FIELD OF THE INVENTION [02] The invention relates to the identification of expression profiles and the nucleic acids involved in colorectal cancer, and to the use of such expression profiles and nucleic acids in diagnosis and prognosis of colorectal cancer. The invention further relates to methods for identifying and using candidate agents and/or targets which modulate colorectal cancer.

BACKGROUND OF THE INVENTION [03] Cancer of the colon and/or rectum (referred to as"colorectal cancer") are significant in Western populations and particularly in the United States. Cancers of the colon and rectum occur in both men and women most commonly after the age of 50. These develop as the result of a pathologic transformation of normal colon epithelium to an invasive cancer. There have been a number of recently characterized genetic alterations that have been implicated in colorectal cancer, including mutations in two classes of genes, tumor- suppressor genes and proto-oncogenes, with recent work suggesting that mutations in DNA repair genes may also be involved in tumorigenesis. For example, inactivating mutations of both alleles of the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, appears to be one of the earliest events in colorectal cancer, and may even be the initiating event.

Other genes implicated in colorectal cancer include the MCC gene, the p53 gene, the DCC (deleted in colorectal carcinoma) gene and other chromosome 18q genes, and genes in the TGF-P signaling pathway. For a review, see Molecular Biology of Colorectal Cancer, pp.

238-299, in Curr. Probl. Cancer, Sept/Oct 1997; see also Willams, Colorectal Cancer (1996); Kinsella & Schofield, Colorectal Cancer : A Scientific Perspective (1993); Colorectal

Cancer : Molecular Mechanisms, Premalignant State and its Prevention (Schmiegel & Schohnerich eds., 2000); Colorectal Cancer : New Aspects of Molecular Biology and Their Clinical Applications (Hanski et al., eds 2000); McArdle et al., Colorectal Cancer (2000); Wanebo, Colorectal Cancer (1993); Levin, The American Cancer Society : Colorectal Cancer (1999) ; Treatment of Hepatic Metastases of Colorectal Cancer (Nordlinger & Jaeck eds., 1993); Management of Colorectal Cancer (Dunitz et al., eds. 1998); Cancer : Principles and Practice of Oncology (Devita et al., eds. 2001) ; Surgical Oncology : Contemporary Principles and Practice (Kirby et al., eds. 2001) ; Offit, Clinical Cancer Genetics : Risk Counseling and Management (1997); Radioimmunotherapy of Cancer (Abrams & Fritzberg eds. 2000); Fleming, AJCC Cancer Staging Handbook (1998) ; Textbook of Radiation Oncology (Leibel & Phillips eds. 2000); and Clinical Oncology (Abeloff et al., eds. 2000).

[04l Imaging of colorectal cancer for diagnosis has been problematic and limited. In addition, metastasis of the tumor to the lumen, and metastasis of tumor cells to regional lymph nodes are important prognostic factors (see, e. g., PET in Oncology : Basics and Clinical Application (Ruhlmann et al. eds. 1999). For example, five year survival rates drop from 80 percent in patients with no lymph node metastases to 45 to 50 percent in those patients who do have lymph node metastases. A recent report showed that micrometastases can be detected from lymph nodes using reverse transcriptase-PCR methods based on the presence of mRNA for carcinoembryonic antigen, which has previously been shown to be present in the vast majority of colorectal cancers but not in normal tissues. Liefers et al., New England J. ofMed. 339 (4): 223 (1998).

[05] Thus, methods that can be used for diagnosis and prognosis of colorectal cancer would be desirable. Accordingly, provided herein are methods that can be used in diagnosis and prognosis of colorectal cancer. Further provided are methods that can be used to screen candidate bioactive agents for the ability to modulate colorectal cancer.

Additionally, provided herein are molecular targets for therapeutic intervention in colorectal and other cancers.

BRIEF SUMMARY OF THE INVENTION [06] The present invention provides novel methods for diagnosis and prognosis evaluation for colorectal cancer, as well as methods for screening for compositions which modulate colorectal cancer. Methods of treatment of colorectal cancer, as well as compositions, are also provided herein.

[07] In one aspect, a method of screening drug candidates comprises providing a cell that expresses an expression profile gene selected from those of Table I. The method further includes adding a drug candidate to the cell and determining the effect of the drug candidate on the expression of the expression profile gene.

[08] In one embodiment, the method of screening drug candidates includes comparing the level of expression in the absence of the drug candidate to the level of expression in the presence of the drug candidate, wherein the concentration of the drug candidate can vary when present, and wherein the comparison can occur after addition or removal of the drug candidate. In a preferred embodiment, the cell expresses at least two expression profile genes. The profile genes may show an increase or decrease.

[09] Also provided herein is a method of screening for a bioactive agent capable of binding to a colorectal cancer modulator protein, the method comprising combining the colorectal cancer modulator protein and a candidate bioactive agent, and determining the binding of the candidate agent to the colorectal cancer modulator protein.

Preferably the colorectal cancer modulator protein is a product encoded by a gene of Table 1 or Table 2.

[10] Further provided herein is a method for screening for a bioactive agent capable of modulating the activity of a colorectal cancer modulator protein. In one embodiment, the method comprises combining the colorectal cancer modulator protein and a candidate bioactive agent, and determining the effect of the candidate agent on the bioactivity of the colorectal cancer modulator protein. Preferably the colorectal cancer modulator protein is a product encoded by a gene of Table 1 or Table 2.

[11] Also provided is a method of evaluating the effect of a candidate colorectal cancer drug comprising administering the drug to a transgenic animal expressing or over-expressing the colorectal cancer modulator protein, or an animal lacking the colorectal cancer modulator protein, for example as a result of a gene knockout.

[12] Additionally, provided herein is a method of evaluating the effect of a candidate colorectal cancer drug comprising administering the drug to a patient and removing a cell sample from the patient. The expression profile of the cell is then determined. This method may further comprise comparing the expression profile to an expression profile of a healthy individual. In a preferred embodiment, said expression profile includes a gene of Table 1 or Table 2.

[13] Moreover, provided herein is a biochip comprising one or more nucleic acid segments of Table 1 or Table 2, wherein the biochip comprises fewer than 1000 nucleic acid probes. Preferable at least two nucleic acid segments are included.

[14] Furthermore, a method of diagnosing a disorder associated with colorectal cancer is provided. The method comprises determining the expression of a gene of Table 1 or Table 2, in a first tissue type of a first individual, and comparing the distribution to the expression of the gene from a second normal tissue type from the first individual or a second unaffected individual. A difference in the expression indicates that the first individual has a disorder associated with colorectal cancer.

[15] In another aspect, the present invention provides an antibody which specifically binds to a protein encoded by a nucleic acid of Table 1 or Table 2 or a fragment thereof. Preferably the antibody is a monoclonal antibody. The antibody can be a fragment of an antibody such as a single stranded antibody as further described herein, or can be conjugated to another molecule. In one embodiment, the antibody is a humanized antibody.

[16] In one embodiment a method for screening for a bioactive agent capable of interfering with the binding of a colorectal cancer modulating protein (colorectal cancer modulator protein) or a fragment thereof and an antibody which binds to said colorectal cancer modulator protein or fragment thereof. In a preferred embodiment, the method comprises combining a colorectal cancer modulator protein or fragment thereof, a candidate bioactive agent and an antibody which binds to said colorectal cancer modulator protein or fragment thereof. The method further includes determining the binding of said colorectal cancer modulator protein or fragment thereof and said antibody. Wherein there is a change in binding, an agent is identified as an interfering agent. The interfering agent can be an agonist or an antagonist. Preferably, the agent inhibits colorectal cancer.

[17] In a further aspect, a method for inhibiting colorectal cancer is provided. The method can be performed in vitro or in vivo, preferably in vivo to an individual. In a preferred embodiment the method of inhibiting colorectal cancer is provided to an individual with cancer. As described herein, methods of inhibiting colorectal cancer can be performed by administering an inhibitor of the activity of a protein encoded by a nucleic acid of Table 1 or Table 2, including an antisense molecule to the gene or its gene product.

[18] Also provided herein are methods of eliciting an immune response in an individual. In one embodiment a method provided herein comprises administering to an individual a composition comprising a colorectal cancer modulating protein, or a fragment

thereof. In another embodiment, the protein is encoded by a nucleic acid selected from those of Table 1 or Table 2. In another aspect, said composition comprises a nucleic acid comprising a sequence encoding a colorectal cancer modulating protein, or a fragment thereof.

[19] Further provided herein are compositions capable of eliciting an immune response in an individual. In one embodiment, a composition provided herein comprises a colorectal cancer modulating protein, preferably encoded by a nucleic acid of Table 1 or Table 2, or a fragment thereof, and a pharmaceutically acceptable carrier. In another embodiment, said composition comprises a nucleic acid comprising a sequence encoding a colorectal cancer modulating protein, preferably selected from the nucleic acids of Table 1 or Table 2 and a pharmaceutically acceptable carrier.

[20] Also provided are methods of neutralizing the effect of a colorectal cancer protein, or a fragment thereof, comprising contacting an agent specific for said protein with said protein in an amount sufficient to effect neutralization. In another embodiment, the protein is encoded by a nucleic acid selected from those of Table 1 or Table 2.

[21] In another aspect of the invention, a method of treating an individual for colorectal cancer is provided. In one embodiment, the method comprises administering to said individual an inhibitor of a colorectal cancer modulating protein. In another embodiment, the method comprises administering to a patient having colorectal cancer an antibody to a colorectal cancer modulating protein conjugated to a therapeutic moiety. Such a therapeutic moiety can be a cytotoxic agent or a radioisotope.

[22] Compounds and compositions are also provided. Other aspects of the invention will become apparent to the skilled artisan by the following description of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS [NOT APPLICABLE] DETAILED DESCRIPTION OF THE INVENTION [23] The present invention provides novel methods for diagnosis and prognosis evaluation for colorectal cancer, as well as methods for screening for compositions which modulate colorectal cancer. The methods herein are related to those of U. S. Patent Application Serial No. 09/525,993 and International Patent Application No.

PCT/US00/07044, each of which is incorporated herein in its entirety.

[24] By"colorectal cancer"herein is meant a colon and/or rectal tumor or cancer that is classified as Dukes stage A or B as well as metastatic tumors classified as Dukes stage Cor D (see, e. g., Cohen et al., Cancer of the Colon, in Cancer : Principles and Practice of Oncology, pp. 1144-1197 (Devita et al., eds., 5th ed. 1997); see also Harrison's Principles oflnternal Medicine, pp. 1289-129 (Wilson et al., eds., 12th ed., 1991).

"Treatment, monitoring, detection or modulation of colorectal cancer"includes treatment, monitoring, detection, or modulation of colorectal disease in those patients who have colorectal disease (Dukes stage A, B, C or D) in which gene expression from a gene in Table 1 or 2, is increased or decreased, indicating that the subject is more likely to progress to metastatic disease than a patient who does not have an increase or decrease in gene expression of a gene in Table 1 or 2. In Dukes stage A, the tumor has penetrated into, but not through, the bowel wall. In Dukes stage B, the tumor has penetrated through the bowel wall but there is not yet any lymph involvement. In Dukes stage C, the cancer involves regional lymph nodes. In Dukes stage D, there is distant metastasis, e. g., liver, lung, etc.

[25] Table 1 provides unigene cluster identification numbers for the nucleotide sequence of genes that exhibit increased expression in colorectal cancer samples.

Tables 1 also provides an exemplar accession number that provides a nucleotide sequence that is part of the unigene cluster. Table 2 provides the nucleic acid and protein sequence of the CBF9 gene as well as the Unigene and Exemplar accession numbers for CBF9.

[26] In one aspect, the expression levels of genes are determined in different patient samples for which either diagnosis or prognosis information is desired, to provide expression profiles. An expression profile of a particular sample is essentially a "fingerprint"of the state of the sample; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state of the cell. That is, normal tissue may be distinguished from colorectal cancer tissue, and within colorectal cancer tissue, different prognosis states (good or poor long term survival prospects, for example) may be determined. By comparing expression profiles of colon tissue in known different states, information regarding which genes are important (including both up-and down- regulation of genes) in each of these states is obtained. The identification of sequences that are differentially expressed in colorectal cancer versus normal colon tissue, as well as differential expression resulting in different prognostic outcomes, allows the use of this information in a number of ways. For example, the evaluation of a particular treatment regime may be evaluated: does a chemotherapeutic drug act to improve the long-term

prognosis in a particular patient. Similarly, diagnosis may be done or confirmed by comparing patient samples with the known expression profiles. Furthermore, these gene expression profiles (or individual genes) allow screening of drug candidates with an eye to mimicking or altering a particular expression profile; for example, screening can be done for drugs that suppress the colorectal cancer expression profile or convert a poor prognosis profile to a better prognosis profile. This may be done by making biochips comprising sets of the important colorectal cancer genes, which can then be used in these screens. These methods can also be done on the protein basis; that is, protein expression levels of the colorectal cancer proteins can be evaluated for diagnostic and prognostic purposes or to screen candidate agents. In addition, the colorectal cancer nucleic acid sequences can be administered for gene therapy purposes, including the administration of antisense nucleic acids, or the colorectal cancer proteins (including antibodies and other modulators thereof) administered as therapeutic drugs.

[27] Thus the present invention provides nucleic acid and protein sequences that are differentially expressed in colorectal cancer, herein termed"colorectal cancer sequences". As outlined below, colorectal cancer sequences include those that are up-regulated (i. e. expressed at a higher level) in colorectal cancer, as well as those that are down-regulated (i. e. expressed at a lower level) in colorectal cancer. In a preferred embodiment, the colorectal cancer sequences are from humans; however, as will be appreciated by those in the art, colorectal cancer sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other colorectal cancer sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc). colorectal cancer sequences from other organisms may be obtained using the techniques outlined below.

[28] Colorectal cancer sequences can include both nucleic acid and amino acid sequences. In a preferred embodiment, the colorectal cancer sequences are recombinant nucleic acids. By the term"recombinant nucleic acid"herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid by polymerases and endonucleases, in a form not normally found in nature. Thus an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined, are both considered recombinant for the purposes of this invention. It is understood that once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, i. e. using the in vivo cellular machinery of the

host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non-recombinantly, are still considered recombinant for the purposes of the invention.

[29] Similarly, a"recombinant protein"is a protein made using recombinant techniques, i. e. through the expression of a recombinant nucleic acid as depicted above. A recombinant protein is distinguished from naturally occurring protein by at least one or more characteristics. For example, the protein may be isolated or purified away from some or all of the proteins and compounds with which it is normally associated in its wild type host, and thus may be substantially pure. For example, an isolated protein is unaccompanied by at least some of the material with which it is normally associated in its natural state, preferably constituting at least about 0.5%, more preferably at least about 5% by weight of the total protein in a given sample. A substantially pure protein comprises at least about 75% by weight of the total protein, with at least about 80% being preferred, and at least about 90% being particularly preferred. The definition includes the production of a colorectal cancer protein from one organism in a different organism or host cell. Alternatively, the protein may be made at a significantly higher concentration than is normally seen, through the use of an inducible promoter or high expression promoter, such that the protein is made at increased concentration levels. Alternatively, the protein may be in a form not normally found in nature, as in the addition of an epitope tag or amino acid substitutions, insertions and deletions, as discussed below.

[30] In a preferred embodiment, the colorectal cancer sequences are nucleic acids. As will be appreciated by those in the art and is more fully outlined below, colorectal cancer sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; for example, biochips comprising nucleic acid probes to the colorectal cancer sequences can be generated. In the broadest sense, then, by"nucleic acid"or "oligonucleotide"or grammatical equivalents herein means at least two nucleotides covalently linked together. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, as outlined below, nucleic acid analogs are included that may have alternate backbones, comprising, for example, phosphoramidate (Beaucage et al., Tetrahedron 49 (10): 1925 (1993) and references therein; Letsinger, J. Org.

Chem. 35: 3800 (1970); Sprinzl et al., Eur. J. Biochem. 81: 579 (1977); Letsinger et al., Nucl.

Acids Res. 14: 3487 (1986) ; Sawai et al, Chem. Lett. 805 (1984), Letsinger et al., J. Am.

Chem. Soc. 110: 4470 (1988); and Pauwels et al., Chemica Scripta 26: 141 91986)),

phosphorothioate (Mag et al., Nucleic Acids Res. 19: 1437 (1991) ; and U. S. Patent No.

5,644,048), phosphorodithioate (Briu et al., J. Am. Chem. Soc. 111: 2321 (1989), O- methylphophoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press), and peptide nucleic acid backbones and linkages (see Egholm, J. Am. Chem. Soc. 114: 1895 (1992); Meier et al., Chem. Int. Ed. Engl. 31: 1008 (1992) ; Nielsen, Nature, 365: 566 (1993); Carlsson et al., Nature 380 : 207 (1996), all of which are incorporated by reference). Other analog nucleic acids include those with positive backbones (Denpcy et al., Proc. Natl. Acad. Sci. USA 92: 6097 (1995); non-ionic backbones (U. S. Patent Nos. 5,386,023,5,637,684,5,602,240,5,216,141°and 4,469,863; Kiedrowshi et al., Angew. Chem. Intl. Ed. English 30: 423 (1991); Letsinger et al., J. Am. Chem. Soc.

110: 4470 (1988) ; Letsinger et al., Nucleoside & Nucleotide 13: 1597 (1994); Chapters 2 and 3, ASC Symposium Series 580,"Carbohydrate Modifications in Antisense Research", Ed.

Y. S. Sanghui and P. Dan Cook; Mesmaeker et al., Bioorganic & Medicinal Chem. Lett. 4: 395 (1994); Jeffs et al., J. Biomolecular NMR 34: 17 (1994); Tetrahedron Lett. 37: 743 (1996)) and non-ribose backbones, including those described in U. S. Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580,"Carbohydrate Modifications in Antisense Research", Ed. Y. S. Sanghui and P. Dan Cook. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids (see Jenkins et al., Chem. Soc. Rev. (1995) ppl69-176). Several nucleic acid analogs are described in Rawls, C & E News June 2,1997 page 35. All of these references are hereby expressly incorporated by reference. These modifications of the ribose-phosphate backbone may be done for a variety of reasons, for example to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip.

[31] As will be appreciated by those in the art, all of these nucleic acid analogs may find use in the present invention. In addition, mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.

[32] Particularly preferred are peptide nucleic acids (PNA) which includes peptide nucleic acid analogs. These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in two advantages. First, the PNA backbone exhibits improved hybridization kinetics. PNAs have larger changes in the melting temperature (Tm) for mismatched versus perfectly matched basepairs. DNA and RNA typically exhibit a 2-4°C drop in Tm for an internal mismatch. With the non-ionic PNA backbone, the drop is closer to

7-9°C. Similarly, due to their non-ionic nature, hybridization of the bases attached to these backbones is relatively insensitive to salt concentration. In addition, PNAs are not degraded by cellular enzymes, and thus can be more stable.

[33] The nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence. As will be appreciated by those in the art, the depiction of a single strand ("Watson") also defines the sequence of the other strand ("Crick") ; thus the sequences described herein also includes the complement of the sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA or a hybrid, where the nucleic acid contains any combination of deoxyribo-and ribo- nucleotides, and any combination of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc. As used herein, the term"nucleoside"includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides. In addition,"nucleoside"includes non- naturally occurring analog structures. Thus for example the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside.

[34] A colorectal cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the colorectal cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.

[35] The isolation of mRNA comprises isolating total cellular RNA by disrupting a cell and performing differential centrifugation. Once the total RNA is isolated, mRNA is isolated by making use of the adenine nucleotide residues known to those skilled in the art as a poly (A) tail found on virtually every eukaryotic mRNA molecule at the 3'end thereof. Oligonucleotides composed of only deoxythymidine [olgo (dT)] are linked to cellulose and the oligo (dT)-cellulose packed into small columns. When a preparation of total cellular RNA is passed through such a column, the mRNA molecules bind to the oligo (dT) by the poly (A) tails while the rest of the RNA flows through the column. The bound mRNAs are then eluted from the column and collected.

[36] The colorectal cancer sequences of the invention can be identified as follows. Samples of normal and tumor tissue are applied to biochips comprising nucleic acid probes. The samples are first microdissected, if applicable, and treated as described above for the preparation of mRNA. Suitable biochips are commercially available, for example

from Affymetrix. Gene expression profiles as described herein are generated, and the data analyzed.

[37] In a preferred embodiment, the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, including, but not limited to lung, heart, brain, liver, breast, kidney, muscle, prostate, small intestine, large intestine, spleen, bone, and placenta. In a preferred embodiment, those genes identified during the colorectal cancer screen that are expressed in any significant amount in other tissues are removed from the profile, although in some embodiments, this is not necessary. That is, when screening for drugs, it is preferable that the target be disease specific, to minimize possible side effects.

[38] In a preferred embodiment, colorectal cancer sequences are those that are up-regulated in colorectal cancer; that is, the expression of these genes is higher in colorectal carcinoma as compared to normal colon tissue."Up-regulation"as used herein means at least about a 1.1 fold change, preferably a 1.5 or two fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred. All accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. GenBank is known in the art, see, e. g., Benson, DA, et al., Nucleic Acids Research 26: 1-7 (1998) and http://www. ncbi. nlm. nih. gov/. In addition, these genes were found to be expressed in a limited amount or not at all in heart, brain, lung, liver, breast, kidney, prostate, small intestine and spleen.

[39] In a preferred embodiment, colorectal cancer sequences are those that are down-regulated in colorectal cancer; that is, the expression of these genes is lower in colorectal carcinoma as compared to normal colon tissue."Down-regulation"as used herein means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred.

[40] Colorectal cancer proteins of the present invention may be classified as secreted proteins, transmembrane proteins or intracellular proteins. In a preferred embodiment the colorectal cancer protein is an intracellular protein. Intracellular proteins may be found in the cytoplasm and/or in the nucleus. Intracellular proteins are involved in all aspects of cellular function and replication (including, for example, signaling pathways); aberrant expression of such proteins results in unregulated or disregulated cellular processes.

For example, many intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity,

polymerase activity and the like. Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various subcellular localizations, and are involved in maintaining the structural integrity of organelles.

[41] An increasingly appreciated concept in characterizing intracellular proteins is the presence in the proteins of one or more motifs for which defined functions have been attributed. In addition to the highly conserved sequences found in the enzymatic domain of proteins, highly conserved sequences have been identified in proteins that are involved in protein-protein interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner. PTB domains, which are distinct from SH2 domains, also bind tyrosine phosphorylated targets. SH3 domains bind to proline-rich targets. In addition, PH domains, tetratricopeptide repeats and WD domains to name only a few, have been shown to mediate protein-protein interactions. Some of these may also be involved in binding to phospholipids or other second messengers. As will be appreciated by one of ordinary skill in the art, these motifs can be identified on the basis of primary sequence; thus, an analysis of the sequence of proteins may provide insight into both the enzymatic potential of the molecule and/or molecules with which the protein may associate.

[42] In a preferred embodiment, the colorectal cancer sequences are transmembrane proteins. Transmembrane proteins are molecules that span the phospholipid bilayer of a cell. They may have an intracellular domain, an extracellular domain, or both.

The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular domain may have enzymatic activity and/or may serve as a binding site for additional proteins. Frequently the intracellular domain of transmembrane proteins serves both roles. For example certain receptor tyrosine kinases have both protein kinase activity and SH2 domains. In addition, autophosphorylation of tyrosines on the receptor molecule itself, creates binding sites for additional SH2 domain containing proteins.

[43] Transmembrane proteins may contain from one to many transmembrane domains. For example, receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/threonine protein kinases contain a single transmembrane domain. However, various other proteins including channels and adenylyl cyclases contain numerous transmembrane domains. Many important cell surface receptors are classified as"seven transmembrane domain"proteins, as they contain 7 membrane spanning regions. Important transmembrane protein receptors include, but are not limited to

insulin receptor, insulin-like growth factor receptor, human growth hormone receptor, glucose transporters, transferrin receptor, epidermal growth factor receptor, low density lipoprotein receptor, epidermal growth factor receptor, leptin receptor, interleukin receptors, e. g. IL-1 receptor, IL-2 receptor, etc.

[44] Characteristics of transmembrane domains include approximately 20 consecutive hydrophobic amino acids that may be followed by charged amino acids.

Therefore, upon analysis of the amino acid sequence of a particular protein, the localization and number of transmembrane domains within the protein may be predicted.

[45] The extracellular domains of transmembrane proteins are diverse ; however, conserved motifs are found repeatedly among various extracellular domains.

Conserved structure and/or functions have been ascribed to different extracellular motifs. For example, cytokine receptors are characterized by a cluster of cysteines and a WSXWS (W= tryptophan, S= serine, X=any amino acid) motif. Immunoglobulin-like domains are highly conserved. Mucin-like domains may be involved in cell adhesion and leucine-rich repeats participate in protein-protein interactions.

[46] Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF and PDGF are circulating growth factors that bind to their cognate receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, neurotrophic factors and the like. Extracellular domains also bind to cell-associated molecules. In this respect, they mediate cell-cell interactions. Cell-associated ligands can be tethered to the cell for example via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins. Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.

[47] Colorectal cancer proteins that are transmembrane are particularly preferred in the present invention as they are good targets for immunotherapeutics, as are described herein. In addition, as outlined below, transmembrane proteins can be also useful in imaging modalities.

[48] It will also be appreciated by those in the art that a transmembrane protein can be made soluble by removing transmembrane sequences, for example through recombinant methods. Furthermore, transmembrane proteins that have been made soluble

can be made to be secreted through recombinant means by adding an appropriate signal sequence.

[49] In a preferred embodiment, the colorectal cancer proteins are secreted proteins; the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway. Secreted proteins are involved in numerous physiological events; by virtue of their circulating nature, they serve to transmit signals to various other cell types. The secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor) or an endocrine manner (acting on cells at a distance). Thus secreted molecules find use in modulating or altering numerous aspects of physiology. colorectal cancer proteins that are secreted proteins are particularly preferred in the present invention as they serve as good targets for diagnostic markers, for example for blood tests.

[50] A colorectal cancer sequence is initially identified by substantial nucleic acid and/or amino acid sequence homology to the colorectal cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.

[51] As used herein, the terms"colorectal cancer nucleic acid","colorectal cancer protein"or"colorectal cancer polynucleotide"or"colorectal cancer-associated transcript"refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25,50,100,200, 500,1000, or more nucleotides, to a nucleotide sequence of or associated with a unigene cluster of Tables 1 or Table 2; (2) bind to antibodies, e. g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence encoded by a nucleotide sequence of or associated with a unigene cluster of Table 1 or Table 2, and conservatively modified variants thereof; (3) specifically hybridize under stringent hybridization conditions to a nucleic acid sequence, or the complement thereof of Table 1 or Table 2 and conservatively modified variants thereof or (4) have an amino acid sequence that has greater than about 60% amino acid sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater amino sequence identity, preferably over a region of over a region of at least about

25,50,100,200,500,1000, or more amino acid, to an amino acid sequence encoded by a nucleotide sequence of or associated with a unigene cluster of Table 1 or Table 2. A polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e. g., human ; rodent, e. g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal. A"colorectal cancer polypeptide"and a"colorectal cancer polynucleotide," include both naturally occurring or recombinant.

[52] Homology in this context means sequence similarity or identity, with identity being preferred. A preferred comparison for homology purposes is to compare the sequence containing sequencing errors to the correct sequence. This homology will be determined using standard techniques known in the art, including, but not limited to, the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2: 482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biool. 48 : 443 (1970), by the search for similarity method of Pearson & Lipman, PNAS USA 85: 2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Drive, Madison, WI), the Best Fit sequence program described by Devereux et al., Nucl. Acid Res.

12: 387-395 (1984), preferably using the default settings, or by inspection.

[53] In a preferred embodiment, the sequences which are used to determine sequence identity or similarity are selected from the sequences set forth in Table 1 or Table 2.

In one embodiment the sequences utilized herein are those set forth in Table 1 or Table 2. In another embodiment, the sequences are naturally occurring allelic variants of the sequences set forth in Table 1 or Table 2. In another embodiment, the sequences are sequence variants as further described herein.

[54] The terms"identical"or percent"identity,"in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i. e., about 60% identity, preferably 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e. g., NCBI web site http://www. ncbi. nlm. nih. gov/BLAST/ or the like). Such sequences are then said to be"substantially identical."This definition also refers to, or may be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions

and/or additions, as well as those that have substitutions, as well as naturally occurring, e. g., polymorphic or allelic variants, and man-made variants. As described below, the preferred algorithms can account for gaps and the like. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.

[55] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.

Preferably, default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.

[56] A"comparison window", as used herein, includes reference to a segment of one of the number of contiguous positions selected from the group consisting typically of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e. g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2: 482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48: 443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85 : 2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e. g., Current Protocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).

[57] Preferred examples of algorithms that are suitable for determining percent sequence identity and sequence similarity include the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25: 3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215: 403-410 (1990). BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http://www. ncbi. nlm. nih. gov/).

This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive- valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra).

These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, e. g., for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89: 10915 (1989)) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands.

[58] The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e. g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90: 5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P (N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001.

Log values may be large negative numbers, e. g., 5, 10,20,30,40,40,70,90,110,150,170, etc.

[59] In one embodiment, the nucleic acid homology is determined through hybridization studies. Thus, for example, nucleic acids which hybridize under high stringency to the nucleic acid sequences which encode the peptides identified in Table 1 or Table 2, or their complements, are considered a colorectal cancer sequence. High stringency

conditions are known in the art; see for example Maniatis et al., Molecular Cloning: A Laboratory Manual, 2d Edition, 1989, and Short Protocols in Molecular Biology, ed.

Ausubel, et al., both of which are hereby incorporated by reference. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology-- Hybridization with Nucleic Acid Probes,"Overview of principles of hybridization and the strategy of nucleic acid assays" (1993). Generally, stringent conditions are selected to be about 5-10°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°C for short probes (e. g. 10 to 50 nucleotides) and at least about 60°C for long probes (e. g. greater than 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.

[60] In another embodiment, less stringent hybridization conditions are used; for example, moderate or low stringency conditions may be used, as are known in the art; see Maniatis and Ausubel, supra, and Tijssen, supra. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization. Exemplary stringent hybridization conditions can be as following: 50% formamide, 5x SSC, and 1% SDS, incubating at 42°C, or, 5x SSC, 1% SDS, incubating at 65°C, with wash in 0.2x SSC, and 0.1% SDS at 65°C.

[61] Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions.

Exemplary"moderately stringent hybridization conditions"include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37°C, and a wash in 1X SSC at 45°C. A positive hybridization is at least twice background. Those of ordinary skill will readily

recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous reference, e. g., and Current Protocols in Molecular Biology, ed. Ausubel, et al.

[62] For PCR, a temperature of about 36°C is typical for low stringency amplification, although annealing temperatures may vary between about 32°C and 48°C depending on primer length. For high stringency PCR amplification, a temperature of about 62°C is typical, although high stringency annealing temperatures can range from about 50°C to about 65°C, depending on the primer length and specificity. Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90°C-95°C for 30 sec-2 min., an annealing phase lasting 30 sec.-2 min., and an extension phase of about 72°C for 1-2 min. Protocols and guidelines for low and high stringency amplification reactions are provided, e. g., in Innis et al., PCR Protocols, A Guide to Methods and Applications (1990).

[63] In addition, the colorectal cancer nucleic acid sequences of the invention are fragments of larger genes, i. e. they are nucleic acid segments."Genes"in this context includes coding regions, non-coding regions, and mixtures of coding and non-coding regions. Accordingly, as will be appreciated by those in the art, using the sequences provided herein, additional sequences of the colorectal cancer genes can be obtained, using techniques well known in the art for cloning either longer sequences or the full length sequences; see Maniatis et al., and Ausubel, et al., supra, hereby expressly incorporated by reference.

[64] An indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid. Thus, a polypeptide is typically substantially identical to a second polypeptide, e. g., where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described above.

Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequences.

[65] Once the colorectal cancer nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombine to form the entire colorectal cancer nucleic acid. Once isolated from its natural source, e. g., contained within a plasmid or other vector

or excised therefrom as a linear nucleic acid segment, the recombinant colorectal cancer nucleic acid can be further-used as a probe to identify and isolate other colorectal cancer nucleic acids, for example additional coding regions. It can also be used as a"precursor" nucleic acid to make modified or variant colorectal cancer nucleic acids and proteins.

