT ATTACAAGGG TACAAATTAC TGCGAATTAA TCAAATTGCC 451 AAAAGATGCT CCAATTANGN TATCAACTCC AGAAAAACTA CTTGATCCGG

501 GCTATTAACA AACACAATGC CATCCATATT CNAAGGGGNT TAATTTCCTA

551 ATCACCAAGA TATGNAGGAC TTTTAATTAT CTTAAAAAGG TGG SEQUENCE 2 [SEQ ID NO: 89]

1 MIFGKGTAKA TSYGAGIIHF LGGIHEIYFP YVLMRPLLFI AVILGGMTGV

51 ATYQATGFGF KSPASPGSFI VYCLNAPRGE FLHMLLGVFL AALVSFWAA

101 LIMKFTREPK QDLEAATAQM ENTKGKKSSV ASKLVSSDKN VNTEENASGN

151 VSETSSSDDD PEALLDNYNT EDVDAHNYNN INHVIFGCDA GMGSSAMGAS 201 MLRNKFKKAG INDITGYKYC D*

SEQUENCE 3 [SEQ ID NO: 62] tgcacatgtt gctcggtg SEQUENCE 4 [SEQ ID NO: 63] GTGGTAATGT TAGTGAAAC

Gene #22 Mycobacteriu phosphate sensor PhoR

SEQUENCE 1 [SEQ ID NO: 64]

1 GGCACGAGCG AGTTCATTAG CTATATATAA GCCTAATCCA GAACCACCCG 51 TTTTTGTATT ACGAGAGTTT TCTACTCTGA ATGTACGTTC GAATATACGT

101 TCTTGTAGTT CTGGTATAAT GCCAATACCT CNATCGCTAA TAGCAATGTC

151 GATAGTATCT TGATCTTTGT TTTCACTAAT ATTAATATCA ATGCGACTAC

201 CAACATTTGA AAATTTTAGC GCATTATCAA GTAAGTTTGT TAAAATACGC

251 TCAAGTGGCG TTCGATATTG ATAAAATGCA TCAATTTCGC TACAGAAATT 301 CACTTCTAAT GTGCGGTTTT CATGTTTGAT ACGTTGCTCC ATATGGTTGC

351 AATATTGATA CAAGTAATTG GTCTAGTTGT ATTAATTCTG GGGGATATGT

401 TTTACCTGTA TTTAAAGTTG ATAAT

SEQUENCE 3 [SEQ ID NO: 65] tataagcctaatccagaacc

SEQUENCE 4 [SEQ ID NO: 66] aacgtatcaaacatgaaaac

Gene #23 UNKNOWN

SEQUENCE 1 [SEQ ID NO: 67]

1 GTACGAGCTC GTGCCGGCAC GAGCGATTGG TGCAGTGAGT TATGTTTTAG

51 AACAATTAGA TGCACCAGTA TATGGATCTA AATTGACAAT AGCGTTAATT 101 AAAGAAAATA TGAAAGCCCG TAATATTGAT AAAAAAGTTC GCTACTACAC

151 AGTTAACAAT GATTCAATTA TGAGATTCAA AAACGTGAAT ATTAGTTTCT

201 TTAATACGAC ACACAGTATT CCTGATAGTT TAGGTGTCTG TATTCACCCT

251 TCATATGGTG CCATTGTGTA TACAGGTGAA TTTAAGTTTG ACCAAAGTTT

301 ACATGGACAT TATGCACCAG ATATTAAACG TATGGCAGAG ATTGGTGAAG

351 AAGGCGTATT TGTCTTAATC AGTGATTCTA CTGAGGCAGA GAAACCTGGA

401 TATAATACTC CCGGAAAATG TAATTGAACA TCATATGTAT GATGCCTTTG 451 CCAAAGTGCG AGGTC

SEQUENCE 3 [SEQ ID NO: 68] tttagaacaattagatgcacc SEQUENCE 4 [SEQ ID NO: 69] tccgggagtattatatccag

Gene #24 Anabaena nitrogen fixation gene

SEQUENCE 1 [SEQ ID NO: 70]

1 GGCCCAAACC CATCCAAGTC CTTTTTAATT GACTTATTTA CATTATTTCT 51 TTAATTTGGA TTAACAAATT TTTTTCTATT TGANCCCTTT AATGTTNACT

101 CCCCGTATCT AACAAGCAAG TGATCATACT TCATTATTTT AGCAACTCCT

151 TAATTTCCTC ATAAATGATG ATAAATATTT CTTTAAACCT TGCTATATCT

201 TCTTTAGTTG TAGTAGCCCC AAATGATAAT CTTATACTAC CTTCAATAGA

251 TTTGTCTGAT AATCCCATTG CAGCCAATAC TTCATTTAAT TTATTACGTT 301 TAGATGAACA AGCACTCGTC GTAGATATCA TAATGTCATA TTTTGAAAAA

351 GCATTAACTA ATACTTCACC TTTTACGCCA GGAAAACTAA GATTTAAAAC

401 GAATGGTGAA CCTGAAGTTG AAGAATTAAT ATAAACTCCA TGATATTTAT

451 TTAAAAATTG ACGGACGTCA TTATTTAACT CAGTAACAAA TGCATTCAAT

501 GCTTCAAAGT TTTCATTAGC TCGTGCC SEQUENCE 3 [SEQ ID NO: 71] ttttagcaactccttaatttcctc

SEQUENCE 4 [SEQ ID NO: 72] gcacgagctaatgaaaactttg Gene #25 UNKNOWN SEQUENCE 1 [SEQ ID NO: 73]

1 GACAACTTGC TAAAGCACGT GATGAAAAAG TAAGTGAATA TGGAATTGAA

51 CAAGCTGATG GTACATTAAT TCAATATGAT AGTGAAGCCA AGATATATGA 101 ACATTTTAAT GTGAATTTTA TACCACCTGC TATGCGAGAA GATGGTAGCG

151 AATTTGATAA AGATCTAAGT AATATCATTA CATTAGATGA TATTAATGGT

201 GATATTCATA TGCATACAAC GTATAGTGAT GGTGCGTTTT CTATTCGAGA

251 CATGGTAGAA GCAAATATCG CAAAAGGTTA TAAATTCATG GTAATTACTG

301 ATCATTCACA AAGTTTACGT GTTGCTAATG GCTTACAAGT GGAAAGACTT 351 TTTANGACAA AAACGAAGGA AATTAAGGCT TTAGATAAAG AATATAGTGA

401 AATTGGATAT TTATTCAGGT ACAAGAAATG GATATATTAA CCTGATGGCT

451 CGCTGGATTA TGATGATGAA ATTTNAGCAC AACTTGGATA TGTNATTGGA

501 GCTATTCAAC AAAGCTTNAN CCAATCAGAA GAACAAATNA TGGAACGGAT

551 TAGCTAATGC ATGTCGCAAT CCATACGTGC GACATATAGC GCATCCAACA 601 GGGCGTATTA TAGGTAGAAG AGATGGTTAT AAACCGAATA TTGAACAATT

651 AATGGCATTA GCTGAAGAAA CGAATACAGT ATTAGAAATT AATGCCAATC

701 CACATCGACT GGATCTTGAA CGCTGAAATC GNTCGNNAAT ATCCAAATGT

751 GAAATTAACT NTTAACACTG ATGGGCATCA TNCAAATCAA TTNGATTTTN

801 TGGAATTATG G SEQUENCE 3 [SEQ ID NO: 74] acgtgatgaaaaagtaagtg

SEQUENCE 4 [SEQ ID NO: 75] tcttgtacctgaataaatatcc

Gene #26 periplasmic binding protein SEQUENCE 1 [SEQ ID NO: 76]

1 AGATCGTTCG CTAATTGACA ATTGATTAAA TCCCCTATTA CAAAATTGGA

51 TATTACCTGT TATATCTAAA AATCCACAAA TTGCTTTAGC AAGTGTTGAT 101 NTGNCGGCAC CATTGTGACC AACTATACTA AGCATTTCTC TTCTATAAAC 97/31114 ι- - ^{ι «}

151 ATTTAATTGA ACATTATTAA GTACACTATT ACTATAGTCA CTATATTGAA

201 CACATACCTC ATTTAATTCT AATAGCGGCN CAGATGTGTA CTTATTATCA

251 TTATGTGCAG ATGTNTCATC TATCCATTTN NNCACTTTAA NTTTAACATG

301 TTCACTCATA CAAACGACAC GTAANTTCGC TAAGTTATCA ATGGATTCGA 351 CATCTACTTC TGNATATTNA AGCGCTGNAC AGTATAATGG NACACGTATG

401 CCTGCTTCTT TAAGCTTAGA TGATTTTAGC AAATCACTAG GCGTTGTATT

451 AGCGATGATT TTTCCATCTT TAAAAAGAAG ANCTCTATCA AACGTATCAT

501 CTAATGANTC TTCTAATCGA TGTTCGACAA TAATCATCGT TGACTTTGTT

551 TCTTCATGAA TATTGTNTAA CAATCTCAGC GTTTCATGTC CTGTCGCAGG 601 ATCTAAATTG GCCAGCGGCT CATCCAATAT TAAAATAGGC GTNCGATGGA

651 TTAATATACC ACCTAATGAA ACGCTCGTGC C

SEQUENCE 2 [SEQ ID NO:90] 1 GTSVSLGGIL IHRTPILILD EPLANLDPAT GHETLRLLXN IHEETKSTMI

51 IVEHRLEXSL DDTFDRXLLF KDGKIIANTT PSDLLKSSKL KEAGIRVPLY

101 CXALXYXEVD VESIDNLAXL RWCMSEHVK XKVXKWIDXT SAHNDNKYTS

151 XPLLELNEVC VQYSDYSNSV LNNVQLNVYR REMLSIVGHN GAXXSTLAKA

201 ICGFLDITGN IQFCNRGFNQ LSISERS SEQUENCE 3 [SEQ ID NO: 77] aattgacaattgattaaatcccc

SEQUENCE 4 [SEQ ID NO: 78] gccaatttagatcctgcgac

SEQUENCE LISTING

(1) GENERAL INFORMATION

(1) APPLICANT: Burnha , Martin Hodgson, John

(11) TITLE OF THE INVENTION: Novel Compounds

(in) NUMBER OF SEQUENCES: 91

(lv) CORRESPONDENCE ADDRESS:

(A) ADDRESSEE: SmithKline Beecham Corporation

(B) STREET: 709 Swedeland Road

(C) CITY: King of Prussia

(D) STATE: PA

(E) COUNTRY: USA

(F) ZIP: 19406-0939

(v) COMPUTER READABLE FORM:

(A) MEDIUM TYPE: Diskette

(B) COMPUTER: IBM Compatible

(C) OPERATING SYSTEM: DOS

(D) SOFTWARE: FastSEQ for Windows Version 2.0

(vi) CURRENT APPLICATION DATA:

(A) APPLICATION NUMBER:

(B) FILING DATE: 25-FEB-1997

(C) CLASSIFICATION:

(vii) PRIOR APPLICATION DATA:

(A) APPLICATION NUMBER: 9604045.6

(B) FILING DATE: 26-FEB-1996

(vm) ATTORNEY/AGENT INFORMATION: (A) NAME: Giπutii, Edward R

(B) REGISTRATION NUMBER: 38,891

(C) REFERENCE/DOCKET NUMBER: GM50007

(ix) TELECOMMUNICATION INFORMATION:

(A) TELEPHONE: 610-270-4478

(B) TELEFAX: 610-270-5090

(C) TELEX:

(2) INFORMATION FOR SEQ ID NO:l:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2111 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1 :

CTAGGAGTAG TATTTGGTTC ATGATTGCCT AATTCAATCA CATCTTTACT TTGCTCTAAG 60

TGCAAATCAC GCAATTGACC ATNTGGATCT CGTCTATCAT AGTCATAAAT ACGGTATGTC 120

GTATCGGATG ATTGTTGTGT CTCTAAAATT AAAATACCCG AACCAATGGC ATGGACAGTG 180

CCAGCAGGAA CATAATAAAA GTCACCGGGC TTAACAGGTA TACGTTTGAA AAGACTGCCA 240

AATTCATGAT TATCAATCAT GTCGATTAAC GCCTGTTTAT TATGTGCATG GACGCCATAA 300

TATAATTTCA GCACCTGGGC TGCATCTAAA TATACCAACA TTCTGTTTTA CCTAGTTCGC 360

CTTCGTGTTT TAAAGCGTAG TCATCATCTG GATGAACTTG AACAGATAAT TTATCATTGG 420

CATCTAATAC TTTAGTTAGC AGAGGGAAAC TATCTCGTGA ATCATTATCG AATAATTCAC 480

GATGTTGTGA CCAAAGTTGA TCTAGGGTCA TATCCTTGTA TGGACCATTG ATAATTGTAT 540

TAGGACCATT TGGATGTGCA GAAATTGCCC AGCATTCACC AGTTGTTTCA TTAGGGATAT 600

CATAGTTAAA TGCTTTTAAT GCATGACCGC CCCAAATTCT GTCTTTAAAA ACGGGTTGTA 660

AAAATAATGC CATAGTTAAA ACTCCTCTAT ATTTTCATTA ATAAGTTATA AATTTCTGTA 720

GTACTGTTGG CATTAATTAG TGATTGGCGT GTCTCATCAT TCATTAACGC TTTAGATAAG 780

CGCTGAAGTA TTTTTAAATG TGTATCCTGA CTGTTGTTTG GTACGGCAAT TAAGAATATC 840

AATTGAGGTA GACTACCATC TAGACTGTCC CATTTAACAC CATGATTATT TTTCATAACA 900

GCTACAATCG GTTGTTTTAC AACATCAGAC TTTGCATGTG GAATGGCCAC GTTCATGCCA 960 ATAGCTGTCG TAGACTCCAT TTCACGTTCT AGTATTGCAT TTTTTAAATG CGATGTGTGC 1020