[66] The colorectal cancer nucleic acids of the present invention are used in several ways. In a first embodiment, nucleic acid probes to the colorectal cancer nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, for example for gene therapy and/or antisense applications. Alternatively, the colorectal cancer nucleic acids that include coding regions of colorectal cancer proteins can be put into expression vectors for the expression of colorectal cancer proteins, again either for screening purposes or for administration to a patient.

[67] In a preferred embodiment, nucleic acid probes to colorectal cancer nucleic acids (both the nucleic acid sequences encoding peptides outlined in the Table 1 or Table 2 and/or the complements thereof) are made. The nucleic acid probes attached to the biochip are designed to be substantially complementary to the colorectal cancer nucleic acids, i. e. the target sequence (either the target sequence of the sample or to other probe sequences, for example in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs. As outlined below, this complementarity need not be perfect; there may be any number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention. However, if the number of mutations is so great that no hybridization can occur under even the least stringent of hybridization conditions, the sequence is not a complementary target sequence. Thus, by"substantially complementary"herein is meant that the probes are sufficiently complementary to the target sequences to hybridize under normal reaction conditions, particularly high stringency conditions, as outlined herein.

[68] A nucleic acid probe is generally single stranded but can be partially single and partially double stranded. The strandedness of the probe is dictated by the structure, composition, and properties of the target sequence. In general, the nucleic acid probes range from about 8 to about 100 bases long, with from about 10 to about 80 bases being preferred, and from about 30 to about 50 bases being particularly preferred. That is, generally whole genes are not used. In some embodiments, much longer nucleic acids can be used, up to hundreds of bases.

[69] In a preferred embodiment, more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used. That

is, two, three, four or more probes, with three being preferred, are used to build in a redundancy for a particular target. The probes can be overlapping (i. e. have some sequence in common), or separate.

[70] As will be appreciated by those in the art, nucleic acids can be attached or immobilized to a solid support in a wide variety of ways. By"immobilized"and grammatical equivalents herein is meant the association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined below. The binding can be covalent or non-covalent. By "non-covalent binding"and grammatical equivalents herein is meant one or more of either electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non- covalent binding of the biotinylated probe to the streptavidin. By"covalent binding"and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds. Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Immobilization may also involve a combination of covalent and non-covalent interactions.

[71] In general, the probes are attached to the biochip in a wide variety of ways, as will be appreciated by those in the art. As described herein, the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be directly synthesized on the biochip.

[72] The biochip comprises a suitable solid substrate. By"substrate"or "solid support"or other grammatical equivalents herein is meant any material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method. As will be appreciated by those in the art, the number of possible substrates are very large, and include, but are not limited to, glass and modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonJ, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses, plastics, etc. In general, the substrates allow optical detection and do not appreciably fluoresce. A preferred substrate is described in copending application entitled

Reusable Low Fluorescent Plastic Biochip, U. S. Application Serial No. 09/270,214, filed March 15,1999, herein incorporated by reference in its entirety.

[73] Generally the substrate is planar, although as will be appreciated by those in the art, other configurations of substrates may be used as well. For example, the probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume. Similarly, the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics.

[74] In a preferred embodiment, the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two.

Thus, for example, the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly preferred. Using these functional groups, the probes can be attached using functional groups on the probes. For example, nucleic acids containing amino groups can be attached to surfaces comprising amino groups, for example using linkers as are known in the art; for example, homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross-linkers, pages 155-200, incorporated herein by reference). In addition, in some cases, additional linkers, such as alkyl groups (including substituted and heteroalkyl groups) may be used.

[75] In this embodiment, the oligonucleotides are synthesized as is known in the art, and then attached to the surface of the solid support. As will be appreciated by those skilled in the art, either the 5'or 3'terminus may be attached to the solid support, or attachment may be via an internal nucleoside.

[76] In an additional embodiment, the immobilization to the solid support may be very strong, yet non-covalent. For example, biotinylated oligonucleotides can be made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.

[77] Alternatively, the oligonucleotides may be synthesized on the surface, as is known in the art. For example, photoactivation techniques utilizing photopolymerization compounds and techniques are used. In a preferred embodiment, the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO 95/35505; U. S. Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which are expressly incorporated by reference; these methods of attachment form the basis of the Affimetrix GeneChipTM technology.

[78] In a preferred embodiment, colorectal cancer nucleic acids encoding colorectal cancer proteins are used to make a variety of expression vectors to express colorectal cancer proteins which can then be used in screening assays, as described below.

The expression vectors may be either self-replicating extrachromosomal vectors or vectors which integrate into a host genome. Generally, these expression vectors include transcriptional and translational regulatory nucleic acid operably linked to the nucleic acid encoding the colorectal cancer protein. The term"control sequences"refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.

[79] Nucleic acid is"operably linked"when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation.

Generally,"operably linked"means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. The transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the colorectal cancer protein; for example, transcriptional and translational regulatory nucleic acid sequences from Bacillus are preferably used to express the colorectal cancer protein in Bacillus. Numerous types of appropriate expression vectors, and suitable regulatory sequences are known in the art for a variety of host cells.

[80] In general, the transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences. In a preferred embodiment, the regulatory sequences include a promoter and transcriptional start and stop sequences.

[81] Promoter sequences encode either constitutive or inducible promoters.

The promoters may be either naturally occurring promoters or hybrid promoters. Hybrid

promoters, which combine elements of more than one promoter, are also known in the art, and are useful in the present invention.

[82] In addition, the expression vector may comprise additional elements.

For example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, for example in mammalian or insect cells for expression and in a procaryotic host for cloning and amplification. Furthermore, for integrating expression vectors, the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct.

The integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for integrating vectors are well known in the art.

[83] In addition, in a preferred embodiment, the expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selection genes are well known in the art and will vary with the host cell used.

[84] The colorectal cancer proteins of the present invention are produced by culturing a host cell transformed with an expression vector containing nucleic acid encoding a colorectal cancer protein, under the appropriate conditions to induce or cause expression of the colorectal cancer protein. The conditions appropriate for colorectal cancer protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained by one skilled in the art through routine experimentation. For example, the use of constitutive promoters in the expression vector will require optimizing the growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction. In addition, in some embodiments, the timing of the harvest is important. For example, the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial for product yield.

[85] Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect and animal cells, including mammalian cells. Of particular interest are Drosophila melangaster cells, Saccharomyces cerevisiae and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, THP1 cell line (a macrophage cell line) and human cells and cell lines.

[86] In a preferred embodiment, the colorectal cancer proteins are expressed in mammalian cells. Mammalian expression systems are also known in the art, and include retroviral systems. A preferred expression vector system is a retroviral vector system such as is generally described in PCT/US97/01019 and PCT/US97/01048, both of which are

hereby expressly incorporated by reference. Of particular use as mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the SV40 early promoter, mouse mammary tumor virus LTR promoter, adenovirus major late promoter, herpes simplex virus promoter, and the CMV promoter. Typically, transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3'to the translation stop codon and thus, together with the promoter elements, flank the coding sequence. Examples of transcription terminator and polyadenlytion signals include those derived form SV40.

[87] The methods of introducing exogenous nucleic acid into mammalian hosts, as well as other hosts, is well known in the art, and will vary with the host cell used.

Techniques include dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, viral infection, encapsulation of the polynucleotide (s) in liposomes, and direct microinjection of the DNA into nuclei.

[88] In a preferred embodiment, colorectal cancer proteins are expressed in bacterial systems. Bacterial expression systems are well known in the art. Promoters from bacteriophage may also be used and are known in the art. In addition, synthetic promoters and hybrid promoters are also useful; for example, the tac promoter is a hybrid of the trp and lac promoter sequences. Furthermore, a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. In addition to a functioning promoter sequence, an efficient ribosome binding site is desirable. The expression vector may also include a signal peptide sequence that provides for secretion of the colorectal cancer protein in bacteria. The protein is either secreted into the growth media (gram-positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria). The bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed. Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin and tetracycline. Selectable markers also include biosynthetic genes, such as those in the histidine, tryptophan and leucine biosynthetic pathways. These components are assembled into expression vectors. Expression vectors for bacteria are well known in the art, and include vectors for Bacillus subtilis, E. coli, Streptococcus cremoris, and Streptococcus lividans, among others. The bacterial expression vectors are transformed

into bacterial host cells using techniques well known in the art, such as calcium chloride treatment, electroporation, and others.

[89] In one embodiment, colorectal cancer proteins are produced in insect cells. Expression vectors for the transformation of insect cells, and in particular, baculovirus- based expression vectors, are well known in the art.

[90] In a preferred embodiment, colorectal cancer protein is produced in yeast cells. Yeast expression systems are well known in the art, and include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis and K. lactis, Pichia guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yarrowia lipolytica.

[91] The colorectal cancer protein may also be made as a fusion protein, using techniques well known in the art. Thus, for example, for the creation of monoclonal antibodies, if the desired epitope is small, the colorectal cancer protein may be fused to a carrier protein to form an immunogen. Alternatively, the colorectal cancer protein may be made as a fusion protein to increase expression, or for other reasons. For example, when the colorectal cancer protein is a colorectal cancer peptide, the nucleic acid encoding the peptide may be linked to other nucleic acid for expression purposes.

[92] In one embodiment, the colorectal cancer nucleic acids, proteins and antibodies of the invention are labeled. By"labeled"herein is meant that a compound has at least one element, isotope or chemical compound attached to enable the detection of the compound. In general, labels fall into three classes: a) isotopic labels, which may be radioactive or heavy isotopes; b) immune labels, which may be antibodies or antigens; and c) colored or fluorescent dyes. The labels may be incorporated into the colorectal cancer nucleic acids, proteins and antibodies at any position. For example, the label should be capable of producing, either directly or indirectly, a detectable signal. The detectable moiety may be a radioisotope, such as 3H, 14C, 32P, 35S, or 125I, a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, beta-galactosidase or horseradish peroxidase. Any method known in the art for conjugating the antibody to the label may be employed, including those methods described by Hunter et al., Nature, 144: 945 (1962); David et al., Biochemistry, 13: 1014 (1974); Pain et al., J. Immunol. Meth., 40: 219 (1981) ; andNygren, J.

Histochem. and Cytochem., 30: 407 (1982).

[93] Accordingly, the present invention also provides colorectal cancer protein sequences. A colorectal cancer protein of the present invention may be identified in

several ways."Protein"in this sense includes proteins, polypeptides, and peptides terms which are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers, those containing modified residues, and non-naturally occurring amino acid polymer.

[94] As will be appreciated by those in the art, the nucleic acid sequences of the invention can be used to generate protein sequences. There are a variety of ways to do this, including cloning the entire gene and verifying its frame and amino acid sequence, or by comparing it to known sequences to search for homology to provide a frame, assuming the colorectal cancer protein has homology to some protein in the database being used.

Generally, the nucleic acid sequences are input into a program that will search all three frames for homology. This is done in a preferred embodiment using the following NCBI Advanced BLAST parameters. The program is blastx or blastn. The database is nr. The input data is as"Sequence in FASTA format". The organism list is"none". The"expect"is 10; the filter is default. The"descriptions"is 500, the"alignments"is 500, and the "alignment view"is pairwise. The"Query Genetic Codes"is standard (1). The matrix is BLOSUM62 ; gap existence cost is 11, per residue gap cost is 1; and the lambda ratio is. 85 default. This results in the generation of a putative protein sequence.

[95] Also included within one embodiment of colorectal cancer proteins are amino acid variants of the naturally occurring sequences, as determined herein.

Preferably, the variants are preferably greater than about 75% homologous to the wild-type sequence, more preferably greater than about 80%, even more preferably greater than about 85% and most preferably greater than 90%. In some embodiments the homology will be as high as about 93 to 95 or 98%. As for nucleic acids, homology in this context means sequence similarity or identity, with identity being preferred. This homology will be determined using standard techniques known in the art as are outlined above for the nucleic acid homologies.

[96] Colorectal cancer proteins of the present invention may be shorter or longer than the wild type amino acid sequences. Thus, in a preferred embodiment, included within the definition of colorectal cancer proteins are portions or fragments of the wild type sequences. herein. In addition, as outlined above, the colorectal cancer nucleic acids of the invention may be used to obtain additional coding regions, and thus additional protein sequence, using techniques known in the art.

[97] In a preferred embodiment, the colorectal cancer proteins are derivative or variant colorectal cancer proteins as compared to the wild-type sequence. That is, as outlined more fully below, the derivative colorectal cancer peptide will contain at least one amino acid substitution, deletion or insertion, with amino acid substitutions being particularly preferred. The amino acid substitution, insertion or deletion may occur at any residue within the colorectal cancer peptide.

[98] Also included in an embodiment of colorectal cancer proteins of the present invention are amino acid sequence variants. These variants fall into one or more of three classes: substitutional, insertional or deletional variants. These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the colorectal cancer protein, using cassette or PCR mutagenesis or other techniques well known in the art, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above. However, variant colorectal cancer protein fragments having up to about 100-150 residues may be prepared by in vitro synthesis using established techniques.

Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the colorectal cancer protein amino acid sequence. The variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics as will be more fully outlined below.

[99] While the site or region for introducing an amino acid sequence variation is predetermined, the mutation per se need not be predetermined. For example, in order to optimize the performance of a mutation at a given site, random mutagenesis may be conducted at the target codon or region and the expressed colorectal cancer variants screened for the optimal combination of desired activity. Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example, M13 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of colorectal cancer protein activities.

[100] Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1 to 20 amino acids, although considerably larger insertions may be tolerated. Deletions range from about 1 to about 20 residues, although in some cases deletions may be much larger.

[101] Substitutions, deletions, insertions or any combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. However, larger changes may be tolerated in certain

circumstances. When small alterations in the characteristics of the colorectal cancer protein are desired, substitutions are generally made in accordance with the following chart: Chart I Original Residue Exemplary Substitutions Ala Ser Arg Lys Asn Gln, His Asp Glu Cys Ser Gln Asn Glu Asp Gly Pro His Asn, Gln Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu Met Leu, Ile Phe Met, Leu, Tyr Ser Thr Thr Ser Trp Tyr Tyr Trp, Phe Val Ile, Leu [102] Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those shown in Chart I. For example, substitutions may be made which more significantly affect: the structure of the polypeptide backbone in the area of the alteration, for example the alpha-helical or beta-sheet structure; the charge or hydrophobicity of the molecule at the target site; or the bulk of the side chain.

The substitutions which in general are expected to produce the greatest changes in the polypeptide's properties are those in which (a) a hydrophilic residue, e. g. seryl or threonyl is substituted for (or by) a hydrophobic residue, e. g. leucyl, isoleucyl, phenylalanyl, valyl or alanyl; (b) a cysteine or proline is substituted for (or by) any other residue; (c) a residue

having an electropositive side chain, e. g. lysyl, arginyl, or histidyl, is substituted for (or by) an electronegative residue, e. g. glutamyl or aspartyl; or (d) a residue having a bulky side chain, e. g. phenylalanine, is substituted for (or by) one not having a side chain, e. g. glycine.

[103] The variants typically exhibit the same qualitative biological activity and will elicit the same immune response as the naturally-occurring analogue, although variants also are selected to modify the characteristics of the colorectal cancer proteins as needed. Alternatively, the variant may be designed such that the biological activity of the colorectal cancer protein is altered. For example, glycosylation sites may be altered or removed.

[104] Covalent modifications of colorectal cancer polypeptides are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a colorectal cancer polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of a colorectal cancer polypeptide. Derivatization with bifunctional agents is useful, for instance, for crosslinking colorectal cancer to a water-insoluble support matrix or surface for use in the method for purifying anti-colorectal cancer antibodies or screening assays, as is more fully described below. Commonly used crosslinking agents include, e. g., 1, l-bis (diazo- acetyl)-2-phenylethane, glutaraldehyde, N-hydroxy-succinimide esters, for example, esters with 4-azido-salicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis- (succinimidyl-propionate), bifunctional maleimides such as bis-N- maleimido-1, 8-octane and agents such as methyl-3- [ (p-azidophenyl)-dithio] pro-pioimi-date.

[105] Other modifications include deamidation of glutaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl, threonyl or tyrosyl residues, methylation of the a-amino groups of lysine, arginine, and histidine side chains [T. E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, pp. 79-86 (1983)], acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.

[106] Another type of covalent modification of the colorectal cancer polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide."Altering the native glycosylation pattern"is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence colorectal cancer polypeptide, and/or adding one or more glycosylation sites that are not present in the native sequence colorectal cancer polypeptide.

[107] Addition of glycosylation sites to colorectal cancer polypeptides may be accomplished by altering the amino acid sequence thereof. The alteration may be made, for example, by the addition of, or substitution by, one or more serine or threonine residues to the native sequence colorectal cancer polypeptide (for 0-linked glycosylation sites). The colorectal cancer amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the colorectal cancer polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.

[108] Another means of increasing the number of carbohydrate moieties on the colorectal cancer polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e. g., in WO 87/05330 published 11 September 1987, and in Aplin and Wriston, colorectal cancer Crit. Rev. Biochem., pp. 259- 306 (1981).

[109] Removal of carbohydrate moieties present on the colorectal cancer polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al., Arch. Biochem. Biophys., 259: 52 (1987) and by Edge et al., Anal. Biochem., 118 : 131 (1981). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo-and exo-glycosidases as described by Thotakura et al., Meth.

Enzymol., 138: 350 (1987).

[110] Another type of covalent modification of colorectal cancer comprises linking the colorectal cancer polypeptide to one of a variety of nonproteinaceous polymers, e. g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U. S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417 ; 4,791,192 or 4,179,337.

[Ill] colorectal cancer polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising a colorectal cancer polypeptide fused to another, heterologous polypeptide or amino acid sequence. In one embodiment, such a chimeric molecule comprises a fusion of a colorectal cancer polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind.

The epitope tag is generally placed at the amino-or carboxyl-terminus of the colorectal cancer polypeptide. The presence of such epitope-tagged forms of a colorectal cancer polypeptide can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the colorectal cancer polypeptide to be readily purified by affinity purification

using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. In an alternative embodiment, the chimeric molecule may comprise a fusion of a colorectal cancer polypeptide with an immunoglobulin or a particular region of an immunoglobulin.

For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule.

[112] Various tag polypeptides and their respective antibodies are well known in the art. Examples include poly-histidine (poly-his) or poly-histidine-glycine (poly- his-gly) tags; the flu HA tag polypeptide and its antibody 12CA5 [Field et al., Mol. Cell.

Biol., 8 : 2159-2165 (1988)] ; the c-myc tag and the 8F9,3C7,6E10, G4, B7 and 9E10 antibodies thereto [Evan et al., Molecular and Cellular Biology, 5: 3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody [Paborsky et al., Protein Engineering, 3 (6): 547-553 (1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al., BioTechnology, 6: 1204-1210 (1988)] ; the KT3 epitope peptide [Martin et al., Science, 255: 192-194 (1992)]; tubulin epitope peptide [Skinner et al., J. Biol. Chem., 266: 15163- 15166 (1991)] ; and the T7 gene 10 protein peptide tag [Lutz-Freyermuth et al., Proc. Natl.

Acad. Sci. USA, 87 : 6393-6397 (1990)].

[113] Also included with the definition of colorectal cancer protein in one embodiment are other colorectal cancer proteins of the colorectal cancer family, and colorectal cancer proteins from other organisms, which are cloned and expressed as outlined below. Thus, probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related colorectal cancer proteins from humans or other organisms. As will be appreciated by those in the art, particularly useful probe and/or PCR primer sequences include the unique areas of the colorectal cancer nucleic acid sequence. As is generally known in the art, preferred PCR primers are from about 15 to about 35 nucleotides in length, with from about 20 to about 30 being preferred, and may contain inosine as needed. The conditions for the PCR reaction are well known in the art.

[114] In addition, as is outlined herein, colorectal cancer proteins can be made that are longer than those depicted in the Table 1 or Table 2 for example, by the elucidation of additional sequences, the addition of epitope or purification tags, the addition of other fusion sequences, etc.

[115] Colorectal cancer proteins may also be identified as being encoded by colorectal cancer nucleic acids. Thus, colorectal cancer proteins are encoded by nucleic acids that will hybridize to the sequences of the sequence listings, or their complements, as outlined herein.

[116] In a preferred embodiment, when the colorectal cancer protein is to be used to generate antibodies, for example for immunotherapy, the colorectal cancer protein should share at least one epitope or determinant with the full length protein. By"epitope"or "determinant"herein is meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC. Thus, in most instances, antibodies made to a smaller colorectal cancer protein will be able to bind to the full length protein. In a preferred embodiment, the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross-reactivity. In a preferred embodiment, the epitope is selected from a peptide encoded by a nucleic acid of Table. In another preferred embodiment, the epitope is selected from the CBF9 peptide sequence shown in Table 2.

[117] In one embodiment, the term"antibody"includes antibody fragments, as are known in the art, including Fab, Fab2, single chain antibodies (Fv for example), chimeric antibodies, etc., either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA technologies.

[118] Methods of preparing polyclonal antibodies are known to the skilled artisan. Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include the CBF9 peptide of Table 2, or a peptide encoded by a nucleic acid of Table 1 or fragment thereof or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's complete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected by one skilled in the art without undue experimentation.

[119] The antibodies may, alternatively, be monoclonal antibodies.

Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256: 495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent will typically include the CBF9 polypeptide or a peptide encoded by a

nucleic acid of Table 1 or a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell [Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103]. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.

[120] In one embodiment, the antibodies are bispecific antibodies.

Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for a colorectal cancer protein or a fragment thereof, the other one is for any other antigen, and preferably for a cell-surface protein or receptor or receptor subunit, preferably one that is tumor specific.

[121] In a preferred embodiment, the antibodies to colorectal cancer are capable of reducing or eliminating the biological function of colorectal cancer, as is described below. That is, the addition of anti-colorectal cancer antibodies (either polyclonal or preferably monoclonal) to colorectal cancer (or cells containing colorectal cancer) may reduce or eliminate the colorectal cancer activity. Generally, at least a 25% decrease in activity is preferred, with at least about 50% being particularly preferred and about a 95- 100% decrease being especially preferred.

[122] In a preferred embodiment the antibodies to the colorectal cancer proteins are humanized antibodies. Humanized forms of non-human (e. g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F (ab') 2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues form a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired

specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321: 522-525 (1986) ; Riechmann et al., Nature, 332: 323-329 (1988) ; and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992)].

[123] Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain.

Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature, 321: 522-525 (1986) ; Riechmann et al., Nature, 332: 323-327 (1988) ; Verhoeyen et al., Science, 239: 1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U. S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

[124] Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227: 381 (1991); Marks et al., J. Mol. Biol., 222: 581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147 (1) : 86-95 (1991)]. Similarly, human antibodies can be made by introducing of human immunoglobulin loci into transgenic animals, e. g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire.

This approach is described, for example, in U. S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5, 633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10,779-783 (1992); Lonberg et al., Nature 368 856-859 (1994); Morrison, Nature 368,812-13 (1994); Fishwild et al., Nature Biotechnology 14,845-51 (1996); Neuberger, Nature Biotechnology 14,826 (1996); Lonberg and Huszar, Intern. Rev.

Immunol. 13 65-93 (1995).

[125] By immunotherapy is meant treatment of colorectal cancer with an antibody raised against colorectal cancer proteins. As used herein, immunotherapy can be passive or active. Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient). Active immunization is the induction of antibody and/or T- cell responses in a recipient (patient). Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised. As appreciated by one of ordinary skill in the art, the antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and under conditions for expression of the antigen.

[126] In a preferred embodiment the colorectal cancer proteins against which antibodies are raised are secreted proteins as described above. Without being bound by theory, antibodies used for treatment, bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted colorectal cancer protein.

[127] In another preferred embodiment, the colorectal cancer protein to which antibodies are raised is a transmembrane protein. Without being bound by theory, antibodies used for treatment, bind the extracellular domain of the colorectal cancer protein and prevent it from binding to other proteins, such as circulating ligands or cell-associated molecules. The antibody may cause down-regulation of the transmembrane colorectal cancer protein. As will be appreciated by one of ordinary skill in the art, the antibody may be a competitive, non-competitive or uncompetitive inhibitor of protein binding to the extracellular domain of the colorectal cancer protein. The antibody is also an antagonist of the colorectal cancer protein. Further, the antibody prevents activation of the transmembrane colorectal cancer protein. In one aspect, when the antibody prevents the binding of other molecules to the colorectal cancer protein, the antibody prevents growth of the cell. The antibody also sensitizes the cell to cytotoxic agents, including, but not limited to TNF-a, TNF-P, IL-1, INF-y and IL-2, or chemotherapeutic agents including 5FU, vinblastine,

actinomycin D, cisplatin, methotrexate, and the like. In some instances the antibody belongs to a sub-type that activates serum complement when complexed with the transmembrane protein thereby mediating cytotoxicity. Thus, colorectal cancer is treated by administering to a patient antibodies directed against the transmembrane colorectal cancer protein.

[128] In another preferred embodiment, the antibody is conjugated to a therapeutic moiety. In one aspect the therapeutic moiety is a small molecule that modulates the activity of the colorectal cancer protein. In another aspect the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the colorectal cancer protein. The therapeutic moiety may inhibit enzymatic activity such as protease or protein kinase activity associated with colorectal cancer.

[129] In a preferred embodiment, the therapeutic moiety may also be a cytotoxic agent. In this method, targeting the cytotoxic agent to tumor tissue or cells, results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with colorectal cancer. Cytotoxic agents are numerous and varied and include, but are not limited to, cytotoxic drugs or toxins or active fragments of such toxins. Suitable toxins and their corresponding fragments include diptheria A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, enomycin and the like. Cytotoxic agents also include radiochemicals made by conjugating radioisotopes to antibodies raised against colorectal cancer proteins, or binding of a radionuclide to a chelating agent that has been covalently attached to the antibody. Targeting the therapeutic moiety to transmembrane colorectal cancer proteins not only serves to increase the local concentration of therapeutic moiety in the colorectal cancer afflicted area, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety.

[130] In another preferred embodiment, the colorectal cancer protein against which the antibodies are raised is an intracellular protein. In this case, the antibody may be conjugated to a protein which facilitates entry into the cell. In one case, the antibody enters the cell by endocytosis. In another embodiment, a nucleic acid encoding the antibody is administered to the individual or cell. Moreover, wherein the colorectal cancer protein can be targeted within a cell, i. e., the nucleus, an antibody thereto contains a signal for that target localization, i. e., a nuclear localization signal.

[131] The colorectal cancer antibodies of the invention specifically bind to colorectal cancer proteins. By"specifically bind"herein is meant that the antibodies bind to the protein with a binding constant in the range of at least 10-4-10-6 M-l, with a preferred range being 10-7-10-9 M-1.

[132] In a preferred embodiment, the colorectal cancer protein is purified or isolated after expression. Colorectal cancer proteins may be isolated or purified in a variety of ways known to those skilled in the art depending on what other components are present in the sample. Standard purification methods include electrophoretic, molecular, immunological and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing. For example, the colorectal cancer protein may be purified using a standard anti-colorectal cancer antibody column. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. For general guidance in suitable purification techniques, see Scopes, R., Protein Purification, Springer-Verlag, NY (1982). The degree of purification necessary will vary depending on the use of the colorectal cancer protein. In some instances no purification will be necessary.

[133] Once expressed and purified if necessary, the colorectal cancer proteins and nucleic acids are useful in a number of applications.

[134] In one aspect, the expression levels of genes are determined for different cellular states in the colorectal cancer phenotype; that is, the expression levels of genes in normal colon tissue and in colorectal cancer tissue (and in some cases, for varying severities of colorectal cancer that relate to prognosis, as outlined below) are evaluated to provide expression profiles. An expression profile of a particular cell state or point of development is essentially a"fingerprint"of the state; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state of the cell. By comparing expression profiles of cells in different states, information regarding which genes are important (including both up-and down-regulation of genes) in each of these states is obtained. Then, diagnosis may be done or confirmed: does tissue from a particular patient have the gene expression profile of normal or colorectal cancer tissue.

[135]"Differential expression,"or grammatical equivalents as used herein, refers to both qualitative as well as quantitative differences in the genes'temporal and/or cellular expression patterns within and among the cells. Thus, a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, for example, normal versus colorectal cancer tissue. That is, genes may be turned on or turned off in a particular state, relative to another state. As is apparent to the skilled artisan, any comparison of two or more states can be made. Such a qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard

techniques in one such state or cell type, but is not detectable in both. Alternatively, the determination is quantitative in that expression is increased or decreased; that is, the expression of the gene is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript. The degree to which expression differs need only be large enough to quantify via standard characterization techniques as outlined below, such as by use of Affymetrix GeneChipTM expression arrays, Lockhart, Nature Biotechnology, 14: 1675-1680 (1996), hereby expressly incorporated by reference. Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, Northern analysis and RNase protection. As outlined above, preferably the change in expression (i. e. upregulation or downregulation) is at least about 50%, more preferably at least about 100%, more preferably at least about 150%, more preferably, at least about 200%, with from 300 to at least 1000% being especially preferred.

[136] As will be appreciated by those in the art, this may be done by evaluation at either the gene transcript, or the protein level; that is, the amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, for example through the use of antibodies to the colorectal cancer protein and standard immunoassays (ELISAs, e tc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc. Thus, the proteins corresponding to colorectal cancer genes, i. e. those identified as being important in a colorectal cancer phenotype, can be evaluated in a colorectal cancer diagnostic test.

[137] In a preferred embodiment, gene expression monitoring is done and a number of genes, i. e. an expression profile, is monitored simultaneously, although multiple protein expression monitoring can be done as well. Similarly, these assays may be done on an individual basis as well.

[138] In this embodiment, the colorectal cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of colorectal cancer sequences in a particular cell. The assays are further described below in the example.

[139] In a preferred embodiment nucleic acids encoding the colorectal cancer protein are detected. Although DNA or RNA encoding the colorectal cancer protein may be detected, of particular interest are methods wherein the mRNA encoding a colorectal cancer protein is detected. The presence of mRNA in a sample is an indication that the colorectal cancer gene has been transcribed to form the mRNA, and suggests that the protein

is expressed. Probes to detect the mRNA can be any nucleotide/deoxynucleotide probe that is complementary to and base pairs with the mRNA and includes but is not limited to oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein. In one method the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample. Following washing to remove the non-specifically bound probe, the label is detected. In another method detection of the mRNA is performed in situ. In this method permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA. Following washing to remove the non-specifically bound probe, the label is detected. For example a digoxygenin labeled riboprobe (RNA probe) that is complementary to the mRNA encoding a colorectal cancer protein is detected by binding the digoxygenin with an anti-digoxygenin secondary antibody and developed with nitro blue tetrazolium and 5-bromo-4-chloro-3- indoyl phosphate.

[140] In a preferred embodiment, any of the three classes of proteins as described herein (secreted, transmembrane or intracellular proteins) are used in diagnostic assays. The colorectal cancer proteins, antibodies, nucleic acids, modified proteins and cells containing colorectal cancer sequences are used in diagnostic assays. This can be done on an individual gene or corresponding polypeptide level. In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes and/or corresponding polypeptides.

[141] As described and defined herein, colorectal cancer proteins, including intracellular, transmembrane or secreted proteins, find use as markers of colorectal cancer.

Detection of these proteins in putative colorectal cancer tissue or patients allows for a determination or diagnosis of colorectal cancer. Numerous methods known to those of ordinary skill in the art find use in detecting colorectal cancer. In one embodiment, antibodies are used to detect colorectal cancer proteins. A preferred method separates proteins from a sample or patient by electrophoresis on a gel (typically a denaturing and reducing protein gel, but may be any other type of gel including isoelectric focusing gels and the like). Following separation of proteins, the colorectal cancer protein is detected by immunoblotting with antibodies raised against the colorectal cancer protein. Methods of immunoblotting are well known to those of ordinary skill in the art.