TCTACATAAC GGCAAATTTT AAGTTTATGA ATCAACATAT CAATTGCTTC GTTTCGAGAC 1080

ATGTCGTGAT CAGTAATTAT CATAGTTTGT TGATCAAAAA CATGAGAAGG TTTATTGAGA 1140

TGTGAATGTT TCGCTCGTGC CATCNACATT GTCAACCTCT GTATCATGTT GTGTAATATC 1200

TGTATCATGA AGTTGCGTGT GTTGCGCTGG TGCATCTACT GCTATAACTG GTGTATTGCG 1260

TNTTAATAAT AGTACAGTAG GCATTGTGAC AAGACTACCT ACTATCNCTC CAAAGATAAA 1320

CCATAATACA TGATCAATAC CACCTAATAC AGCCACGATT GGACCTCCAT GTGCGACTCT 1380

ATCGCCGACA CCACCAATGN CTGCAATGAC TGATGCAATC ATTGCACCAA TGATGTTTGC 1440

AGGTATAATG CGCAATGGAT CTTGGGCTGC GAAAGGAATA GCACCTTCAG TAATNCCAAA 1500

TAGTCCCATA GTGAAGGNAG CCTTACCCAT TTCTCTTTCG GAATGATTGA ATTTATACTT 1560

NTGAACANAC GTTGCTAAAC CTAAACCGAT TGGTGGTGTA CATACANCAA CTGCGACCAT 1620

ACCCATAACG GCGTAATTAC CTTCAGCAAT AAGTGCTGAG CCAAATAAAA ATGCTACCTT 1680

GTTTAATTGG ACCGCCCATA TCGAAGGCGA TCATCGCACC TATAATCATC GACAAGTATA 1740

ATAATATTAG CACCTTGCAT ACTTTTTAAC CAGGGTTGTT AGGAATGCCG CAAAAATATT 1800

AGAAATCGTG CACCGATTAA AAATATAAAT ATCAATCCTA ACAACGACCG ATGAAATAAT 1860

GGGAATAATA ATGATAGGCA TAATTGGTGC CATTGCTTTT GGAACTTTAA TATCTTTAAT 1920

CCACTTTGCG ATATAACCTG CTAAGAAACC AGCAACAATA CCACCTAAAA ATCCTGCGCC 1980

TGCATCACTG CCATAAAAAC TACCGTCAGC AGCGATAGCG CCGCCAATCA TACCAGGAAC 2040

AAGACCGGGC TTGTCAGCGA TACTAACAGC GATATATCCA GCTCGTGCCG AATTCGGCAC 2100

GAGCTCGTGC C 2111

(2) INFORMATION FOR SEQ ID NO: 2:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2:

ACCCTCTGTA TCATGTTG 18

(2) INFORMATION FOR SEQ ID NO:3: ( ) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(11) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3 :

GTGCGATGAT CGCCTTGG 18

(2) INFORMATION FOR SEQ ID NO: 4:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 809 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: :

CGGCTCTTCG TAATATTGAT AATGTGCAAT ATTTNAAGAA TAATCAATTT ATTGAAGAAG 60

AAACCGTAGT GACCGTGAGC GAATATCGAA NCGGCTATTG ATAGAATACG TACTGAAATG 120

GACCCGAATG AATATCGAAG NCGATATAAA TGGTAGACCT AAACATATTT ACAGTATTTA 180

TCGGNAAATG ATGAAGCAGA AAAAACAATT TGATCAAATT TTTGATTTGT TGGCGATACG 240

TGTTATTGTC AATTCTATTA ATGATTGTTA TGCGATACTT GGGTTGGTGC ATACGTTATG 300

GAAACCGATG CCAGGACGTT TTAAAGATTA TATTGCAATG CCTAAACAAA ATTTGTATCA 360

GTCATTGCAT ACTACAGTAG TAGGTCCAAA TGGAGACCCG CTCGAAATCC AAATACGAAC 420

GTTTGATATG CACGAAATTG CTGAGCATGG TGTTGCAGCA CACTGGGCTT ACAAAGAAGG 480

TAAAAAAGTA AGTGAAAAAG ATCAAACTTA TCAAAATAAG TTAAATTGGT TAAAAGAATT 540

AGCTGAAGCG GATCATACAT CGTCTGACGC TCAAGAATTT ATGGAAACCT TATAATATGA 600

CTTACAGAGT GACAAAGTAT ACGCATTTAC CCCAGGGAGT GATGTTATTG AGTNGGCATA 660

TGGTGCTGTG CCGATTGGAT TTTGGCTTAT GCGAATCACA GGGAANGTAG GTAATAAGAT 720

GATTGGCGCC CAGGTGGAAT GGCAAAATTG TACCANATTG ACTTATNTTT TCACAAAACA 780 GGCGGATATT GTTGGAAATA CCGTTCTAG 809

(2) INFORMATION FOR SEQ ID NO: 5:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5 :

AGATACGTAC TGAAATGG 18

(2) INFORMATION FOR SEQ ID NO: 6:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6:

CCTGTGATTC GCATAAGC 18

(2) INFORMATION FOR SEQ ID NO: 7:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1090 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (11) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: :

GTGATGTGGC TAAACGCTTA AATGCAAATA TATATGTGTC TGGCGAAGGT GAAGATGCAT 60

TAGGGTATAA AAATATGCCA TCAAAAACAC AATTTGTTAA ACATGGAGAT ATCATTCAAG 120

TAGGCAATGT TAAATTAGAA GTTCTGCATA CTCCAGGACA CACGCCTGAA AGTATTAGCT 180

TTTTACTCAC TGATTTAGGT GGTGGNTCAN GTGTTCCGAT GGGATTATTT AGTGGTGACT 240

TTATTTNTGN TGGTGATATA GGTAGACCTG ATTTATTAGA AAAATCTTGT TCAAATAAAG 300

GGTTCGGCAC GAAATTAGCG CGAAACAAAT GTATGAGTCC GATCAAAATA TTAAAAATTT 360

ACCAGACTAT GTTCAAATCT GGCCGGGTCA TGGTGCTGGA AGCCCTTGTG GTAAAGCATT 420

AGGTGCCATA CCTATATCTA CAATAGGTTA TGAGAAAATT AATAACTGGG CATTTAATGA 480

AATTGATGAG ACTAAATTTA TTGNNTCATT AACATCAAAT CAACCAGCAC CACCNCATCA 540

TTGTGCACAA ATGAAACAAG TTANTCAGTG TGGCATGAAT TTATNTCAAT CATATGATGT 600

TTATCCNAGC TTAGATNATA AGAGAGTAGC ATTTGATCTT CGCGTAGCAA AGAGGGCTTT 660

CACGGGTGGC CACACAAAAG GAACAATCAA TATACCATAC AACAAAAACT TTATTANTCA 720

ANTTGGGTGG GTACTTAGAT TNTGAAAAAG ATATAGATTT AATTGGAGAT AAATCTACTG 780

TTGAGAAAAG CGAAACACAC TTTACAATTA ATTGGGTTTG ATAAGGTAGC AGGCTATCGT 840

NTGCCAAAAT CAGGCATTTC ACCCCAGTCC GNTCATAGCG CTGATATGAC AGGTAAAGAA 900

GAACATGTAT TAGACGTACG TAATGATGAA GAGTGGAATA ATGGACACTT AGNTCAAGCA 960

GTTAATATTC CACATGGTAA ATTATTAAAT GAAAATATTC CTTTTAATAA AGAGGATAAA 1020

ATATATGTAC ATTGTCAGTC AGGTGTTAGA AGNTCAATTG CAGTGGGGTA TATTGGGAAA 1080

GCAAAGGCTT 1090

(2) INFORMATION FOR SEQ ID NO: 8:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8 : TTCGGGTGTT TTACCTTC 18

(2) INFORMATION FOR SEQ ID NO:9:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:

TGCAGCAAGC CTTTTCTC 18

(2) INFORMATION FOR SEQ ID NO: 10:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2247 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10:

AGCAGAATCT TTTTTAGCAT GATCTGTCAT AATGATCATA CGCTCTGGAT TTAAATCAGC 60

TAAATGTTCA GTGTCTAATT GTAAGTAAGG TCCTTTCAAA TATTTACTTA AACCTTGTGT 120

TACATCGTCA CTTAATGCAT TTTTAAATCC TAGNTCGTTT AAAAATTGTC CAACATATGA 180

ATAGTGTGGA TGTGCTAATA AACCAGCTTT AGCAACTACT GCTGGAAGCA CTTTGTGATT 240

TCTATCAAAT TTAATTTCAT CTTTATACTT ATTGATTAAT TTATCATGCT CAGCAAGACG 300

TTTNNCGCCT TCTTTNTCTT TATTTAAAGC TTTAGCAATT GTTGTTGAAC GAATTAATAT 360

TGTGGGTGTA GTCTCCATCA AAACTCTTTA ATGATAATGT GGTGCAATGT GGGCTAATTC 420

TTTATTAATA CCCTTATGTC TACTGCTATC AGNGATAATT AATCCCGGNT TTAATTTACT 480

AATNTCTCTT AAGTTNGCTT GTTACGTGTA CCTACAGAAG TATTACCCCC AATTTTTCTC 540 TTACTGGGTT ATGATACGTT TTTTCTTACC ATCATCAGCA ATACCAACTT GGTNTAACGG 600

CTATATGCTG NTAATGCAAC CTTGCAAATG AGTACTCTAA TACAACGATA CGTTGTGCAT 660

CTTTAGGTAC TTTTACTGTA CCATTTTCAT CTTTTACCCG AAATAGTATC TTTAGTTGAT 720

GATTCTTCTT TTACTTGAAT TATCCGTATT ACCACAAGCT GCAACTAAAA GTAAGGCAAC 780

TATTAATCCC AATATACTAA AAGTTTTTAG ACCTCTCATC NGTCCCACTC CTTAATATGT 840

ATANCTTCAT TTATTATTTT ATTGATAACA ATTATCATTG TCAAGTAGCG TTCAATCTTT 900

TTTATATTTC TAAAATGTAT GACTATATAT TTCCTCTAAT AATTATGACT ACAATTAGCA 960

CATTTCCTTA GACAAAATAC TGATAATGTA TCATTGCTAT ATCATCTTTG CATTAATACA 1020

ATTGACACCA CTTAGCATGA CCGNTATCCC TGTAATTCAG CTGATATTAT CTGTTGCAAT 1080

TTTATGTGAC GAACTGTTGC ACTTAATTTG ATAANTCAAC AANTACAANA NATCTAAGTT 1140

GAACAATTAT GATACAACCG TGCAAACGAT ATGTAGTATA ACTTGTCAAC TTAGAATTAT 1200

TGATAAATAT ATTAATATTG GTTTACCATA GCAGGAGATT TCACATCAAA ATTTTGAAGT 1260

AGCGTATCAA TCTTTGAATC ATCAATATAT ACCTTATGTA AATTTTTCAT ATACATCGAA 1320

TGAGAAAGTG CTTCATAATT TAATGAAAAA GATATATGAT CTCCAACTTG ATAGTGTCCT 1380

TGACCATTTA AATCAAGCAT TAAATGATCA CTCGAAGCGC CTAAAATATT GATATGCTGA 1440

TCCATAGGTG AAATATTATC GACTTGTGTA TCTNAAATAA CCAATATCTA CAATAGCTTG 1500

TAAGAATGAT TCATGCGTGT GTGTATTAAC TCGAGGTTTA ATTTCTAAAA TCTCAGCCTC 1560

CAATGTAATC GCATCTTGAT ATAACATAGC GAATCGCTTG ATTTGCGTTG TTTCAACAAC 1620

TCTAAACAAC GTNTCANCTA TTCGGAANTC AATTTATTTT TACCCAAATC AATATATAAA 1680

AGGTGGGGGG NAACATGCTC CGAATTACCA CCCGGAAATA ATTTNCANTC GATATCCTAT 1740

TTCTCTTNCA ACAGCTGAGA CGAATCGATT AATCATAAAG ATATCANCAC CACTTGGCGC 1800

ATCAGATTTA AAACACATAA AATTGAATGC TAAACCTACA AAATGGATAT TTTNCAAGTG 1860

AATAATCTCT TTANTATAAT CTAAAACATC ATAAGTCAGA ACACCTTCAC GGACATCTTT 1920

CCAATCTACC ATTAATAAAA TCTTATGTTT TTTTCCTAAA ACTTCTGCTA CTTCATTTAT 1980

NTGATGTATG GTAGATAATT CTGTGTGGAT ACTCATATCA ACTTTCCTCT ATCATATCTG 2040

AAATCTCTTT TGNGGGAGGC GTACGCAATA ACGTATATGT TAAATCCTGA TCTGCAATAC 2100

TAATTATGTT ATCCAATCTG GATTCTGCAA CATGATTGAT ACCTAACGCT TTTAAGCTTN 2160

CTACAATGGT ACGGGCANCA GCTATACACT TAATTACTGG TGTGANTNGN ATATTTTTAC 2220

TTTGAAAACT NNGTGGAGGT ACTTGGG 2247

(2) INFORMATION FOR SEQ ID NO:11:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (11) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11:

TGTAAGTAAG GTCCTTTC 18

(2) INFORMATION FOR SEQ ID NO: 12:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12:

TAATACTTCT GTAGGTAC 18

(2) INFORMATION FOR SEQ ID NO: 13:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1789 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:

GGCACGAGCG GCACGAGCGT GTTGTATCAA GATTTTGTAG GCAGTTTTAC AACGTCCGAT 60

TCAGCAAGTT ATGCACAAGA TTTTAAATCT GAGGAAAACG CTAAAAAGAT TGCTGAAACT 120

TTAAATCTTT TATATCAATT AACAGGCAAT CAAAACGGTG TGAAAGTTGT GAAAGAAGTT 180

GTGGATAGAA CTGACTTGTC ATCTGATAAA TCAGTTGATA GCGAAACAAT GTAACTATAC 240 TAAGTTATGA GCATTACGCT CATAGCTTTC TTAGAAAGTA GGTGTAGTTT TGGATGATAT 300