[142] In another preferred method, antibodies to the colorectal cancer protein find use in in situ imaging techniques. In this method cells are contacted with from one to many antibodies to the colorectal cancer protein (s). Following washing to remove non-specific antibody binding, the presence of the antibody or antibodies is detected. In one embodiment the antibody is detected by incubating with a secondary antibody that contains a detectable label. In another method the primary antibody to the colorectal cancer protein (s) contains a detectable label. In another preferred embodiment each one of multiple primary antibodies contains a distinct and detectable label. This method finds particular use in simultaneous screening for a plurality of colorectal cancer proteins. As will be appreciated by one of ordinary skill in the art, numerous other histological imaging techniques are useful in the invention.

[143] In a preferred embodiment the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths. In addition, a fluorescence activated cell sorter (FACS) can be used in the method.

[144] In another preferred embodiment, antibodies find use in diagnosing colorectal cancer from blood samples. As previously described, certain colorectal cancer proteins are secreted/circulating molecules. Blood samples, therefore, are useful as samples to be probed or tested for the presence of secreted colorectal cancer proteins. Antibodies can be used to detect the colorectal cancer by any of the previously described immunoassay techniques including ELISA, immunoblotting (Western blotting), immunoprecipitation, BIACORE technology and the like, as will be appreciated by one of ordinary skill in the art.

[145] In a preferred embodiment, in situ hybridization of labeled colorectal cancer nucleic acid probes to tissue arrays is done. For example, arrays of tissue samples, including colorectal cancer tissue and/or normal tissue, are made. In situ hybridization as is known in the art can then be done.

[146] It is understood that when comparing the fingerprints between an individual and a standard, the skilled artisan can make a diagnosis as well as a prognosis. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis.

[147] In a preferred embodiment, the colorectal cancer proteins, antibodies, nucleic acids, modified proteins and cells containing colorectal cancer sequences are used in prognosis assays. As above, gene expression profiles can be generated that correlate to colorectal cancer severity, in terms of long term prognosis. Again, this may be done on either a protein or gene level, with the use of genes being preferred. As above, the colorectal

cancer probes are attached to biochips for the detection and quantification of colorectal cancer sequences in a tissue or patient. The assays proceed as outlined for diagnosis.

[148] In a preferred embodiment, any of the three classes of proteins as described herein are used in drug screening assays. The colorectal cancer proteins, antibodies, nucleic acids, modified proteins and cells containing colorectal cancer sequences are used in drug screening assays or by evaluating the effect of drug candidates on a"gene expression profile"or expression profile of polypeptides. In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, Zlokarnik, et al., Science 279,84-8 (1998), Heid, 1996 #69.

[149] In a preferred embodiment, the colorectal cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified colorectal cancer proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the colorectal cancer phenotype. As above, this can be done on an individual gene level or by evaluating the effect of drug candidates on a"gene expression profile". In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, see Zlokarnik, supra.

Having identified the differentially expressed genes herein, a variety of assays may be executed. In a preferred embodiment, assays may be run on an individual gene or protein level. That is, having identified a particular gene as up regulated in colorectal cancer, candidate bioactive agents may be screened to modulate this gene's response; preferably to down regulate the gene, although in some circumstances to up regulate the gene.

[150] The phrase"functional effects"in the context of assays for testing compounds that modulate activity of a colorectal cancer protein or colorectal cancer nucleic acid includes the determination of a parameter that is indirectly or directly under the influence of a colorectal cancer protein or nucleic acid, e. g., a physical (direct), or phenotypic or chemical effect (indirect), such as the ability to increase or decrease cellular proliferation.

It includes cell cycle arrest, the ability of cells to proliferate, and other characteristics of proliferating cells."Functional effects"include in vitro, in vivo, and ex vivo activities.

[151] By"determining the functional effect"is meant assaying for a compound that increases or decreases a parameter that is indirectly or directly under the influence of a colorectal cancer protein or nucleic acid, e. g., physical, phenotypic and chemical effects. Such functional effects can be measured by any means known to those

skilled in the art, e. g., physical effects such as changes in spectroscopic characteristics (e. g., fluorescence, absorbance, refractive index); hydrodynamic (e. g., shape); chromatographic; or solubility properties for the protein; measuring ligand binding activity or binding assays, e. g. binding to antibodies; measuring changes in ligand binding activity; and chemical or phenotypic effects such as measuring inducible markers or transcriptional activation of the protein; measuring cellular proliferation; measuring cell surface marker expression; measurement of changes in protein levels for colorectal cancer-associated sequences; measurement of RNA stability; phosphorylation or dephosphorylation; signal transduction, e. g., receptor-ligand interactions, second messenger concentrations (e. g., cAMP, IP3, or intracellular Ca2+) ; identification of downstream or reporter gene expression (CAT, luciferase, (3-gal, GFP and the like), e. g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, and inducible markers.

[152]"Inhibitors","activators", and"modulators"of colorectal cancer polynucleotide and polypeptide sequences are used to refer to activating, inhibitory, or modulating molecules identified using in vitro and in vivo assays of colorectal cancer polynucleotide and polypeptide sequences. Inhibitors are compounds that, e. g., bind to, partially or totally block activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity or expression of colorectal cancer proteins or nucleic acids, e. g., antagonists."Activators"are compounds that increase, open, activate, facilitate, enhance activation, sensitize, agonize, or up regulate colorectal cancer protein or nucleic acid activity.

Inhibitors, activators, or modulators also include genetically modified versions of colorectal cancer proteins, e. g., versions with altered activity, as well as naturally occurring and synthetic ligands, antagonists, agonists, antibodies, antisense molecules, peptides, ribozymes, small chemical molecules and the like. Such assays for inhibitors and activators include, e. g., expressing colorectal cancer protein in vitro, in cells, or cell membranes, applying putative modulator compounds, and then determining the functional effects on activity, as described above.

[153] Samples or assays comprising colorectal cancer proteins or colorectal cancer nucleic acids that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of inhibition. Control samples (untreated with inhibitors) are assigned a relative activity value of 100%. Inhibition of colorectal cancer is achieved when the activity value relative to the control is about 80%, preferably 50%, more preferably 25-0%. Activation of

colorectal cancer is achieved when the activity value relative to the control (untreated with activators) is 110%, more preferably 150%, more preferably 200-500% (i. e., two to five fold higher relative to the control), more preferably 1000-3000% higher.

[154] As will be appreciated by those in the art, this may be done by evaluation at either the gene or the protein level; that is, the amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the gene product itself can be monitored, for example through the use of antibodies to the colorectal cancer protein and standard immunoassays.

[155] In a preferred embodiment, gene expression monitoring is done and a number of genes, i. e. an expression profile, is monitored simultaneously, although multiple protein expression monitoring can be done as well.

[156] In this embodiment, the colorectal cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of colorectal cancer sequences in a particular cell. The assays are further described below.

[157] Generally, in a preferred embodiment, a candidate bioactive agent is added to the cells prior to analysis. Moreover, screens are provided to identify a candidate bioactive agent which modulates colorectal cancer, modulates colorectal cancer proteins, binds to a colorectal cancer protein, or interferes between the binding of a colorectal cancer protein and an antibody.

[158] The term"candidate bioactive agent"or"test compound"or"drug candidate"or"modulator"or grammatical equivalents as used herein describes any molecule, either naturally occurring or synthetic, e. g., protein, oligopeptide (e. g., from about 5 to about 25 amino acids in length, preferably from about 10 to 20 or 12 to 18 amino acids in length, preferably 12,15, or 18 amino acids in length), small organic molecule, polysaccharide, lipid, fatty acid, polynucleotide, oligonucleotide, etc., to be tested for the capacity to directly or indirectly modulate colorectal cancer sequences, including both nucleic acid and protein sequences. The test compound can be in the form of a library of test compounds, such as a combinatorial or randomized library that provides a sufficient range of diversity. Test compounds are optionally linked to a fusion partner, e. g., targeting compounds, rescue compounds, dimerization compounds, stabilizing compounds, addressable compounds, and other functional moieties. Conventionally, new chemical entities with useful properties are generated by identifying a test compound (called a"lead compound") with some desirable property or activity, e. g., inhibiting activity, creating variants of the lead compound, and

evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis.

[159] In preferred embodiments, the bioactive agents modulate the expression profiles, or expression profile nucleic acids or proteins provided herein. In a particularly preferred embodiment, the candidate agent suppresses a colorectal cancer phenotype, for example to a normal colon tissue fingerprint. Similarly, the candidate agent preferably suppresses a severe colorectal cancer phenotype. Generally a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i. e., at zero concentration or below the level of detection.

[160] In one aspect, a candidate agent will neutralize the effect of a colorectal cancer protein. By"neutralize"is meant that activity of a protein is either inhibited or counter acted against so as to have substantially no effect on a cell.

[161] Candidate agents encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 daltons. Preferred small molecules are less than 2000, or less than 1500 or less than 1000 or less than 500 D. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Particularly preferred are peptides.

[162] Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonucleotides. Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available or readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through conventional chemical, physical and biochemical means. Known pharmacological agents may be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification to produce structural analogs.

[163] In a preferred embodiment, the candidate bioactive agents are proteins. By"protein"herein is meant at least two covalently attached amino acids, which includes proteins, polypeptides, oligopeptides and peptides. The protein may be made up of naturally occurring amino acids and peptide bonds, or synthetic peptidomimetic structures.

Thus"amino acid", or"peptide residue", as used herein means both naturally occurring and synthetic amino acids. For example, homo-phenylalanine, citrulline and noreleucine are considered amino acids for the purposes of the invention."Amino acid"also includes imino acid residues such as proline and hydroxyproline. The side chains may be in either the (R) or the (S) configuration. In the preferred embodiment, the amino acids are in the (S) or L- configuration. If non-naturally occurring side chains are used, non-amino acid substituents may be used, for example to prevent or retard in vivo degradations.

[164] In a preferred embodiment, the candidate bioactive agents are naturally occurring proteins or fragments of naturally occurring proteins. Thus, for example, cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, may be used. In this way libraries of procaryotic and eucaryotic proteins may be made for screening in the methods of the invention. Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred.

[165] In a preferred embodiment, the candidate bioactive agents are peptides of from about 5 to about 30 amino acids, with from about 5 to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. The peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or"biased" random peptides. By"randomized"or grammatical equivalents herein is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. Since generally these random peptides (or nucleic acids, discussed below) are chemically synthesized, they may incorporate any nucleotide or amino acid at any position.

The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.

[166] In one embodiment, the library is fully randomized, with no sequence preferences or constants at any position. In a preferred embodiment, the library is biased.

That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities. For example, in a preferred embodiment, the nucleotides or amino acid residues are randomized within a defined class, for example, of hydrophobic

amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc., or to purines, etc.

[167] In a preferred embodiment, the candidate bioactive agents are nucleic acids, as defined above.

[168] As described above generally for proteins, nucleic acid candidate bioactive agents may be naturally occurring nucleic acids, random nucleic acids, or"biased" random nucleic acids. For example, digests of procaryotic or eucaryotic genomes may be used as is outlined above for proteins.

[169] In a preferred embodiment, the candidate bioactive agents are organic chemical moieties, a wide variety of which are available in the literature.

[170]"Antibody"refers to a polypeptide comprising a framework region from an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively. Typically, the antigen-binding region of an antibody will be most critical in specificity and affinity of binding.

[171] An exemplary immunoglobulin (antibody) structural unit comprises a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one"light" (about 25 kD) and one"heavy"chain (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chains respectively.

[172] Antibodies exist, e. g., as intact immunoglobulins or as a number of well-characterized fragments produced by digestion with various peptidases. Thus, for example, pepsin digests an antibody below the disulfide linkages in the hinge region to produce F (ab)'2, a dimer of Fab which itself is a light chain joined to VU-CUL by a disulfide bond. The F (ab)'2 may be reduced under mild conditions to break the disulfide linkage in the hinge region, thereby converting the F (ab)'2 dimer into an Fab'monomer. The Fab' monomer is essentially Fab with part of the hinge region (see Fundamental Immunology (Paul ed., 3d ed. 1993). While various antibody fragments are defined in terms of the

digestion of an intact antibody, one of skill will appreciate that such fragments may be synthesized de novo either chemically or by using recombinant DNA methodology. Thus, the term antibody, as used herein, also includes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e. g., single chain Fv) or those identified using phage display libraries (see, e. g., McCafferty et al., Nature 348: 552-554 (1990)) [173] For preparation of antibodies, e. g., recombinant, monoclonal, or polyclonal antibodies, many technique known in the art can be used (see, e. g., Kohler & Milstein, Nature 256: 495-497 (1975); Kozbor et al., Immunology Today 4: 72 (1983) ; Cole et al., pp. 77-96 in Monoclonal Ahtibodies and Cancer Therapy, Alan R. Liss, Inc. (1985) ; Coligan, Current Protocols in Immunology (1991) ; Harlow & Lane, Antibodies, A Laboratory Manual (1988) ; and Goding, Monoclonal Antibodies : Principles and Practice (2d ed. 1986)). The genes encoding the heavy and light chains of an antibody of interest can be cloned from a cell, e. g., the genes encoding a monoclonal antibody can be cloned from a hybridoma and used to produce a recombinant monoclonal antibody. Gene libraries encoding heavy and light chaims of monoclonal antibodies can also be made from hybridoma or plasma cells. Random combinations of the heavy and light chain gene products generate a large pool of antibodies with different antigenic specificity (see, e. g., Kuby, Immunology (3rd ed. 1997)). Techniques for the production of single chain antibodies or recombinant antibodies (U. S. Patent 4,946,778, U. S. Patent No. 4,816,567) can be adapted to produce antibodies to polypeptides of this invention. Also, transgenic mice, or other organisms such as other mammals, may be used to express humanized or human antibodies (see, e. g., U. S.

Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, Marks et al., BiolTechnology 10: 779-783 (1992); Lonberg et al., Nature 368 : 856-859 (1994); Morrison, Nature 368 : 812-13 (1994); Fishwild et al., Nature Biotechnology 14: 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and Lonberg & Huszar, Intern. Rev.

Immunol. 13: 65-93 (1995)). Alternatively, phage display technology can be used to identify antibodies and heteromeric Fab fragments that specifically bind to selected antigens (see, e. g., McCafferty et al., Nature 348 : 552-554 (1990); Marks et al., Biotechnology 10: 779-783 (1992)). Antibodies can also be made bispecific, i. e., able to recognize two different antigens (see, e. g., WO 93/08829, Traunecker et al., EMBO J 10: 3655-3659 (1991) ; and Suresh et al., Methods in Enzymology 121: 210 (1986)). Antibodies can also be heteroconjugates, e. g., two covalently joined antibodies, or immunotoxins (see, e. g., U. S. Patent No. 4,676,980, WO 91/00360; WO 92/200373; and EP 03089).

[174] Methods for humanizing or primatizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially performed following the method of Winter and co- workers (see, e. g., Jones et al., Nature 321: 522-525 (1986); Riechmann et al., Nature 332: 323-327 (1988) ; Verhoeyen et al., Science 239: 1534-1536 (1988) and Presta, Curr. Op.

Struct. Biol. 2: 593-596 (1992)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U. S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non- human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

[175] A"chimeric antibody"is an antibody molecule in which (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and/or species, or an entirely different molecule which confers new properties to the chimeric antibody, e. g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity.

[176] In one embodiment, the antibody is conjugated to an"effector"moiety.

The effector moiety can be any number of molecules, including labeling moieties such as radioactive labels or fluorescent labels, or can be a therapeutic moiety. In one aspect the antibody modulates the activity of the protein.

[177] After the candidate agent has been added and the cells allowed to incubate for some period of time, the sample containing the target sequences to be analyzed is added to the biochip. If required, the target sequence is prepared using known techniques.

For example, the sample may be treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR occurring as needed, as will be appreciated by those in the art. For example, an in vitro transcription with labels covalently attached to the nucleosides is done. Generally, the nucleic acids are labeled with biotin-FITC or PE, or with cy3 or cy5.

[178] In a preferred embodiment, the target sequence is labeled with, for example, a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected. Alternatively, the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. As known in the art, unbound labeled streptavidin is removed prior to analysis.

[179] As will be appreciated by those in the art, these assays can be direct hybridization assays or can comprise"sandwich assays", which include the use of multiple probes, as is generally outlined in U. S. Patent Nos. 5,681,702,5,597,909,5,545,730, 5, 594, 117, 5, 591, 584, 5,571,670,5,580,731,5,571,670,5,591,584,5,624,802,5,635,352, 5, 594, 118, 5,359,100,5,124,246 and 5,681,697, all of which are hereby incorporated by reference. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.

[180] A variety of hybridization conditions may be used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allows formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration pH, organic solvent concentration, etc.

[181] These parameters may also be used to control non-specific binding, as is generally outlined in U. S. Patent No. 5,681,697. Thus it may be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.

[182] The reactions outlined herein may be accomplished in a variety of ways, as will be appreciated by those in the art. Components of the reaction may be added simultaneously, or sequentially, in any order, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents may be included in the assays.

These include reagents like salts, buffers, neutral proteins, e. g. albumin, detergents, etc which

may be used to facilitate optimal hybridization and detection, and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used, depending on the sample preparation methods and purity of the target.

[183] Once the assay is run, the data is analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.

[184] The screens are done to identify drugs or bioactive agents that modulate the colorectal cancer phenotype. Specifically, there are several types of screens that can be run. A preferred embodiment is in the screening of candidate agents that can induce or suppress a particular expression profile, thus preferably generating the associated phenotype. That is, candidate agents that can mimic or produce an expression profile in colorectal cancer similar to the expression profile of normal colon tissue is expected to result in a suppression of the colorectal cancer phenotype. Thus, in this embodiment, mimicking an expression profile, or changing one profile to another, is the goal.

[185] In a preferred embodiment, as for the diagnosis and prognosis applications, having identified the differentially expressed genes important in any one state, screens can be run to alter the expression of the genes individually. That is, screening for modulation of regulation of expression of a single gene can be done; that is, rather than try to mimic all or part of an expression profile, screening for regulation of individual genes can be done. Thus, for example, particularly in the case of target genes whose presence or absence is unique between two states, screening is done for modulators of the target gene expression.

[186] In a preferred embodiment, screening is done to alter the biological function of the expression product of the differentially expressed gene. Again, having identified the importance of a gene in a particular state, screening for agents that bind and/or modulate the biological activity of the gene product can be run as is more fully outlined below.

[187] Thus, screening of candidate agents that modulate the colorectal cancer phenotype either at the gene expression level or the protein level can be done.

[188] In addition screens can be done for novel genes that are induced in response to a candidate agent. After identifying a candidate agent based upon its ability to suppress a colorectal cancer expression pattern leading to a normal expression pattern, or modulate a single colorectal cancer gene expression profile so as to mimic the expression of the gene from normal tissue, a screen as described above can be performed to identify genes

that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated colorectal cancer tissue reveals genes that are not expressed in normal tissue or colorectal cancer tissue, but are expressed in agent treated tissue. These agent specific sequences can be identified and used by any of the methods described herein for colorectal cancer genes or proteins. In particular these sequences and the proteins they encode find use in marking or identifying agent treated cells. In addition, antibodies can be raised against the agent induced proteins and used to target novel therapeutics to the treated colorectal cancer tissue sample.

[189] Thus, in one embodiment, a candidate agent is administered to a population of colorectal cancer cells, that thus has an associated colorectal cancer expression profile. By"administration"or"contacting"herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface. In some embodiments, nucleic acid encoding a proteinaceous candidate agent (i. e. a peptide) may be put into a viral construct such as a retroviral construct and added to the cell, such that expression of the peptide agent is accomplished ; see PCT US97/01019, hereby expressly incorporated by reference.

[190] Once the candidate agent has been administered to the cells, the cells can be washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.

[191] Thus, for example, colorectal cancer tissue may be screened for agents that reduce or suppress the colorectal cancer phenotype. A change in at least one gene of the expression profile indicates that the agent has an effect on colorectal cancer activity. By defining such a signature for the colorectal cancer phenotype, screens for new drugs that alter the phenotype can be devised. With this approach, the drug target need not be known and need not be represented in the original expression screening platform, nor does the level of transcript for the target protein need to change.

[192] In a preferred embodiment, as outlined above, screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself can be done. The gene products of differentially expressed genes are sometimes referred to herein as"colorectal cancer modulator proteins". The colorectal cancer modulator protein may be a fragment, or

alternatively, be the full length protein to a fragment shown herein. Preferably, the colorectal cancer modulator protein is a fragment of approximately 14 to 24 amino acids long. More preferably the fragment is a soluble fragment.

[193] In a preferred embodiment, the fragment is charged and from the c- terminus. In one embodiment, the c-terminus of the fragment is kept as a free acid and the n- terminus is a free amine to aid in coupling, i. e., to cysteine. In another embodiment, the fragment is an internal peptide overlapping hydrophilic stretch the protein. In a preferred embodiment, the termini is blocked. In another preferred embodiment, the fragment is a novel fragment from the N-terminal. In one embodiment, the fragment excludes sequence outside of the N-terminal, in another embodiment, the fragment includes at least a portion of the N-terminal."N-terminal"is used interchangeably herein with"N-terminus"which is further described above.

[194] In one embodiment the colorectal cancer proteins are conjugated to an immunogenic agent as discussed herein. In one embodiment the colorectal cancer protein is conjugated to BSA.

[195] Thus, in a preferred embodiment, screening for modulators of expression of specific genes can be done. This will be done as outlined above, but in general the expression of only one or a few genes are evaluated.

[196] In a preferred embodiment, screens are designed to first find candidate agents that can bind to differentially expressed proteins, and then these agents may be used in assays that evaluate the ability of the candidate agent to modulate differentially expressed activity. Thus, as will be appreciated by those in the art, there are a number of different assays which may be run; binding assays and activity assays.

[197] In a preferred embodiment, binding assays are done. In general, purified or isolated gene product is used; that is, the gene products of one or more differentially expressed nucleic acids are made. In general, this is done as is known in the art.

For example, antibodies are generated to the protein gene products, and standard immunoassays are run to determine the amount of protein present. Alternatively, cells comprising the colorectal cancer proteins can be used in the assays.

[198] Thus, in a preferred embodiment, the methods comprise combining a colorectal cancer protein and a candidate bioactive agent, and determining the binding of the candidate agent to the colorectal cancer protein. Preferred embodiments utilize the human colorectal cancer protein, although other mammalian proteins may also be used, for example

for the development of animal models of human disease. In some embodiments, as outlined herein, variant or derivative colorectal cancer proteins may be used.

[199] Generally, in a preferred embodiment of the methods herein, the colorectal cancer protein or the candidate agent is non-diffusably bound to an insoluble support having isolated sample receiving areas (e. g. a microtiter plate, an array, etc.). The insoluble supports may be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports include microtiter plates, arrays, membranes and beads. These are typically made of glass, plastic (e. g., polystyrene), polysaccharides, nylon or nitrocellulose, teflon, etc. Microtiter plates and arrays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable. Preferred methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protein is bound to the support), direct binding to"sticky"or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety.

[200] In a preferred embodiment, the colorectal cancer protein is bound to the support, and a candidate bioactive agent is added to the assay. Alternatively, the candidate agent is bound to the support and the colorectal cancer protein is added. Novel binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like.

[201] The determination of the binding of the candidate bioactive agent to the colorectal cancer protein may be done in a number of ways. In a preferred embodiment, the candidate bioactive agent is labeled, and binding determined directly. For example, this may be done by attaching all or a portion of the colorectal cancer protein to a solid support,

adding a labeled candidate agent (for example a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps may be utilized as is known in the art.

[202] By"labeled"herein is meant that the compound is either directly or indirectly labeled with a label which provides a detectable signal, e. g. radioisotope, fluorescers, enzyme, antibodies, particles such as magnetic particles, chemiluminescers, or specific binding molecules, etc. Specific binding molecules include pairs, such as biotin and streptavidin, digoxin and antidigoxin etc. For the specific binding members, the complementary member would normally be labeled with a molecule which provides for detection, in accordance with known procedures, as outlined above. The label can directly or indirectly provide a detectable signal.

[203] In some embodiments, only one of the components is labeled. For example, the proteins (or proteinaceous candidate agents) may be labeled at tyrosine positions using 125I, or with fluorophores. Alternatively, more than one component may be labeled with different labels ; using 125I for the proteins, for example, and a fluorophor for the candidate agents.

[204] In a preferred embodiment, the binding of the candidate bioactive agent is determined through the use of competitive binding assays. In this embodiment, the competitor is a binding moiety known to bind to the target molecule (i. e. colorectal cancer), such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding as between the bioactive agent and the binding moiety, with the binding moiety displacing the bioactive agent.

[205] In one embodiment, the candidate bioactive agent is labeled. Either the candidate bioactive agent, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present. Incubations may be performed at any temperature which facilitates optimal activity, typically between 4 and 40°C. Incubation periods are selected for optimum activity, but may also be optimized to facilitate rapid high through put screening. Typically between 0.1 and 1 hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.

[206] In a preferred embodiment, the competitor is added first, followed by the candidate bioactive agent. Displacement of the competitor is an indication that the candidate bioactive agent is binding to the colorectal cancer protein and thus is capable of binding to, and potentially modulating, the activity of the colorectal cancer protein. In this

embodiment, either component can be labeled. Thus, for example, if the competitor is labeled, the presence of label in the wash solution indicates displacement by the agent.

Alternatively, if the candidate bioactive agent is labeled, the presence of the label on the support indicates displacement.

[207] In an alternative embodiment, the candidate bioactive agent is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor may indicate that the bioactive agent is bound to the colorectal cancer protein with a higher affinity. Thus, if the candidate bioactive agent is labeled, the presence of the label on the support, coupled with a lack of competitor binding, may indicate that the candidate agent is capable of binding to the colorectal cancer protein.

[208] In a preferred embodiment, the methods comprise differential screening to identity bioactive agents that are capable of modulating the activity of the colorectal cancer proteins. In this embodiment, the methods comprise combining a colorectal cancer protein and a competitor in a first sample. A second sample comprises a candidate bioactive agent, a colorectal cancer protein and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the colorectal cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the colorectal cancer protein.

[209] Alternatively, a preferred embodiment utilizes differential screening to identify drug candidates that bind to the native colorectal cancer protein, but cannot bind to modified colorectal cancer proteins. The structure of the colorectal cancer protein may be modeled, and used in rational drug design to synthesize agents that interact with that site.

Drug candidates that affect colorectal cancer bioactivity are also identified by screening drugs for the ability to either enhance or reduce the activity of the protein.

[210] Positive controls and negative controls may be used in the assays.

Preferably all control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein. Following incubation, all samples are washed free of non- specifically bound material and the amount of bound, generally labeled agent determined.

For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.

[211] A variety of other reagents may be included in the screening assays.

These include reagents like salts, neutral proteins, e. g. albumin, detergents, etc which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components may be added in any order that provides for the requisite binding.

[212] Screening for agents that modulate the activity of colorectal cancer proteins may also be done. In a preferred embodiment, methods for screening for a bioactive agent capable of modulating the activity of colorectal cancer proteins comprise the steps of adding a candidate bioactive agent to a sample of colorectal cancer proteins, as above, and determining an alteration in the biological activity of colorectal cancer proteins.

"Modulating the activity of colorectal cancer"includes an increase in activity, a decrease in activity, or a change in the type or kind of activity present. Thus, in this embodiment, the candidate agent should both bind to colorectal cancer proteins (although this may not be necessary), and alter its biological or biochemical activity as defined herein. The methods include both in vitro screening methods, as are generally outlined above, and in vivo screening of cells for alterations in the presence, distribution, activity or amount of colorectal cancer proteins.

[213] Thus, in this embodiment, the methods comprise combining a colorectal cancer sample and a candidate bioactive agent, and evaluating the effect on colorectal cancer activity. By"colorectal cancer activity"or grammatical equivalents herein is meant one of the colorectal cancer's biological activities, including, but not limited to, cell division, preferably in colon tissue, cell proliferation, tumor growth, transformation of cells.

In one embodiment, colorectal cancer activity includes activation of a gene identified by a nucleic acid of Table 1. An inhibitor of colorectal cancer activity is the inhibition of any one or more colorectal cancer activities.

[214] In a preferred embodiment, the activity of the colorectal cancer protein is increased ; in another preferred embodiment, the activity of the colorectal cancer protein is decreased. Thus, bioactive agents that are antagonists are preferred in some embodiments, and bioactive agents that are agonists may be preferred in other embodiments.

[215] In a preferred embodiment, the invention provides methods for screening for bioactive agents capable of modulating the activity of a colorectal cancer protein. The methods comprise adding a candidate bioactive agent, as defined above, to a cell comprising colorectal cancer proteins. Preferred cell types include almost any cell. The

cells contain a recombinant nucleic acid that encodes a colorectal cancer protein. In a preferred embodiment, a library of candidate agents are tested on a plurality of cells.

[216] In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, for example hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i. e. cell-cell contacts).

In another example, the determinations are determined at different stages of the cell cycle process.

[217] In this way, bioactive agents are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the colorectal cancer protein. In one embodiment,"colorectal cancer protein activity"as used herein includes at least one of the following: colorectal cancer activity, binding to the colorectal cancer protein, activation of the colorectal cancer protein or activation of substrates of the colorectal cancer protein by the colorectal cancer protein. In one embodiment, colorectal cancer activity is defined as the unregulated proliferation of colon tissue, or the growth of cancer in colon tissue. In one aspect, colorectal cancer activity as defined herein is related to the activity of the colorectal cancer protein in the upregulation of the colorectal cancer protein in colon cancer tissue.

[218] In another embodiment, colorectal cancer protein activity includes at least one of the following: colorectal cancer activity, binding to the CBF9 nucleic acid or poly peptide of Table 2 or binding toa nucleic acid of Table 1, or a peptide encoded by a nucleic acid of Table 1 or activation of substrates of the gene products identified by a nucleic acid of Table 1 or substrates of CBF9, which is shown in Table 2. In one aspect, colorectal cancer activity as defined herein is related to the activity of genes defined by the nucleic acids of Table 1 or of CBF9 as defined in Table 2, in colon cancer tissue.

[219] In one embodiment, a method of inhibiting colon cancer cell division is provided. The method comprises administration of a colorectal cancer inhibitor.

[220] In another embodiment, a method of inhibiting tumor growth is provided. The method comprises administration of a colorectal cancer inhibitor.

[221] In a further embodiment, methods of treating cells or individuals with cancer are provided. The method comprises administration of a colorectal cancer inhibitor.

[222] In one embodiment, a colorectal cancer inhibitor is an antibody as discussed above. In another embodiment, the colorectal cancer inhibitor is an antisense molecule. Antisense molecules as used herein include antisense or sense oligonucleotides

comprising a singe-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for colorectal cancer molecules. A preferred antisense molecule is for the colorectal cancer sequences referenced in Table 1 or Table 2, or for a ligand or activator thereof. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, for example, Stein and Cohen (Cancer Res. 48 : 2659,1988) and van der Krol et al.

(BioTechniques 6: 958,1988).

[223] Antisense molecules may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a sense or an antisense oligonucleotide may be introduced into a cell containing the target nucleic acid sequence by formation of an oligonucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.

[224] The compounds having the desired pharmacological activity may be administered in a physiologically acceptable carrier to a host, as previously described. The agents may be administered in a variety of ways, orally, parenterally e. g., subcutaneously, intraperitoneally, intravascularly, etc. Depending upon the manner of introduction, the compounds may be formulated in a variety of ways. The concentration of therapeutically active compound in the formulation may vary from about 0.1-100 wt. %. The agents may be administered alone or in combination with other treatments, i. e., radiation.

[225] The pharmaceutical compositions can be prepared in various forms, such as granules, tablets, pills, suppositories, capsules, suspensions, salves, lotions and the like. Pharmaceutical grade organic or inorganic carriers and/or diluents suitable for oral and topical use can be used to make up compositions containing the therapeutically-active compounds. Diluents known to the art include aqueous media, vegetable and animal oils and fats. Stabilizing agents, wetting and emulsifying agents, salts for varying the osmotic

pressure or buffers for securing an adequate pH value, and skin penetration enhancers can be used as auxiliary agents.

[226] Without being bound by theory, it appears that the various colorectal cancer sequences are important in colorectal cancer. Accordingly, disorders based on mutant or variant colorectal cancer genes may be determined. In one embodiment, the invention provides methods for identifying cells containing variant colorectal cancer genes comprising determining all or part of the sequence of at least one endogeneous colorectal cancer genes in a cell. As will be appreciated by those in the art, this may be done using any number of sequencing techniques. In a preferred embodiment, the invention provides methods of identifying the colorectal cancer genotype of an individual comprising determining all or part of the sequence of at least one colorectal cancer gene of the individual. This is generally done in at least one tissue of the individual, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced colorectal cancer gene to a known colorectal cancer gene, i. e. a wild-type gene.