TCAGAAAATA AAAAAAGAGC TTTCTGAATT AGTTGAACGT GTTGATGATG TTGAAATACT 360

AGCAAACGAA ACAGCTGATC ATGTGCTTGA ACTTAGAGAG GAACATAAGC AACATCATAA 420

TGAACTAAGA GAATCTCATA AAGAACTTAA AGATAAGCAA GATAAAGTTG TAGATGAGAA 480

TTTAGAGCAA ACAAAGATAT TAAACAGAAT TGAAGAAAGA TATCANACGC AAGTAGNTGT 540

TGNGCAAAAA AATGAAGAAA AGACACTCGC CCAAAATAAA TGGCTCGTAG GTGCCATATG 600

GGCGCTTGTA ACAATTGTTA TGATTGCAGT CATTACTGCA TCAATTNCTG CGTTATTACC 660

TTAAGGGAGG TGGACATAAT GAGTTGGGCA AGATGGTTAT CATGTTATTT GTNTGGTCGT 720

AAATGTAAAT AATGTTTTTG GTCAGTGCAT CGGCACTGGC TTTTTATTTT GATTGAAAAG 780

AGGTACGTAC ATGGTATTAC ACAGCTCACA AGACAGGAAG CATACTCCAA GTGAAGTTGG 840

GAAGTGTTGT TAATACCAAG TAAGTAGGAT ATCTGANATG TATAATAGAG TAAAAATGAA 900

ATCTTTTTAT TATAGACACA TATAAAAAGT GTATAGTAAT ATATGTATGT ATAATTAAAT 960

GATAATCATT TCATAATTAT TGTATATAAC TAAATAACTA CTTAACANAA ATAATTATGC 1020

TTTAGAGNTG ACCANNATGA NNNANNCCAG CATTTACATT ACTTTTATTC ATTGCCCTNA 1080

CGTTGACNAC AAGTCCCANT TGTAAATGGT AGCGAGAAAA GCGNAGNAAT AAATGCGAAA 1140

GATTTGCGAA AAAAGTCTGA ATTCCAGGGN ACAGCTTTAG NCAATCTTAN NCANATCTAT 1200

TATTACNATG NNANAGCTAN AACTGAAAAT AAAGAGAGTC CNCGACCACA TTTTTACAGC 1260

ATACTATATT GTTTANAGGC TTTTTTACAG ATCATTCGTG GTATANCGAT TTATTAGTAG 1320

ATTNTGATTC NNAGGATATT GTTNATAAAA ATAAAGGGNA AANAGTAGAC TTGTATGGTG 1380

CTTATTATGG TTATCAATGT GCGGGTGGTA CACCACACAA AACAGCTTGT ATGTATGGTG 1440

GTGTAACGTT ACATGATAAT AATCGATTGA CCGAAGAGAA AAAAGTGCCG ATCAATTTAT 1500

GGCTAGACGG TAAACANAAT ACAGTACCTT TGGAAACGGT TAAAACGAAT AAGAAAAATG 1560

TAACTGTTCA GGAGTTGGAT CTTCAAGCAA GACGTTATTT ACAGGAAAAA TATAATTTAT 1620

ATAACTCTGA TGTTTTTGAT GGGAAGGTTC AGAGGGGATT AATCGTGTTT CATACTTCTA 1680

CAGAACCTTC GGTTAATTAC GATTAATTTG GTGCTCAAGG ACAGTATTCA NATACACTAT 1740

TAAGAATNTA TAGAGATAAT AAAACGATTA ACTCTGAAAA CNTGCGTAG 1789

(2) INFORMATION FOR SEQ ID NO: 14:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14:

ATCCCCTCTG AACCTTCC 18

(2) INFORMATION FOR SEQ ID NO: 15:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH. 18 base pairs

(B) TYPE: nucleic acid

⁽C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15:

AAATGGTAGC GAGAAAAG 18

(2) INFORMATION FOR SEQ ID NO: 16:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 3797 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16:

TCAAATGCAG TCAGGGAAGC AATAGGACGA TATGCATAAA GGAGATGGTA AAGTGGAACA 60

GTGACAGAAG GTAAAGACAC GCTTCAATCA TCGGAGNCAT CAATCAANCA CAAAATAGTA 120

AAACAATCAG GAACGCAAAA TGATAATCAA GTAAAGCAAG ATTCTGGAAC GACAAGGTTC 180

TAAACAGTCA CACCAAAATA ATGCGACTAA TAATACTGAA CGTCAAAATG ATCAGGTTCA 240

AAATACCCAT CATGCTGAAC GTAATGGATC ACAATCGACA ACGTCACAAT CGAATGATGT 300

TGATAAATCA CAACCATCCA TTCCGGCACA AAAGGTATTA CCCAATCATG ATAAAGCAGC 360

ACCAACTTCA ACTACACCCC CGTCTAATGA TAAAACTGCA CCTAAATCAA CAAAAGCACA 420 AGATGCAACC ACGGACAAAC ATCCAAATCA ACAAGATACA CATCAACCCG CGTGCCTCAA 480

ATCATAGATG CAAAGCAAGA TGATACTGTT CGCCAAAGTG AACAGAAACC ACAAGTTGGC 540

GATTTAAGTA AACATATCGA TGGTCAAAAT TCCCCAGAGA AACCGACAGA TAAAAATACT 600

GATAATAAAC AACTAATCAA AGATGCGCTT CAAGCGCCTA AAACACGTTC GACTACAAAT 660

GCAGCAGCAG ATGCTAAAAA GGTTCGACCA CTTAAAGCGA ATCAAGTACA ACCACTTAAC 720

AAATATCCAG TTGTTTTTGT ACATGGATTT TTAGGATTAG TAGGCGATAA TGCACCTGCT 780

TTATATCCAA ATTATTGGGG TGGAAATAAA TTTAAAGTTA TCGAGGGAAT TGAGAAAGCA 840

AGGCTATAAT GTACATCAAG CAAGTGTAAG TGCATTTGGT AGTAACTATG ATCGCGCTGT 900

AGAACTTTAT TATTACATTA AAGGTGGTCA CGAGCGTAGA TTATGGCGCA GCACATGCAG 960

CTAAATACGG ACATGAGCGC TATGGTAAGA CTTATAAAGG AATCATGCCT AATTGGGAAC 1020

CTGGTAAAAA GGTACATCTT GTAGGGCATA GTATGGGTGG TCAAACAATT CGTTTAATGG 1080

AAGAGTTTTT AAGAAATGGT AACAAAGAAG AAATTGCCTA TCATAAAGCG CATGGTGGAG 1140

AAATATCACC ATTATTCACT GGTGGTCATA ACAATATGGT TGCATCAATC ACAACATTAG 1200

CAACACCACA TAATGGTTCA CAAGCAGCTG ATAAGTTTGG AAATACAGAA GCTGTTAGAA 1260

AAATCATGTT CGCTTTAAAT CGATTTATGG GTAACAAGTA TTCCGAATAT CGATTTAGGA 1320

TTAACGCAAT GGGGCTTTAA ACAATTACCA AATGAGAGTT ACATTGACTA TATTAAAACG 1380

CGTTAGTAAA AGCAAAATTT GGACATCAGA CGATAATGCT GCCTATGATT TAACGTTAGA 1440

TGGCTCTGCA AAATTGAACA ACATGACAAG TATGAATCCT AATATTACGT ATACGACTTA 1500

TACAGGTGTG TCTTCACATA CTGGTCCATT AGGGCACGAA AATCCTGCCG AATTAGGCAC 1560

GAGACATTTT TCTTAATGGA TACAACGAGT AGAATTATTG GTCATGATGC AAGAGAAGAA 1620

TGGCGTAAAA ATGATGGTGT CGTACCAGTG ATTTCGTCGT TACATCCATC CAATCAACCA 1680

TTTATTAATG TTACGAATGA TGAACCTGCC ACACGCAGAG GTATCTGGCA AGTTAAACCA 1740

ATCATACAAG GATGGGATCA TGTCGATTTT ATCGGTGTGG ACTTCCTGGA TTTCAACACC 1800

GTAAGGTGCA GAACTTGCCA ACTTCTATAC AGGTATAATA AATGACTTGT TGCGTGTGGA 1860

AGCGNCTGAA AGTAAAGGAA CACAATTGAA AGCAAGTTAA ATTCATCTTC TGAATTTAAT 1920

AGGCTATGTA AATCGTGCTG TTATCATGGC ACATCAGATA TAAGTAGCAT CACAGTGTTG 1980

AATCTCAAAA TAGTAAAGTG AAATAAAGCG CCTGTCTCAT TAGCGAAAAC TAAAGGGACA 2040

GGCGTATCTG TTTATGAGCT TAATAAATTG TATGAATAAT ATGGTTGATC GAATAACTGT 2100

TTATCATTGA TGATAAATTT GAGTTTTTTA AAAATAATTG ATATATTACA CCATTGTTAT 2160

AGCGTTTAAA GAAATCAACC CAACTTTACG ATAAATAGTG ATTGCTTCGT CATTAGGTCT 2220

ACGATCAAAA TCATGCTCGT TTTTATTCAC GCGTTCAAAT GTTGAATGTG GAACATGATT 2280

CATGATATGT TCGCTTTCCT CAACGGGAAC ATCATAATCG CCATTACAAT GCGCAATGAA 2340

AACAGGTGGA AGTGTTTTAA GNTCATCTGG TGCAATATTA TATTTTGAAT CAGTATAATC 2400

ANCAATGTTA ATCATATTTA TCCATTTACC TGTGCCACGT GCATAAACGT AGAGTAAAAA 2460

ACGTGTGCGA TTTGATCTTG ANCAACCGGT GTTGGTGAAG TGAGTTGTCC AATCATTGTT 2520

TCGTTTATGC TTTGAGCTAT TTTTGCGTAA TACCTATTAG TTGTTTTAAA AGGGTTCAGT 2580

GTTGATGCGA CTATAACCAT AAAAATCAAT AACACCATCA ATATCTCTGT CTCGTGCAAT 2640 TAATAAGACT TAAATATGCA CCTGATGATC TGCCAAAGGT AAAAATAGGG CAATTAGAAT 2700

ATTGTGATTG AATCGCATCG AATGATGCGT AGACATCCTC AATAATGCAA TCGAGACTTA 2760

CTTCTGGTAA TAAACGATAA CTTAGTTGAA TTAAATCGTA ATGTTCCGTA AGGATATCGA 2820

TATACTGTGG GGATAAATCG TTAGCTTTAC CGAACATTAA TCCACCACCG TGGATGTAGA 2880

CAATAACGCC TTTTGTTGGT TGATTTTTTG CTTTAATAAT TGTGTAAGGT AATGCAAATG 2940

CATCTTTAGT AATTACTTTA TATTTAATTT CAGTCACGAT TTAATAGGCT CCTTAGGAAT 3000

CCGATATTGA TGTCATTATA ACACTGTCNT NAATTTCCAT GNAAAATAGT CTTAAGACGA 3060

TGAGTCATGA TAATTCTGTT CCAATTGACG TAAAGCGTCN CGGGTATGCT TCTTTAGACC 3120

TTCCCCATAA TCCATCATTT TAACAATATC TTTAAAAGCA GCATGTGGNA TGGCTAAATC 3180

TTCTAAATCT GCCATAGAAA ATTCAAGATT GATATCATGT GGTCGCTGTT CAGCAAGTTT 3240

ATGCACAAAG TCAGGTTCTG TGACCAAAGG CGAAGACATG CCGACCATAT CTGCATGTTG 3300

TAAAGCATCT AAAGCAGACT CTGGAGAATT AATCCCGCCA CTTGCAATTA AAGGGATACG 3360

ACCTGCTAAA TGTTCATAGA CAATTTGGTT AACTGGTCGA CCGAAATGAT CACCTGGTGT 3420

ACGAGACGTA TTTTGATAAA TATGTCGACC CCAGCTAGCG ATTGCTAAGT ATTGGATGTT 3480

TGAAACGTCC ATGACCCAAT CGATTAATTG GTTGAACTCG TCAATGGTAT ATCCTAAATC 3540

ACTGCCTCTG GTTTCTTCTG GCGTTGCTCG AAATCCTAAA ATAAAATTGT CAGGTGCTTC 3600

TTTATCAATC ACTTCTTGTA CCGCACGCAT AACTTCTAAA CATAATCTTG CACGATTTTT 3660

TAATGAGTCG GCACCGTAAT GGTCTGTACG TCTATTTGAA AAAGTTGAGA AAAATGTTTG 3720

AATCAGCAAA CGTTGTGCAA TCGAAATTTC CACACCATCA AAACCTGCTT TAATCGCGCG 3780

TGCATCGAGC TCGTGCC 3797

(2) INFORMATION FOR SEQ ID NO: 17:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17:

GACTAATAAT ACTGAACG 18

(2) INFORMATION FOR SEQ ID NO: 18: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18:

TCTGTCGGTT TCTCTGGG 18

(2) INFORMATION FOR SEQ ID NO: 19:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1422 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19:

CAGGCGTTTC CTCNGGTACN TGTTGCNNGC CTTTAATTAC CGACNCTGCA ATANCCAAAC 60

CGACCAGGTC GGATAGGGNA TATGTACCTG TTTTAGGACG ACCAATCGCT TGCCCAGTTA 120

AAGCATCCAC ATCTACNATG CTTANCTTGT GTTGCTCGGC GCGATACAGA ATATCATTCA 180

TTGTGTGCGT GCCGACTCTA TTTGCGACAA AGCCAGGCAC ATCATTGACG ACAATGACAC 240

CTTTACCTAA TACATTGTGC GCGAAATTTT TTACATCTAA TATGATAGAT TCCTTCGTGT 300

GTGACGTAGG TATTAACTCC ACTAATTNCA TAATACGTGG TGGGTTAAAG AAATGTAGAC 360

CAAAGAATCG CTCTTGATCC TTCTCGTTAA ATGCTTGAGC AATCGCATTA ATTGGGATTA 420

CCTGATGTAT TTGTAGCAAA TAAAGCATCT TCTNTAGCAT GTTGTAGAAC TTGTTGCCAA 480

ACAGCATGCT TAATTTCAAT ATCTTCTTTG ACTGCTTCGA TATATAAATC AGNATCATCA 540

TTTACCAAGT CATCATCAAA ATTACCATAT GTTAAATGAC TCACTAGATT TAAGTCGAAT 600

AGTAGCGGCC GTTTCTTATC TGTAATTTTA TCGTAAGATT TTTTCGCAAT GAGATTTGGA 660

TCGTTTGTGT CCACTACAAT ATCTAATAGT TTTACTTTAA GTCCAGCATN CACAAAGAGT 720

GCTGCCAGTT GAGCGCCCAT CGTGCCTGCG CCAAGAACGG TTACTTTATT AATTGTCATA 780 GTGATTCCTC CAATTTAGGT GAGGATAAGA TAACCATTAA GATAATTGGA ATAACGNTGC 840