[227] The sequence of all or part of the colorectal cancer gene can then be compared to the sequence of a known colorectal cancer gene to determine if any differences exist. This can be done using any number of known homology programs, such as Bestfit, etc.

In a preferred embodiment, the presence of a a difference in the sequence between the colorectal cancer gene of the patient and the known colorectal cancer gene is indicative of a disease state or a propensity for a disease state, as outlined herein.

[228] In a preferred embodiment, the colorectal cancer genes are used as probes to determine the number of copies of the colorectal cancer gene in the genome.

[229] In another preferred embodiment colorectal cancer genes are used as probed to determine the chromosomal localization of the colorectal cancer genes.

Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in colorectal cancer gene loci.

[230] Thus, in one embodiment, methods of modulating colorectal cancer in cells or organisms are provided. In one embodiment, the methods comprise administering to a cell an anti-colorectal cancer antibody that reduces or eliminates the biological activity of an endogeneous colorectal cancer protein. Alternatively, the methods comprise administering to a cell or organism a recombinant nucleic acid encoding a colorectal cancer protein. As will be appreciated by those in the art, this may be accomplished in any number

of ways. In a preferred embodiment, for example when the colorectal cancer sequence is down-regulated in colorectal cancer, the activity of the colorectal cancer gene is increased by increasing the amount of colorectal cancer in the cell, for example by overexpressing the endogeneous colorectal cancer or by administering a gene encoding the colorectal cancer sequence, using known gene-therapy techniques, for example. In a preferred embodiment, the gene therapy techniques include the incorporation of the erogenous gene using enhanced homologous recombination (EHR), for example as described in PCT/US93/03868, hereby incorporated by reference in its entirety. Alternatively, for example when the colorectal cancer sequence is up-regulated in colorectal cancer, the activity of the endogeneous colorectal cancer gene is decreased, for example by the administration of a colorectal cancer antisense nucleic acid.

[231] In one embodiment, the colorectal cancer proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to colorectal cancer proteins, which are useful as described herein. Similarly, the colorectal cancer proteins can be coupled, using standard technology, to affinity chromatography columns. These columns may then be used to purify colorectal cancer antibodies. In a preferred embodiment, the antibodies are generated to epitopes unique to a colorectal cancer protein; that is, the antibodies show little or no cross-reactivity to other proteins. These antibodies find use in a number of applications. For example, the colorectal cancer antibodies may be coupled to standard affinity chromatography columns and used to purify colorectal cancer proteins. The antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the colorectal cancer protein.

[232] In one embodiment, a therapeutically effective dose of a colorectal cancer or modulator thereof is administered to a patient. By"therapeutically effective dose" herein is meant a dose that produces the effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques. As is known in the art, adjustments for colorectal cancer degradation, systemic versus localized delivery, and rate of new protease synthesis, as well as the age, body weight, general health, sex, diet, time of administration, drug interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by those skilled in the art.

[233] A"patient"for the purposes of the present invention includes both humans and other animals, particularly mammals, and organisms. Thus the methods are

applicable to both human therapy and veterinary applications. In the preferred embodiment the patient is a mammal, and in the most preferred embodiment the patient is human.

[234] The administration of the colorectal cancer proteins and modulators of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, intranasally, transdermally, intraperitoneally, intramuscularly, intrapulmonary, vaginally, rectally, or intraocularly. In some instances, for example, in the treatment of wounds and inflammation, the colorectal cancer proteins and modulators may be directly applied as a solution or spray.

[235] The pharmaceutical compositions of the present invention comprise a colorectal cancer protein in a form suitable for administration to a patient. In the preferred embodiment, the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both acid and base addition salts."Pharmaceutically acceptable acid addition salt"refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like.

"Pharmaceutically acceptable base addition salts"include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Particularly preferred are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.

[236] The pharmaceutical compositions may also include one or more of the following: carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, corn and other starches; binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol. Additives are well known in the art, and are used in a variety of formulations.

[237] In a preferred embodiment, colorectal cancer proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above. Similarly,

colorectal cancer genes (including both the full-length sequence, partial sequences, or regulatory sequences of the colorectal cancer coding regions) can be administered in gene therapy applications, as is known in the art. These colorectal cancer genes can include antisense applications, either as gene therapy (i. e. for incorporation into the genome) or as antisense compositions, as will be appreciated by those in the art.

[238] In a preferred embodiment, colorectal cancer genes are administered as DNA vaccines, either single genes or combinations of colorectal cancer genes. Naked DNA vaccines are generally known in the art. Brower, Nature Biotechnology, 16: 1304-1305 (1998).

[239] In one embodiment, colorectal cancer genes of the present invention are used as DNA vaccines. Methods for the use of genes as DNA vaccines are well known to one of ordinary skill in the art, and include placing a colorectal cancer gene or portion of a colorectal cancer gene under the control of a promoter for expression in a colorectal cancer patient. The colorectal cancer gene used for DNA vaccines can encode full-length colorectal cancer proteins, but more preferably encodes portions of the colorectal cancer proteins including peptides derived from the colorectal cancer protein. In a preferred embodiment a patient is immunized with a DNA vaccine comprising a plurality of nucleotide sequences derived from a colorectal cancer gene. Similarly, it is possible to immunize a patient with a plurality of colorectal cancer genes or portions thereof as defined herein. Without being bound by theory, expression of the polypeptide encoded by the DNA vaccine, cytotoxic T- cells, helper T-cells and antibodies are induced which recognize and destroy or eliminate cells expressing colorectal cancer proteins.

[240] In a preferred embodiment, the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine. Such adjuvant molecules include cytokines that increase the immunogenic response to the colorectal cancer polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are known to those of ordinary skill in the art and find use in the invention.

[241] In another preferred embodiment colorectal cancer genes find use in generating animal models of colorectal cancer. As is appreciated by one of ordinary skill in the art, when the colorectal cancer gene identified is repressed or diminished in colorectal cancer tissue, gene therapy technology wherein antisense RNA directed to the colorectal cancer gene will also diminish or repress expression of the gene. An animal generated as such serves as an animal model of colorectal cancer that finds use in screening bioactive drug candidates. Similarly, gene knockout technology, for example as a result of

homologous recombination with an appropriate gene targeting vector, will result in the absence of the colorectal cancer protein. When desired, tissue-specific expression or knockout of the colorectal cancer protein may be necessary.

[242] It is also possible that the colorectal cancer protein is overexpressed in colorectal cancer. As such, transgenic animals can be generated that overexpress the colorectal cancer protein. Depending on the desired expression level, promoters of various strengths can be employed to express the transgene. Also, the number of copies of the integrated transgene can be determined and compared for a determination of the expression level of the transgene. Animals generated by such methods find use as animal models of colorectal cancer and are additionally useful in screening for bioactive molecules to treat colorectal cancer.

EXAMPLES [243] It is understood that the examples described herein in no way serve to limit the true scope of this invention, but rather are presented for illustrative purposes. All references and sequences of accession numbers cited herein are incorporated by reference in their entirety.

[244] Example 1 Tissue Preparation, Labeling Chips, and Fingerprints [245] Purify total RNA from tissue using TRIzol Reagent [246] Estimate tissue weight. Homogenize tissue samples in lml of TRIzol per 50mg of tissue using a Polytron 3100 homogenizer. The generator/probe used depends upon the tissue size. A generator that is too large for the amount of tissue to be homogenized will cause a loss of sample and lower RNA yield. Use the 20mm generator for tissue weighing more than 0.6g. If the working volume is greater than 2ml, then homogenize tissue in a 15ml polypropylene tube (Falcon 2059). Fill tube no greater than 10ml.

HOMOGENIZATION [247] Before using generator, it should have been cleaned after last usage by running it through soapy H20 and rinsing thoroughly. Run through with EtOH to sterilize.

Keep tissue frozen until ready. Add TRIzol directly to frozen tissue then homogenize.

[248] Following homogenization, remove insoluble material from the homogenate by centrifugation at 7500 x g for 15 min. in a Sorvall superspeed or 12,000 x g for 10 min. in an Eppendorf centrifuge at 4oC. Transfer the cleared homogenate to a new tube (s). The samples may be frozen now at-60 to-70oC (and kept for at least one month) or you may continue with the purification.

PHASE SEPARATION [249] Incubate the homogenized samples for 5 minutes at room temperature.

[250] Add 0. 2ml of chloroform per lml of TRIzol reagent used in the original homogenization.

[251] Cap tubes securely and shake tubes vigorously by hand (do not vortex) for 15 seconds.

[252] Incubate samples at room temp. for 2-3 minutes. Centrifuge samples at 6500rpm in a Sorvall superspeed for 30 min. at 4oC. (You may spin at up to 12,000 x g for 10 min. but you risk breaking your tubes in the centrifuge.) RNA PRECIPITATION [253] Transfer the aqueous phase to a fresh tube. Save the organic phase if isolation of DNA or protein is desired. Add 0. 5ml of isopropyl alcohol per lml of TRIzol reagent used in the original homogenization. Cap tubes securely and invert to mix. Incubate samples at room temp. for 10 minutes. Centrifuge samples at 6500rpm in Sorvall for 20min. at 4oC.

RNA WASH [254] Pour off the supernate. Wash pellet with cold 75% ethanol. Use lml of 75% ethanol per lml of TRIzol reagent used in the initial homogenization. Cap tubes securely and invert several times to loosen pellet. (Do not vortex). Centrifuge at <8000rpm (<7500 x g) for 5 minutes at 4oC.

[255] Pour off the wash. Carefully transfer pellet to an eppendorf tube (let it slide down the tube into the new tube and use a pipet tip to help guide it in if necessary).

Depending on the volumes you are working with, you can decide what size tube (s) you want to precipitate the RNA in. When I tried leaving the RNA in the large 15ml tube, it took so long to dry (i. e. it did not dry) that I eventually had to transfer it to a smaller tube. Let pellet

dry in hood. Resuspend RNA in an appropriate volume of DEPC H20. Try for 2-5ug/ul.

Take absorbance readings.

[256] Purify poly A+ mRNA from total RNA or clean up total RNA with Qiagen's RNeasy kit [257] Purification of poly A+ mRNA from total RNA. Heat oligotex suspension to 37oC and mix immediately before adding to RNA. Incubate Elution Buffer at 70oC. Warm up 2 x Binding Buffer at 65oC if there is precipitate in the buffer. Mix total RNA with DEPC-treated water, 2 x Binding Buffer, and Oligotex according to Table 2 on page 16 of the Oligotex Handbook. Incubate for 3 minutes at 65oC. Incubate for 10 minutes at room temperature.

1258] Centrifuge for 2 minutes at 14,000 to 18,000 g. If centrifuge has a "soft setting,"then use it. Remove supernatant without disturbing Oligotex pellet. A little bit of solution can be left behind to reduce the loss of Oligotex. Save sup until certain that satisfactory binding and elution of poly A+ mRNA has occurred.

[259] Gently resuspend in Wash Buffer OW2 and pipet onto spin column Centrifuge the spin column at full speed (soft setting if possible) for 1 minute.

[260] Transfer spin column to a new collection tube and gently resuspend in Wash Buffer OW2 and centrifuge as describe herein.

[261] Transfer spin column to a new tube and elute with 20 to 100 ul of preheated (70oC) Elution Buffer. Gently resuspend Oligotex resin by pipetting up and down.

Centrifuge as above. Repeat elution with fresh elution buffer or use first eluate to keep the elution volume low.

[262] Read absorbance, using diluted Elution Buffer as the blank.

[263] Before proceeding with cDNA synthesis, the mRNA must be precipitated. Some component leftover or in the Elution Buffer from the Oligotex purification procedure will inhibit downstream enzymatic reactions of the mRNA.

Ethanol Precipitation [264] Add 0.4 vol. of 7.5 M NH40Ac + 2.5 vol. of cold 100% ethanol.

Precipitate at-20oC 1 hour to overnight (or 20-30 min. at-70oC). Centrifuge at 14,000- 16,000 x g for 30 minutes at 4oC. Wash pellet with 0. 5ml of 80% ethanol (-20oC) then centrifuge at 14,000-16,000 x g for 5 minutes at room temperature. Repeat 80% ethanol wash. Dry the last bit of ethanol from the pellet in the hood. (Do not speed vacuum).

Suspend pellet in DEPC H20 at lug/ul concentration.

Clean up total RNA using Qiagen's RNeasy kit [265] Add no more than lOOug to an RNeasy column. Adjust sample to a volume of lOOul with RNase-free water. Add 350ul Buffer RLT then 250ul ethanol (100%) to the sample. Mix by pipetting (do not centrifuge) then apply sample to an RNeasy mini spin column. Centrifuge for 15 sec at >10, 000rpm. If concerned about yield, re-apply flowthrough to column and centrifuge again.

[266] Transfer column to a new 2-ml collection tube. Add 500ul Buffer RPE and centrifuge for 15 sec at >10, 000rpm. Discard flowthrough. Add 500ul Buffer RPE and centrifuge for 15 sec at >10, 000rpm. Discard flowthrough then centrifuge for 2 min at maximum speed to dry column membrane. Transfer column to a new 1.5-ml collection tube and apply 30-50ul of RNase-free water directly onto column membrane. Centrifuge 1 min at >10, 000rpm. Repeat elution.

[267] Take absorbance reading. If necessary, ethanol precipitate with ammonium acetate and 2.5X volume 100% ethanol.

[268] Make cDNA using Gibco's"SuperScript Choice System for cDNA Synthesis"kit First Strand cDNA Synthesis [269] Use 5ug of total RNA or lug of polyA+ mRNA as starting material.

For total RNA, use 2ul of SuperScript RT. For polyA+ mRNA, use lul of SuperScript RT.

Final volume of first strand synthesis mix is 20ul. RNA must be in a volume no greater than lOul. Incubate RNA with lul of lOOpmol T7-T24 oligo for 10 min at 70C. On ice, add 7 ul of 4ul5Xlst Strand Buffer, 2ul of O. 1M DTT, and 1 ul of lOmM dNTP mix. Incubate at 37C for 2 min then add SuperScript RT Incubate at 37C for 1 hour.

Second Strand Synthesis

Place 1st strand reactions on ice.

Add: 91ul DEPC H20 30ul 5X 2nd Strand Buffer 3ul lOmM dNTP mix lul lOU/ul E. coli DNA Ligase 4ul lOU/ul E. coli DNA Polymerase lul 2U/ul RNase H [270] Make the above into a mix if there are more than 2 samples. Mix and incubate 2 hours at 16C.

[271] Add 2ul T4 DNA Polymerase. Incubate 5 min at 16C. Add lOul of 0. 5M EDTA [272] Clean up cDNA [273] Phenol: Chloroform : Isoamyl Alcohol (25: 24: 1) purification using Phase-Lock gel tubes: [274] Centrifuge PLG tubes for 30 sec at maximum speed. Transfer cDNA mix to PLG tube. Add equal volume of phenol : chloroform : isamyl alcohol and shake vigorously (do not vortex). Centrifuge 5 minutes at maximum speed. Transfer top aqueous solution to a new tube. Ethanol precipitate: add 7.5X 5M NH40ac and 2.5X volume of 100% ethanol. Centrifuge immediately at room temp. for 20 min, maximum speed. Remove sup then wash pellet 2X with cold 80% ethanol. Remove as much ethanol wash as possible then let pellet air dry. Resuspend pellet in 3ul Rase-free water.

In vitro Transcription (IVT) and labeling with biotin Pipet 1. 5ul of cDNA into a thin-wall PCR tube.

Make NTP labeling mix: Combine at room temperature: 2ul T7 lOxATP (75mM) (Ambion) 2ul T7 lOxGTP (75mM) (Ambion) 1. 5ul T7 lOxCTP (75mM) (Ambion) 1. 5ul T7 lOxUTP (75mM) (Ambion) 3.75ul lOmM Bio-11-UTP (Boehringer-Mannheim/Roche or Enzo) 3.75ul lOmM Bio-16-CTP (Enzo)

2ul 1 Ox T7 transcription buffer (Ambion) 2ul lOx T7 enzyme mix (Ambion) [275] Final volume of total reaction is 20ul. Incubate 6 hours at 37C in a PCR machine.

RNeasy clean-up of IVT product [276] Follow previous instructions for RNeasy columns or refer to Qiagen's RNeasy protocol handbook.

[277] cRNA will most likely need to be ethanol precipitated. Resuspend in a volume compatible with the fragmentation step.

Fragmentation [278] 15 ug of labeled RNA is usually fragmented. Try to minimize the fragmentation reaction volume; a 10 ul volume is recommended but 20 ul is all right. Do not go higher than 20 ul because the magnesium in the fragmentation buffer contributes to precipitation in the hybridization buffer.

[279] Fragment RNA by incubation at 94 C for 35 minutes in 1 x Fragmentation buffer.

5 x Fragmentation buffer: 200 mM Tris-acetate, pH 8. 1 500 mM KOAc 150 mM MgOAc [280] The labeled RNA transcript can be analyzed before and after fragmentation. Samples can be heated to 65C for 15 minutes and electrophoresed on 1% agarose/TBE gels to get an approximate idea of the transcript size range Hybridization [281] 200 ul (lOug cRNA) of a hybridization mix is put on the chip. If multiple hybridizations are to be done (such as cycling through a 5 chip set), then it is recommended that an initial hybridization mix of 300 ul or more be made.

Hybrization Mix: fragment labeled RNA (50ng/ul final conc.) 50 pM 948-b control oligo 1.5 pM BioB 5 pM BioC 25 pM BioD 100 pM CRE 0. lmg/ml herring sperm DNA 0. 5mg/ml acetylated BSA to 300 ul with lxMES hyb. buffer [282] The instruction manuals for the products used herein are incorporated herein in their entirety.

Labeling Protocol Provided Herein Hybridization reaction: Start with non-biotinylated IVT (purified by RNeasy columns) (see example 1 for steps from tissue to IVT) IVT antisense RNA; 4 ug : ul Random Hexamers (1 µg/µl) : 4 pi H20 : ul 14 RI -Incubate 70°C, 10 min. Put on ice.

Reverse transcription: 5X First Strand (BRL) buffer: 6 ul 0.1 MDTT : 3 50X dNTP mix: 0.6 H20: 2. 4 µl Cy3 or Cy5 dUTP (lmM) : 3 SS RT II (BRL): 1 µl 16 ul

-Add to hybridization reaction.

-Incubate 30 min., 42°C.

-Add 1 ul SSII and let go for another hour.

Put on ice.

-50X dNTP mix (25mM of cold dATP, dCTP, and dGTP, 1 OmM of dTTP : 25 ul each of 100mM dATP, dCTP, and dGTP; 10 ul of 100mM dTTP to 15 ul H20. dNTPs from Pharmacia) RNA degradation: 86 gl H20 -Add 1.5 µl 1M NaOH/ 2mM EDTA, incubate at 65°C, 10 min.

10 µl 10N NaOH 4 µl 50mM EDTA U-Con 30 500 u. l TE/sample spin at 7000g for 10 min, save flow through for purification Qiagen purification : -suspend u-con recovered material in 500µl buffer PB -proceed w/normal Qiagen protocol DNAse digest: -Add 1, ul of 1/100 dil of DNAse/30µl Rx and incubate at 37°C for 15 min.

-5 min 95°C to denature enzyme Sample preparation : -Add: Cot-1 DNA : 10 µl 50X dNTPs: 1 µl Na pyro phosphate: 7.5 ul 10mg/ml Herring sperm DNA lul of 1/10 dilution 21.8 final vol.

-Dry down in speed vac.

-Resuspend in 15 µ1 H20.

-Add 0.38 ul 10% SDS.

-Heat 95°C, 2 min.

-Slow cool at room temp. for 20 min.

Put on slide and hybridize overnight at 64°C.

Washing after the hybridization : 3X SSC/0.03% SDS: 2 min. 37.5 ml 20X SSC+0.75ml 10% SDS in 250ml H20 1X SSC: 5 min. 12.5 ml 20X SSC in 250ml H20 0.2X SSC: 5 min. 2.5 ml 20X SSC in 250ml H20 Dry slides in centrifuge, 1000 RPM, lmin.

[283] Scan using appropriate Photomultiplier tube (PMT) and fluorescent excitation and emission channels.

[284] The results are shown in Table 1 and Table 2. The lists of genes come from colorectal tumors from a variety of stages of the disease. The genes that are up regulated in the tumors (overall) were also found to be expressed at a limited amount or not at all in the body map. The body map consists of at least 28 tissue types, including Adrenal Gland, Bladder, Bone Marrow, Brain, Breast, Cervix, Colon, Diaphragm, Heart, Kidney, Liver, Lung, Lymph Node, Muscle, Pancreas, Prostate, Rectum, Salivary Gland, Skin, Small Intestine, Spinal Cord, Spleen, Stomach, Testis, Thymus, Thyroid Trachea and Uterus. As indicated, some of the Accession numbers include expression sequence tags (ESTs). Thus, in one embodiment herein, genes within an expression profile, also termed expression profile genes, include ESTs and are not necessarily full length.

[285] Table 1 shows Accession numbers for 1747 genes upregulated in colon tumor tissue. The table provides the exemplar accession numbers, Unigene ID numbers, unique Eos codes, descriptions of the genes encoded, and relative amount of expression as compared with expression in other normal body tissue.

TABLE 1. GENES INVOLVED IN COLORECTAL CANCER PKey Primekey (unique probeset identifier) Ex. Accn. Exemplar accession number Probeset Eos Code number Unigene# Unigene number Pkey Probeset Ex Accn UniG ID UniGene Title Ratio TumMet/Body 332264 EOS32195 N72849 Hs. 115263 epiregulin 17. 6 332716 EOS32647 L00058 Hs.79070 v-myc avian myelocytomatosis viral oncogene homolog 15. 0 312845 EOS12776 AI911215 Hs.186555 ESTs 14. 3 310257 EOS10188 AW389247 Hs,148826 ESTs 11. 6 322567 EOS22498 AF155108 EST cluster (not in UniGene) 11.5 331060 EOS30991 N75081 Hs. 21648 ESTs 10. 3 322303 EOS22234 W07459 EST cluster (not in UniGene) 9.6 301891 EOS01822 AF131855 Hs.106127 Homo sapiens clone 25056 mRNA sequence 9. 5 318524 EOS18455 AW291511 Hs. 253687 ESTs 8. 9 314001 EOS13932 AW168495 Hs. 8750 ESTs 7. 8 331183 EOS31114 T40769 Hs. 8469 EST 7. 3 315429 EOS15360 AW009951 Hs.206892 ESTs 7. 3 303344 EOS03275 AA255977 Hs. 250646 ESTs ; Highly similar to ubiquity-conjugating enzyme [M. musculus] 6.7 313625 EOS13556 AW468402 Hs.254020 ESTs 6. 7 307084 EOS07015 A1160527 EST singleton (not in UniGene) with exon hit 6. 1 314943 EOS14874 A1476797 Hs. 184572 ceìl division cycle 2; G1 to S and G2 to M 6. 1 303753 EOS03684 AW503733 Hs. 170315 ESTs 5. 7 315593 EOS15524 AW198103 Hs. 158154 ESTs 5. 3 313604 EOS13535 AI745325 Hs.182286 ESTs; Moderately similar to !!! ! ALU SUBFAMILY SB2 WARNING ENTRY !! ! ! [H. sapiens) 5.1 312319 EOS12250 AA216698 Hs. 180780 Homo sapiens agrin precursor mRNA ; partial cds 5. 1 312614 EOS12545 AI766732 Hs.201194 ESTs 4. 8 323176 EOS23107 AW071648 Hs. 123199 ESTs 4. 8 317916 EOS17847 A1565071 Hs. 159983 ESTs 4. 7 301846 EOS01777 R20002 Hs.6823 ESTs; Wealky similar to intrinsic factor-B12 receptor precursor [H. sapiens] 4.6 311157 EOS11088 AI990122 Hs.196988 ESTs 4. 6 332640 EOS32571 AA417152 Hs.5101 protein regulator of cytokinesis 1 4.6 311728 EOS11659 AW083000 Hs. 184776 ribosomal protein L23a 4. 5 313774 EOS13705 AW136836 Hs. 144583 ESTs 4. 5 312339 EOS12270 AA524394 ESTcluster (notinUniGene) 4.4 315369 EOS15300 AA764918 Hs. 256531 ESTs 4. 3 303756 EOS03687 AI738488 Hs.115838 ESTs 4. 3 301050 EOS00981 AW136973 Hs. 144475 ESTs ; Weakly similar to mitogen inducible gene mig-2 [H. sapiens] 4. 3 300319 EOS00250 AW157646 Hs. 153506 ESTs ; Weakly simllar to microtubule-aclin crosslinking factor [M.musculus] 4.3 300664 EOS00595 A1444628 Hs. 256809 ESTs 4. 3 302655 EOS02586 AJ227892 EST cluster (not in UniGene) with exon hit 4. 1 315175 EOS15106 A1025842 Hs. 152530 ESTs 4. 1 330786 EOS30717 D60374 Hs. 258712 EST 4. 1 310875 EOS10806 T47764 Hs.132917 ESTs 4. 1 313425 EOS13356 AA745689 Hs. 186838 ESTs ; Weakly similar to similar to zinc finger 5 protein from Gallus gallus ; U51640 [H. sapiens) 4.0 301804 EOS0173 AA581004 EST cluster (not in UniGene) with exon hit 4. 0 332203 EOS32134 H49388 Hs. 102082 EST 3. 9 322968 EOS22899 AI905228 EST cluster (not in UniGene) 3.8 321524 EOS21455 N79126 EST cluster (not in UniGene) 3.8 302476 EOS02407 AF182294 EST cluster (not in UniGene) with exon hit 3. 8 303295 EOS03226 AA205625 Hs. 208067 ESTs 3. 8 310016 EOS09947 AW449612 Hs. 152475 ESTs 3 7 324871 EOS24802 AW297755 Hs. 148832 ESTs 3. 7 322887 EOS22818 AI986306 Hs.233460 ESTs ; Weakly similar to KIAA0969 protein [H. sapiens] 3.7 313171 EOS13102 N67879 Hs. 157695 ESTs 37 321638 EOS21569 AI356352 Hs.108932 ESTs 3. 7 320445 EOS20376 R33916 EST cluster (not in UniGene) 3.6 302149 EOS02080 AI383794 Hs.152337 protein arginine N-methyltransferase 3(hnRNP methyltransferase S. cerevisiae)-like 3 3.6 316905 EOS16836 AW138241 Hs. 210846 ESTs 3. 6 313166 EOS13097 A1801098 Hs. 151500 ESTs 3. 6 323338 EOS23269 R74219 Hs. 23348 S-phase kinase-associated protein 2 (p45) 3.5 311434 EOS11365 AW016607 Hs.201582 ESTs 3.5 312742 EOS12673 AI650363 Hs.116462 ESTs 3. 4 323587 EOS23518 AI905527 Hs.141901 ESTs; Moderately similar to IIII ALU SUBFAMILY SP WARNING ENTRY ! ! ! ! [H. sapiens] 3.4 317390 EOS17321 AW136551 Hs. 181245 ESTs 34<BR> <BR> <BR> 315282 EOS15213 A1222165 Hs. 144923 ESTs 34 318565 EOS18496 AI440137 Hs.164989 ESTs 3.4 307586 EOS07517 AI285499 EST singleton (not in UniGene) with exon hit 3. 4 321052 EOS20983 AW372884 Hs. 240770 nucìearcapbindingproteinsubunit2 ; 20kD 3. 3 324338 EOS24269 AL138357 Hs.247514 ESTs 3. 3 <BR> <BR> 307517 EOS07448 A1275055 Hs. 164989 ESTs 33 314852 EOS14783 A1903735 Hs. 137527 ESTs ; Weakly similar to X-linked retinopathy protein [H.sapiens] 3.3 324657 EOS24588 AW451142 Hs. 255628 ESTs 3. 2 314912 EOS14843 A1431345 Hs. 161784 ESTs 3. 2 324790 EOS24721 A1334367 Hs. 159337 ESTs 3. 2 315498 EOS15429 AA628539 Hs.116252 ESTs ; Moderately similar to! ! !! ALU SUBFAMILY J WARNING ENTRY ! ! ! ! [H. sapiens] 3.2 312857 EOS12788 AA772279 Hs. 126914 ESTs 3. 2

300762 EOS00693 A1497778 Hs. 168053 ESTs 3.2 325587 EOS25518 c12_hs gi]6682462[ref] gn 1+126724 126967 ex 77 CDSI 2.442443099 CH. 12_hs girl6682462 3.2 320654 EOS20585 AW263086 Hs. 118112 ESTs 3.2 316715 EOS16646 A1440266 Hs. 170673 ESTs 3.1 333279 EOS33210 CH22_522FG_126_1_LINK_EM : AC005500. GENSCAN. 8-1 CH22_FGENES,126_1 3.1 309689 EOS09620 AW236171 Hs. 181357 laminin receptor 1 (67kD ; ribosomal protein SA) 3.1 323846 EOS23777 AA337621 Hs. 137635 ESTs 3.1 324678 EOS24609 Api990739 Hs. 236511 ESTs; Moderately similar to RNA splicing-related protein [R, norvegicus] 3.1 308362 EOS08293 A1613519 EST singleton (not in UniGene) with exon hit 3.1 308615 EOS08546 AI738593 EST singieton (not in UniGene) with exon hit 3.0 315397 EOS15328 AA218940 Hs. 137516 ESTs 3. 0 302236 EOS02167 A1128606 Hs. 167558 zinc finger protein 161 3.0 321693 EOS21624 AA700017 Hs. 173737 ras-related C3 botulinum toxin substrate 1 (rho family; small GTP binding protein Pad) 3.0 330814 EOS30745 AA015730 Hs. 247277 ESTs; Weakly similar to transformation-related protein [H. sapiens] 3.0 302977 EOS02908 AW263124 EST cluster (not in UniGene) with exon hit 3.0 327516 EOS27447 c_2_hs gi]6117815[ref] gn 6+199078 199216 ex 44 CDSI 9.151391551 CH. 02-hs 6117815 2.9 333278 EOS33209 CH22_521FG_125_2_LINK_EN : AC005500. GENSCAN. 7-2 CH22_FGENES.125_2 2.9 302088 EOS02019 U77629 Hs. 135639 achaete-scute complex (Drosophila) homolog-like 2 2.9 322718 EOS22649 AF150270 Hs. 233322 ESTs ; WeaklysimilartocDNAESTEMBL : T01156 comes from this gene [C. eiegans] 2.9 329154 EOS29085 c_x_hs gi]5868686[ref] gn 2- 200851 201356 ex 13 CDSI 30.28 506 1812 CH. Xhsgi 9il5868686 2. 9 315978 EOS15909 AA830893 Hs. 119769 ESTs 2.9 302677 EOS02608 H63227 Hs. 132880 ESTs ; Highìysimilartoubiquitn-conjugatngenzyme [M. musculus] 2.9 315007 EOS14938 Api806583 Hs. 125291 ESTs 2. 9 303780 EOS03711 A1424014 Hs. 243450 ESTs ; Moderately similar to KIAA0456 protein [H. sapiens] 2.9 331362 EOS31293 AA417956 Hs. 40782 ESTs 2.9 335815 EOS35746 CH22_3187FG_618_3_LINK_EM : AC005500. GENSCAN. 510-3 CH22_FGENES.618_3 2.8 332070 EOS32001 AA598545 Hs. 228138 EST 2.8 315720 EOS15651 AW291875 Hs. 163900 ESTs 2.8 311913 EOS11844 A1358522 Hs. 221417 ESTs 2. 8 331014 EOS30945 H98597 Hs. 30340 ESTs 2.8 322035 EOS21966 AL137517 EST cluster (not in UniGene) 2.8 338057 EOS37988 CH22 6558FGUNKEM : AC005500. GENSCAN. 160-1 CH22_EM : AC005500. GENSCAN. 160-1 2.8 335829 EOS35760 CH22_3202FG_620_3_LINK_EM: AC005500. GENSCAN. 512-3 CH22_FGENES.620_3 2.8 312136 EOS12067 AW451469 Hs. 209990 ESTs 2.8 303132 EOS03063 AI929819 Hs. 193330 ESTs 2. 8 317548 EOS17479 A1654187 Hs. 195704 ESTs 2. 8 325585 EOS25516 c12_hs gi[6682462]ref# gn 1+73476 73574 ex 57 CDSi 8.5299309 7 CH. 12_hs girl6682462 2.7 334631 EOS34562 CH22_1939FG_416_7_LINK_EM: AC005500. GENSCAN. 277-7 CH22_FGENES.416_7 2.7 329156 EOS29087 c_x_hs gi[5868686[ref] gn 2 - 202013 202341 ex 3 3 CDSf 10.23 329 1814 CH. X_hs gi]5868686 2.7 318615 EOS18546 A1133617 Hs. 191088 ESTs 2. 7 300734 EOS00665 AW205197 Hs. 240951 ESTs 2. 7 324430 EOS24361 AA464018 EST cluster (not in UniGene) 2.7 322296 EOS22227 W76326 Hs. 251937 ESTs 2. 7 303842 EOS03773 A1337304 Hs. 126268 ESTs ; Weakly similar to similar to PDZ domain [C. elegans] 2.7 320909 EOS20840 D62269 EST cluster (not in UniGene) 2.7 325195 EOS25126 T20258 Hs. 171443 ESTs ; Weakly similar to actin binding protein MAYVEN [H. sapiens] 2.7 324959 EOS24890 AW367745 Hs. 143137 ESTs 2. 7 309997 EOS09928 A1291621 Hs. 145199 ESTs 2. 7 329367 EOS29298 c_x_hs gi[5868842]ref# gn 1-87201 87587 ex 14 CDSI 8.13 387 3908 CH. khis 9il5868842 2.7 316697 EOS16628 AW293174 Hs. 252627 ESTs 2. 7 313600 EOS13531 AA429564 Hs. 185802 ESTs 2. 7 301471 EOS01402 AA995014 Hs. 129544 ESTs ; Weakly similar to ORF YLL027w [S. cerevisiae] 2.6 300810 EOS00741 A1076890 Hs. 186949 ESTs 2.6 319976 EOS19907 N48809 Hs. 250824 ESTs 2.6 313434 EOS13365 W92070 Hs. 231902 ESTs 2.6 333849 EOS33780 CH22_1118FG_290_8_LINK_EM : AC005500. GENSCAN. 146-7 CH22_FGENES.290_8 2.6 330744 EOS30675 AA406142 Hs. 12393 dTDP-D-g ! ucose4 ; 6-dehydratase 2.6 309398 EOS09329 AW081820 EST singleton (not in UniGene) with exon hit 2.6 338727 EOS38658 CH22_7523FG_LINK_EM : AC005500. GENSCAN. 500-2 CH22_EM : AC005500. GENSCAN. 500-2 2.6 324620 EOS24551 AA448021 EST cluster (not in UniGene) 2.6 335755 EOS35686 CH22_3122FG_604_4_LINK_EM : AC005500. GENSCAN. 493-9 CH22_FGENES.604_4 2.6 315858 EOS15789 AA737345 EST cluster (not in UniGene) 2.6 307288 EOS07219 AI205169 EST singleton (not in UniGene) with exon hit 2.5 330542 EOS30473 U23942 Hs. 226213 cytochrome P450 ; 51 #lanosterol 14-alpha-demethylase) 2.5 335896 EOS35827 CH22_3273FG_635_4_LINK_EM : AC005500. GENSCAN. 525-6 CH22_FGENES.635_4 2.5 316578 EOS16509 AA775623 Hs. 211683 ESTs 2.5 329193 EOS29124 c_x_hs gi[5868716[ref] gn 3 +168095 168181 ex 9 9 CDSI-1. 1187 2064 CH. X_hs gi[5868716 2.5 315193 EOS15124 Api241331 Hs. 131765 ESTs 2.5 319478 EOS19409 R06841 EST cluster (not in UniGene) 2.5

334727 EOS34658 CH22_2038FG_424_1_LINK_EM : AC005500. GENSCAN. 285-3 CH22_FGENES.424_1 5 328113 EOS28044 c_6_hs gi[5868024]ref#gn 2-80378 80491 ex 23 CDSi 3.89 114 3247 CH. 06_hs gi#5868024 315214 EOS15145 A1915927 Hs. 34771 ESTs 2. 5 324718 EOS24649 A1557019 Hs. 116467 ESTs 2. 5 313326 EOS13257 A1088120 Hs. 122329 ESTs 2. 5 319480 EOS19411 R06933 Hs. 184221 ESTs 2. 5 317902 EOS17833 A1828602 Hs. 211265 ESTs 2. 5 323341 EOS23272 AL134875 Hs. 192386 ESTs 2. 5 336003 EOS35934 CH22_3385FG_664_4_LINK_DJ32I10.GENSCAN.5-4 CH22_FGENES.664_4 2. 5 322992 EOS22923 AA142891 Hs. 193165 ESTs 2. 5 314911 EOS14842 AW292329 Hs. 163481 ESTs 2. 5 313603 EOS13534 AW468119 ESTcluster (notinUniGene) 2.5 306469 EOS06400 AA983792 EST singleton (not in UniGene) with exon hit 2. 5 324716 EOS24646 AI739168 EST cluster (not in UniGene) 2.5 302455 EOS02386 AA356923 Hs. 240770 nuclear cap binding protein subunit 2 ; 20kD 2. 4 321023 EOS20954 H25135 Hs. 125608 ESTs 2. 4 302099 EOS02030 AL021397 Hs. 137576 ribosomal protein L34 pseudogene 1 2. 4 314092 EOS14023 A1984040 Hs. 226946 ESTs 2. 4 318587 EOS18518 AA779704 Hs. 168830 ESTs 2. 4 303702 EOS03633 AW500748 Hs. 224961 ESTs ; Weakly similar to 73 kDA subunit of cleavage and polyadenylation specificity factor [H. sapiens] 2.4 301822 EOS01753 X17033 Hs. 1142 integrin ; alpha 2 (CD49B; alpha 2 subunit of VLA-2 receptor) 2.4 322694 EOS22625 AI110872 EST cluster (not in UniGene) 2.4 323333 EOS23264 AA228883 EST cluster (not in UniGene) 2.4 301954 EOS01885 AJ009936 Hs. 118138 nuclear receptor subfamily 1 ; group) ; member2 ~ 2.4 331363 EOS31294 AA421562 Hs. 91011 anterior gradient 2 (Xenepus laevis) homolog 2. 4 303811 EOS03742 AW182340 Hs. 246155 ESTs ; Weakly similar to DNA TOPOISOMERASE I [H. sapiens] 2.4 308243 EOS08174 AI560037 EST singleton (notin UnlGene) with exon hit 2. 4 336021 EOS35952 CH22_3404FG_669_10_LINK_DJ32I10. GENSCAN. 9-15 CH22_FGENES.669_10 2. 4 334789 EOS34720 CH22_2101FG_432_14_LINK_EM : AC005500. GENSCAN. 293-17 CH22_FGENES.432_14 2. 4 320807 EOS20738 AA086110 Hs. 188536 Homo sapiens clone 24838 mRNA sequence 2. 4 328903 EOS28834 c_8_hs gi#5868514#ref# gn 1 + 23625 24468 ex 3 5 CDSi 91.18 844 219 CH. 08_hs gi#5868514 2. 4 338759 EOS38690 CH22_7581FG_LINK_EM : AC005500. GENSCAN. 517-6 CH22_EM : AC005500. GENSCAN. 517-6 2. 3 333769 EOS33700 CH22_1036FG_271_8_LINK_EM : AC005500. GENSCAN. 127-8 CH22_FGENES.271_8 2. 3 303597 EOS03528 A1792141 Hs. 143560 ESTs ; Wealky similar to brain mitochondrial carrier protein-1 [H.sapiens] 2.3 305898 EOS05829 AA872838 Hs. 242463 keratin 8 2. 3 304439 EOS04370 AA398882 EST singleton (not in UniGene) with exon hit 2. 3 301604 EOS01535 AA373124 Hs. 105837 ESTs ; Weakly similar to C17G10.1 [C. elegans] 2.3 315071 EOS15002 AA552690 Hs. 152423 ESTs 2. 3 330565 EOS30496 U51095 Hs. 1545 caudal type homeo box transcription factor 1 2. 3 331589 EOS31520 N71027 Hs. 41856 ESTs 2. 3 303216 EOS03147 AA581439 Hs. 152328 ESTs 2. 3 324988 EOS24919 T06997 EST cluster (not in UniGene) 2.3 312996 EOS12927 AA249018 EST cluster (not in UniGene) 2.3 332314 EOS32245 T25862 Hs. 101774 ESTs 2. 3 313325 EOS13256 A1420611 Hs. 127832 ESTs 2. 3 322991 EOS22922 C18965 Hs. 159473 ESTs 2. 3 335496 EOS35427 CH22_2848FG_571_4_LINK_EM: AC005500. GENSCAN. 460-25 CH22_FGENES.571_4 2. 3 315135 EOS15066 AA627561 Hs. 192446 ESTs 2. 3 319488 EOS19419 AW250340 EST cluster (not in UniGene) 2.3 323571 EOS23502 AA984133 Hs. 153260 c-Cbl-interacling protein 2. 3 322826 EOS22757 A1807883 Hs. 156932 ESTs 2. 3 322221 EOS22152 AI890619 Hs. 179662 nucleosome assembly protein 1-like 1 2. 3 312242 EOS12173 A1380207 Hs. 125276 ESTs 2. 3 315238 EOS15169 AA593867 Hs. 170890 ESTs 2. 3 315168 EOS15099 AA622130 Hs. 152524 ESTs 2. 3 300504 EOS00435 AW204624 Hs. 192927 ESTs ; Weakly similar to Lim kinase [H. sapiens] 2.3 323243 EOS23174 W44372 EST clusler (not in UnlGene) 2.3 331628 EOS31559 R80965 Hs. 204079 ESTs 2. 3 320746 EOS20677 AA128302 EST cluster (not in UniGene) 2.3 324598 EOS24529 AA502659 Hs. 163986 ESTs 2. 3 308667 EOS08598 Al758754 EST singleton (not in UniGene) with exon hit 2. 2 302944 EOS02875 AA34078 Hs. 256204 ESTs ; Weakly similar to cyclic nucleotide-gated channel beta subunit [R. norvegicus] 2.2 316291 EOS16222 AW375974 Hs. 156704 ESTs 2. 2 315296 EOS15227 AA876905 Hs. 125286 ESTs 2. 2 33415D EOS34081 CH22_1429FG_339_1_LINK_EM:AC005500.GENSCAN.189-1 # CH22_FGENES,339_1 2. 2 331380 EOS31311 AA453266 Hs. 246131 ESTs 2. 2 321795 EOS21726 A1796896 Hs. 222446 ESTs 2. 2 331493 EOS31424 N34357 Hs. 44571 ESTs 2. 2 312890 EOS12821 A1813654 Hs. 127478 ESTs 2. 2 315583 EOS15514 AW003622 Hs. 126555 ESTs 2. 2 314306 EOS14237 A1697901 Hs. 192425 ESTs 2. 2 314138 EOS14069 AA740616 EST cluster (not in UniGene) 2.2 302656 EOS02587 AW293005 Hs. 220905 ESTs 2. 2 313564 EOS13495 AA810141 Hs. 192182 ESTs Z2 332792 EOS32723 CH22_8FG_3_2_LINK_C4G1. GENSCAN. 3-2 CH22_FGENES.3_2 2. 2

332020 EOS31951 AA488895 Hs. 105219 ESTs 2. 2 315143 EOS15074 AA878324 Hs. 192734 ESTs 2. 2 313385 EOS13316 A1032087 Hs. 176711 ESTs 2. 2 323835 EOS23766 AL042005 EST cluster (not in UniGene) 2. 2 314014 EOS13945 AW291847 Hs. 121715 ESTs; Weakly slmilar to HP protein [H.sapiens] 2.2 336016 EOS35947 CH22_3399FG_669_5_LINK_DJ32I10. GENSCAN. 9-10 CH22_FGENES.669_5 2. 2 323218 EOS23149 AF131846 Hs. 13396 Homo sapiens clone 25028 mRNA sequence 2. 2 338059 EOS37990 CH22_6561FG_LINK_EM:AC005500.GENSCAN.160-4 CH22_EM : AC005500. GENSCAN. 160-4 2. 2 302613 EOS02544 AA371059 Hs. 251636 ubiquiUn specific protease 3 2. 2 304852 EOS04783 AA588595 EST singleton (not in UniGene) with exon hit 2. 2 308457 EOS08388 A1669859 EST singleton (not in UniGene) with exon hit 2. 2 311736 EOS11667 AA765B97 EST cluster (not in UniGene) 2.2 334183 EOS34114 CH22_1464FG_350_13_LINK_EM: AC005500. GENSCAN. 209-16 CH22_FGENES.350_13 2. 2 315021 EOS14952 AA533447 EST cluster (not in UniGene) 2. 2 303013 EOS02944 F07898 Hs. 214190 interieukin enhancer binding factor 12. 2 315006 EOS14937 A1538613 Hs. 135657 ESTs 2. 2 337534 EOS37465 CH22_5803FG_828_3_ CH22_FGENES.828-3 2. 2 303276 EOS03207 AA431599 Hs. 132799 ESTs 2. 1 318617 EOS18548 AW247252 Hs. 75514 nucleoside phosphorylase 2. 1 330760 EOS30691 AA448663 Hs. 30469 ESTs 2. 1 319545 EOS19476 R83716 Hs. 14355 ESTs 2. 1 312252 EOS12183 A1128388 Hs. 143655 ESTs 2. 1 322882 EOS22813 AW248508 Hs. 2491 DiGeorge syndrome critical region gene 2 2. 1 312684 EOS12615 AW294020 Hs. 117721 ESTs 2. 1 315782 EOS15713 AW515455 Hs. 115558 ESTs ; Weakly similar to !! I ! ALU SUBFAMILY J WARNING ENTRY ! ! !! [H. sapiens] 2.1 320076 EOS20007 A1653733 Hs. 204079 ESTs 2. 1 300566 EOS00497 H86709 Hs. 21371 son of seveniess (Drosophila) homolog 1 2. 1 300908EOS00839AA618335 Hs. 146137 ESTs; Weakly similar to putative [C.elegans] 2.1 314778 EOS14709 AW079559 Hs. 152258 ESTs 2. 1 319233 EOS19164 R21054 Hs. 211522 ESTs 2. 1 335488 EOS35419 CH22_2840FG_570_20_LINK_EM: AC005500. GENSCAN. 460-15 CH22_FGENES.570_20 2.1 334616 EOS34547 CH22_1923FG_411_15_LINK_EM : AC005500. GENSCAN. 274-22 CH22_FGENES. 411_15 2. 1 306792 EOS06723 A1042426 EST singleton (not in UniGene) with exon hit 2. 1 301661 EOS01592 A1815558 EST cluster (not in UniGene) with exon hit 2. 1 311332 EOS11263 AW292247 Hs. 255052 ESTs 2. 1 314785 EOS14716 A1538226 Hs. 135184 ESTs 2. 1 301460 EOS01391 AW196758 Hs. 165998 DKFZP564M2423 protein 2. 1 332015 EOS31946 AA487910 Hs. 208800 ESTs ; Weakly similar to ! ! ! !ALU CLASS B WARNING ENTRY !!!! [H. sapiens] 2.1 321529 EOS21460 A1269506 Hs. 146066 ESTs 2.1 323740 EOS23671 AA324643 Hs. 246106 ESTs 2. 1 336019 EOS35950 CH22_3402FG_669_8_LINK_DJ32I10. GENSCAN. 9-13 CH22_FGENES.669_8 2. 1 314954 EOS14885 AA521381 Hs. 187726 ESTs 2. 1 303037 EOS02968 AF118395 EST cluster (not in UniGene) with exon hit 2. 1 302056 EOS01987 AI457532 Hs. 126082 ESTs ; Moderately similar to ROSA26AS [M. musculus] 2.1 315178 EOS15109 AW362945 Hs. 162459 ESTs 2. 1 332246 EOS32177 N57927 Hs. 120777 ESTs ; Weakly similar to RNA POLYMERASE II ELONGATION FACTOR ELL2 [H. sapiens] 2.0 334288 EOS34219 CH22_1577FG_369_18_LINK_EM: AC005500. GENSCAN. 229-18 CH22-FGENES. 369-18 2. 0 324690 EOS24621 N88286 Hs. 132808 ESTs ; Weakly similar to Similar to S. pombe-rad4+kut5+product [H. sapiens] 2.0 305257 EOS05188 AA679005 EST singleton (not in UniGene) with exon hit 2. 0 311315 EOS11246 AW450536 Hs. 209260 ESTs 2. 0 311988 EOS11919 AW016096 Hs. 13801 ESTs 2. 0 302638 EOS02569 AA463798 Hs. 102696 ESTs ; Weakly similar to C11 D2. 4 [C. elegans] 2.0 320531 EOS20462 W03691 Hs. 24884 ESTs ; Moderately similar to RNA polymerase I associated factor [M. musculus] 2.0 323604 EOS23535 A1751438 Hs. 182827 ESTs ; Weakly similar to !!!! ALU SUBFAMILY SQ WARNING ENTRY ! ! !! [H. sapiens] 2.0 308852 EOS08783 A1829848 Hs. 182937 pepUdylprolyl isomerase A (cyclophilin A) 2.0 320521 EOS20452 N31464 Hs. 24743 ESTs 2. 0 331306EOS31237AA252079 Hs. 63931 dachshund (Drosophila) homolog 2. 0 314941 EOS14872 AA515902 Hs. 130650 ESTs 2. 0 336684 EOS36615 CH22_4167FG_46_1_ CH22_FGENES.46-1 2. 0 301137 EOS01068 AF049569 Hs. 137096 ESTs 2. 0 338454 EOS38385 CH22_7128FG_LINK_EM: AC005500. GENSCAN. 360-4 CH22_EM : AC005500. GENSCAN. 360-4 2.0 309700 EOS09631 AW241170 Hs. 179661 Homo sapiens clone 24703 beta-tubulin mRNA; complete cds 2. 0 330262 EOS30193 c_5_p2 gi#6671884#gb#A gn 1+67913 68053 ex 3 3 CDSI 5. 41 141 597 CH. 05_p2 gi#6671884 2. 0 324163 EOS24094 AL046827 Hs. 134651 ESTs 2. 0 316493 EOS16424 AA766142 Hs. 131810 ESTs ; Weakly similar to !!!! ALU SUBFAMILY J WARNING ENTRY ! ! ! ! [H. sapiens] 2. 0 311873 EOS11804 AA730045 Hs. 187866 ESTs 2. 0 326757 EOS26688 c20_hs gi#6249610#ref# gn 3 + 74531 74597 ex 13 CDSf 9.52 671416 CH. 20_hs gi#6249610 2. 0 319167 EOS19098 F05984 Hs. 250138 protein phosphatase 2C ; magnesium-dependent; catalytc subunit 2. 0 316011 EOS15942 AW516953 Hs. 201372 ESTs 2. 0 313635 EOS13566 AA507227 Hs. 6390 ESTs 2. 0 310027 EOS09958 AW449009 Hs. 126647 ESTs 2. 0 336662 EOS36593 CH22_4138FG_41_1_ CH22_FGENES.41-1 2. 0 334648 EOS34579 CH22_1956FG_417_15_LINK_EM : AC005500, GENSCAN. 278-15 CH22_FGENES. 417_15 2. 0 308676 EOS08607 A1761036 ESTsingleton (notinUniGene) withexonhit 2. 0 312047 EOS11978 AA588275 Hs. 14258 ESTs 2. 0

324826 EOS24757 M704806 Hs. 143842 ESTs 2. 0 322889 EOS22820 M081924 Hs. 211417 ESTs 2. 0 316345 EOS16276 AW139408 Hs. 152940 ESTs 2. 0 313922 EOS13853 A1702038 Hs. 100057 ESTs 2. 0 319423 EOS19354 T83024 Hs. 15119 ESTs 2.0 320244 EOS20175 AA296922 Hs. 129778 gastrointestinal peptide 2.0 308957 EOS08888 Api869642 EST singleton (not in UniGene) with exon hit 2.0 334223 EOS34154 CH22_1507FG_360_4_LINK_EM:AC005500.GENSCAN.218-4 CH22_FGENES.360_4 1. 9 302980 EOS02911 W93435 EST cluster (not in UniGene) with exon hit 1.9 312153 EOS12084 AA759250 Hs. 153028 cytochrome b-561 1.9 326460 EOS26391 c19_hs gil5867400lreg gn 3-142633142935 ex 12 CDSI 19.03 3031731 CH. 19_hs gi#5867400 1. 9 319962 EOS19893 H06350 Hs. 135056 ESTs 1.9 307064 EOS06995 A1149335 EST singleton (not in UniGene) with exon hit 1.9 331608 EOS31539 N89861 Hs. 44162 ESTs; Weakly similar to cDNA EST yk342h12.5 comes from this gene [C.elegans] 1.9 328142 EOS28073 c_6_hs gi#5868050#ref# gn 1-9656 9778 ex 2 6 CDSi 11.11 123 3339 CH. 06_hs gi!5868050 1. 9 312527 EOS12458 A1695522 Hs. 191271 ESTs 1. 9 318581 EOS18512 AA769058 ESTcluster (notinUniGene) 1.9 319979 EOS19910 AB018281 Hs. 107479 KIAA0738 gene product 1.9 336107 EOS36038 CH22_3496FG_696_3_LiNK_DA59H1 8. GENSCAN. 4-3 CH22_FGENES. 696_3 1.9 305232 EOS05163 AA670052 Hs. 195188 glyceraldehyde-3-phosphate dehydrogenase 1.9 315043 EOS14974 AA806538 Hs. 130732 ESTs 1.9 323377 EOS23308 AA133260 Hs. 8454 protein kinase; cAMP-dependent; regulatory; type it ; alpha 1. 9 338260 EOS38191 CH22_6863FG_LINK_EM : AC005500. GENSCAN. 279-10 CH22_EM : AC005500. GENSCAN. 279-10 1.9 334891 EOS34822 CH22_2208FG_452_5_LINK_EM : AC005500. GENSCAN. 341-8 CH22_FGENES.452_5 1. 9 316055 EOS15986 AA693880 ESTcluster (notinUniGene) 1.9 312414 EOS12345 Aì915014 Hs. 164235 ESTs ; Weakly similar to !!!! ALU SUBFAMILY J WARNING ENTRY !!!! [H. sapiens] 1.9 300225 EOS00156 A1989963 Hs. 197505 ESTs 1. 9 332607 EOS32538 R41791 Hs. 36566 LIM domain kinase 1 1. 9 312405 EOS12336 AI523875 EST cluster (not in UniGene) 1.9 313605 EOS13536 A1761786 Hs. 204674 ESTs 1. 9 337755 EOS37686 CH22_6105FG_LINK_EM: AC000097. GENSCAN. 109-2 CH22_EM : AC000097. GENSCAN. 109-2 1.9 323216 EOS23147 AA332145 EST cluster (not in UniGene) 1.9 334872 EOS34803 CH22_2186FG_450_2_LINK_EM : AC005500. GENSCAN. 339-2 CH22_FGENES.450_2 1.9 332034 EOS31965 AA489847 Hs. 112019 ESTs ; Moderately similar to ! ! ! ! ALU SUBFAMILY J WARNING ENTRY !!!! [H. sapiens] 1.9 332103 EOS32034 AA609161 Hs. 112657 ESTs ; Weakly similar to ORF YOR243c [S. cerevisiae] 1.9 318196 EOS18127 A1056776 Hs. 133397 ESTs 1.9 329141 EOS29072 c_x_hs gi#6017060#ref# gn 1+343924 343997 ex 2 3 CDSi 8. 53 74 1715 CH. Xhsgi ! 6017060 1.9 321539 EOS21470 N98619 Hs. 62461 ARP2 (actin-rehted protein 2 ; yeast) homolog 1.9 313881 EOS13812 AA535580 Hs. 16331 ESTs 1.9 314046 EOS13977 AW021917 Hs. 181878 ESTs 1.9 336045 EOS35976 CH22_3430FG_679_7_LINK_DJ32I10. GENSCAN. 18-8 CH22_FGENES.679_7 1.9 324799 EOS24730 AW272262 Hs. 250468 ESTs 1.9 312656 EOS12587 AW152449 Hs. 226469 ESTs 1.9 324662 EOS24593 AW504689 EST cluster (not in UniGene) 1.9 323930 EOS23861 AA570698 Hs. 193203 ESTs 1.9 314465 EOS14396 AA602917 Hs. 156974 ESTs 1.9 335897 EOS35828 CH22_3274FG_635_5_LINK_EM : AC005500. GENSCAN. 525-7 CH22_FGENES.635_5 1.9 321746 EOS21677 AI806500 Hs. 102652 ESTs, WeakìysimilartoKIM0437 [H. sapiens] 1.9 335687 EOS35618 CH22_3048FG_596_2_LINK_EM:AC005500. GENSCAN. 488-2 CH22_FGENES.596_2 1.9 330731 EOS30662 AA278816 Hs. 177204 ESTs 1.9 315542 EOS15473 AA079476 Hs. 109857 ESTs ; Highly similar to CGI-89 protein [H. sapiens] 1.9 336379 EOS36310 CH22_3791FG_821_7_LINK_BA232E17. GENSCAN. 4-19 CH22_FGENES.821_7 1.9 305691 EOS05622 AA813590 Hs. 119500 karyopherin alpha 4 (importin alpha 3) 1.9 310639 EOS10570 AW269082 Hs. 175162 ESTs 1.9 327481 EOS27412 c_2_hs gi#5867783#ref# gn 3 +104472 104673 ex 14 CDSf 14.33 2021308 CH. 02_hs gi#5867783 1.9 301910 EOS01841 T84852 Hs. 98370 cytochromeP540famitymemberpredictedfromESTs 1.9 335478 EOS35409 CH22_2830FG_569_1_LINK_EM : AC005500. GENSCAN. 456-1 CH22_FGENES.569_1 1.9 331135 EOS31066 R61398 Hs. 4197 ESTs 1.9 335690 EOS35621 CH22_3051FG_596_5_LINK_EM : AC005500. GENSCAN. 488-5 CH22_FGENES.596_5 1.9 308047 EOS07978 AI459633 EST singleton (not in UniGene) with exon hit 1.9 334500 EOS34431 CH22_1800FG_397_16_LINK_EM : AC005500. GENSCAN. 260-18 CH22_FGENES.397_16 1.9 338250 EOS38181 CH22_6848FG_LINK_EM: AC005500. GENSCAN. 269- 2 CH22_EM : AC005500.GENSCAN. 269-2 1.8 320618 EOS20549 A1220276 Hs. 235228 EST 1.8 335044 EOS34975 CH22_2367FG_480_1_LINK_EM:AC005500.GENSCAN.374-1 CH22_FGENES. 480_1 1.8 313789 EOS13720 A1167810 Hs. 217743 ESTs 1.8 311911 EOS11842 A1087123 Hs. 114434 ESTs ; Weakly similar to ! ! ! ! ALU SUBFAMILY J WARNING ENTRY ! III [H. sapiens] 1.8 320180 EOS20111 M846203 Hs. 193974 ESTs ; Weakly similar to altematively spliced product using exon 13A [H. sapiens] 1.8

311036 EOS10967 A1539227 Hs. 214039 ESTs 1. 8 323903 EOS23834 AA773580 Hs. 193598 ESTs 1.8 318676 EOS18607 T57448 Hs. 15467 ESTs ; Moderately similar to putative phosphoinositide 5-phosphalase typeII [M. musculus] 1.8 303007 EOS02938 AA478876 Hs. 7037 pallid (mouse) homolog ; pallidin 1.8 334806 EOS34737 CH22_2119FG_435_7_LINK_EM:AC005500.GENSCAN.296-6 CH22_FGENES.435_7 1.8 311767 EOS11698 Agio76686 Hs. 190066 ESTs 1.8 331750 EOS31681 AA284372 Hs. 111471 ESTs 1.8 314872 EOS14803 AI144254 Hs. 239726 ESTs 1.8 314071 EOS14002 AA192455 Hs. 188690 ESTs 1.8 328450 EOS28381 c_7_hs gi#5868425#ref# gn 2-209192 209321 ex 2 3 CDSI 10.41 130 1407 CH. 07_hs gi#5868425 1.8 328857 EOS28788 c_7_hs gi#6381927#ref# gn 3-80557 81051 ex 11 CDSo 41.51 495 6090 CH. 07_hs gi#6381927 1.8 313781 EOS13712 AA078836 EST cluster (not in UniGene) 1.8 336953 EOS36884 CH22_4746FG_361_22_ CH22_FGENES. 361-22 1.8 300233 EOS00164 AI380777 Hs. 189402 ESTs 1.8 326862 EOS26793 c20_hs gi#6552465#ref# gn 2+107702 107782 ex 12 13 CDSi 3. 62 81 2149 CH. 20_hs gi#6552465 1.8 312364 EOS12295 R40111 Hs. 187618 ESTs 1.8 321541 EOS21472 A1220292 Hs. 254467 ESTs 1.8 307432 EOS07363 AI244259 Hs. 181165 eukaryotic translation elongation actor 1 alpha 1 1.8 320921 EOS20852 R94038 Hs. 199538 inhibin ; beta C 1.8 333110 EOS33041 CH22_338FG_79_16_LINK_EM : AC000097. GENSCAN. 59-15 CH22_FGENES.79_16 1.8 324914 EOS24845 AA847510 Hs. 161292 ESTs 1.8 312681 EOS12612 AM28149 Hs. 193124 pyruvate dehydrogenase kinase ; isoenzyme 3 1.8 335697 EOS35628 CH22_3058FG_596_12_LINK_EM : AC005500. GENSCAN. 488-13 CH22_FGENES.596_12 1.8 308462 EOS08393 Ah671311 EST singleton (not in UniGene) with exon hit 1.8 312138 EOS12069 T89405 Hs. 218851 ESTs ; Weakly similar to !!!! ALU SUBFAMILY JWARNING ENTRY !!!! [H.sapiens] 1.8 309116 EOS09047 AI927149 Hs. 29797 ribosomal protein L10 1.8 320730 EOS20661 AA534539 Hs. 151072 ESTs 1.8 300844 EOS00775 AL042759 Hs. 191762 ESTs 1.8 337570 EOS37501 CH22_5856FG_LINK_C65E1. GENSCAN. 4-2 CH22_C65E1. GENSCAN. 4-2 1.8 332756 EOS32687 D63479 Hs. 115907 diacylglycerol kinase ; delta (130kD) 1.8 332161 EOS32092 AA621523 Hs. 165464 ESTs 1.8 300942 EOS00873 AW275006 Hs. 195969 ESTs 1.8 300680 EOS00611 AW468066 Hs. 257712 ESTs ; Weakly similar to KIAA0986 protein [H. sapiens] 1.8 328783 EOS28714 c_7_hs gi#5868309#ref# gn 5-73658 73822 ex 2 5 CDSi 0.78165 5371 CH. 07_hs gi#5868309 1.8 307542 EOS07473 Al280859 EST singleton (not in UniGene) with exon hit 1.8 331975 EOS31906 AA464972 Hs. 99624 ESTs 1.8 321532 EOS21463 T77886 Hs. 83428 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) 1.8 318721 EOS18652 Z28504 EST cluster (not in UniGene) 1.8 302124 EOS02055 AB023967 Hs. 145078 regulatorofdifferentiation (in S. pombe) 1 1.8 323541 EOS23472 AI185116 Hs. 104613 ESTs ; WeaklysimilartoSimilarto S. cerevisiaehypotheücaìproteinL3111 [H. sapiens] 1.8 331057 EOS30988 N71399 Hs. 28143 ESTs 1.8 316860 EOS16791 AW139099 Hs. 127489 ESTs 1.8 330601 EOS30532 U90916 Hs. 82845 Human clone 23815 mRNA sequence 1.8 307334 EOS07265 AI214811 Hs. 220615 ESTs ; WeaklysimilartoTFII-ìprotein [H. sapiens] 1.8 323195 EOS23126 A1064982 Hs. 117950 multifunctionalpoXypepüdesimilartoSAICARsynthetaseandAIRcar boxylase 1. 8 303856 EOS03787 AA968589 Hs. 944 glucose phosphate isomerase 1.8 321553 EOS21484 H92449 Hs. 116405 ESTs 332705 EOS32636 T59161 Hs. 76293 thymosin ; beta 10 1.8 333139 EOS33070 CH22_368FG_83_16_LINK_EM : AC000097. GENSCAN. 67-19 CH22_FGENES.83_16 1.8 338997 EOS38928 CH22 _7881FG_LINK_DA59H18.GENSCAN.8-22 CH22_DA59H18. GENSCAN. 8-22 1.8 301509 EOS01440 A1025435 Hs. 117532 ESTs 1.8 314522 EOS14453 AI732331 Hs. 187750 ESTs ; Moderately similar to ! ! ! ! ALU CLASS C WARNING ENTRY ! ! !! [H. sapiens] 1.8 303072 EOS03003 AF157833 EST cluster (not in UniGene) with exon hit 1.8 305271 EOS05202 AA679895 EST singleton (not in UniGene) with exon hit 1.8 335287 EOS35218 CH22_2629FG_ I_LINK_EM. *AC005500, GENSCAN. 420-4 CH22_FGENES.526_11 1.8 321286 EOS21217 Aì380940 ESTcluster (notinilniGene) 1.8 318740 EOS18671 NM_002543 EST cluster (not in UniGene) 1.8 323465 EOS23396 AA287406 EST cluster (not in UniGene) 1.8 300611 EOS00542 N75450 EST cluster (not in UniGene) with exon hit 1.8 306235 EOS06166 AA932299 EST singleton (not in UniGene) with exon hit 1.8 336721 EOS36652 CH22_4244FG_83_17_ CH22_FGENES. 83-17 1.8 311291 EOS11222 AA782601 Hs. 122684 ESTs 1.8 310247 EOS10178 Ai224982 Hs. 211454 ESTs 1.8 316564 EOS16495 Api743571 Hs. 168799 ESTs ; Weakly similar to ! ! !! ALU SUBFAMILY J WARNING ENTRY !! ! ! [H. sapiens] 1.8 328170 EOS28101 c_6_hs gi#5868071#ref# gn 1+93170 93295 ex 9 9 CDSI 13.31 126 3591 CH. 06_hs gel5868071 1.8 300909 EOS00840 AW295479 Hs. 154903 ESTs ; Weakly similar to Ab ! substrate ena [D. melanogaster] 1.8 330869 EOS30800 AA115197 Hs. 183702 ESTs 1.8 311048 EOS10979 AA506952 Hs. 210508 ESTs 1.8 333764 EOS33695 CH22_1031FG_271_3_LINK_EM : AC005500. GENSCAN. 127-3 CH22_FGENES.271_3 1.8 338862 EOS38793 CH22_7715FG_LINK_DJ32I10.GENSCAN. 1-6 CH22_DJ32I10. GENSCAN. 1-6 1.8 331467 EOS31398 N22206 Hs. 43112 ESTs 1.8 327742 EOS27673 c_5_hs gi#5867944#ref# gn 3 - 143307 143512 ex 13 CDSI 11.07 206 172