TATTTTATNA AATTAATTAA GTATCTTTGA CAAGACATCT CAGNCTCTTT ATTTTAAGGA 900

AAAAGCTTTA TGCTTAAAAT AAGTCTTTTT TAGTGAAATT AATGCATCTC ATATAATTAT 960

TTGCTATTTA TACGAAAGCA GAATCTCCAG TCAAAGCGCG TCCAATTACT AAGGCATTAA 1020

TTTCATGTGT ACCTTCGTAC GTGTAAATCG CTTCTGCATC AGAGAAGAAA CGTGCAATAT 1080

CATAATCGTC AGCTAGTATG CCATTACCAC CTGTAATACC GCGGCCCATA GCTACTGTCT 1140

CACGCAAACG TAAGGCATTC ATCATCTTCG CCGGTGAAGT TGCAACCTCG TCATATTCAC 1200

CATGTGCTTG CATATTAGCT AATTGAGCAC ATGTTGCCAT TGCTTGAGCT AAATTACCTT 1260

GCATCATTGC TAGCTTNTCT TGTATTAACT GATATTTACT AATTGGGTNT GCCGAATTGC 1320

TTACGCTCAA GTGACATAAT CTAATGTGGC ACGTAAAGCG CCAGCCATAC CACCTGTAGC 1380

CATATAAGCA ACGCCTGCTC TCCGGTGGAA TAAAGAATTT TG 1422

(2) INFORMATION FOR SEQ ID NO:20:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: Single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:

ATGTACCTGT TTTAGGAC 18

(2) INFORMATION FOR SEQ ID NO: 21:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

( i i ) MOLECULE TYPE : Genomic cDNA

( xi ) SEQUENCE DESCRI PTION : SEQ ID NO : 21 : GAGTCATTTA ACATATGG 18

( 2 ) INFORMATION FOR SEQ I D NO : 22 :

( l ) S EQUENCE CHARACTERI STICS :

(A ) LENGTH : 811 base pairs

( B ) TYPE : nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22:

ATACTTTGAT TTTAGATGAA GCTGATGAAA TGATGAATAT GGGATTCATC GATGATATGA 60

GATTTATTAT GGATAAAATT CCAGCAGTAC AACGTCAAAC AATGTTGTTC TCAGCTACAA 120

TGCCTAAAGC AATCCAAGCT TTAGTACAAC AATTTATGAA ATCACCAAAA ATCATTAAGA 180

CAATGAATAA TGAAATGTCT GATCCACAAA TCGAAGAATT CTATACAATT GTTAAAGAAT 240

TAGAGAAATT TGATACATTT ACAAATTTCC TAGATGTTCA TCAACCTGAA TTAGCAATCG 300

TATTCGGACG TACAAAACGT CGTGTTGATG AATTAACAAG TGCTTTGATT TCTAAAGGAT 360

ATAAAGCTGA AGGCTTACAT GGTGATATTA CACAAGCGAA ACGTTTAGAA GTATTAAAGA 420

AATTTAAAAA TGACCAAATT AATATTTTAG TCGCTACTGA TGTAGCAGCA AGAGGACTAG 480

ATATTTCTGG TGTGAGTCAT GTTTATAACT TTGATATACC TCAAGATACT GAAAGCTATA 540

CACACCGTAT TGGTCGTACG GGTCGGTGCT GGTAAAGAAG GTATCGCTTG TAACGTTTGG 600

TTAATCCAAT CGAAATGGAT TATATCAAGA CAAATTGAAG ATGCAAACGG GTAGAAAAAT 660

GAGTGACTCC GCCACCTCAT CGGTAAGAAG TACTTCCAAG CACGTGAGGA TGACATCAAA 720

GGAAAAGGTG GAAACTGGAT GTCTTTAAGA GTCAAGAATC ACGCTGGAAA CGCATTCTTC 780

AGAGGTGGGT AAATTGAATT TTACGATGTG G 811

(2) INFORMATION FOR SEQ ID NO:23:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23:

GATGAAGCTG ATGAAATG 18

(2) INFORMATION FOR SEQ ID NO: 24:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24:

TATCTAGTCC TCTTGCTG 18

(2) INFORMATION FOR SEQ ID NO:25:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 960 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:

TAATTCGCAA TAGGAGTGAT GAATATCATA AATTTTACCC TCCAAATGAA GCTAATGAAG 60

TCCTGGACCC GAGTAAGACG CATGTAGCCA AGCTAAAATA ATCCACTCTA CCTTATCTTT 120

AGTTAATAAT GTTACTAAAT GTTGTTCATA CGCTGCTTTT GAATCAAATT GTTTTGGTTC 180

ATTAATATAA ACAGGAATAT CGTGCTTGTT TGCTCTATCT ATACAAAACG CATTTTGATG 240 ATCCGTATAT AGCNCCGTAA CTTCAATATT TTCAAGTTTT CCTGATTCAA CATGCTCAAC 300

TATATTTTCA AAGTTACTTC CTGAACCTGA TGCAAAAATC GCAATTTTAA CCATTGTTAT 360

ACCCCCAACA ATTCAATTGC AGTTGACTCA TTTTTCACAA TATGACCAAT TTGATAAGCT 420

TCCACATTTT GTTCTGCTAA AATCTTCAAA GCGCGTCGAT GCATCTTTTT CATCAACGAT 480

AACCGTATAG CCAATACCCA TGTTAAAAAT GTTATACATT TCATTTGTGT CTATATTGCC 540

TTGTTGTTGT AACCAATCAA ATATTTTTGG CGTTGGAAAT GATGTAGTAT CAATTCTAGC 600

AGCATATCCG GCTGGCAATG CACGTGGAAT ATTTTCATAA AAACCTCCAC CAGTAATATG 660

ATTCATTGCC TTAATAGAAA CTTCTTTTTT TAAAGCAAGT ACAGGTNTGA CATATAATTT 720

AGTTGGCTCT AAAAAGACAT CTATAAATGG ACGATTATCG NAGGGTGATG CCAAATCAAT 780

GNCTGATTCA NTAATTAATN TGCGCACTAA ACTGTNTCCA TTNGANTGAA TGNCACTTGG 840

ACGCAAGTCC TATAACAACT TGGCCCTCTT NCAATTCTTG AACCATCTTA CAATAGNCAA 900

CCTTTTTCAA CTGCTCCAAC AGCAAATCCG GCTACATCAT ATTCACCTTC GTGATACATT 960

(2) INFORMATION FOR SEQ ID NO:26:

( ) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26:

ATAAGCTTCC ACATTTTG 18

(2) INFORMATION FOR SEQ ID NO:27:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27:

GATAATCGTC CATTTATA 18

(2) INFORMATION FOR SEQ ID NO:28:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 541 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28:

GGCACGAGCG CTAAATAATT AATATTTAGT TTTTAAGTTA TTAATAACGT AGGGATATTA 60

ATTTTAAAAG AAGCAGACAA AATGGTGTTT GCTTCTTTTT TATGTCGTAT AAGTAATAAA 120

TAAAACAGTT TGATTTTAAA ATGAAAGCGT AAAAATGGTA AAATATCCCA AAATTGATTG 180

TGATATAATT ATAAGGAAAA TGAGCAATTT ATGAAAAAAG TTTACGNACA AATCGGAGAA 240

TTAAAACTAA ATAATTATCA AAACAACGTC AATATTTAGT TGAATACTCA GACTTTAGCC 300

CATGGCCAAG TGGGGAAGAC AGCATATATT AGTAAAGGTG AATGATTTGT TATTACTCAC 360

TCGAAAATAG AAAGACAAGA TTTTAACGAT TAAAATAAAC TATTTTACAA ATAAAGTAAA 420

ATTAATTTAT TANGCTAATA ATGCAAAAAA TTAAAAAGTA ATGGACAAAG AGATAATGAT 480

ATGGCTCAAG AGGTAATAAA ATAGAGGTGG ACGCACACTA AATGGGGAAG TTAATACAAG 540 G 541

(2) INFORMATION FOR SEQ ID NO:29:

(_l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA 97/31114

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:

GCACGAGCGC TAAATTTG 18

(2) INFORMATION FOR SEQ ID NO:30:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:

CTTCCCCATT TAGTGTGC 18

(2) INFORMATION FOR SEQ ID NO:31:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2334 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31:

CCACCCANCT GATTATAATG TTTTAGCANG AGCTAGACTT GGTTGGTTAC CATCATATCC 60

ACAATTTAAT AAAAATAGTT TGTTGTTTGC AGAAGAAGCT AAAGATGAAG GCATTGAGTC 120

GAATGAGGCA ATTTTAAAAC GAGCGATAAA TGGAAGTTAA GTCAAAACAA ACGCAATTTG 180

CGATAGAAGA TCCGGATTTG AAAAAGAATC ATCCGGAAAT CACTGTTTAT ATGGCGCTCA 240

AATCTAATCT CAAGTTCTGC AAAAGGTCAA GAATACTTTA TGAAGCATTT ACTTGGCACA 300

AAATCAGGGT TATTAGCTAC ACCAAATGAA GATGAAAAGC CAGAAGAAAT TACGTGGCGT 360

GAGGAAACAA CAGGGAAATT AGATTTAGTC GTTTCTTTAG ATTTCAGAAT GACAGCAACA 420 CCTTTATATT CTGACATTGT TTTGCCAGCA GCGACTTGGT ATGAGAAGCA TGATTTGTCA 480

TCTACAGATA TGCATCCATA TGTACATCCT TTTAATCCAG CTATTGATCC ATTATGGGAA 540

TCGCGTTCAG ACTGGGATAT TTATAAAACG TTGGCAAAAG CATTTTCAGA AATGGCAAAA 600

GACTATTTAC CTGGAACGTT TAAAGATGTT GTGACAACTC CACTTAGTCA TGATACAAAG 660

CAAGAAATTT CAACACCATA CGGCGTAGTG AAAGATTGGT CGAAGGGTGA AATTGAAGCG 720

GTACCTGGAC GTACAATGCC TAACTTTGCA ATTGTAGAAC GCGACTACAC TAAAATTTAC 780

GACAAATATG TCACGCTTGG TCCTGTACTT GAAAAAGGGA AAGTTGGAGC ACATGGTGTA 840

AGTTTCGGTG TCAGTGAACA ATATGAAGAA TTAAAAAGTA TGTTAGGTAC GTGGAGTGAT 900

ACAAATGATG ATTCTGTGAG AGCGAATCGT CCGCGTATTG ATACAGCACG TAATGTAGCA 960

GATGCAATAC TAAGTATTTC ATCTGCTACG AATGGTAAAT TATCACAAAA ATCATATGAA 1020

GATCTTGAAG AACAAACTGG AATGCCGTTA AAAGATATTT CTAGCGAACG TGCTGCTGAG 1080

AAAATTCGTT TTTAAATATA ACTTCACAAC CACGAGAAGT AATACCGACA GCAGTATTCC 1140

CAGGTTCAAA TAAACAAGGT CGACGATATT CACCATTTAC AACGAATATA GAACGTCTAG 1200

TACCTTTTAG AACATTAACA GGACGTCAAA GTTATTATGT GGATCACGAA GTTTTCCAAC 1260

AATTTGGGGA GAGCTTACCA GTATATAAAC CGACATTGCC GCCAATGGTA TTTGGGAATA 1320

GAGATAAGAA AATTAANGGT GGTACAGATG CTTTGGTACT GCGTTATTTA ACGCCTCATG 1380

GANAATGGAA TATACACTCA ATGTATCAAG ATAATAAGCA TATGTTGACA CTATTTAGAG 1440

GTGTCCACCG GTTTGGATAT CANATGAAGA TGCTGNAAAA CACGATATCC AAGATAATGA 1500

TTGGCTAGAA GTGTATANCC GTAATGGTGT TGTAACGGCA AGAGCAGTTA TTTCGCATCG 1560

TATGCCTAAA GGTACAATGT TTATGTATCA TGCACAAGAT AAACATATTC AAACGCCTGG 1620

GTCAGAAATT ACAGATACAC GTGGTGGTTC ACACAACGCG CCGACTAGAA TCCATTTGAA 1680

ACCAACACAA CTAGTCGGAG GATACGCACA AATTAGTTAT CACTTTAATT ATTATGGACC 1740

AATTGGGAAC CAAAGGGATT TATATGTAGC AGTTAGAAAG ATGAAGGAGG TTAATTGGCT 1800

TGAAGATTAA AGCGCAAGTT GCGATGGTAT TAAATTTAGA TAAATGCATA GGATGCCATA 1860

CGTGTAGTGT GACATGTAAA AACACTTGGA CAAATCGTCC AGGTGCTGAG TAACATGTGG 1920

TTCAATAACG TAGAAACGAA GCCAGGTGTA GGGTATCCGA AACGTTGGGA AGACCAAGAA 1980

CACTACAAAG GTGGTTGGGT ACTAAANTCG TAAAGGGAAA CTTGAATTAA AATCTGGAAG 2040

TAGAATTTCA CAAATTGCTT TAGGTAAAAT TTTTTATAAC CCAGATATNC CATTAATAAA 2100

AGATTATTAT GANCCATGGA NCTATAATTA TGAACATTTA ACAACTGCGA AATCAGGGAA 2160

GCATTCGCCA GTTGCTAGAG CGTATTCAGA AATTACAGGG GATAACATTG AAATTGAATG 2220

GGGACCTAAC TGGGAAGATG ACTTAGCAGG TGGTCATGTT ACAGGCCCAA AAGATCCTAA 2280

CATACACAAA ATAGAAGAAG AGATTAAATT CCAATTTGAC GAAACTTTTA TGAG 2_-34

(2) INFORMATION FOR SEQ ID NO:32:

(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs O 97/31114

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(11) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32:

ATTGATCCAT TATGGGAA 18

(2) INFORMATION FOR SEQ ID NO: 33:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33:

CATATTGTTC ACTGACAC 18

(2) INFORMATION FOR SEQ ID NO:34:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 638 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34:

AGTTATTGTA TTTAAAAATG TTTCATTTCA ATATCAAAGT GATGCATCCT TCACATTGAA 60 AGATGTTTCT TTTAATATAC CTAAAGGTCA GTGGACATCT ATTGTTGGTC ATAACGGTTC 120

TGGAAAATCT ACAATTGNCA AGTTAATGAT TGGCATAGAG AAAGTTAAAT CTGGAGAAAT 180

TTTTTATAAT AATCAAGCTA TAACTGATGA TAATTNTGAA AAGTTAAGAA AAGACATAGG 240

AATTGTATNT CAGAATCCGG ATAATCAATN TGTTGGNTCA ATTGTAAAAT ACGATGTGGC 300

ATTTGGACTC GAAAATCATG CGGNTCCACA TGACGAAATG CATAGAAGAG TCAGCGAAGC 360

ACTTAAACAA GTTGATATGT TAGAACGTGC AGATTATGAC CCTAATGCAT TATCGGGGGG 420

ACAGAAGCAG CGTGTGGCTA TAGCAAGTGT ATTAGCACTT AACCCTCTGT CATTATATAG 480

ATGAGGCGAC TCTATGTTAG GATCCCTGAT GCACGTCAAA TTTATGGGAT TTAGNGAGAA 540

AGTAANTCAG ACATTATATA CAATCATTCT ATACGCATGA TTTATCTGAG GCGATGAGNA 600

GATCAAGTAT CCGTATGATA AGGACTTNCT TTTAAGGC 638

(2) INFORMATION FOR SEQ ID NO: 35:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:

GTTTCATTTC AATATCAA 18

(2) INFORMATION FOR SEQ ID NO: 36:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36: ATCTATATAA TGACAGAG 18

(2) INFORMATION FOR SEQ ID NO: 37:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1496 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:

GTTAATCAAG TATCGAAGCG GAACAATCAT ACTTTAATGT TGAAGATTTA TATNGCGAAC 60

AAGCGATGGT CCTAGTGCGT AATATTAATT TAGCACTGCG CGCACAATAT TTGTTNGNAT 120

CTNATGTCGA TTACTTTGTA TATNNTGGTG ATATTGTTTT AACTGACCNC ATTACAGGTC 180

GTNTGTTACC GGNAACTAAG TTGCAAGCTG GACTTCACCA NGCTATTGAA GCGAAAGAAG 240

GTATGGAGGT TTCAACAGAT AAAAGTGTTA TGCCAACCAA TTACCCTTCC AGAATTTATT 300

TAAACTTTTT GAATCAATTT TCAGGTATGA CAAGCTACAG GAAAATTAGG CGAATCAGAG 360

TTCTTTGATT TGTATTCANA AATAGTCGTA CAAGCACCCA ACTGATAAAG CGATTCAACG 420

TATCGATGAA CCAGATAAAG TGTTTCGTTC AGTTGATGAG AAAAACATCG CGATGATTCA 480

TTGATATAGT TGAACTTCAT GANNCGGGGC CGACCGGTTT TACCTCATAA CCGAGNACTG 540

CTGAAGCGGC TTGAATACTT TTCNGAAGTA TTATTCCAAA TGGATATTCC TAATAATTTA 600

CTCATTGCGC AAAATGTTCC AAAAGAAGCG CAGATGATAG CTGAAGCAGG CCAAATTGGT 660

TCCATGACTG TTGCGACTAG TATGGCAGGT CGAGGCACAG ATATTAAACT TGGTGAAGGT 720

GTCGAAGCAT TAGCTGGATT AGCTGTTATT ATTCATGAAC ATATGGAAAA TAGCCGTGTA 780

GACAGGCAAT TACGTGGTCG TTCTGGTAGA CAAGGGGATC CGGGATCATC TTGTATATAT 840

ATTTCACTAG ATGATTATTT AGNTAAGCGA TGGAGCGATA GTAATTTAGC GGAAAATAAT 900

CAATTATATT CANTAGATGC ACAACGATTA TCGCAAAGTA ATTTGTTTAA TCGNAAAGTT 960

AAGCAAATTG TAGTTAAAGC GCAGCGTATC TCGGAAAGAA CAAGGGGTTA AAGCTCGGTG 1020

AAATGGCTTA ATTGAATTTG NNAAAAAGCA TNAGTATTCA GCGAAGATCT TNGTATTTAC 1080

GANGGAACGC AAATCCGAGT TTTTAGAAAT TAGATTGATG CTGAGAATCC NAGATTTTTA 1140

ANGCGGTTAG CTTAAAGATT GTATTTGAAA TNGTTTGGGG NAATGANGGA AANGGTGCTA 1200

ACAAAATCGC GNGTTGGGCG AGTATATTTT ATCAAAAATT TAAGTTNCCA ATTTAATAAA 1260

GATGTGGCTT GTGTTAATTT TAAAGATAAG CAAGCAGNAG TGACATTTTT ATTAGAGCAA 1320

TTTGAAAAGC AATTAGCTTT GGANTCCGTA AAAACATGCA ANGNGCATAT TATTATAATA 1380 TTNCCGGCCA AAANGTCTTT NGGGAAAGCA ATTGATNCAA GTTGGGGTTA GGAACAAGTC 1440 GGCTTTTNAC AACAANTTAA NAGCAAGCGN TAATCAAACG ACAAAANTGG CAACCT 1496

(2) INFORMATION FOR SEQ ID NO: 38:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38:

CCGCTAAATT ACTATCGC 18

(2) INFORMATION FOR SEQ ID NO: 39:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 39:

CTGAAGCGGC TTGAATAC 18

(2) INFORMATION FOR SEQ ID NO: 0:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 955 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single (D) TOPOLOGY: linear

(11) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40:

ATATAAATTA TTTAAGCGTA TGGTTTTACT TCGATTGCAC CCTTCATTTT CATCATTGAA 60

CACCATGCTT AATATAATCC ATATATTTGT GGCTCTAAAG NCTTTCCTCC CACCGTATAA 120

TGTCTGCTGC TTTTTCAGCT AACATTAAAA CAGGTGCGTG TATATTGCCA TTTGTCGTAC 180

GTGGCATAGC GGATGCATCA ACTACACGTA AATTTTCCAT ACCGTGGACT TTCATTGTTA 240

ACGGGTCAAC TACTGCCATT GGATNCTGAA GCAGGACCCA TTTTAGCACN ACAAGATGGG 300

TGTAATNCTG TTTCACCATC TCNACGGAAN NCAATCAAGN ATTTCTTCGT CTGTTTGCAC 360

TTCTGGGTCC TGGGTGAAAT TTCTCCACCA TTGAATGGAT CCATTGCTTT TTGAGATAAG 420

ATATTTCTTG CTACACGAAT TGCTTCTACC CATTCTNTTT TATCTTCTTC TGTTGATAAA 480

TAATTAAAGC GGATACTTGG TTTTTCGAAT GGATCTTTAG ATTTGATTGG CACGAGCTAC 540

CACGAGAGTT TGAATACATT GGTCCTACGT GAACTTGATA ACCATGTGCG ACCGCTGCCT 600

TTTGACCATC ATATCTTACA NCTATTGGTA AGAAATGGAA CATTAAGTTA GGATAATCAA 660

CTTCGTTATT TGAACGTACA AATCCGCCAC CTTCAAAATG GTTAGATGCT GCTGCACCTG 720

TACGTGTGAA AATCCAGTGG TAAACCAATT AAATGGCATG CGCCTTGATA TCTAAGCTTG 780

GCTGTAATGA TACAGGTTTC CTTACATTTA TGTTGAATGT ATACCTCTAA GTGATCTTCC 840

AAAGTTTTCA CCCACACCTG GTAAATGAAC ACGTGGCTCA ATGCCTTTTG ATTTTAGGAA 900

CTCTGAATCA CCGATACCAG ATAATTGTAG TAATTGTGGC GTTATTGAAT GCCCC 955

(2) INFORMATION FOR SEQ ID NO: 41 :

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic ac d

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:

GAAGCAGGAC CCATTTTA 18 (2) INFORMATION FOR SEQ ID NO: 42:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42:

GATTTTCACA CGTACAGG 18

(2) INFORMATION FOR SEQ ID NO: 43:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 497 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3:

GAATTCCTAC ATAATACTTT TGTTTACCTT GTGTCAGTTT ATACAACGGT GGCTGTGCAA 60

TATACACATA GCCTGCTTCA ATTAACGGTC TCATAAATCG ATAGAAGAAT GTTAATAACA 120

ATGTTCTAAT ATGCGCTCCA TCCACATCGG CATCAGTCAT AATGACGATT TTGTGATATC 180

TTGCTTTCGC TAGATCAAAG TCGCCACCGA TTCCTGTACC AAATGCTGTG ATCATTTGAC 240

GAATTTCATT GTTATTCAAA ATTCTATCTA ATCGTGCTTT NTCAACATTT AATATCTTAC 300

CTCGTAATGG TAAAATCGCC TGCGTTCTAG AGTCACGACA GATTTTGGTG GACCCCCNGC 360

AGAGTCCCCT TCGACTAAGA AAATCTCACA TTCTTCAGGA CTTTTACTAG AGCAATCGGC 420

TAATTTACTG GAAGACTGCT ACATCTACGC TGATTTACGA GGTGTTACTT CAGGGCTTTN 480

TCGAGACACG TGCANGT 497

(2) INFORMATION FOR SEQ ID NO: 4 : (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4:

CATAATACTT TTGTTTACC 19

(2) INFORMATION FOR SEQ ID NO: 45:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45:

AGTAACACCT CGTAAATC 18

(2) INFORMATION FOR SEQ ID NO: 46 :

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1443 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46:

CTANCNAANG GAANTTCAGC ATCCTTAAAA ATACCTATTT GACTGTAGAA ACCTTTTGNT 60

GCGTACAATA TCTAAACCTT GTCGTGCTGC TGGAACTGCA CCTGAACATT CAACAACAAC 120

ATCTGCACCG TAACCGTCTG TAATTCCATT GATATACGTT TTTAAGTCTG TGTGTTGTAA 180

ATTGACTACA TAATCCATGT GCAATGCTTC TGCTTTATCT AATCTGACTT NGTGGCANTG 240

TCCAATCCAG TTACCACAAC AGGTGCGCCT TTACTTTTCA ACACTTGTGC TACAAGTAAT 300

CCGATTGGCC CAGGTCCCAT TACAACTGCT ACATCGCCAG AGTTCACTTG AATCTTAGAA 360

ACGCCATGAT GTGCACATGC TAATGGTTCT TGTCATAGCT GCAGACTGAT ACGATACTTC 420

CGCTTCTGGA ATATGATNCA AACTTTCTTC ACGTGCAATG ACATAATTAG TAAATGCGCC 480

ATCAACTTGT GTTCCAATAC CTTTTCG.ATG GTTGCATAAA TGATAGTTTT TTGATTTACA 540

GGAATCACAC TCATTACANA CCATAGAATG TAGTTTCAGA AGTGACNCGG TCACCAACTT 600

TAAAATCNTT AACGTCTGCT CCCAACTTCA ACGATNTCAC CAGAAAATTC ATGACCTAAT 660

GTCACTGGAA AATTAACTTN ATAATGCCCT TCATAAGTAT GAAGGTCTGT GCCACAAATT 720

CCTGCATAAT GTACTTTAAT CTTTACTTTA TCATCTAGCG GTGTTGCAAC TTCTTTATCA 780

AGAAGTTCTA AGTTGCCATG TCCTTCTCTT GTTTTTACTA AAGCTTCCAC CACAAACACN 840

TCGANTTTTT ANTTGNAATA GACTNNATAG NTTNAAGATA AGATAGTTAN CGATATTNCC 900

ACCTTGATCA ATACTTGANA TTTCAGATGA ACCTTTTGNC ATTTGTACAT TCGTACCTTT 960

CGCCATATCT GTGAAAATGG GTGCTACGTC TGTTGCAATA TATAATGAAA TTGCAATCAT 1020

AATCGTACCC ACAATGACAG AATGAATAAT GTTTCCTCTT GCTGCACCAA CAATAAACGC 1080

GACAACAAAT GGTATAGTTG CTAAGTCACC AAAAGGTAGT ACTTGGTTTC CTGGTAAAAT 1140

AACGGCTAAT AAAACAGTGA TAGGTACTAA AATTAATGCT GTCGAAATAA CCGCTGGATG 1200

ACCTAATGCT ACAGCCGCAT CCAATCCAAT ATAAATTTCA CGTTCGCCAA AACGTTTATT 1260

TAGCCATGTT CTTGCAGACT CTGAAACTGG CATTAAACCT TCCATTAAGA TTTTTACCAT 1320

TCTAGGCATT AAGACCATTA CTGCAGCCAT TGACATTCCT AAATTAATGA TGTCTCCAGG 1380

TTTGTAACCT GCTAACACAC CAATACCTAA ACCTAAAATT AAGCCGACAA ATATAGACTC 1440

TCC 1443

(2) INFORMATION FOR SEQ ID NO:47:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA 97/31114

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 47:

GTTCTAAGTT GCCATGTC 18

(2) INFORMATION FOR SEQ ID NO: 8:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 48:

CCTAGAATGG TAAAAATC 18

(2) INFORMATION FOR SEQ ID NO:49:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1642 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49:

CCATTTAAAA GTATTGTAAA ATCATCCACN TTNTATAAAC CAACCACNTT AACNTTTTTG 60

ACATTTGTTA TCCGATGAGA TTAAAAGATA TCAATNAATA CAATTTTTAN AATTAATGTC 120

ACTATGTTTT CCGATAATAT NACCCAATCA TCGNAATGTT ACCCATTTAT AAAATGANAA 180

ATCNTTGACA TAGGTANAGG GAATGTATAT TGGTCNCGGA TCACTTAAAT TAAACCCANA 240

TCATGTCATC TGGTAATGTN TCAATGTTAA TTGCTCCTGA AGCGGCGTAN ACTTTAATCT 300

TCCATGTTAA ATGAGTAAAT TGATGCGTCA ACTCNAAAAT AGGTGTTTCT NCTGGNTGAA 360 TGTCATGACC GATTTTTTCA NTCATTTTAC GTCTANCATG CTCACTATCN AACATAGGAN 420