CH. 05_hs 9il5867944 1.8 320955 EOS20886 AL049415 Hs. 204290 Homo sapiens mRNA; cDNA DKFZp586N2119 (from clone DKFZp586N2119) 1.8 323589 EOS23520 AW390054 Hs. 192843 ESTs 1.8 319951 EOS19882 AA307665 Hs. 14559 ESTs 1.8 333763 EOS33694 CH22_1030FG_271_2_LINK_EM : AC005500. GENSCAN. 127-2 CH22_FGENES.271_2 1. 7 331046 EOS30977 N66563 Hs. 191358 ESTs 1.7 320001 EOS19932 AA873350 EST cluster (not in UniGene) 1.7 316869 EOS16800 AI954880 Hs. 134604 ESTs 17 310774 EOS10705 AW134483 Hs. 164371 ESTs 1.7 319379 EOS19310 T91443 Hs. 193963 ESTs 1.7 321549 EOS21480 AA470984 Hs. 161947 ESTs 1. 7 300823 EOS00754 A) 863068 Hs. 222665 ESTs ; Weakly similar to putative zinc finger protein NY-REN-34 antigen [H. sapiens] 1.7 324228 EOS24159 A1798146 Hs. 207780 ESTs 1.7 313902 EOS13833 A1308165 Hs. 156242 ESTs 1. 7 308928 EOS08859 AI863908 EST singleton (not in UniGene) with exon hit 1.7 333770 EOS33701 CH22_1037FG_272_1_LINK_EM:AC005500. GENSCAN. 127-10 CH22_FGENES.272_1 1.7 316934 EOS16865 A1571647 Hs. 146170 ESTs 1.7 313219 EOS13150 N74924 Hs. 182099 ESTs 1. 7 317360 EOS17291 AI125252 Hs. 126419 ESTs 1. 7 303530 EOS03461 A1274851 Hs. 258744 ESTs 1.7 334739 EOS34670 CH22_2051FG_424_14_LINK_EM:AC005500. GENSCAN. 285-16 CH22_FGENES. 424_14 1.7 337670 EOS37601 CH22_5996FG_LINK_EM : AC000097. GENSCAN. 57-2 CH22EM : AC000097. GENSCAN. 57-2 1.7 312079 EOS12010 T79745 Hs. 189717 ESTs 1.7 320211 EOS20142 AL039402 Hs. 125783 DEME-6 protein 1.7 316218 EOS16149 AW207642 Hs. 174021 ESTs 1.7 335682 EOS35613 CH22_3043FG_595_2_LINK_EM : AC005500. GENSCAN. 487-11 CH22_FGENES.595_2 1.7 330696 EOS30627 AA022632 Hs. 15825 ESTs 1.7 314449 EOS14380 AL042667 Hs. 225539 ESTs 1.7 311972 EOS11903 N51511 Hs. 188449 ESTs 1.7 307691 EOS07622 AI318285 Hs. 182371 prothymosin; alpha (gene sequence 28) 1.7 338249 EOS38180 CH22_6847FG_LINK_EM : AC005500. GENSCAN. 269-1 CH22_EM : AC005500. GENSCAN. 269-1 1. 7 326399 EOS26330 c19_hs gi#5867353#ref# gn 1 + 6385 6536 ex 6 6 CDSI 10.69152 684 CH. 19_hs gi#5867353 1.7 313290 EOS13221 AI753247 Hs. 206454 ESTs 1.7 301615 EOS01546 W39477 EST cluster (not in UniGene) with exon hit 1.7 307034 EOS06965 AI142526 EST singleton (not in UniGene) with exon hit 1.7 313577 EOS13508 AA565051 Hs. 155029 ESTs 1.7 324703 EOS24634 AB009282 Hs. 31086 Homo sapiens mRNA for cytochromeb5 ; partial cds 1.7 321317 EOS21248 A1937060 Hs. 202040 ESTs ; Weakly similar to KIAA0938 protein [H. sapiens] 1. 7 312278 EOS12209 AW205234 Hs. 201587 ESTs 1. 7 333358 EOS33289 CH22_604FG_141_9_LINK_EM : AC005500. GENSCAN. 21-9 CH22_FGENES.141_9 1.7 322735 EOS22666 AA086123 EST cluster (not in UniGene) 1.7 326752 EOS26683 c20_hs gi#5867615#ref# gn 1-1214 1562 ex 22 CDSf 33.07 349 1366 CH.20_hs gi#5867615 1.7 314733 EOS14664 AW452355 Hs. 256037 ESTs 1.7 312902 EOS12833 AW292797 Hs. 130316 ESTs 1.7 322653 EOS22584 A1828854 Hs. 171891 ESTs 1.7 336015 EOS35946 CH22_3398FG_669_4_LINK_DJ32I10.GENSCAN. 9-9 CH22_FGENES. 669_4 1.7 324500 EOS24431 AW269819 Hs. 169905 ESTs 1.7 310900 EOS10831 AI922728 Hs. 165803 ESTs ; Weakly similar to !!!! ALU SUBFAMILY SB WARNING ENTRY ! !!! [H. sapiens] 1.7 337908 EOS37839 CH22_6323FG_LINK_EM : AC005500. GENSCAN. 57-1 CH22_EM : AC005500. GENSCAN. 57-1 1.7 304084 EOS04015 T91986 EST singleton (not in UniGene) with exon hit 1, 7 332539 EOS32470 AA412528 Hs. 20183 ESTs ; Weakly similar to cDNA EST EMBL : T01421comesfromthisgene [C. elegans] 1.7 314332 EOS14263 AL037551 Hs. 95612 ESTs 1.7 321412 EOS21343 AW366305 EST cluster (not in UniGene) 1.7 312187 EOS12118 AA700439 Hs. 188490 ESTs 1.7 314147 EOS14078 A1656135 Hs. 129805 ESTs 1.7 303131 EOS03062 AW081061 Hs. 103180 aetin-ìike 6 1. 7 331341 EOS31272 AA303125 Hs. 119009 ESTs ; Weakly similarto ! ! ! ! ALU SUBFAMILY SB2 WARNING ENTRY I ! ! ! [H. sapiens] 1. 7 313615 EOS13546 AW295194 Hs. 25264 DKFZP434N126 protein 1.7 329598 EOS29529 c10_p2 gi#3962482#gb#A gn 4+39924 40220 ex 2 3 CDS ! 8.71 297 420 CH. 10_p2 gi#3962482 1.7 303579 EOS03510 AA381124 Hs. 193353 ESTs ; Weakly similar to ! ! ! ! AW SUBFAMILY J WARNING ENTRY !!! ! [H. sapiens] 1.7 331692 EOS31623 W93592 Hs. 47343 ESTs 1 7 323977 EOS23908 AW328177 Hs. 234713 ESTs 1.7 332930 EOS32861 CH22-151FGJB_4_LINK-C2OHl2. GENSCAN. 29-4 CH22_FGENES. 384 1.7 326596 EOS26527 c19_hs gi#6138928#ref# gn 4+133386 133563 ex 7 9 CDSi-1.32 178 3520 CH. 19_hs gi#6138928 1.7 314946 EOS14877 A1097229 Hs. 217484 ESTs ; Weakly similar to !!!! ALU SUBFAMILY J WARNING ENTRY ! ! ! ! [H. sapiens] 1.7 315357 EOS15288 AA608684 Hs. 121705 ESTs ; Moderately similar to !! ! ! ALU CLASS C WARNING ENTRY ! ! !! [H.sapiens] 1.7 324728 EOS24659 AA303024 EST cluster (not in UniGene) 1.7 317501 EOS17432 AA931245 Hs. 137097 ESTs 1.7 332219 EOS32150 N22508 Hs. 139315 ESTs 1. 7 335369 EOS35300 CH22_2718FG_543_7_LINK_EM : AC005500. GENSCAN. 432-9 CH22_FGENES.543_7 1.7 322417 EOS22348 W36286 Hs. 171873 ESTs ; Weakly similar to PUTATIVE STEROID DEHYDROGENASE KIK-i [M. musculus] 1.7

316100 EOS16031 AW203986 Hs. 213003 ESTs 1.7 314866 EOS14797 AW305124 Hs. 191682 ESTs 1.7 300328 EOS00259 AW015860 Hs. 224623 ESTs 1.7 315676 EOS15607 AW002565 Hs. 136590 ESTs 1.7 314183 EOS14114 AA748600 EST cluster (not in UniGene) 1.7 321354 EOS21285 AA078493 EST cluster (not in UniGene) 1.7 311904 EOS11835 T86907 Hs. 119371 ESTs 1. 7 322890 EOS22821 AA082030 EST cluster (not in UniGene) 1.7 302759 EOS02690 AI885815 Hs. 184727 ESTs 1. 7 324600 EOS24531 AA503297 Hs. 117108 ESTs 1. 7 314973 EOS14904 AW273128 Hs. 254669 EST 1. 7 324432 EOS24363 AA464510 EST cluster (not in UniGene) 1.7 331520 EOS31451 N49068 Hs. 93966 ESTs 1. 7 308380 EOS08311 Api623988 EST singleton (not in UniGene) with exon hit 1.7 331010 EOS30941 H95039 Hs. 32168 KIAA0442 protein 1.7 325363 EOS25294 c12_hs gi#5866920#ref# gn 7+700446 700516 ex 6 8 CDSi-6.5871 113 CH. 12_hs gi#5866920 1.7 310470 EOS10401 A1281848 Hs. 165547 ESTs 1.7 330711 EOS30642 AA164687 Hs. 177576 mannosyl (alpha-1 ; 3-)-glycoprotein beta-1 ; 4-N-acetylglucosaminyltransferase ; isoenzyme A 1.7 332074 EOS32005 AA599012 Hs. 22826 ESTs 1. 7 309732 EOS09663 AW262211 Hs. 5662 guanine nucleotide binding protein (G protein); beta polypeptide 2-like 1 1.6 306337 EOS06268 AA954221 Hs. 73742 ribosoma ! protein ; large ; PO 1.6 335189 EOS35120 CH22_2525FG_507_4_LINK_EM : AC005500. GENSCAN. 400-4 CH22_FGENES.507_4 1.6 316253 EOS16184 A1919537 Hs. 118056 ESTs 1.6 332908 EOS32839 CH22_129FG _36_12_LINK_C20H12. GENSCAN. 28-9 CH22_FGENES.36_12 1.6 310002 EOS09933 A1439096 Hs. 25832 ESTs 1.6 332258 EOS32189 N68670 Hs. 103808 ESTs ; Weakly similar to RanBPM [H. sapiens] 1.6 336182 EOS36113 CH22_3576FG_715_2_LINK_DA59H18.GENSCAN. 19-3 CH22_FGENES.715_2 1.6 328987 EOS28918 c_9_hs gi#5868535#ref# gn 1-25705 25764 ex 3 10 CDSi 9.9060438 CH. 09_hs 9il5868535 1.6 324481 EOS24412 A1916284 Hs. 199671 ESTs 1.6 331406 EOS31337 AA610064 Hs. 23440 K1AA1105 protein 1.6 332280 EOS32211 R38100 Hs. 106294 ESTs 1.6 332173 EOS32104 F09281 Hs. 90424 ESTs 1.6 335739 EOS35670 CH22_3102FG_601_10_LINK_EN : AC005500. GENSCAN. 491-10 CH22_FGENES.601_10 1.6 332104 EOS32035 AA609177 Hs. 109363 ESTs 1.6 315033 EOS14964 A1493046 Hs. 146133 ESTs 1.6 334740 EOS34671 CH222052FG 424J5UNKEM : AC005500. GENSCAN. 285-17 CH22_FGENES. 424_15 1.6 334783 EOS34714 CH22_2095FG_432_8_LINK_EM : AC005500. GENSCAN. 293-11 CH22_FGENES.432_8 1.6 308010 EOS07941 Api439190 Hs. 181165 eukaryofic translation elongation factor 1 alpha 1 1.6 304521 EOS04452 AA464716 EST singleton (not in UniGene) with exon hit 1.6 318719 EOS18650 Z25900 Hs. 18724 Homo sapiens mRNA ; cDNA DKFZp564F093 (from clone DKFZp564F093) 1.6 321920 EOS21851 N63915 EST cluster (not in Un ! Gene) 1.6 315019 EOS14950 AA532807 Hs. 105822 ESTs 1.6 320793 EOS20724 AL049980 Hs. 184216 DKFZP564C152 protein 1.6 305371 EOS05302 AA714180 EST singleton (not in UniGene) with exon hit 1.6 305054 EOS04985 AA634127 Hs. 182426 ribosomal protein S2 1.6 314643 EOS14574 A1587502 Hs. 192088 ESTs 1.6 308186 EOS08117 AI537940 EST singleton (not in UniGene) with exon hit 1.6 319371 EOS19302 R00321 Hs. 174928 ESTs 1.6 331700 EOS31631 Z40011 Hs. 180582 ESTs 1.6 316955 EOS16886 AW203959 Hs. 149532 ESTs 1. 6 314961 EOS14892 AW008061 Hs. 231994 ESTs 1.6 336676 EOS36607 CH22_4154FG_43_4_ CH22_FGENES. 43-4 1.6 322801 EOS22732 A1831910 Hs. 163734 ESTs 1.6 303363 EOS03294 AI964095 Hs. 226801 ESTs ; Weakly similar to DIA-156 protein [H. sapiens] 1.6 328105 EOS28036 c_6_hs gi#5868020#ref# gn 11-301705 301784 ex 47 CDSi 5.30 80 3147 CH. 06_hs gi#5868020 1.6 325481 EOS25412 c12_hs gi#5866957#ref gn 3 + 47590 47672 ex 4 7 CDSi 2.69 831895 CH. 12_hs gi#5866957 1.6 315361 EOS15292 A1335229 Hs. 122031 ESTs 1.6 324902 EOS24833 D31323 Hs. 211188 ESTs 1.6 336018 EOS35949 CH22 _3401FG_669_7_LINK_DJ32I10.GENSCAN. 9-12 CH22_FGENES.669_7 1.6 308747 EOS08678 Api804500 Hs. 181165 eukaryotictranstation elongation factor 1 alpha 1 1.6 328251 EOS28182 c_6_hs gi#6381891#ref# gn 4 + 124444 124557 ex 2 3 CDSI 0.40 114 4554 CH. 06_hs gi#6381891 1.6 303153 EOS03084 U09759 Hs. 8325 mitogen-activated protein kinase 9 1.6 327809 EOS27740 c_5_hs gi#5867968#ref# gn 3+54610 54761 ex 44 CDSL 0. 78 152 993 CH. 05_hs gi#5867968 1.6 314107 EOS14038 AA806113 Hs. 189025 ESTs 1.6 300304 EOS00235 A1637934 Hs. 224978 ESTs 1.6 313009 EOS12940 W52010 Hs. 191379 ESTs 1.6 331074 EOS31005 R08440 yf19f9. s1 Scares fetal liver spleen 1 NFLS Homo sapiens cDNA clone IMAGE : 127337 3'similar to contains Alu repeUGve element ;, mRNA sequence 1.6 335773 EOS35704 CH22_3142FG_607_9_LINK_EM : AC005500. GENSCAN. 496-4 CH22_FGENES.607_9 1.6 334991 EOS34922 CH22_2312FG_469_11_LINK_EM : AC005500. GENSCAN. 365-11 CH22_FGENES.469_11 1.6 322959 EOS22890 AI267606 EST cluster (not in UniGene) 1.6

323731 EOS23662 AA323414 EST cluster (not in UniGene) 1.6 331073 EOS31004 R07998 Hs. 18628 ESTs ; Weakly similar to 1111 ALU SUBFAMILY J WARNING ENTRY ! ! !! [H. sapiens] 1.6 313573 EOS13504 A1076259 Hs. 190337 ESTs 1. 6 316949 EOS16880 AA856749 Hs. 124620 ESTs 1.6 328084 EOS28015 c_6_hs gi#6469819#ref# gn 3 - 155366 155459 ex 14 CDSL 1.23 94 2982 CH. 06_hs gi#6469819 1.6 331526 EOS31457 N49967 Hs. 46624 ESTs 1.6 317987 EOS17918 AW138174 Hs. 130651 ESTs 1.6 325594 EOS25525 c13_hs gi#5866992#ref# gn 4-470474 470566 ex 2 3 CDSi 8.09 93 68 CH. 13_hs gi#5866992 1.6 310848 EOS10779 A1459554 Hs, 161286 ESTs 1.6 309268 EOS09199 A) 985821 Hs. 62954 ferritin ; heavy polypeptide 1 1.6 304518 EOS04449 AA461438 EST singleton (not in UniGene) with exon hit 1.6 331065 EOS30996 N90584 Hs. 9167 Homosapiensclone25085mRNAsequence 1.6 306501 EOS06432 AA987294 EST slngleton (not in UniGene) with exon hit 1.6 323289 EOS23220 AL134235 Hs. 222442 ESTs 1. 6 334630 EOS34561 CH22_1938FG_416_6_LINK_EM: AC005500. GENSCAN. 277-6 CH22_FGENES.416_6 1.6 302025 EOS01956 A1091466 Hs. 127241 DKFZP564F052 protein 1.6 328998 EOS28929 c_9_hs gij5868538jreft gn 1 + 40996 41104 ex 1 3 CDSf 11.00109 480 CH. 09 hsgil5868538 1.6 313197 EOS13128 A1738851 Hs. 222487 ESTs 1.6 338763 EOS38694 CH22J585FG_LìNK_EM : AC005500. GENSCAN. 517-16 CH22_EM : AC005500. GENSCAN. 517-16 1.6 332247 EOS32178 N58172 Hs. 109370 ESTs 1.6 316724 EOS16655 AA810788 Hs. 123337 ESTs 1. 6 303306 EOS03237 AA215297 EST cluster (not in UniGene) with exon hit 1.6 306336 EOS06267 AA954198 EST singleton (not in UniGene) with exon hit 1.6 308256 EOS08187 A1565498 ESTsingReton (notinUniGene) withexonhit 1.6 307056 EOS06987 A1148675 EST singleton (not in UnlGene) with exon hit 1.6 321370 EOS21301 AJ227900 ESTcluster (notinUniGene) 1.6 336262 EOS36193 CH22_3661FG_754_9_LINK_DA59H18. GENSCAN. 57-11 CH22_FGENES. 754_9 1.6 335497 EOS35428 CH22_2849FG_571_5_LINK_EM : AC005500. GENSCAN. 460-26 CH22_FGENES.571_5 1.6 309582 EOS09513 AW169657 EST singleton (not in UniGene) with exon hit 1.6 329563 EOS29494 c10_p2 gi#3962490#gb#A gn 1-410 635 ex 22 CDSf 13.80 226 267 CH. 10_p2 gi#3962490 1.6 332504 EOS32435 AA053917 Hs. 15106 chromosome 14 open reading frame 1 1.6 308090 EOS08021 A1474601 Hs. 2186 eukaryotic translation eìongation factor 1 gamma 1.6 331752 EOS31683 AA287312 Hs. 191648 ESTs 1.6 330881 EOS30812 AA132986 Hs. 69321 ESTs ; Weakly similar to Similiar to mucin and several other Ser-Thr-rich proteins [S. cerevisiae] 1.6 315647 EOS15578 AA648983 Hs. 212911 ESTs 1.6 336766 EOS36697 CH22_4341FG_143_20_ CH22_FGENES. 143-20 1. 6 302592 EOS02523 AA294921 Hs. 250811 v-ral simian leukemia viral oncogene homolog B (ras related ; GTP binding protein) 1.6 315076 EOS15007 A1623817 Hs. 168457 ESTs 1.6 337056 EOS36987 CH22_4946FG_441_4_ CH22_FGENES. 441-4 1.6 322175 EOS22106 AF085975 EST cluster (not in UniGene) 1.6 336833 EOS36764 CH22_4504FG_242_2_ CH22_FGENES. 242-2 1.6 334902 EOS34833 CH22_2219FG_452_16_LINK_EM : AC005500. GENSCAN. 341-19 CH22_FGENES.452_16 1.6 318671 EOS18602 AA188823 Hs. 212621 ESTs 1.6 308064 EOS07995 A1469273 Hs. 181165 eukaryoue translafion elongation factor 1 alpha 1 1.6 320559 EOS20490 AB021981 Hs. 159322 solue carrier family 35 (UDP-N-acelylglucosamine (UDP-GlcNAc) transporter); member 3 1.6 317881 EOS17812 A1827248 Hs. 224398 ESTs 1.6 313078 EOS13009 N49730 EST cluster (not in UniGene) 1.6 338689 EOS38620 CH22_7464FG_LINK_EM : AC005500. GENSCAN. 475-3 CH22_EM : AC005500. GENSCAN. 475-3 1.6 311804 EOS11735 AA135159 Hs. 203349 ESTs 1.6 316359 EOS16290 A1472213 Hs. 123415 ESTs 1.6 330182 EOS30113 c_4_p2 gi#5123954#emb# gn 4 + 120156 120245 ex 22 CDSl 4.699011 CH. 04_p2 gi#5123954 1.6 334718 EOS34649 CH22_2028FG_421_29_LINK_EM : AC005500. GENSCAN. 282-29 CH22_FGENES.421_29 1.6 324196 EOS24127 AA405524 Hs. 178000 ESTs 1.6 305350 EOS05281 AA706676 EST singleton (not in UniGene) with exon hit 1.6 331469 EOS31400 N22273 Hs. 39140 ESTs 1. 6 305715 EOS05646 AA826884 EST singleton (not in UnlGene) with exon hit 1.6 314460 EOS14391 A1263231 Hs. 145607 ESTs 1.6 317634 EOS17565 AA953088 Hs. 127550 ESTs 1.6 335293 EOS35224 CH22_2635FG_527_6_LINK_EM : AC005500. GENSCAN. 421-9 CH22_FGENES.527_6 1.6 305611 EOS05542 AA782331 EST singleton (not in UniGene) with exon hit 1.6 310430 EOS10361 A1670843 Hs. 200257 ESTs 1. 6 323696 EOS23627 AA641201 Hs. 222051 ESTs 1.6 300610 EOS00541 N72596 Hs. 99120 DEAD/H (Asp-Glu-Ala-Asp/His) boxpoìypeptide, Ychromosome 1.6 327364 EOS27295 c_1_hs gi#6552412#ref# gn 2- 115235 115396 ex 19 CDSi 2.77 162 3007 CH. 01_hs gi#6552412 1.6 324848 EOS24779 AW021857 EST cluster (not in UniGene) 1.6 321491 EOS21422 H70665 Hs. 183960 ESTs 1.6 336367 EOS36298 CH22_3779FG_818_11 _LINK_BA232E17. GENSCAN. 3-17 CH22_FGENES.818_11 1.6 331549 EOS31480 N56866 Hs. 237507 EST 1.6 328332 EOS28263 c_7_hs gi#5868375#ref# gn 6+280154 280289 ex 3 5 CDSi-1.04 136 516 CH. 07_hs gi#5868375 1.5 322817 EOS22748 C02420 EST cluster (not in Un ! Gene) 1. 5

303983 EOS03914 AW514111 Hs. 181165 eukaryouc translation elongation factor 1 alpha 1 1. 5 329434 EOS29365 c_y_hs gi#5868883#ref# gn 1-31124 31263 ex 3 20 CDS ! 6.38140 241 CH. Y_hs gi#5868883 1.5 338196 EOS38127 CH22_6763FG_LINK_EM : AC005500. GENSCAN. 235-16 CH22_EM : AC005500. GENSCAN. 235-16 1.5 308488 EOS08419 AI682148 Hs. 179661 Homo sapiens clone 24703 beta-tubulin mRNA ; complete cds 1. 5 314883 EOS14814 AW178807 Hs. 246182 ESTs 1.5 307095 EOS07026 A1167910 EST singleton (not in UniGene) with exon hit 1.5 306953 EOS06884 A1124971 EST singleton (not in UniGene) with exon hit 1.5 331786 EOS31717 AA398539 Hs. 97369 EST 1.5 303509 EOS03440 AW378236 Hs. 256050 ESTs 1.5 324515 EOS24446 AW501686 Hs. 163539 ESTs 1.5 339323 EOS39254 CH22_8284FG_LINK_BA354I12. GENSCAN. 23-2 CH22_BA354I12. GENSCAN. 23-2 1.5 306563 EOS06494 AA995296 EST singleton (not in UniGene) with exon hit 1.5 316076 EOS16007 AW297895 Hs. 116424 ESTs 1.5 325622 EOS25553 c14_hs gi#5867000#ref# gn 2 + 69994 70075 ex 6 8 CDSi 9. 40 82194 CH. 14hsgi) 5867000 1.5 309632 EOS09563 AW193261 Hs. 156110 Immunoglobulin kappa variable 1 D-8 1.5 314926 EOS14857 A1380838 Hs. 124835 ESTs 1.5 3l4458 EOS14389 Al217440 Hs. 143873 ESTs 1. 5 335219 EOS35150 CH22_2558FG_513_2_LINK_EM : AC005500. GENSCAN. 406-2 CH22_FGENES.513_2 1.5 301079 EOS01010 AA305047 Hs. 183654 ESTs ; Weakly similar to unknown [S. cerevisiael 1.5 334122 EOS34053 CH22_1400FG_333_3_LINK_EM : AC005500. GENSCAN. 185-27 CH22_FGENES.333_3 1.5 308139 EOS08070 Api494477 EST singleton (not in UniGene) with exon hit 1.5 317412 EOS17343 A1301528 Hs. 132604 ESTs 1.5 315073 EOS15004 AW452948 Hs. 257631 ESTs 1.5 313139 EOS13070 AA362113 EST cluster (not in UniGene) 1.5 307012 EOS06943 AI140212 EST singleton (not in UniGene) with exon hit 1.5 322895 EOS22826 AW470295 Hs. 192152 ESTs 1.5 303779 EOS03710 AA897296 Hs. 221266 ESTs 1.5 312344 EOS12275 A1742618 Hs. 181733 ESTs ; Weakly similar to nitrilase homolog 1 [H. sapiens] 1.5 323632 EOS23563 AL039950 EST cluster (not in UniGene) 1.5 332336 EOS32267 T96130 Hs. 137551 ESTs 1.5 304547 EOS04478 AA486189 EST singleton (not in UniGene) with exon hit 1.5 335692 EOS35623 CH22_3053FG_596_7_LINK_EM: AC005500. GENSCAN. 488-7 CH22_FGENES.596_7 1.5 328333 EOS28264 c_7_hs gi#5868375#ref# gn 6 + 282506 282664 ex 4 5 CDS 7. 71 159 517 CH. 07_hs 9il5868375 1.5 304143 EOS04074 R88737 EST singteton (not in UniGene) with exon hit 1.5 329625 EOS29556 c11_p2 gi#4567169#gb#A gn 2-85893 85984 ex 3 5 CDSi 2.24 92 29 CH. 11_p2 gi#4567169 1.5 329960 EOS29891 c16_p2 gi#5091594#gb#A gn-1031 1162 ex 1 3 CDSi 10.75 132 415 CH. 16_p2 gi#5091594 1 5 318975 EOS18906 Z44110 EST cluster (not in UniGene) 1.5 321875 EOS21806 N49122 EST cluster (not in UniGene) 1.5 320451 EOS20382 R26944 Hs. 180777 Homo sapiens mRNA ; cDNA DKFZp564M0264 (from cìone DKFZp564M0264) 1.5 336020 EOS35951 CH22_3403FG_669_9_LìNK_DJ32110. GENSCAN. 9-14 CH22_FGENES.669_9 1.5 332581 EOS32512 T28799 Hs. 2913 EphB3 1.5 338622 EOS38553 CH22_7384FG_LINK_EM : AC005500. GENSCAN. 451-1 CH22_EM:AC005500.GENSCAN. 451-1 1.5 330397 EOS30328 D14659 Hs. 154387 KIAA0103 gene product 1.5 314359 EOS14290 AA205569 Hs. 194193 ESTs 1.5 313456 EOS13387 AW380579 Hs. 209657 ESTs 1.5 318486 EOS18417 H09123 Hs. 139258 ESTs 1.5 318175 EOS18106 AA644624 EST cluster (not in UniGene) 1.5 335684 EOS35615 CH22_3045FG_595_4_LINK_EM : AC005500. GENSCAN. 487-13 CH22_FGENES.595_4 1.5 327814 EOS27745 c_5_hs gi#5867968#ref# gn 6+69377 70566 ex 1 2 CDSf 86.15 1190 999 CH. 05_hs gi#5867968 1.5 322120 EOS22051 W84351 Hs. 213846 ESTs 1. 5 311749 EOS11680 R06249 Hs. 13911 ESTs 1.5 329797 EOS29728 c14_p2 gi#6523160#emb# gn 1-1061610894 ex 3 6 CDSi 5.86 2791549 CH. 14_p2 gií6523160 1.5 330630 EOS30561 X78669 Hs. 79088 reticulocalbin 2 ; EF-hand calcium binding domain 1.5 303777 EOS03708 AA348491 EST cluster (not in UniGene) with exon hit 1.5 309656 EOS09587 AW197060 Hs. 195188 glyceraldehyde-3-phosphate dehydrogenase 1.5 326165 EOS26096 c17_hs gi#5867208#ref# gn 2 - 62787 62929 ex 1 10 CDSI 0.87 143 2037 CH. 17_hs gi#5867208 1.5 308328 EOS08259 A1590571 Hs. 186412 EST 1.5 300601 EOS00532 AI762130 Hs.165619 ESTs 1.5 303610 EOS03541 AA323288 EST cluster (not in UniGene) with exon hit 1.5 307856 EOS07787 A1366158 EST singleton (not in UniGene) with exon hit 1.5 319920 EOS19851 R54575 Hs. 13337 ESTs ; Weakly similarto similar to Phosphoglucomutase and phosphomannomutase phosphoserine [C. elegans] 1.5 332167 EOS32098 D57389 Hs. 75447 ra) A binding protein 1 1. 5 316427 EOS16358 A1241019 Hs. 145644 ESTs 1.5 303886 EOS03817 AW365963 EST cluster (not in UniGene) with exon hit 1.5 314292 EOS14223 AA732590 Hs. 134740 ESTs 1.5 315408 EOS15339 AW273261 Hs. 216292 ESTs 1.5 335698 EOS35629 CH22_3059FG_597_1_LINK_EM : AC005500. GENSCAN. 489-1 CH22 FGENES.597_1 1.5 315084 EOS15015 Ai821085 Hs. 187796 ESTs 1.5