ATTGCCACAT ACCATACNAT AATTNTTCCC TACGCTTTTG CAACAGATAT TGACCTTGAT 480

TATTTCTAAT TAANAAGACG GATTGCTCAA TTACNTTTTT ACTTACATTT TTAGATTTAA 540

CAGGTAACTT TTCAAATGGA CCTTTATCAA ATGCCTCACA GTTTTCTTGN ACTGGACNAA 600

ATAAGCATAA TGGATTTTTT GGTGNACAAA TTAATGCCCC TAATTCCATC ATAGCTTGAT 660

TAAACGTTCC AGCTTCTGTA GTAACATACG GTAACAATTC TTGTTCGTAC GATTTCCTCG 720

TCGATTGTAA TTTAATATCT CGATAGTCAT CATTCAATCT AGACCATACG CGAAAAACAT 780

TTCCGTCTAC AGTTGCTAGT GGTACATTAT ATGCAATGCT CATTACTGCA GCTTGTGTGT 840

ATGGGCCAAC ACCTTTTAAC GCTTTAAATT GATCAGGATC TTTGGGAACT AAGCCTTCAT 900

ATTTATCANA AACTTCTTTA ATCGCCGTAT GAAAATTTCG AGCTCTACTA TAATATCCTA 960

AGCCTTCCCA ATACTTTAAC ACTTCATCTT CCGAAGCTTG ACTCAAAACT TCCACAGTTG 1020

GAAATCGGNC ACCAAAACGA TGATAATAGT CAATAACTGT TTTAACTTGT GTCTGTTGTA 1080

ACATGACCTC ACTTAACCAA ATATAGTACG GATTGGTCGT TTGTCGCCAT GGCATTTCTC 1140

TTTGATTTTC ATCAAACCAG TGTATCAAAT TTTCTTTAAA ACTAGACTGC TGATACATTT 1200

ATAAAACCCT TTCCTCACCA AAATTAATTG TCTTTACTCA TAATGTTTTT ATTGTACATT 1260

AAAATCATGG TTAGTATGTA AGTTAATTTA GTTATNTGCG AAATTGGATT ATAATAGTAT 1320

ATATAATATT ATGAAATGAG TGAACTGATA TGGACACTGC AACACATATC GCAATTGGGG 1380

TGGGCCTTAC AGCACTTGCA ACTCAAGATC CAGCAATGGC TTCTACGTTT GGTGCAACAG 1440

CTACAACCCT TATCGTTGGT TCATTAATTC CTGATGGGGA TANTGTNCTT AAATTANAGG 1500

ACANTGCAAC ATATATTTCG NATCATAGAG GNATNACGTC ATNCCATCCC CTCCCACAAN 1560

NNTATGNCCA GTCNCNTTTA CANTTTNTAT NTNTTCACGT CACTNTNGCT GGTANGCATC 1620

CCNCCTCACG TATGGCTTGT GG 1642

(2) INFORMATION FOR SEQ ID NO:50:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 50:

TCCTGAAGCG GCGTATAC 97/31114

(2) INFORMATION FOR SEQ ID NO:51:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51:

TATGAAGGCT TAGTTCCC 18

(2) INFORMATION FOR SEQ ID NO: 52:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 514 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 52:

GGGAAAAAAA GAAAACCTTC CAAAATACGG GAAATTGAAA TTAATTANCC GGAGAGACCA 60

NATAGGAAGT AATTGATAAT GGAAGTTTCC CCANAATTTA ACAAGCTAAA AGAGTTTGGG 120

TGCCTTTTAC AAGATAAGCA TGCCAATACA GTCATTTCAC GCACACTGTT GNCCACTATG 180

AGTTAAAGCT TGCTGAAGGT TATGAAACAC ATTTAGTGGG AATAAAAAAC AATAATAACG 240

AGGTCATTGC AGCTTGCTTA CTTACTGCTG TACCTGTTAT GAAAGTGTTC AAGTATTTTT 300

ATTCAAATCG CGGTCCAGTG ATCGATTATG AAAATCAAGA ACTCGTACAC TTTTTCTTTA 360

ATGAATTATC ANAATATGTT AAAAAACATC GTTGTCTATA CCTACATATC GATCCATATT 420

TACCATATCA ATACTTGAAT CATGATGGCG AGATTACAGG TAAGGCTGGT AATGATTGGT 480

TCTTTGATAA AATGAGTAAC TTAGGATTTG AACG 514

(2) INFORMATION FOR SEQ ID NO:53: 97/31114

(I) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(II) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:

GAGGTCATTG CAGCTTGC 18

(2) INFORMATION FOR SEQ ID NO:54.

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 54:

CAAATCCTAA GTTACTCATT 20

(2) INFORMATION FOR SEQ ID NO: 55:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 479 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

In) MOLECULE TYPE: Genomic cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 55:

CGCACATAAC GTGCAGCATA TGCAGCTGAG CGGTCTACTT TTTGTAGGAT CCTTACCACT 60

GAAGCATCCG CCACCATGAC GTGCATAGCC ACCATACGTA TCAACAATGA TTTTACGTCC 120

TGTTAATCCT GCATCACCTT GAGGTCCACC GATTACAAAG CGTCCTGTAG GATTGATGTA 180

GAATTTAGTT TGTTCATTAA TCAAGTTTTC TGGAACAGTT GGATAAATGA CATGCGCTTT 240

GATGTCTTCT TGAATTTGTT CAAGTGTCAC ATCATCAGCA TGTTGTGTTG ATACGACAAT 300

CGTATCAATA CGTACTGGGT TATCATTTTC ATCATATTCA ACAGTGACCT GAACTTTACC 360

GTCTGGTCGT AAATAATTCA ACGTCTCGNG CCATCTTTTA CGCACATCAG ATTAAACGTT 420

TGGGGCAATT GGGTGTGATA AATTAAATTG CTAGAGGGAT GTACGTTTCT TGTTTCAAT 479

(2) INFORMATION FOR SEQ ID NO:56:

(i. SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:

ACGTGCATAG CCACCATA 18

(2) INFORMATION FOR SEQ ID NO:57:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:57: ACAAGAAACG TACATCCC

18

⁽2⁾ INFORMATION FOR SEQ ID NO:58:

⁽l⁾ SEQUENCE CHARACTERISTICS:

(A) LENGTH: 857 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58:

ACAACCCTNC AGTGCTTGGC CAATTAGGTA GAGAATTTNA CCTAGGTAAN TTAATGCGAT 60

AAAGCCCAAG TTTGTAAAAT GTCCNTTGTG CGCCAATTTG TTCCTGTACN TANTGGGANC 120

TATTTTAGGA TTCTTATCAG GGATATTTCC CAAGGGTTTT GTTGACNCCT TAATCATGCG 180

TGCGTGTGAT GTTATGTTGG CAATTCCCCA AGTTATGTTG TAACGTTAGC ATTAATTTGC 240

ATTGTTTGGA ATGGGTGCCG AAAATATTAT CATGGCATTT ATTTTGACGC GTTGGGCATG 300

GTTCTGTCGT GTTATACGTA CAAGTGTTAT GCAGTACACT GCTTCTGACC ATGTCAGATT 360

TGCTAAAACA ATCGGTATGA ATCATATGAA AATTATTCAC AAACATATTA TGCCGTTAAC 420

ATTAGCAGAT ATTGCTATCA TCTCTAGTAG TTCGATGTGT TCAATGATCT TGCAAATATC 480

TGGCTTTTCA TTTTTAGGAT TAGGTGTCAA AGCGCCTACT GCAGAGTGGG GCATGATGCT 540

TAACGAAGCT AGAAAAGTGA TGTTTACACA TCCTGAAATG ATGTTTGNGC CAGGTATTGC 600

CATAGGGATT ATAGTGATGG CATTTAACTT CTTATCCGAT GCTTTACAAA ATTGNTATTG 660

GATCCCCCGC ATCTCTTTCT TAAAGATAAA CTTCCGCNCC TTGTGAAAAA AGGGAGTGGN 720

GCAATCATGA CATTGTTAAC AAGCTAAGCA TTTGGCGATT ACAGATACCT GGACAGATCA 780

ACCACCGTGA GTGATGTGAN TTTNNCAATT AACTAAGGGG TGAAACTCTA GGCNTTATTG 840

GGGAAAGTGG TAGCGGT ₈₅₇

(2) INFORMATION FOR SEQ ID NO: 59:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear ⁽ii⁾ MOLECULE TYPE: Genomic cDNA

⁽xi⁾ SEQUENCE DESCRIPTION: SEQ ID NO:59:

ATATTATCAT GGCATTTA

IB

⁽2⁾ INFORMATION FOR SEQ ID NO: 60:

⁽l⁾ SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic ac d

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

⁽n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 60:

ATCTTTAAGA AAGAGATG

18

(2) INFORMATION FOR SEQ ID NO: 61:

⁽l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 593 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

⁽ii) MOLECULE TYPE: Genomic cDNA

⁽xi⁾ SEQUENCE DESCRIPTION: SEQ ID NO: 61:

GAATTCTTGC ACATGTTGCT CGGTGTCTTC CTTGCTGCAC TTGTATCATT CGTTGTAGCT 60

GCTTTAATTA TGAAGTTCAC TAGAGAACCA AAGCAGGATT TAGAAGCTGC GACAGCTCAA 120

ATGGAAAATA CTAAAGGGAA AAAATCAAGC GTTGCTTCTA AGTTAGTATC TTCTGATAAA 180

AATGTTAATA CAGAAGAAAA TGCTAGTGGT AATGTTAGTG AAACATCTTC ATCAGATGAT 240 GATCCTGAAG CGCTATTGGA TAATTACAAC ACTGAAGATG TTGATGCACA CAATTACAAT 300

AATATAAATC ATGTTATTTT TGGCTGCGAT GCGGGTATGG GTTCTTNGGT GCAAATGGGG 360

TGCAAGCATT GTTACNGTNA TTAAATTTTA AAAAGGCGGC AATTAATGAT ATTACAAGGG 420

TACAAATTAC TGCGAATTAA TCAAATTGCC AAAAGATGCT CCAATTANGN TATCAACTCC 480

AGAAAAACTA CTTGATCCGG GCTATTAACA AACACAATGC CATCCATATT CNAAGGGGNT 540

TAATTTCCTA ATCACCAAGA TATGNAGGAC TTTTAATTAT CTTAAAAAGG TGG 593

(2) INFORMATION FOR SEQ ID NO: 62:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 62:

TGCACATGTT GCTCGGTG 18

(2) INFORMATION FOR SEQ ID NO: 63:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 63:

GTGGTAATGT TAGTGAAAC 19

(2) INFORMATION FOR SEQ ID NO: 64: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 425 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 64:

GGCACGAGCG AGTTCATTAG CTATATATAA GCCTAATCCA GAACCACCCG TTTTTGTATT 60

ACGAGAGTTT TCTACTCTGA ATGTACGTTC GAATATACGT TCTTGTAGTT CTGGTATAAT 120

GCCAATACCT CNATCGCTAA TAGCAATGTC GATAGTATCT TGATCTTTGT TTTCACTAAT 180

ATTAATATCA ATGCGACTAC CAACATTTGA AAATTTTAGC GCATTATCAA GTAAGTTTGT 240

TAAAATACGC TCAAGTGGCG TTCGATATTG ATAAAATGCA TCAATTTCGC TACAGAAATT 300

CACTTCTAAT GTGCGGTTTT CATGTTTGAT ACGTTGCTCC ATATGGTTGC AATATTGATA 360

CAAGTAATTG GTCTAGTTGT ATTAATTCTG GGGGATATGT TTTACCTGTA TTTAAAGTTG 420

ATAAT 425

(2) INFORMATION FOR SEQ ID NO: 65:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 65:

TATAAGCCTA ATCCAGAACC 20

(2) INFORMATION FOR SEQ ID NO: 66:

(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(11) MOLECULE TYPE: Genomic cDNA

(x ) SEQUENCE DESCRIPTION: SEQ ID NO: 66:

AACGTATCAA ACATGAAAAC 20

(2) INFORMATION FOR SEQ ID NO:67:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 465 base pairs

(B) TYPE: nucleic ac d

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

( ) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:

GTACGAGCTC GTGCCGGCAC GAGCGATTGG TGCAGTGAGT TATGTTTTAG AACAATTAGA 60

TGCACCAGTA TATGGATCTA AATTGACAAT AGCGTTAATT AAAGAAAATA TGAAAGCCCG 120

TAATATTGAT AAAAAAGTTC GCTACTACAC AGTTAACAAT GATTCAATTA TGAGATTCAA 180

AAACGTGAAT ATTAGTTTCT TTAATACGAC ACACAGTATT CCTGATAGTT TAGGTGTCTG 240

TATTCACCCT TCATATGGTG CCATTGTGTA TACAGGTGAA TTTAAGTTTG ACCAAAGTTT 300

ACATGGACAT TATGCACCAG ATATTAAACG TATGGCAGAG ATTGGTGAAG AAGGCGTATT 360

TGTCTTAATC AGTGATTCTA CTGAGGCAGA GAAACCTGGA TATAATACTC CCGGAAAATG 420

TAATTGAACA TCATATGTAT GATGCCTTTG CCAAAGTGCG AGGTC 465

(2) INFORMATION FOR SEQ ID NO:68:

(ι) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single (D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 68:

TTTAGAACAA TTAGATGCAC C

21

(2) INFORMATION FOR SEQ ID NO: 69:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69:

TCCGGGAGTA TTATATCCAG 20

(2) INFORMATION FOR SEQ ID NO:70:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 527 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:

GGCCCAAACC CATCCAAGTC CTTTTTAATT GACTTATTTA CATTATTTCT TTAATTTGGA 60

TTAACAAATT TTTTTCTATT TGANCCCTTT AATGTTNACT CCCCGTATCT AACAAGCAAG 12C

TGATCATACT TCATTATTTT AGCAACTCCT TAATTTCCTC ATAAATGATG ATAAATATTT 180 /31114

CTTTAAACCT TGCTATATCT TCTTTAGTTG TAGTAGCCCC AAATGATAAT CTTATACTAC 240

CTTCAATAGA TTTGTCTGAT AATCCCATTG CAGCCAATAC TTCATTTAAT TTATTACGTT 300

TAGATGAACA AGCACTCGTC GTAGATATCA TAATGTCATA TTTTGAAAAA GCATTAACTA 360

ATACTTCACC TTTTACGCCA GGAAAACTAA GATTTAAAAC GAATGGTGAA CCTGAAGTTG 420

AAGAATTAAT ATAAACTCCA TGATATTTAT TTAAAAATTG ACGGACGTCA TTATTTAACT 480

CAGTAACAAA TGCATTCAAT GCTTCAAAGT TTTCATTAGC TCGTGCC 527

(2) INFORMATION FOR SEQ ID NO: 71:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71:

TTTTAGCAAC TCCTTAATTT CCTC 24

(2) INFORMATION FOR SEQ ID NO: 72:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 72:

GCACGAGCTA ATGAAAACTT TG 22

(2) INFORMATION FOR SEQ ID NO:73: 7/31114

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 811 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(i ) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 73:

GACAACTTGC TAAAGCACGT GATGAAAAAG TAAGTGAATA TGGAATTGAA CAAGCTGATG 60

GTACATTAAT TCAATATGAT AGTGAAGCCA AGATATATGA ACATTTTAAT GTGAATTTTA 120

TACCACCTGC TATGCGAGAA GATGGTAGCG AATTTGATAA AGATCTAAGT AATATCATTA 180

CATTAGATGA TATTAATGGT GATATTCATA TGCATACAAC GTATAGTGAT GGTGCGTTTT 240

CTATTCGAGA CATGGTAGAA GCAAATATCG CAAAAGGTTA TAAATTCATG GTAATTACTG 300

ATCATTCACA AAGTTTACGT GTTGCTAATG GCTTACAAGT GGAAAGACTT TTTANGACAA 360

AAACGAAGGA AATTAAGGCT TTAGATAAAG AATATAGTGA AATTGGATAT TTATTCAGGT 420

ACAAGAAATG GATATATTAA CCTGATGGCT CGCTGGATTA TGATGATGAA ATTTNAGCAC 480

AACTTGGATA TGTNATTGGA GCTATTCAAC AAAGCTTNAN CCAATCAGAA GAACAAATNA 540

TGGAACGGAT TAGCTAATGC ATGTCGCAAT CCATACGTGC GACATATAGC GCATCCAACA 600

GGGCGTATTA TAGGTAGAAG AGATGGTTAT AAACCGAATA TTGAACAATT AATGGCATTA 660

GCTGAAGAAA CGAATACAGT ATTAGAAATT AATGCCAATC CACATCGACT GGATCTTGAA 720

CGCTGAAATC GNTCGNNAAT ATCCAAATGT GAAATTAACT NTTAACACTG ATGGGCATCA 780

TNCAAATCAA TTNGATTTTN TGGAATTATG G 811

(2) INFORMATION FOR SEQ ID NO: 74:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs

(B) TYPE: nucleic ac d

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 74: 7/31114

ACGTGATGAA AAAGTAAGTG 20

(2) INFORMATION FOR SEQ ID NO:75:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(u) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:

TCTTGTACCT GAATAAATAT CC 22

(2) INFORMATION FOR SEQ ID NO:76:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 681 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO.-76:

AGATCGTTCG CTAATTGACA ATTGATTAAA TCCCCTATTA CAAAATTGGA TATTACCTGT 60

TATATCTAAA AATCCACAAA TTGCTTTAGC AAGTGTTGAT NTGNCGGCAC CATTGTGACC 120

AACTATACTA AGCATTTCTC TTCTATAAAC ATTTAATTGA ACATTATTAA G"ΑCACTATT 180

ACTATAGTCA CTATATTGAA CACATACCTC ATTTAATTCT AATAGCGGCN C _ATGTGTA 240

CTTATTATCA TTATGTGCAG ATGTNTCATC TATCCATTTN NNCACTTTAA NTTTAACATG 300

TTCACTCATA CAAACGACAC GTAANTTCGC TAAGTTATCA ATGGATTCGA CATCTACTTC 360

TGNATATTNA AGCGCTGNAC AGTATAATGG NACACGTATG CCTGCTTCTT TAAGCTTAGA 420

TGATTTTAGC AAATCACTAG GCGTTGTATT AGCGATGATT TTTCCATCTT TAAAAAGAAG 480

ANCTCTATCA AACGTATCAT CTAATGANTC TTCTAATCGA TGTTCGACAA TAATCATCGT 540 97/31114

TGACTTTGTT TCTTCATGAA TATTGTNTAA CAATCTCAGC GTTTCATGTC CTGTCGCAGG 600 ATCTAAATTG GCCAGCGGCT CATCCAATAT TAAAATAGGC GTNCGATGGA TTAATATACC 660 ACCTAATGAA ACGCTCGTGC C 681

(2) INFORMATION FOR SEQ ID NO:77:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(x ) SEQUENCE DESCRIPTION: SEQ ID NO: 77:

AATTGACAAT TGATTAAATC CCC 23

(2) INFORMATION FOR SEQ ID NO: 78:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:

GCCAATTTAG ATCCTGCGAC 20

(2) INFORMATION FOR SEQ ID NO: 79:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 164 amino acids

(B) TYPE: amino acid 7/31114

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Protien

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79:

Met Gly Met Val Ala Val Xaa Val Cys Thr Pro Pro He Gly Leu Gly

1 5 10 15

Leu Ala Thr Xaa Val Xaa Lys Tyr Lys Phe Asn His Ser Glu Arg Glu

20 25 30

Met Gly Lys Ala Xaa Phe Thr Met Gly Leu Phe Gly He Thr Glu Gly

35 40 45

Ala He Pro Phe Ala Ala Gin Asp Pro Leu Arg He He Pro Ala Asn

50 55 60

He He Gly Ala Met He Ala Ser Val He Ala Xaa He Gly Gly Val 65 70 75 80

Gly Asp Arg Val Ala His Gly Gly Pro He Val Ala Val Leu Gly Gly

85 90 95

He Asp His Val Leu Trp Phe He Phe Gly Xaa He Val Gly Ser Leu

100 105 110

Val Thr Met Pro Thr Val Leu Leu Leu Xaa Arg Asn Thr Pro Val He

115 120 125

Ala Val Asp Ala Pro Ala Gin His Thr Gin Leu His Asp Thr Asp He

130 135 140

Thr Gin His Asp Thr Glu Val Asp Asn Val Asp Gly Thr Ser Glu Thr 145 150 155 160

Phe Thr Ser Gin

(2) INFORMATION FOR SEQ ID NO:80:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 155 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear 7/31114

(11) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO.-80:

Met Asn He Glu Xaa ASD He Asn Gly Arg Pro Lys His He Tyr Ser

1 5 10 15

He Tyr Arg Xaa Met Met Lys Gin Lys Lys Gin Phe Asp Gin He Phe

20 25 30

Asp Leu Leu Ala He Arg Val He Val Asn Ser He Asn Asp Cys Tyr

35 40 45

Ala He Leu Gly Leu Val His Thr Leu Trp Lys Pro Met Pro Gly Arg

50 55 60

Phe Lys Asp Tyr He Ala Met Pro Lys Gin Asn Leu Tyr Gin Ser Leu 65 70 75 80

His Thr Thr Val Val Gly Pro Asn Gly Asp Pro Leu Glu He Gin He

85 90 95

Arg Thr Phe Asp Met His Glu He Ala Glu His Gly Val Ala Ala His

100 105 110

Trp Ala Tyr Lys Glu Gly Lys Lys Val Ser Glu Lys Asp Gin Thr Tyr

115 120 125

Gin Asn Lys Leu Asn Trp Leu Lys Glu Leu Ala Glu Ala Asp His Thr

130 135 140

Ser Ser Asp Ala Gin Glu Phe Met Glu Thr Leu 145 150 155

(2) INFORMATION FOR SEQ ID NO:81:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 139 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:81: 7/31114

Asp Val Ala Lys Arg Leu Asn Ala Asn He Tyr Val Ser Gly Glu Gly

1 5 10 15

Glu Asp Ala Leu Gly Tyr Lys Asn Met Pro Ser Lys Thr Gin Phe Val

20 25 30

Lys His Gly Asp He He Gin Val Gly Asn Val Lys Leu Glu Val Leu

35 40 45

His Thr Pro Gly His Thr Pro Glu Ser He Ser Phe Leu Leu Thr Asp

50 55 60

Leu Gly Gly Gly Ser Xaa Val Pro Met Gly Leu Phe Ser Gly Asp Phe 65 70 75 80

He Xaa Xaa Gly Asp He Gly Arg Pro Asp Leu Leu Glu Lys Ser Cys

85 90 95

Ser Asn Lys Gly Phe Gly Thr Lys Leu Ala Arg Asn Lys Cys Met Ser

100 105 110

Pro He Lys He Leu Lys He Tyr Gin Thr Met Phe Lys Ser Gly Arg

115 120 125

Val Met Val Leu Glu Ala Leu Val Val Lys His 130 135

(2) INFORMATION FOR SEQ ID NO: 82:

(I) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 91 amino acids

(B) TYPE: ammo acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(II) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:

Met Tyr Gly Gly Val Thr Leu His Asp Asn Asn Arg Leu Thr Glu Glu

1 5 10 15

Lys Lys Val Pro He Asn Leu Trp Leu Asp Gly Lys Xaa Asn Thr Val

20 25 30

Pro Leu Glu Thr Val Lys Thr Asn Lys Lys Asn Val Thr Val Gin Glu 97/31114

35 40 45

Leu Asp Leu Gin Ala Arg Arg Tyr Leu Gin Glu Lys Tyr Asn Leu Tyr

50 55 60

Asn Ser Asp Val Phe Asp Gly Lys Val Gin Arg Gly Leu He Val Phe 65 70 75 80 h s Thr Ser Thr Glu Pro Ser Val Asn Tyr Asp 85 90

(2) INFORMATION FOR SEQ ID NO:83:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 153 ammo acids

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 83:

Met Leu Xaa Lys Met Leu Tyr Leu Leu Gin He His Gin Val He Pro

1 5 10 15

He Asn Ala He Ala Gin Ala Phe Asn Glu Lys Asp Gin Glu Arg Phe

20 25 30

Phe Gly Leu His Phe Phe Asn Pro Pro Arg He Met Xaa Leu Val Glu

35 40 45

Leu He Pro Thr Ser His Thr Lys Glu Ser He He Leu Asp Val Lys

50 55 60

Asn Phe Ala His Asn Val Leu Gly Lys Gly Val He Val Val Asn Asp 65 70 75 80

Val Pro Gly Phe Val Ala Asn Arg Val Gly Thr His Thr Met Asn Asp

85 90 95

He Leu Tyr Arg Ala Glu Gin His Lys Xaa Ser Xaa Val Asp Val Asp

100 105 110

Ala Leu Thr Gly Gin Ala He Gly Arg Pro Lys Thr Gly Thr Tyr Xaa

115 120 125

Leu Ser Asp Leu Val Gly Leu Xaa He Ala Xaa Ser Val He Lys Gly 97/31114

130 135 140

Xaa Gin Xaa Val Pro Glu Glu Thr Pro 145 150

(2) INFORMATION FOR SEQ ID NO:84:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 271 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 84:

Met Lys His Leu Leu Gly Thr Lys Ser Gly Leu Leu Ala Thr Pro Asn

1 5 10 15

Glu Asp Glu Lys Pro Glu Glu He Thr Trp Arg Glu Glu Thr Thr Gly

20 25 30

Lys Leu Asp Leu Val Val Ser Leu Asp Phe Arg Met Thr Ala Thr Pro

35 40 45

Leu Tyr Ser Asp He Val Leu Pro Ala Ala Thr Trp Tyr Glu Lys His

50 55 60

Asp Leu Ser Ser Thr Asp Met His Pro Tyr Val His Pro Phe Asn Pro 65 70 75 80

Ala He Asp Pro Leu Trp Glu Ser Arg Ser Asp Trp Asp He Tyr Lys

85 90 95

Thr Leu Ala Lys Ala Phe Ser Glu Met Ala Lys Asp Tyr Leu Pro Gly

100 105 110

Thr Phe Lys Asp Val Val Thr Thr Pro Leu Ser H s Asp Thr Lys Gin

115 120 125

Glu He Ser Thr Pro Tyr Gly Val Val Lys Asp Trp Ser Lys Gly Glu

130 135 140

He Glu Ala Val Pro Gly Arg Thr Met Pro Asn Phe Ala He Val Glu 145 150 155 160

Arg Asp Tyr Thr Lys He Tyr Asp Lys Tyr Val Thr Leu Gly Pro Val 7/31114

165 170 175

Leu Glu Lys Gly Lys Val Gly Ala His Gly Val Ser Phe Gly Val Ser

180 185 190

Glu Gin Tyr Glu Glu Leu Lys Ser Met Leu Gly Thr Trp Ser Asp Thr

195 200 205

Asn Asp Asp Ser Val Arg Ala Asn Arg Pro Arg He Asp Thr Ala Arg

210 215 220

Asn Val Ala Asp Ala He Leu Ser He Ser Ser Ala Thr Asn Gly Lys 225 230 235 240

Leu Ser Gin Lys Ser Tyr Glu Asp Leu Glu Glu Gin Thr Gly Met Pro

245 250 255

Leu Lys Asp He Ser Ser Glu Arg Ala Ala Glu Lys He Arg Phe 260 265 270

(2) INFORMATION FOR SEQ ID NO:85:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 143 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85:

Met Asp He Pro Asn Asn Leu Leu He Ala Gin Asn Val Pro Lys Glu

1 5 10 15

Ala Gin Met He Ala Glu Ala Gly Gin He Gly Ser Met Thr Val Ala

20 25 30

Thr Ser Met Ala Gly Arg Gly Thr Asp He Lys Leu Gly Glu Gly Val

35 40 45

Glu Ala Leu Ala Gly Leu Ala Val He He His Glu His Met Glu Asn

50 55 60

Ser Arg Val Asp Arg Gin Leu Arg Gly Arg Ser Gly Arg Gin Gly Asp 65 70 75 80

Pro Gly Ser Ser Cys He Tyr He Ser Leu Asp Asp Tyr Leu Xaa Lys 97/31114

85 90 95

Arg Trp Ser Asp Ser Asn Leu Ala Glu Asn Asn Gin Leu Tyr Ser Xaa

100 105 110

Asp Ala Gin Arg Leu Ser Gin Ser Asn Leu Phe Asn Arg Lys Val Lys

115 120 125

Gin He Val Val Lys Ala Gin Arg He Ser Glu Arg Thr Arg Gly 130 135 140

(2) INFORMATION FOR SEQ ID NO:86:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 221 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 86:

Gly Glu Ser He Phe Val Gly Leu He Leu Gly Leu Gly He Gly Val

1 5 10 15

Leu Ala Gly Tyr Lys Pro Gly Asp He He Asn Leu Gly Met Ser Met

20 25 30

Ala Ala Val Met Val Leu Met Pro Arg Met Val Lys He Leu Met Glu

35 40 45

Gly Leu Met Pro Val Ser Glu Ser Ala Arg Thr Trp Leu Asn Lys Arg

50 55 60

Phe Gly Glu Arg Glu He Tyr He Gly Leu Asp Ala Ala Val Ala Leu 65 70 75 80

Gly His Pro Ala Val He Ser Thr Ala Leu He Leu Val Pro He Thr

85 90 95

Val Leu Leu Ala Val He Leu Pro Gly Asn Gin Val Leu Pro Phe Gly

100 105 110

Asp Leu Ala Thr He Pro Phe Val Val Ala Phe He Val Gly Ala Ala

115 120 125

Arg Gly Asn He He His Ser Val He Val Gly Thr He Met He Ala 130 135 140

He Ser Leu Tyr He Ala Thr Asp Val Ala Pro He Phe Thr Asp Met 145 150 155 160

Ala Lys Gly Thr Asn Val Gin Met Xaa Lys Gly Ser Ser Glu Xaa Ser

165 170 175

Ser He Asp Gin Gly Gly Asn He Xaa Asn Tyr Leu He Xaa Xaa Leu

180 185 190

Xaa Ser Leu Xaa Gin Xaa Lys Xaa Arg Xaa Val Cys Gly Gly Ser Phe

195 200 205

Ser Lys Asn Lys Arg Arg Thr Trp Gin Leu Arg Thr Ser 210 215 220

(2) INFORMATION FOR SEQ ID NO: 87:

(l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 322 ammo acids (3) TYPE: am o acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:

Met Tyr Gin Gin Ser Ser Phe Lys Glu Asn Leu He His Trp Phe Asp

1 5 10 15

Glu Asn Gin Arg Glu Met Pro Trp Arg Gin Thr Thr Asn Pro Tyr Tyr

20 25 30

He Trp Leu Ser Glu Val Met Leu Gin Gin Thr Gin Val Lys Thr Val

35 40 45

He Asp Tyr Tyr His Arg Phe Gly Xaa Arg Phe Pro Thr Val Glu Val

50 55 60

Leu Ser Gin Ala Ser Glu Asp Glu Val Leu Lys Tyr Trp Glu Gly Leu 65 70 75 80

Gly Tyr Tyr Ser Arg Ala Arg Asn Phe His Thr Ala He Lys Glu Val

85 90 95

Xaa Asp Lys Tyr Glu Gly Leu Val Pro Lys Asp Pro Asp Gin Phe Lys 100 105 110

Ala Leu Lys Gly Val Gly Pro Tyr Thr Gin Ala Ala Val Met Ser He

115 120 125

Ala Tyr Asn Val Pro Leu Ala Thr Val Asp Gly Asn Val Phe Arg Val

130 135 140

Trp Ser Arg Leu Asn Asp Asp Tyr Arg Asp He Lys Leu Gin Ser Thr 145 150 155 160

Arg Lys Ser Tyr Glu Gin Glu Leu Leu Pro Tyr Val Thr Thr Glu Ala

165 170 175

Gly Thr Phe Asn Gin Ala Met Met Glu Leu Gly Ala Leu He Cys Xaa

180 185 190

Pro Lys Asn Pro Leu Cys Leu Phe Xaa Pro Val Gin Glu Asn Cys Glu

195 200 205

Ala Phe Asp Lys Gly Pro Phe Glu Lys Leu Pro Val Lys Ser Lys Asn

210 215 220

Val Ser Lys Xaa Val He Glu Gin Ser Val Xaa Leu He Arg Asn Asn 225 230 235 240

Gin Gly Gin Tyr Leu Leu Gin Lys Arg Arg Glu Xaa Leu Xaa Tyr Gly

245 250 255

Met Trp Gin Xaa Pro Met Xaa Asp Ser Glu His Xaa Arg Arg Lys Met

260 265 270

Xaa Glu Lys He Gly His Asp He Xaa Pro Xaa Glu Thr Pro He Xaa

275 280 285

Glu Leu Thr His Gin Phe Thr His Leu Thr Trp Lys He Lys Val Tyr

290 295 300

Ala Ala Ser Gly Ala He Asn He Xaa Thr Leu Pro Asp Asp Met Xaa 305 310 315 320

Trp Val

(2) INFORMATION FOR SEQ ID N0:8E

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 151 am o acids

(B) TYPE: ammo acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear 97/31114

(ii) MOLECULE TYPE: Protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 88:

Met Gly Ala Glu Asn He He Met Ala Phe He Leu Thr Arg Trp Ala

1 5 10 15

Trp Phe Cys Arg Val He Arg Thr Ser Val Met Gin Tyr Thr Ala Ser

20 25 30

Asp His Val Arg Phe Ala Lys Thr He Gly Met Asn Asp Met Lys He

35 40 45

He His Lys His He Met Pro Leu Thr Leu Ala Asp He Ala He He

50 55 60

Ser Ser Ser Ser Met Cys Ser Met He Leu Gin He Ser Gly Phe Ser 65 70 75 80

Phe Leu Gly Leu Gly Val Lys Ala Pro Thr Ala Glu Trp Gly Met Met

85 90 95

Leu Asn Glu Ala Arg Lys Val Met Phe Thr His Pro Glu Met Met Phe

100 105 110

Xaa Pro Gly He Ala He Gly He He Val Met Ala Phe Asn Phe Leu

115 120 125

Ser Asp Ala Leu Gin Asn Xaa Tyr Trp He Pro Arg He Ser Phe Leu

130 135 140

Lys He Asn Phe Arg Xaa Leu 145 150

(2) INFORMATION FOR SEQ ID NO:89:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 221 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 89:

Met He Phe Gly Lys Gly Thr Ala Lys Ala Thr Ser Tyr Gly Ala Gly

1 5 10 15

He He His Phe Leu Gly Gly He His Glu He Tyr Phe Pro Tyr Val

20 25 30

Leu Met Arg Pro Leu Leu Phe He Ala Val He Leu Gly Gly Met Thr

35 40 45

Gly Val Ala Thr Tyr Gin Ala Thr Gly Phe Gly Phe Lys Ser Pro Ala

50 55 60

Ser Pro Gly Ser Phe He Val Tyr Cys Leu Asn Ala Pro Arg Gly Glu 65 70 75 80

Phe Leu His Met Leu Leu Gly Val Phe Leu Ala Ala Leu Val Ser Phe

85 90 95

Val Val Ala Ala Leu He Met Lys Phe Thr Arg Glu Pro Lys Gin Asp

100 105 110

Leu Glu Ala Ala Thr Ala Gin Met Glu Asn Thr Lys Gly Lys Lys Ser

115 120 125

Ser Val Ala Ser Lys Leu Val Ser Ser Asp Lys Asn Val Asn Thr Glu

130 135 140

Glu Asn Ala Ser Gly Asn Val Ser Glu Thr Ser Ser Ser Asp Asp Asp 145 150 155 160

Pro Glu Ala Leu Leu Asp Asn Tyr Asn Thr Glu Asp Val Asp Ala His

165 170 175

Asn Tyr Asn Asn He Asn His Val He Phe Gly Cys Asp Ala Gly Met

Gly Ser Ser Ala Met Gly Ala Ser Met Leu Arg Asn Lys Phe Lys Lys

195 200 205

Ala Gly He Asn Asp He Thr Gly Tyr Lys Tyr Cys Asp 210 215 220

(2) INFORMATION FOR SEQ ID NO: 90:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 227 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single (D) TOPOLOGY: linear

(11) MOLECULE TYPE: protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 0:

Gly Thr Ser Val Ser Leu Gly Gly He Leu He His Arg Thr Pro He

1 5 10 15

Leu He Leu Asp Glu Pro Leu Ala Asn Leu Asp Pro Ala Thr Gly His

20 25 30

Glu Thr Leu Arg Leu Leu Xaa Asn He His Glu Glu Thr Lys Ser Thr

35 40 45

Met He He Val Glu His Arg Leu Glu Xaa Ser Leu Asp Asp Thr Phe

50 55 60

Asp Arg Xaa Leu Leu Phe Lys Asp Gly Lys He He Ala Asn Thr Thr 65 70 75 80

Pro Ser Asp Leu Leu Lys Ser Ser Lys Leu Lys Glu Ala Gly He Arg

85 90 95

Val Pro Leu Tyr Cys Xaa Ala Leu Xaa Tyr Xaa Glu Val Asp Val Glu

100 105 110

Ser He Asp Asn Leu Ala Xaa Leu Arg Val Val Cys Met Ser Glu His

115 120 125

Val Lys Xaa Lys Val Xaa Lys Trp He Asp Xaa Thr Ser Ala His Asn

130 135 140

Asp Asn Lys Tyr Thr Ser Xaa Pro Leu Leu Glu Leu Asn Glu Val Cys 145 150 155 160

Val Gin Tyr Ser Asp Tyr Ser Asn Ser Val Leu Asn Asn Val Gin Leu

165 170 175

Asn Val Tyr Arg Arg Glu Met Leu Ser He Val Gly His Asn Gly Ala

180 185 190

Xaa Xaa Ser Thr Leu Ala Lys Ala He Cys Gly Phe Leu Asp He Thr

195 200 205

Gly Asn He Gin Phe Cys Asn Arg Gly Phe Asn Gin Leu Ser He Ser

210 215 220

Glu Arg Ser 225

11 (2) INFORMATION FOR SEQ ID NO: 91:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(n) MOLECULE TYPE: Genomic DNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 91:

GCTCCTAAAA GGTTACTCCA CCGGC 25

Claims

What is claimed is:

1. An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of:

(a) a polynucleotide having at least a 70% identity to a polynucleotide encoding a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ

ID Nos: 1 ,4,7,10,13,16,19,22,25 and 28;

(b) a polynucleotide which is complementary to the polynucleotide of (a); and

(c) a polynucleotide comprising at least 15 sequential bases of the polynucleotide of (a) or (b).

2. The polynucleotide of Claim 1 wherein the polynucleotide is DNA.

3. The polynucleotide of Claim 1 wherein the polynucleotide is RNA.

4. The polynucleotide of Claim 2 comprising the nucleotide sequence selected from the group consisting of SEQ ID Nos: 1 ,4,7,10,13,16,19,22,25 and 28.

5. An isolated polynucleotide comprising a member selected from the group consisting of:

(a) a polynucleotide having at least a 70% identity to a polynucleotide encoding the polypeptide expressed contained in NCIMB Deposit No. 40771 and selected from the group consisting of SEQ ID NOs: 1 ,4,7,10,13,16,19,22,25 and 28;

(b) a polynucleotide complementary to the polynucleotide of (a); and

(c) a polynucleotide comprising at least 15 bases of the polynucleotide of (a) or

(b).

6. A vector comprising the DNA of Claim 2.

7. A host cell comprising the vector of Claim 6.

8. A process for producing a polypeptide comprising: expressing from the host cell of Claim 7 a polypeptide encoded by said DNA.

9. A process for producing a cell which expresses a polypeptide comprising transforming or transfecting the cell with the vector of Claim 6 such that the cell expresses the polypeptide encoded by the cDNA contained in the vector.

10. A process for producing a polypeptide of the invention or fragment comprising culturing a host of claim 7 under conditions sufficient for the production of said polypeptide or fragment.

1 1. A polypeptide comprising an amino acid sequence selected from the group consisting essentially of: 79,80,81,82,83,84,85,86,87 and 88.

12. An antibody against the polypeptide of claim 1 1.

13. An antagonist which inhibits the activity of the polypeptide of claim 1 1.

14. A method for the treatment of an individual having need of a polypeptide of the invention comprising: administering to the individual a therapeutically effective amount of the polypeptide of claim 1 1.

15. The method of Claim 14 wherein said therapeutically effective amount of the polypeptide is administered by providing to the individual DNA encoding said polypeptide and expressing said polypeptide in vivo.

16. A method for the treatment of an individual having need to inhibit a polypeptide of the invention comprising: administering to the individual a therapeutically effective amount of the antagonist of Claim 13.

17. A process for diagnosing a disease related to expression of the polypeptide of claim 1 1 comprising:

determining a nucleic acid sequence encoding said polypeptide.

18. A diagnostic process comprising: analyzing for the presence of the polypeptide of claim 1 1 in a sample derived from a host.

19. A method for identifying compounds which bind to and inhibit an activity of the polypeptide of claim 1 1 comprising:

contacting a cell expressing on the surface thereof a binding for the polypeptide, said binding being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said binding, with a compound to be screened under conditions to permit binding to the binding; and

determining whether the compound binds to and activates or inhibits the binding by detecting the presence or absence of a signal generated from the interaction of the compound with the binding.

20. A method for inducing an immunological response in a mammal which comprises inoculating the mammal with a polypeptide of the invention, or a fragment or variant thereof, adequate to produce antibody to protect said animal from disease.

21. A method of inducing immunological response in a mammal which comprises, through gene therapy, delivering gene encoding a fragment of a polypeptide of the invention or a variant thereof, for expressing such polypeptide, or a fragment or a variant thereof in vivo in order to induce an immunological response to produce antibody to protect said animal from disease.

22. An immunological composition comprising a DNA which codes for and expresses a polynucleotide of the invention or protein coded therefrom which, when introduced into a mammal, induces an immunological response in the mammal to a given such polynucleotide or protein coded therefrom.

23. A polynucleotide consisting essentially of a DNA sequence obtainable by screening an appropriate library containing the complete gene for a polynucleotide sequence of the invention under stringent hybridization conditions with a probe having the sequence of said polynucleotide sequence or a fragment thereof; and isolating said DNA sequence.