302299 EOS02230 R64632 Hs. 182167 hemoglobin ; gamma A 1.5 306803 EOS06734 A1055860 Hs. 193717 interleukin 10 1.5 315802 EOS15733 AA677540 Hs. 117064 ESTs 1. 5 326257 EOS26188 c17_hs gi#5867264#ref# gn 6 + 222712 222819 ex 2 2 CDS# 4.46 108 3597 CH. 17_hs gi#5867264 1.5 319599 EOS19530 H56112 EST cluster (not in UniGene) 1.5 321891 EOS21822 AW157424 Hs. 165954 ESTs 1.5 335164 EOS35095 CH22_2500FG_502_8_LINK_EM : AC005500. GENSCAN. 396-23 CH22_FGENES.520_8 1.5 327133 EOS27064 c21_hs gi#6682522#ref# gn 1 + 38069 38938 ex 2 2 CDSI 63. 42 8701583 CH, 21_hs gi#6682522 1.5 317460 EOS17391 AA926980 Hs. 131347 ESTs 1.5 332344 EOS32275 W45574 Hs. 252497 ESTs 1.5 328801 EOS28732 c_7_hs gi#58688321#ref# gn 1 - 44492 44609 ex 2 3 CDSi 1.711185525 CH. 07_hs gi#5868321 1.5 321677 EOS21608 N44545 Hs. 251865 ESTs 1.5 331858 EOS31789 AA421163 Hs. 163848 ESTs 1.5 309243 EOS09174 Al972052 EST singleton (not in UniGene) with exon hit 1.5 326213 EOS26144 c17_hs gi#5867224#ref# gn 3-60751 60927 ex 14 CDSI 2.06177 2687 CH. 17_hs gi#5867224 1.5 321632 EOS21563 AA419617 ESTcluster (notinUniGene) 1.5 321424 EOS21355 AA057301 EST cluster (not in UniGene) 1.5 322465 EOS22396 AA137152 Hs. 3784 ESTs ; Highly similar to phosphoserien aminotransferase [H. sapiens] 1.5 333391 EOS33322 CH22_637FG_144_6_LINK_EM: AC005500. GENSCAN. 25-6 CH22_FGENES. 144_6 1.5 333384 EOS33315 CH22_630FG_143_23_LINK_EM : AC005500. GENSCAN. 24-17 CH22_FGENES. 143_23 1.5 334784 EOS34715 CH22_2096FG_432_9_LINK_EM : AC005500. GENSCAN. 293-12 CH22_FGENES.432_9 1.5 334078 EOS34009 CH22_1356FG_327_33_LINK_EM: AC005500. GENSCAN. 181-35 CH22_FGENES. 32733 1.5 335158 EOS35089 CH22_2494FG_502_2_LINK_EM : AC005500. GENSCAN. 396-17 CH22_FGENES. 5022 1. 5 335062 EOS34993 CH22_2388FG_482_17_LINK_EM : AC005500. GENSCAN. 376-16 CH22_FGENES.482_17 1.5 333243 EOS33174 CH22_482FG_111_7_LINK_EM : AC000097. GENSCAN. 120-6 CH22_FGENES.111_7 1.5 306380 EOS06311 AA968861 EST singleton (not in UniGene) with exon hit 1.5 320809 EOS20740 Al540299 EST cluster (not in UniGene) 1.5 332813 EOS32744 CH22_29FG_8_1_LINK_C65E1. GENSCAN. 2-2 CH22_FGENES.8_1 1.5 335817 EOS35748 CH22_3189FG_618_5_LINK_EM : AC005500. GENSCAN. 510-5 CH22_FGENES. 6185 1.5 319551 EOS19482 AA761668 EST cluster (not in UniGene) 1.5 334472 EOS34403 CH22_1771FG_394_3_LINK_EM : AC005500. GENSCAN. 257-3 CH22_FGENES. 394_3 1.5 333029 EOS32960 CH22_255FG_68_3__LINK_EM:AC0000097. GENSCAN. 40-3 CH22_FGENES.68_3 1.5 308055 EOS07986 Al468091 Hs. 119252 tumor protein; translatinally-controlled 1 1.5 302882 EOS02813 AW403330 EST cluster (not in UniGene) with exon hit 1.5 314033 EOS13964 AA167125 EST cluster (not in UniGene) 1.5 324928 EOS24859 A1932285 Hs. 160569 ESTs 1.5 329524 EOS29455 c10_p2 gi#3983507#gb#A gn 6 - 38025 38143 ex 3 3 CDSl 2.40119170 CH. 10_p2 gi#3983507 1.5 333131 EOS33062 CH22_360FG_83_6_LINK_EM: AC000097. GENSCAN. 67-10 CH22-FGENES, 83-6 1.5 332085 EOS32016 AA600353 Hs. 173933 ESTs ; Weakly similar to NUCLEAR FACTOR 1/X [H. sapiens] 1.5 305369 EOS05300 AA714040 EST singleton (not in UniGene) with exon hit 1.5 300344 EOS00275 AW291487 Hs. 213659 ESTs 1.5 325071 EOS25002 H09693 EST cluster (not in UniGene) 1.5 323693 EOS23624 AW297758 Hs. 249721 ESTs 1.5 321899 EOS21830 N55158 Hs. 135252 ESTs 1.5 331857 EOS31788 AA421160 Hs. 9456 SWI/SNF related ; matix associated ; actindependentregutatorofchromatin ; subfamily a ; member5 1.5 334850 EOS34781 CH22_2164FG_439_36_LINK_EM : AC005500. GENSCAN. 311-13 CH22_FGENES.439_36 1.5 322610 EOS22541 AF180919 EST cluster (not in UniGene) 1.5 335332 EOS35263 CH22_2677FG_535_6_LINK_EM:AC005500.GENSCAN. 426-6 CH22_FGENES.535_6 1.5 307565 EOS07496 A1282468 EST singleton (not in UniGene) with exon hit 1.5 314140 EOS14071 A1216473 Hs. 154297 ESTs 1.5 323011 EOS22942 AA580288 EST cluster (not in UniGene) 1.5 325366 EOS25297 c12_hs gil5866920lren gn 9-920962 921713 ex 1 8 CDSI 15.95 752167 CH. 12_hs gi#5866920 1.5 322306 EOS22237 W75935 Hs. 146083 ESTs 1.5 311034 EOS10965 A1564023 Hs. 171467 ESTs ; Highly similar to NKG2-D TYPE II INTEGRAL MEMBRANE PROTEIN [H, sapiens] 1.5 305081 EOS05012 AA641638 EST singleton (not in UniGene) with exon hit 1.5 322933 EOS22864 AA099759 EST cluster (not in UniGene) 1.5 335221 EOS35152 CH22_2560FG_513_4_LINK_EM: AC005500. GENSCAN. 406-4 CH22_FGENES. 513_4 1.5 304948 EOS04879 AA613107 EST singleton (not in UniGene) with exon hit 1.5 334900 EOS34831 CH222217FG 452 14LiNKEM : AC005500. GENSCAN. 341-17 CH22_FGENES.452_14 1.5 318404 EOS18335 Aì654108 Hs. 135125 ESTs 1.5 339358 EOS39289 CH22_8328FG_LINK_BA354I12.GENSCAN. 31-3 CH22_BA354I12. GENSCAN. 31-3 1.5 327074 EOS27005 c21_hs gi#6531965#ref# gn 58 + 4039993 4040096 ex 3 4 CDSi 0.681041284

CH. 21-hs g ! 16531965 1.5 326054 EOS25985 c17_hs gi#5867184#ref# gn 2-146342146469 ex 3 4 CDSi 10.00128 426 CH. 17_hs gi#5867184 1.5 326892 EOS26823 c20_hs gi#6682511#ref# gn 5 + 119424 119500 ex 29 30 CDSI 18.89 77 2313 CH. 20_hs gi#6682511 1.5 328767 EOS28698 c_7_hs gil6017031lren gn 1-35625 35723 ex 4 4 CDSf 5. 63 99 5262 CH. 07_hs gi#6017031 1.5 337772 EOS37703 CH22_6125FG_LINK_EM : AC000097. GENSCAN. 119-11 CH22_EM : AC000097. GENSCAN. 119-11 1.5 312199 EOS12130 AW43B602 Hs. 191179 ESTs 1.5 303506 EOS03437 AA#40605 Hs. 105887 ESTs 1.5 325176 EOS25107 T52843 EST cluster (not in UniGene) 1.5 302023 EOS01954 AF060567 Hs. 126782 sushi-repeat protein 1.5 305833 EOS05764 AA857836 Hs. 181165 eukaryotic translatin elongation factor 1 alpha 1 1.5 309131 EOS09062 Al929175 Hs. 119122 ribosomal protein L13a 1.5 334184 EOS34115 CH22_1465FG_350_15_LINK_EM:AC005500. GENSCAN. 209-17 CH22_FGENES.350_15 1.5 335188 EOS35119 CH22_2524FG_507_3_LINK_EM: AC005500. GENSCAN. 400-3 CH22_FGENES.507_3 1.5 304813 EOS04744 AA584540 EST singleton (not in UniGene) with exon hit 1.5 315359 EOS15290 M608808 Hs. 225118 ESTs 1.5 324434 EOS24365 AA707249 Hs. 98789 ESTs 1.5 327910 EOS27841 c_6_hs gi#5868162#ref# gn 1 + 21622 21748 ex 6 7 CDSi 3.69127 449 CH. 06_hs gi#5868162 1.4 335671 EOS35602 CH22_3031FG_592_3_LINK_EM : AC005500. GENSCAN. 485-4 CH22_FGENES.592_3 1.4 334943 EOS34874 CH22_2264FG_465_8_LINK_EM : AC005500. GENSCAN. 359-8 CH22_FGENES.65_8 1.4 326393 EOS26324 c19_hs gi#5867341#ref# gn 2 + 41702 41841 ex 5 5 CDSI 20.15 140 504 CH. 19_hs gil5867341 1. 4 305296 EOS05227 M687181 EST singleton (not in UniGene) with exon hit 1.4 307243 EOS07174 AI199957 EST singleton (not in UniGene) with exon hit 1.4 320066 EOS19997 AW364885 Hs. 112442 ESTs 1.4 311465 EOS11396 Api758660 Hs. 206132 ESTs 1.4 302822 EOS02753 AW404176 Hs. 111611 ribosomal protein L27 1.4 304987 EOS04918 AA618044 EST singleton (not in UniGene) with exon hit 1.4 330892 EOS30823 AA149579 Hs. 118258 ESTs 1.4 333385 EOS33316 CH22_631FG_143_24_LINK_EM: AC005500. GENSCAN. 24-18 CH22_FGENES.143_24 1.4 302626 EOS02557 AB021870 EST cluster (not in UniGene) with exon hit 1.4 318042 EOS17973 AW294522 Hs. 149991 ESTs 1.4 339361 EOS39292 CH22_8331FG_LINK_BA354I12.GENSCAN. 32-3 CH22_BA354I12. GENSCAN. 32-3 1.4 309000 EOS08931 Al880489 EST singleton(not in UniGene) with exon hit 1. 4 306004 EOS05935 AA889992 EST singleton (not in UniGEne) with exon hit 1.4 329539 EOS29470 c10_p2 gi#3983503#gb#U gn 1 - 1 326 ex 13 CDSI 41.66 326 212 CH. 10_p2gil3983503 1.4 313663 EOS13594 AI953261 Hs. 169813 ESTs 1.4 323538 EOS23469 AW247696 EST cluster (not in UniGene) 1.4 337595 EOS37526 CH22_5884FG_LINK_C20H12. GENSCAN. 8-1 CH22_C20H12. GENSCAN. 8-1 1.4 303149 EOS03080 M312995 EST cluster (not in UniGene) with exon hit 1.4 308484 EOS08415 AI679292 EST singleton (not in UniGene) with exon hit 1.4 300912 EOS00843 AW138724 Hs. 168974 ESTs 1.4 315158 EOS15089 AA744438 Hs. 142476 ESTs ; Weakly similar to ! ! ! ! ALU CLASS D WARNING ENTRY ! !! ! [H.sapiens] 1. 4 300462 EOS00393 AA746501 Hs. 14217 ESTs 1.4 312730 EOS12661 A1804372 Hs. 208661 ESTs 1.4 316868 EOS16799 A1660898 Hs. 195602 ESTs 1.4 337629 EOS37560 CH22_5933FG_LINK_C20H12. GENSCAN. 28-35 CH22_C20H12. GENSCAN. 28-35 1.4 332518 EOS32449 D16562 Hs. 155433 ATPsynthase ; H+ transporting ; mitochondrial F1 complex ; gamma polypeptide 1 1.4 337422 EOS37353 CH22_5624FG_760_2_ CH22_FGENES. 760-2 1.4 328835 EOS28766 c_7_hs gi#5868339#ref# gn 5 + 88053 88461 ex 3 3 CDSI 13.78 409 5775 CH. 07_hs gi#5868339 1.4 338282 EOS38213 CH22_6897FG LINK_EM : AC005500. GENSCAN. 291-4 CH22_EM : AC005500. GENSCAN. 291-4 1.4 337895 EOS37826 CH22 6303FGUNKEM : AC005500. GENSCAN. 56-2 CH22_EM : AC005500. GENSCAN. 56-2 1.4 320330 EOS20261 AF026004 Hs. 141660 chloride channel 2 1.4 314302 EOS14233 AA813118 Hs. 163230 ESTs 1.4 313280 EOS13211 A1285537 Hs. 222830 ESTs 1.4 333222 EOS33153 CH22_459FG_105_2_LINK_EM : AC000097. GENSCAN. 109-6 CH22_FGENES.105_2 1.4 305726 EOS05657 AA828156 EST singleton (not in UniGene) with exon hit 1.4 312674 EOS12605 A1762475 Hs. 151327 ESTs ; Moderately similar to !! ! ! ALU SUBFAMILY J WARNING ENTRY [H. sapiens] 1.4 315869 EOS15800 A1033547 Hs. 132826 ESTs 1.4 327010 EOS26941 c21_hs gi#5867664#ref# gn 12 + 941057 941139 ex 9 9 CDSI 7.44 83 790 CH. 21_hs gi#5867664 1.4 325892 EOS25823 c16_hs gi#5867088#ref# gn 1-1049810652 ex 2 3 CDSi 3.94155 870 CH. 16_hs gil5867088 1.4 302575 EOS02506 AF071164 Hs. 249171 homeo box A11 1.4 301970 EOS01901 AB028962 Hs. 120245 KIAA1039 protein 1.4 332207 EOS32138 H61475 Hs. 237353 EST 1. 4 316024 EOS15955 AA707141 Hs. 193388 ESTs 1.4 314599 EOS14530 AW206512 Hs. 186996 ESTs 1.4 333585 EOS33516 CH22_846FG_203_4_LINK_EM : AC005500. GENSCAN. 74-6

CH22_FGENES.203_4 1.4 324670 EOS24601 A1525557 EST cluster (not in UniGene) 1.4 321307 EOS21238 R85409 EST cluster (not in UniGene) 1.4 335170 EOS35101 CH22_2506FG_503_1_LINK_EM: AC005500. GENSCAN. 397-1 CH22_FGENES.503_1 1. 4 328274 EOS28205 c_7_hs gi#5868219#ref# gn 2 - 31244 31439 ex 111 CDSI 13.06 196 9 CH. 07_hs gi#5868219 1.4 336880 EOS36811 CH22_4619FG_318_8_ CH22_FGENES. 318-8 1.4 313825 EOS13756 AA215470 EST cluster (not in UniGene) 1.4 318410 EOS18341 A1138418 Hs. 144935 ESTs 1.4 335361 EOS35292 CH22_2710FG_541_11_LINK_EMAC005500. GENSCAN. 431-16 CH22_FGENES.541_11 1.4 319802 EOS19733 AI701489 Hs. 202501 ESTs 1.4 334769 EOS34700 CH22 2081 FG 429 4 UNKEM : AC005500. GENSCAN. 290-9 CH22_FGENES.429_4 1.4 312709 EOS12640 AW069181 Hs. 141146 ESTs ; Weakly similar to transformation-related protein [H. sapiens] 1.4 330004 EOS29935 c16_p2 gi#6623963#gb#A gn 5-78872 78999 ex 2 6 CDSi 19. 93128 728 CH. 16_p2 gi#6623963 1.4 313103 EOS13034 A1184303 Hs. 143806 ESTs 1.4 326359 EOS26290 c18_hs gi#5867293#ref# gn 1 + 9436 9494 ex 2 3 CDSI 2.165988 CH. 18_hs gi#5867293 1.4 305211 EOS05142 AA668563 EST singleton (not in UniGene) with exon hit 1.4 334628 EOS34559 CH22_1936FG_416_4_LINK_EM: AC005500. GENSCAN. 277-4 CH22_FGENES.416_4 1.4 326919 EOS26850 c21_hs gi#6456782#ref# gn 2 - 40486 41046 ex 1 5 CDSI 17.70 561 157 CH. 21_hs gi#6456782 1.4 315527 EOS15458 A1791138 Hs. 116768 ESTs 1.4 306090 EOS06021 AA908609 EST singleton (not in UniGene) with exon hit 1.4 303316 EOS03247 AF033122 Hs. 14125 p53 regulated PA26 nuclear protein 1. 4 303642 EOS03573 AW299459 EST cluster (not in UniGene) with exon hit 1.4 314357 EOS14288 AA781795 Hs. 122587 ESTs 1. 4 337102 EOS37033 CH22_5033FG_472_7_ CH22_FGENES. 472-7 1.4 304384 EOS04315 AA235482 Hs. 62954 festin ; heavy polypeptide 1 1.4 315117 EOS15048 AA828609 Hs. 192044 ESTs 1.4 305750 EOS05681 AA835250 EST singleton (not in UniGene) with exon hit 1.4 311726 EOS11657 AW081766 Hs. 253920 ESTs 1.4 326996 EOS26927 c21_hs gi#5867660#ref# gn 4 - 63212 63404 ex 2 6 CDSi 15.70 193 622 CH. 21_hs gi#5867660 1.4 330257 EOS30188 c_5_p2 gi#6671881#gb#A gn 2 - 143228 143393 ex 19 CDSI 11.31 166 586 CH. 05_p2 gi#6671881 1. 4 323864 EOS23795 AA340724 Hs. 214028 ESTs 1.4 338204 EOS38135 CH22_6773FG_LINK_EM:AC005500.GENSCAN.241-3 CH22_EM : AC005500. GENSCAN. 241-3 1.4 314025 EOS13956 A) 983981 Hs. 189114 ESTs. 1.4 315974 EOS15905 AW029203 Hs. 191952 ESTs 1.4 335599 EOS35530 CH22_2957FG_581_39_LINK_EM : AC005500. GENSCAN. 476-37 CH22_FGENES.581_39 1.4 335364 EOS35295 CH22_2713FG_543_2_LINK_EM : AC005500. GENSCAN. 432-4 CH22_FGENES.543_2 1.4 303634 EOS03565 AI953377 Hs. 169425 ESTs ; Weakly similar to predicted using Genefinder [C. elegans] 1.4 315626 EOS15557 AA808598 Hs. 35353 ESTs ; Weakly similarto H21P03. 2 [C. elegans] 1.4 329936 EOS29867 c16_p2 gi#6165200#gb#A gn 4-8276182920 ex 3 4 CDSi 1. 15 160 199 CH. 16_p2 9il6165200 1.4 328632 EOS28563 c_7_hs gi#5868247#ref# gn 1 + 76734 76853 ex 14 CDSf 13.95120 3764 CH. 07_hs gi#5868247 1.4 330207 EOS30138 c_5_p2 gi#6013606#gb#A gn 3 - 109912 110004 ex 2 4 CDSi 6.54 93174 CH. 05_p2 gi#6013606 1.4 329919 EOS29850 c16_p2 gií6223624ígbjA gn 6-103492103681 ex 18 CDSI 6.18190 93 CH. 16_p2 gi#6223624 1.4 331916 EOS31847 AA446131 Hs. 124918 ESTs 1.4 317617 EOS17548 T58194 EST cluster (not in UniGene) 1.4 331943 EOS31874 AA453418 Hs. 178272 ESTs 1.4 306413 EOS06344 AA973288 EST singleton (not in UniGene) with exon hit 1.4 313607 EOS13538 N94169 Hs. 194258 ESTs ; Moderately similar to ! ! !! ALU SUBFAMILY SC WARNING ENTRY ! ! ! ! [H. sapiens] 1.4 336292 EOS36223 CH22 _3691FG_783_3_LINK_BA354I12. GENSCAN. 4-7 CH22_FGENES. 783_3 1.4 330453 EOS30384 HG3976-HT4246 Pou-DomainDnaBindingFactorPitl, Pituitary-Specific 1.4 324602 EOS24533 AA503620 Hs. 213239 ESTs 1.4 332183 EOS32114 H08225 Hs. 177181 ESTs 1.4 320032 EOS19963 A1699772 Hs. 202361 ESTs ; Weakly similar to X-linked re6nopathy protein [H. sapiens] 1.4 333156 EOS33087 CH22_387FG_89_6_LINK_EM : AC000097. GENSCAN. 84-8 CH22_FGENES.89_6 1.4 334156 EOS34087 CH22_1435FG_340_6_LINK_EM : AC005500. GENSCAN. 190-7 CH22_FGENES.340_6 1.4 334303 EOS34234 CH22_1594FG_373_6_LINK_EM : AC005500. GENSCAN. 233-5 CH22_FGENES.373_6 1.4 325513 EOS25444 c12_hs gi#6017035#ref# gn 1-34295 34490 ex 2 7 CDSi 6.49196 2471 CH, 12_hs gií6017035 1.4 302758 EOS02689 AA984563 EST cluster (not in UniGene) with exon hit 1.4 329557 EOS29488 c10_p2 gií3962492ígbíA gn 6-53197 53647 ex 2 2 CDSf 37.68 451247 CH. 10 p2 gií3962492 1.4 331717 EOS31648 AA190888 Hs. 153881 ESTs ; Highly similar to NY-REN-62 antigen [H. sapiens] 1.4 325885 EOS25816 c16_hs gi#5867087_ref# gn 11 + 193212193377 ex 1 3 CDSf 43. 19166 792 CH. 16_hs gií5867087 1.4 312160 EOS12091 AA805903 Hs. 184371 ESTs 1.4 328882 EOS28813 c_7_hs gi#6552423#ref# gn 2 - 157669 157826 ex 4 6 CDSi 4. 91 158 6200

CH. 07 hs gií6552423 1 4 339028 EOS38959 CH22_7925FG_LINK_DA59H18. GENSCAN. 22-8 CH22_DA59H18. GENSCAN. 22-8 1.4 323497 EOS23428 A1523613 Hs. 221544 ESTs 1. 4 316897 EOS16828 AA838114 EST cluster (not in UniGene) 1.4 312479 EOS12410 AI950844 Hs. 128738 ESTs ; Weakly similar to non-lens beta gamma-crystallin like protein [H, sapiens] 1.4 338535 EOS38466 CH227251FGUNK LINK_EM : AC005500. GENSCAN. 404-3 CH22_EM : AC005500. GENSCAN. 404-3 1.4 312754 EOS12685 R99834 Hs. 250383 ESTs 1.4 327527 EOS27458 c_2_hs gi#6381882#ref# gn 2 - 98950 99040 ex 4 8 CDSi 5.78 911768 CH. 02_hs gi#6381882 1.4 324714 EOS24645 AA574312 Hs. 245737 ESTs 1.4 302347 EOS02278 AF039400 Hs. 194659 chloride channel ; calcium activated ; family member 1 1.4 338008 EOS37939 CH22_6490FG_LINK_EM : AC005500. GENSCAN. 127-9 CH22_EM : AC005500. GENSCAN. 127-9 1. 4 315590 EOS15521 AA640637 Hs. 225817 ESTs 1.4 320825 EOS20756 NM_004751 EST cluster (not in UniGene) 1.4 300930 EOS00861 A1289481 Hs. 136371 ESTs 1.4 335225 EOS35156 CH22_2564FG_513_10_LINK_EM : AC005500. GENSCAN. 406-9 CH22_FGENES.513_10 1.4 337303 EOS37234 CH22_5442FG_681_5_ CH22_FGENES. 681-5 1.4 317198 EOS17129 Aì810384 Hs. 128025 ESTs 1. 4 308991 EOS08922 AI879831 EST singleton (not in UniGene) with exon hit 1.4 325472 EOS25403 c12_hs gi#6017034#ref# gn 7 - 289581 289657 ex 2 6 CDSi 4. 74 77 1786 CH. 12_hs ! 6017034 1.4 301266 EOS01197 AA829774 EST cluster (not in UniGene) with exon hit 1.4 330901 EOS30832 AA157818 Hs. 238380 Human endogenous retroviral protease mRNA ; complete cds 1.4 313406 EOS13337 A1248314 Hs. 132932 ESTs 1.4 301454 EOS01385 A1751738 ESTcluster (notintJniGene) withexonhit 1.4 317269 EOS17200 AA906411 Hs. 127378 ESTs 1.4 338876 EOS38807 CH22_7733FG_LINK_DJ32I10.GENSCAN. 4-2 CH22_DJ32I10. GENSCAN. 4-2 1.4 328481 EOS28412 c_7_hs gi#5868449#ref# gn 1-8987 9180 ex 4 31 CDSi 10.00194 2103 CH. 07_hs gi#5868449 1.4 314022 EOS13953 AW452420 Hs. 248678 ESTs 1.4 307640 EOS07571 AI301992 EST singleton (not in UniGene) with exon hit 1.4 315541 EOS15472 A1168233 Hs. 123159 ESTs; Weakly similar to KIAA0668 protein [H.sapients] 1.4 315489 EOS15420 AA628245 Hs. 191847 ESTs 1.4 327815 EOS27746 c_5_hs gi#5867968#ref# gn 6 + 70804 71401 ex 2 2 CDSI 27.99 5981000 CH. 05_hs 5867968 1.4 339319 EOS39250 CH228280FGUNrLBA354J12. GENSCAN. 22-19 CH22_BA354I12.GENSCAN 22-19 1.4 322564 EOS22495 W86440 Hs. 118344 ESTs 1.4 323812 EOS23743 AW081373 Hs. 199199 ESTs 1. 4 303540 EOS03471 AA355607 Hs. 173590 ESTs ; Weakly similar to MMSET type [H.sapiens] 1.4 337902 EOS37833 CH22_6314FG_LINK_EM : AC005500. GENSCAN. 56-13 CH22_EM : AC005500. GENSCAN. 56-13 1.4 335289 EOS35220 CH22_2631FG_527_2_LINK_EM : AC005500. GENSCAN. 421-2 CH22_FGENES.527_2 1.4 327919 EOS27850 c_6_hs gi#5868165#ref# gn 6 + 547701 547800 ex 14 14 CDSI-0.20 100 505 CH. 06_hs gi#5868165 1.4 337674 EOS37605 CH22_6005FG_LINK_EM : AC000097. GENSCAN. 67-4 CH22_EM : AC000097. GENSCAN. 67-4 1.4 320087 EOS20018 AF032387 Hs. 113265 small nuclear RNA activating complex ; polypepride 4 ; l90kD 1.4 334939 EOS34870 CH22_2259FG_465_3_LINK_EM : AC005500. GENSCAN. 359-3 CH22_FGENES.465_3 1.3 303443 EOS03374 AA320525 EST cluster (not in UniGene) with exon hit 1. 3 325929 EOS25860 c16_hs gi#5867125#ref# gn 2-51715 51996 ex 1 1 CDSo 29.05 2821594 CH. 16_hs gi#5867125 1. 3 327745 EOS27676 c_5_hs gi#6531959#ref# gn 1 - 229066 229124 ex 3 6 CDSI 3.0159177 CH. 05_hs ! 6531959 1.3 335166 EOS35097 CH22_2502FG_502_10_LINK_EM : AC005500. GENSCAN. 396-25 CH22_FGENES.502_10 1.3 324497 EOS24428 AW152624 Hs. 136340 ESTs 1.3 338374 EOS38305 CH22_7017FG_LINK_EM : AC005500. GENSCAN. 327-1 CH22_EM: AC005500. GENSCAN. 327-1 1.3 313601 EOS13532 R32458 Hs. 257711 ESTs 1.3 321415 EOS21346 AI377596 Hs. 3337 transmembrane 4 superfamily member 1 1.3 305309 EOS05240 AA699717 EST singleton (not in UniGene) with exon hit 1. 3 330447 EOS30378 HG3546-HT3744 Pre-Mma Splicing Factor Sf2p33, Alt. Splice Form 1 1.3 308578 EOS08509 A1708573 EST singleton (not in UniGene) with exon hit 1.3 315344 EOS15275 AW292176 Hs. 245834 ESTs 1.3 330503 EOS30434 M55024 Human cell surface glycoprotein P3. 58 mRNA, partial cds 1.3 308227 EOS08158 AI559126 Hs. 195188 glyceraldehyde-3-phosphate dehydrogenase 1. 3 332222 EOS32153 N28271 Hs. 176618 ESTs 1. 3 323961 EOS23892 AL044428 Hs. 207345 ESTs 1.3 314530 EOS14461 A1052358 Hs. 131741 ESTs 1.3 320503 EOS20434 Nu-005897 EST cluster (not in UniGene) 1.3 306820 EOS06751 A1074408 EST singleton (not in UniGene) with exon hit 1.3 304165 EOS04096 H73265 EST singleton (not in UniGene) with exon hit 1.3 324302 EOS24233 AA543008 Hs. 136806 ESTs : Weakly similar to !!!! ALU SUBFAMILY J WARNING ENTRY ! ! ! ! [H. sapiens] 1.3 319128 EOS19059 AA393820 EST cluster (not in UniGene) 1. 3 317092 EOS17023 A1286162 Hs. 125657 ESTs 1.3 304998 EOS04929 AA621203 EST singleton (not in UniGene) with exon hit 1.3 331433 EOS31364 H68097 Hs. 161023 EST 1.3 333348 EOS33279 CH22_594FG_140_2_LINK_EM : AC005500. GENSCAN. 20-2

CH22_FGENES.140_2 1.3 333619 EOS33550 CH22_880FG_219_3_LINK_EM:AC005500. GENSCAN. 87-2 CH22_FGENES.29 1. 3 335903 EOS35834 CH22_3280FG_635_11_LINK_EM : AC005500. GENSCAN. 525-14 CH22_FGENES.635_11 1.3 326219 EOS26150 c17_hs gií5867226íren gn 11-264008 264274 ex 3 5 CDSI 5.74 267 2847 CH. 17_hs gi#5867226 1. 3 324456 EOS24387 AW500954 EST cluster (not in UniGene) 1.3 316405 EOS16336 AA757900 Hs. 202624 ESTs 1.3 314361 EOS14292 AL038765 Hs. 161304 ESTs 1.3 328546 EOS28477 c_7_hs gi#5868487#ref# gn 1-1754717722 ex 2 3 CDSi 9, 96176 3284 CH, 07_hs gií5868487 1, 3 335871 EOS35802 CH22_3246FG_629_19_LINK_EM: AC005500. GENSCAN. 519-18 CH22_FGENES. 629_19 1.3 303735 EOS03666 AA707750 Hs. 202616 ESTs ; Weakly similar to cis-Golgi matrix protein GM130 [R. norvegicus] 1.3 324048 EOS23979 AA378739 EST cluster (not in UniGene) 1. 3 326720 EOS26651 c20_hs gi#6552456#ref# gn 1 + 84525 84677 ex 5 7 CDSi 11.78 153 1031 CH. 20_hs gi#6552456 1.3 322309 EOS22240 AF086372 EST cluster (not in UniGene) 1.3 322136 EOS22067 AF075083 EST cluster (not in UniGene) 1.3 313460 EOS13391 AW028655 Hs. 136033 ESTs 1. 3 306275 EOS06206 AA936312 EST singleton (not in UniGene) with exon hit 1.3 321974 EOS21905 N76794 EST cluster (not in UniGene) 1.3 327600 EOS27531 c_3_hs gi#604462#ref# gn 1 - 2621 2862 ex 14 CDSI-4. 01 2421407 CH. 03_hs 6004462 1.3 329086 EOS29017 cxhs gi#5868604#ref# gn 1 - 35489 35588 ex 2 9 CDSi 2.55100 719 CH, X_hs gi#5868604 1.3 336919 EOS36850 CH22_4690FG_346_6_ CH22_FGENES. 346-6 1.3 302767 EOS02698 H94900 Hs. 17882 ESTs 1.3 334786 EOS34717 CH22_2098FG_432_11_LINK_EM:AC005500. GENSCAN. 293-14 CH22_FGENES.432_11 1.3 302472 EOS02403 AA317451 Hs. 241451 SWIISNF related ; matrix associated ; acün dependentreguìaiorofchromatin ; subfamily a ; member 1 1.3 333033 EOS32964 CH22_259FG_68_8_LINK_EM : AC000097. GENSCAN. 40-8 CH22_FGENES.68_8 1.3 330493 EOS30424 M27826 Hs. 238380 Human endogenous retroviral protease mRNA ; complete cds 1.3 330506 EOS30437 M61906 Hs. 6241 phosphoinosiüde-3-kinase ; Regulatory subunit; polypeptide 1 (p85 alpha) 1.3 313932 EOS13863 Ai147601 Hs. 154087 ESTs 1, 3 314394 EOS14325 A1380563 Hs. 130816 ESTs 1.3 323033 EOS22964 A1744284 Hs. 221727 ESTs 1.3 326431 EOS26362 c19_hs gi#5867371#ref# gn 1 + 15855 15971 ex 4 6 CDSi 7.791171108 CH. 19_hs gi#5867371 1.3 335547 EOS35478 CH22_2902FG_576_8_LINK_EM:AC005500. GENSCAN. 467-8 CH22_FGENES.576_8 1.3 300548 EOS00479 A1026836 Hs. 114689 ESTs 1. 3 316504 EOS16435 AW135854 Hs. 132458 ESTs 1. 3 335756 EOS35687 CH22_3123FG_604_5_LINK_EM : AC005500. GENSCAN. 493-10 CH22_FGENES.604_5 1.3 301209 EOS01140 A1809912 Hs. 159354 ESTs 1. 3 306610 EOS06541 A1000635 EST singleton (not in UniGene) with exon hit 1.3 314439 EOS14370 AI539443 Hs. 137447 ESTs 1.3 315396 EOS15327 AW296107 Hs. 152686 ESTs 1.3 335914 EOS35845 CH223291FG636 10LiNKEM : AC005500. GENSCAN. 526-10 CH22_FGENES.636_10 1.3 333734 EOS33665 CH22_1000FG_260_2_LINK_EM:AC005500. GENSCAN. 119-7 CH22_FGENES. 260_2 1.3 312370 EOS12301 AA744692 Hs. 166539 ESTs 1.3 304636 EOS04567 AA524031 EST singleton (not in UniGene) with exon hit 1.3 323166 EOS23097 AA291001 EST cluster (not in UniGene) 1.3 338702 EOS38633 CH22_7482FG_LINK_EM:AC005500. GENSCAN. 480-1 CH22_EM : AC005500. GENSCAN. 480-1 1.3 322331 EOS22262 AF086467 EST cluster (not in UniGene) 1.3 318706 EOS18637 A1383593 Hs. 159148 ESTs 1.3 331186 EOS31117 T41159 Hs. 8418 ESTs 1.3 334764 EOS34695 CH22_2076FG_428_13_LINK_EM : AC005500. GENSCAN, 289-13 CH22_FGENES.428_13 1.3 327565 EOS27496 c_3_hs gi#5867811#ref# gn 1 + 32516 32778 ex 2 3 CDSi 0.20 263 368 CH. 03_hs gi#5867811 1.3 335524 EOS35455 CH22_2879FG_572_4_LINK_EM : AC005500. GENSCAN. 461-4 CH22_FGENES.572_4 1.3 308050 EOS07981 AI460004 EST singleton (not in UniGene) with exon hit 1.3 334172 EOS34103 CH22_1452FG_345_5_LINK_EM: AC005500. GENSCAN. 208-6 CH22_FGENES.349_5 1.3 315674 EOS15605 AA651923 Hs. 191850 ESTs 1.3 334876 EOS34807 CH22_2190FG_450_6_LINK_EM:AC005500. GENSCAN. 339-6 CH22_FGENES.450_6 1.3 315606 EOS15537 AW298724 Hs. 202639 ESTs 1.3 338779 EOS38710 CH227610FGUNKEM : AC005500. GENSCAN. 526-15 CH22_EM:AC005500.GENSCAN. 526-15 1.3 333511 EOS33442 CH22_766FG_171_5_LINK_EM : AC005500. GENSCAN. 51-5 CH22_FGENES.171_5 1.3 329254 EOS29185 c_x_hs gi#5868733#ref# gn 1 + 4133 4214 ex 1 2 CDSi-0, 36 82 2833 CH. X_hs gií5868733 1.3 319510 EOS19441 W88633 Hs. 254562 ESTs 1.3 339418 EOS39349 CH22_8411FG_LINK_DJ579N16.GENSCAN.11-4 CH22_DJ579N16. GENSCAN. 11-4 1.3 321012 EOS20943 AA737314 EST cluster (not in Un ! Gene) 1.3

333217 EOS33148 CH22_454FG_104_9_LINK_EM : AC000097. GENSCAN. 108-8 CH22_FGENES.104_9 1.3 338561 EOS38492 CH22_7294FG_LINK_EM:AC005500. GENSCAN. 421-5 CH22_EM : AC005500. GENSCAN, 421-5 1.3 335742 EOS35673 CH22_3105FG_601_13_LINK_EM:AC005500.GENSCAN.491-14 CH22_FGENES. 601-13 1.3 334993 EOS34924 CH22_2314FG_469_14_LINK_EM:AC005500.GENSCAN.365-16 CH22_FGENES.69_14 1.3 323430 EOS23361 AW062479 EST cluster (not in UniGene) 1.3 306069 EOS06000 AA906983 EST singleton (not in UniGene) with exon hit 1.3 331681 EOS31612 W85712 Hs. 119571 collagen ; type III ; alpha 1 (Ehters-Dantos syndrome type IV ; autosomat dominant) 1. 3 337986 EOS37917 CH22_6441FG_LINK_EM:AC005500. GENSCAN. 110-7 CH22_EM : AC005500. GENSCAN. 110-7 1. 3 313204 EOS13135 AI800518 Hs. 118158 ESTs 1.3 323189 EOS23120 AL121194 Hs. 120589 ESTs 1.3 318171 EOS18102 AA381202 EST cluster (not in UniGene) 1.3 307156 EOS07087 AI186762 EST singleton (not in UniGene) with exon hit 1.3 332713 EOS32644 AA349792 Hs. 78489 mutY (E. coli) homolog 1.3 312828 EOS12759 A1865455 Hs. 211818 ESTs ; Moderately similar to ! ! ! ! ALU SUBFAMILY J WARNING ENTRY !!! ! [H. sapiens] 1. 3 301127 EOS01058 AA758109 Hs. 121072 ESTs 1.3 311260 EOS11191 A1672509 Hs. 196582 ESTs 1.3 338364 EOS38295 CH227007FGUNK EM : AC005500. GENSCAN. 323-7 CH22_EM : AC005500. GENSCAN. 323-7 1.3 337904 EOS37835 CH22_6318FG_LINK_EM:AC005500.GENSCAN.56-17 CH22_EM : AC005500. GENSCAN. 56-17 1.3 329347 EOS29278 c_x_hs gi#6456785#ref# gn 1 + 1843318897 ex 4 4 CDSI 43. 39 465 3718 CH. X_hs girl6456785 1.3 313329 EOS13260 AW293704 Hs. 122658 ESTs 1. 3 314367 EOS14298 AA535749 ESTcluster (notinUniGene) 1.3 317098 EOS17029 A1123513 Hs. 125456 ESTs 1.3 306462 EOS06393 AA983397 EST singleton (not in UniGene) with exon hit 1.3 301254 EOS01185 A1049624 EST cluster (not in UniGene) with exon hit 1.3 335504 EOS35435 CH22_2856FG_571_15_LINK_EM:AC005500. GENSCAN. 460-34 CH22_FGENES.571_15 1.3 334270 EOS34201 CH22_1559FG_366_211NK_EM : AC005500. GENSCAN. 228-3 CH22_FGENES.368_2 1.3 334324 EOS34255 CH22_1616FG_375_1_LINK_EM : AC005500. GENSCAN. 235-1 CH22_FGENES.375_1 1.3 304254 EOS04185 AA046273 Hs. 111334 festin ; iightpoiypeptide 1.3 305731 EOS05662 AA829363 EST singleton (not in UniGene) with exon hit 1.3 323284 EOS23215 AA279381 Hs. 190010 ESTs 1.3 322007 EOS21938 AW410646 Hs. 165739 ESTs 1.3 334537 EOS34468 CH22_1839FG_403_2_LINK_EM : AC005500. GENSCAN. 268-2 CH22_FGENES.403_2 1.3 302360 EOS02291 AJ010901 Hs. 198267 mucin 4; tracheobronchial 1.3 311641 EOS11572 A1948829 Hs. 213786 ESTs 1.3 324643 EOS24574 AI436356 Hs. 130729 ESTs 1.3 327554 EOS27485 c _3_hs gií5867801íren gn 2-23092 23191 ex 2 6 CDSi 10. 44100107 CH. 03_hs gi#5867801 1.3 312165 EOS12096 AW292139 Hs. 115789 ESTs 1.3 304679 EOS04610 AA548741 EST singleton (not in UniGene) with exon hit 1.3 319564 EOS19495 AA026777 Hs. 169732 ESTs 1.3 310860 EOS10791 AW015920 Hs. 161359 ESTs 1.3 337161 EOS37092 CH22_5180FG_561_3_ CH22_FGENES. 561-3 1.3 311155 EOS11086 A1634410 Hs. 197608 EST 1.3 336846 EOS36777 CH22_4540FG_263_5_ CH22_FGENES. 263-5 1.3 310985 EOS10916 T51842 EST cluster (not in UniGene) 1. 3 329499 EOS29430 c10_p2 gi#1983518#gb#A gn 5 + 33463 33789 ex 1 1 CDSo 34.50 327 97 CH. 10_p2 gi#3983518 1.3 334924 EOS34855 CH22_2244FG_459__LINK_EM : AC005500. GENSCAN. 351-2 CH22_FGENES.459_2 1.3 330861 EOS30792 AA084064 Hs. 185747 ESTs 1.3 324658 EOS24589 A1694767 Hs. 129179 ESTs 1.3 323362 EOS23293 AL135067 Hs. 117182 ESTs 1.3 330468 EOS30399 L10343 Hs. 112341 protease inhibitor 3 ; skin-derived (SKALP) 1.3 314198 EOS14129 AA897581 Hs. 128773 ESTs 1.3 339436 EOS39367 CH22_8431FG_LINK_DJ579N16. GENSCAN. 19-1 CH22_DJ579N16. GENSCAN. 19-1 1.3 312483 EOS12414 A1417526 Hs. 184636 ESTs 1.3 321505 EOS21436 H73183 Hs. 129885 ESTs 1.3 332254 EOS32185 N64702 Hs. 194140 ESTs 1.3 328253 EOS28184 c_6_hs gi#6381894#ref# gn 1-44114509 ex 1 5 CDSI 4.20 99 4561 CH. 06_hs gi#6381894 1. 3 332357 EOS32288 W73417 Hs. 103183 EST 1.3 329017 EOS28948 c_x_hs gi#6682532#ref# gn 7-255591 255672 ex 3 3 CDSf 12.94 82 22 CH. x_hs 6682532 1.3 337504 EOS37435 CH22_5739FG_803_2_ CH22_FGENES. 803-2 1.3 316625 EOS16556 AA780307 Hs. 122156 ESTs 1.3 335389 EOS35320 CH22_2739FG_545_1_LINK_EM : AC005500. GENSCAN. 436-1 CH22_FGENES.545_1 1.3 310017 EOS09948 A1188739 Hs. 148488 ESTs 1. 3 314354 EOS14285 AL037984 Hs. 208982 ESTs ; Weakly similar to ! ! !! ALU SUBFAMILY J WARNING ENTRY !!!! [H. sapiens] 1.3 324641 EOS24572 AI732515 Hs. 189218 ESTs 1.3 335207 EOS35138 CH22_2546FG_510_4_LINK_EM : AC005500. GENSCAN. 402-3 CH22_FGENES.510_4 1.3 333673 EOS33604 CH22_934FG_246_5_LINK_EM: AC005500. GENSCAN. 101-3

CH22_FGENES. 246 5 1.3 334370 EOS34301 CH22_1664FG_378_18_LINK_EM: AC005500. GENSCAN. 240-1 CH22_FGENES.378_18 1.3 328690 EOS28621 c_7_hs gi#6588001#ref# gn 7 - 571207 571274 ex 13 CDSI 3.34 68 4325 CH. 07_hs gi#6588001 1.3 323208 EOS23139 AA203415 Hs. 136200 ESTs 1.3 307010 EOS06941 AI140014 EST singleton (not in UniGene) with exon hit 1.3 316563 EOS16494 AI587083 Hs. 200558 ESTs ; Weakly similar to ! ! ! ! ALUSUBFAMILYSPWARNINGENTRY ! ! ! ! [H. sapiens] 1.3 312219 EOS12150 H73505 Hs. 117874 ESTs 1.3 319884 EOS19815 T73234 EST cluster (not in UniGene) 1.3 334720 EOS34651 CH22_2030FG_421_31_LINK_EM : AC005500. GENSCAN. 282-31 CH22_FGENES.421_31 1.3 335836 EOS35767 CH22_3210FG_621_3_LINK_EM : AC005500. GENSCAN. 513-3 CH22_FGENES. 6213 1.3 305448 EOS05379 AA737894 Hs. 29797 ribosomal protein L10 1.3 314885 EOS14816 A1049878 Hs. 133032 ESTs 1.3 320130 EOS20061 A1820675 Hs. 203804 ESTs 1.3 310567 EOS10498 Al691065 Hs. 155780 ESTs 1.3 323898 EOS23829 AA347566 EST cluster (not in UniGene) 1.3 336132 EOS36063 CH22_3522FG_703_2_LINK_DA59H18. GENSCAN. 9-2 CH22_FGENES.703_2 1.3 337958 EOS37889 CH22 6403FGUNKEM : AC005500. GENSCAN. 98-6 CH22_EM : AC005500. GENSCAN. 98-6 1.3 305630 EOS05561 AA804508 EST singleton (not in UniGene) with exon hit 1.3 334916 EOS34847 CH22_2235FG_457_7_LINK_EM : AC005500. GENSCAN. 347-1 CH22_FGENES. 457_7 1.3 333542 EOS33473 CH22799FG1784UNKEM : AC005500. GENSCAN. 59-4 CH22_FGENES.178_4 1.3 331151 EOS31082 R82331 Hs. 164599 ESTs 1.3 315095 EOS15026 AA831815 Hs. 243788 ESTs 1.3 331593 EOS31524 N72150 Hs. 50193 EST 1.3 323767 EOS23698 A1807408 Hs. 166368 ESTs 1.3 334561 EOS34492 CH12_1866FG_405_1_LINK_EM : AC005500. GENSCAN. 270-5 CH22_FGENES. 4051 1.3 308191 EOS08122 A1538878 EST singleton (not in UniGene) with exon hit 1.3 319571 EOS19502 N91399 Hs. 220826 ESTs 1.3 316200 EOS16131 A1914535 Hs. 221377 ESTs 1.3 305996 EOS05927 AA889338 Hs. 163356 EST 1.2 318055 EOS17986 Al249193 Hs. 145945 ESTs 1.2 315570 EOS15501 A1860360 Hs. 160316 ESTs 1.2 320792 EOS20723 AW236504 Hs. 247020 ESTs 1.2 331649 EOS31580 W20364 Hs. 55412 ESTs ; Weakly similarto c29 [M. musculus] 1.2 303839 EOS03770 Z45939 EST cluster (not in UniGene) with exon hit 1.2 324399 EOS24330 AA814768 Hs. 21396 ESTs 1.2 317172 EOS17103 A1741232 Hs. 206744 ESTs 1.2 312452 EOS12383 A1692643 Hs. 172749 ESTs 1.2 325482 EOS25413 c12_hs gi#5866957#ref# gn 3 + 47957 48078 ex 5 7 CDSi 10.251221896 CH. 12_hs gi#5866957 1. 2 311395 EOS11326 R23313 EST cluster (not in UniGene) 1.2 336124 EOS36055 CH22_3513FG_701_9_LINK_DA59H18. GENSCAN. 8-9 CH22_FGENES. 7019 1.2 320082 EOS20013 AA487678 Hs. 189738 ESTs 1.2 312168 EOS12099 T92251 Hs. 198882 ESTs 1.2 338000 EOS37931 CH22_6472FG_LINK_EM : AC005500. GENSCAN. 119-5 CH22EM : AC005500. GENSCAN. 119-5 1. 2 338852 EOS38783 CH22_7705FG_LINK_DJ246D7. GENSCAN. 12-1 CH22_DJ246D7. GENSCAN. 12-1 1.2 312090 EOS12021 N57692 Hs. 118064 ESTs 1.2 316480 EOS16411 Api749921 Hs. 205377 ESTs 1.2 333259 EOS33190 CH22_500FG_118_LINK_EM : AC005500. GENSCAN. 2-7 CH22_FGENES.118_7 1.2 335211 EOS35142 CH22_2550FG_511_2_LINK_EM : AC005500. GENSCAN. 403-2 CH22-FGENES. 511-2 1.2 321950 EOS21881 AA594780 Hs. 172318 ESTs 1.2 337937 EOS37868 CH22_6370FG_LINK_EM : AC005500. GENSCAN. 86-1 CH22_EM : AC005500. GENSCAN. 86-1 1.2 316576 EOS16507 Al732114 Hs. 193046 ESTs ; Weakly similar to !!! ! ALU SUBFAMILY J WARNING ENTRY ! ! ! ! [H. sapiens] 1.2 322770 EOS22701 AA045796 Hs. 159971 SWIISNF related ; matrix associated; actin dependent regulator of chromatin; subfamily b ; member 1 1.2 329369 EOS29300 c_x_hs gi#5868842#ref# gn 1 - 121148 121516 ex 3 4 CDSi 8.503693910 CH. X_hs gi#5868842 1.2 304183 EOS04114 H91161 EST singleton (not in UniGene) with exon hit 1.2 339370 EOS39301 CH22_8343FG_LINK_BA232E17. GENSCAN. 1-12 CH22_BA232E17. GENSCAN. 1-12 1.2 303941 EOS03872 AW473878 Hs. 156110 Immunoglobulinkappavariable1D-8 1.2 302245 EOS02176 H18835 EST cluster (not in UniGene) with exon hit 1.2 335255 EOS35186 CH22-2597FGL517_2_LINK_EM : AC005500. GENSCAN. 411-2 CH22_FGENES.517_2 1.2 316610 EOS16541 AW087973 Hs. 126731 ESTs 1.2 314915 EOS14846 AA573072 Hs. 187748 ESTs ; Weakly similar to !!! ! ALU SUBFAMILY J WARNING ENTRY !!!! [H. sapiens] 1.2 315426 EOS15357 A1391486 Hs. 128171 ESTs 1.2 334003 EOS33934 CH122_1281FG_310_28_LINK_EM : AC005500. GENSCAN. 167-27 CH22_FGENES.310_28 1.2 304350 EOS04281 AA186871 EST singleton (not in UniGEne) with exon hit 1.2 325173 EOS25104 AI133215 Hs. 144662 ESTS ; Moderately similar to ! ! ! ! ALUSUBFAMILYJWARNINGENTRY ! ! ! ! [H. sapiens] 1.2 312313 EOS12244 AW293341 Hs. 122505 ESTs 1.2 333366 EOS33297 CH22_612FG_142_3_LINK_EM: AC005500. GENSCAN. 22-6

CH22_FGENES.142_3 1.2 334970 EOS34901 CH22_2291FGL466_3 LINK-2 CH22_FGENES.466_3 1.2 338668 EOS38599 CH22 7441FG _ L ! NK_EM : AC005500. GENSCAN. 465-1 CH22_EM : AC005500. GENSCAN. 465-1 1.2 336502 EOS36433 CH223926FG 833 8 LiNKDJ579N16. GENSCAN. 5-9 CH22_FGENES.833_8 1.2 309438 EOS09369 AW102802 Hs. 225787 ESTs ; Moderately similar to hypothetical protein [H. sapiens] 1.2 336194 EOS36125 CH22 _3591FG_717_ 20_LINK_DA59H18. GENSCAN. 20-19 CH22_FGENES.717_20 1.2 336678 EOS36609 CH22_4156FG_43_6_ CH22_FGENES. 43-6 1.2 321401 EOS21332 W90406 Hs. 35962 ESTs 1.2 306026 EOS05957 M902309 EST singleton (not in UniGene) with exon hit 1.2 336434 EOS36365 CH22_3854FG_826_1_LINK_BA232E17.GENSCAN.8-1 CH22_FGENES.826_1 1.2 315257 EOS15188 AW157431 Hs. 248941 ESTs 1.2 328349 EOS28280 c_7_hs gi#5868383#ref# gn 7-260704 260804 ex 2 9 CDSi 4. 37 101 621 CH. 07_hs gi#58688383 1.2 326112 EOS26043 c17_hs gi#5867192#ref# gn 1 + 2151 2725 ex 11 CDSI 54.87 575 1272 CH. 17_hs gi#5867192 1.2 333995 EOS33926 CH22_1272FG_310_19_LINK_EM: AC005500. GENSCAN. 167-18 CH22_FGENES.310_19 1.2 323683 EOS23614 A1380045 Hs. 225033 ESTs 1.2 330143 EOS30074 c21_p2 gi#4210430#Emb#gn 3 + 184737 184848 ex 4 4 CDSI 1.71 112111 CH. 21_p2 gi#4210430 1.2 329789 EOS29720 c14_p2 gi#6469354#emb# gn - 2 - 118977 119036 ex 1 3 CDSI 1. 19 60 1517 CH. 14_p2gií6469354 1.2 324397 EOS24328 M307836 Hs. 118758 ESTs ; Weakly similar to RLF [H. sapiens] 1.2 308729 EOS08660 A1799766 Hs. 208627 EST 1.2 323939 EOS23870 AW499632 Hs. 115696 ESTs 1.2 333444 EOS33375 CH22 694FG 1531 LìNK_EM : AC005500. GENSCAN. 34-1 CH22_FGENES.153_1 1.2 306302 EOS06233 AA937901 EST singleton (not in UniGene) with exon hit 1.2 313693 EOS13624 AW469180 Hs. 170651 ESTs 1.2 316652 EOS16583 AA789249 EST cluster (not in UniGene) 1.2 332325 EOS32256 T79428 Hs. 191264 ESTs 1.2 336235 EOS36166 CH22_3633FG_740_2_LINK_DA59H18. GENSCAN. 44-2 CH22_FGENES. 740 2 1.2 319436 EOS19367 R02750 EST cluster (not in UniGene) 1.2 312335 EOS12266 AW043620 Hs. 236993 ESTs 1.2 322109 EOS22040 A1884327 Hs. 244737 ESTs 1.2 328466 EOS28397 c_7_hs gi#5868434#ref# gn 1-1564315900 ex 12 CDSI 2.36 2581608 CH. 07_hs gi#5868434 1.2 323244 EOS23175 T70731 EST cluster (not in UniGene) 1. 2 312510 EOS12441 M779907 Hs. 117558 ESTs 1.2 314853 EOS14784 AA729232 Hs. 153279 ESTs 1.2 336946 EOS36877 CH22_4731FG_355_2_ CH22_FGENES.355-2 1.2 303874 EOS03805 AA258921 EST cluster (not in UniGene) with exon hit 1.2 312658 EOS12589 AA730280 Hs. 120936 ESTs 1.2 308354 EOS08285 Api611044 EST singleton (not in UniGene) with exon hit 1.2 310073 EOS10004 A1335004 Hs. 148558 ESTs 1.2 324777 EOS24708 AA744046 Hs. 133350 ESTs 1.2 300897 EOS00828 A1890356 Hs. 127804 ESTs 1.2 308371 EOS08302 A1620666 Hs. 242510 EST 1.2 306358 EOS06289 AA961821 EST singleton (not in UniGene) with exon hit 1.2 312295 EOS12226 AA578233 Hs. 173863 ESTs 1.2 319792 EOS19723 R20317 Hs. 22968 ESTs 1.2 338546 EOS38477 CH22J267FG_LINK_EM : AC005500. GENSCAN. 410-1 CH22_EM : AC005500. GENSCAN. 410-1 1.2 314546 EOS14477 AW007211 Hs. 186672 ESTs 1.2 338494 EOS38425 CH22_7184FG_LINK_EM: AC005500. GENSCAN. 385-5 CH22_EM : AC005500. GENSCAN. 385-5 1.2 331131 EOS31062 R54797 Hs. 26238 EST; Weakly similarto reverse transcriptase homolog [H. sapiens] 1.2 309939 EOS09870 AW419122 EST singleton (not in UniGene) with exon hit 1.2 332932 EOS32863 CH22_153FG_38_6_lINK_C20H12. GENSCAN. 29-6 CH22_FGENES.38_6 1.2 309653 EOS09584 AW196800 Hs. 180842 ribosomal protein L13 1.2 318647 EOS18578 Aì526152 ESTcluster (notinlJniGene) 1.2 304044 EOS03975 T52479 Hs. 252259 ribosome protein S3 1.2 330307 EOS30238 c_7_p2 gi#4877982#gb#A gn 2 + 107384 107559 ex 2 4 CDSi 9.96 176 4 CH. 07_p2 gií4877982 1.2 314499 EOS14430 AL044570 Hs. 147975 ESTs 1.2 338053 EOS37984 CH22_6552FG_LINK_EM : AC005500. GENSCAN. 158-1 CH22_EM : AC005500. GENSCAN. 158-1 1.2 332991 EOS32922 CH22_215FG_56_4_LINK_EM : AC000097. GENSCAN. 17-4 CH22_FGENES.56_4 1.2 306308 EOS06239 AA946870 EST singleton (not in UniGene) with exon hit 1.2 338120 EOS38051 CH22_6655FG_LINK_EM : AC005500. GENSCAN. 195-1 CH22_EM : AC005500. GENSCAN. 195-1 1.2 313703 EOS13634 A1161293 Hs. 146862 ESTs ; Weakly similar to KIAA0525 protein [H. sapiens] 1.2 330563 EOS30494 U50553 Hs. 147916 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3 1.2 332886 EOS32817 CH22_106FG_33_7_LINK_C20H12. GENSCAN. 22-9 CH22_FGENES.33_7 1.2 303844 EOS03775 U94362 Hs. 58589 glycogenin 2 1.2 321755 EOS21686 AI215881 Hs. 144042 ESTs 1.2 333532 EOS33463 CH22J89FG_175_19_LINK_EM : AC005500. GENSCAN. 53-25

CH22_FGENES.175_19 1.2 332863 EOS32794 CH22_81FG_28_3_LINK_C20H12. GENSCAN. 18-3 CH22_FGENES.28_3 333254 EOS33185 CH22_495FG_118_2_LINK_EM: AC005500. GENSCAN. 2-2 CH22_FGENES.118_2 1.2 317459 EOS17390 A1367254 Hs. 131248 ESTs 1.2 315353 EOS15284 AW452608 Hs. 129817 ESTs 1.2 300732 EOS00663 A1369956 Hs. 257891 ESTs 1.2 303502 EOS03433 AA488528 EST cluster (not in UniGene) with exon hit 1.2 333126 EOS33057 CH22_355FG_82_3_LINK_EM : AC000097. GENSCAN. 66-10 CH22_FGENES.82_3 1.2 332929 EOS32860 CH22_150FG_38_3_LINK_C20H12. GENSCAN. 29-3 CH22_FGENES.38_3 1.2 329502 EOS29433 c10_p2 gi#3983517#gb#U gn 1 + 75 338 ex 1 1 CDSo 46.82 264100 CH. 10_p2 gi#3983517 1.2 333408 EOS33339 CH22_657FG_145_6_LINK_EM : AC005500. GENSCAN. 26-6 CH22_FGENES.145_6 1.2 315472 EOS15403 AA828850 Hs. 165469 ESTs 1.2 328290 EOS28221 c_7_hs gi#5868363#ref# gn 2 - 127366 127496 ex 1 5 CDSI 5. 24 131 289 CH. 07_hs gi#5868363 1.2 328662 EOS28593 c_7_hs gi#6004473#ref# gn 22 + 1184773 1184855 ex 7 8 CDSi 12.72 83 3916 CH. 07_hs gií6004473 1.2 319808 EOS19739 T58960 EST cluster (not in UniGene) 1.2 303929 EOS03860 AW470753 EST singleton (not in UniGene) with exon hit 1.2 315712 EOS15643 AI950133 Hs. 120882 ESTs; Moderately similar to !!!! ALU SUBFAMILY J WARNING ENTRY !!!! [H. sapiens] 1.2 307391 EOS07322 Api225058 EST singleton (not in UniGene) with exon hit 1.2 335499 EOS35430 CH22_2851FG_571_8_LINK_EM : AC005500. GENSCAN. 460-28 CH22_FGENES.571_8 1.2 303792 EOS03723 C75094 Hs. 199839 ESTs ; Highlysimilarto NG22 [H. sapiens] 1.2 327287 EOS27218 c_1_hs gi#5867479#ref# gn 1 - 62838 63024 ex 4 5 CDSi 11.66 187 1628 CH. 01_hs gi#5867479 1.2 317713 EOS17644 A1733306 Hs. 128071 ESTs 1.2 330137 EOS30068 c2f_p2 gi#4210430#emb#gn 1 - 21220 21377 ex 2 3 CDSi 1. 89158104 CH, 21_p2 gi#4210430 1.2 308157 EOS08088 AI510824 Hs. 75968 thymosin; beta 4; X chromsome 1. 2 314452 EOS14383 AL042699 Hs. 209222 ESTs 1.2 308268 EOS08199 Api567509 Hs. 172928 collagen; type I; alpha 1 1.2 321467 EOS21398 X13075 EST cluster (not in UniGene) 1.2 320993 EOS20924 AL050145 Hs. 225986 Homo sapiens mRNA ; cDNA DKFZp586C2020 (from clone DKFZp586C2020) 1.2 336778 EOS36709 CH22 4367FG 159 4 CH22FGENES. 159-4 1.2 319827 EOS19758 T62778 ESTcluster (notinUniGene) 1.2 308249 EOS08180 A1560998 EST singleton (not in UniGene) with exon hit 1.2 310094 EOS10025 AW450967 Hs. 235240 ESTs 1.2 336902 EOS36833 CH22_2655FG_331_2_ CH22_FGENES. 331-2 1.2 339044 EOS38975 CH22_7944FG_LINK_DA59H18.GENSCAN. 27-5 CH22_DA59H18.GENSCAN.27-5 1.2 336675 EOS36606 CH22_4153FG_43_3_ CH22_FGENES. 43-3 1.2 303563 EOS03494 AA367699 Hs. 118787 transforming growth factor ; beta-induced ; 68kD 1.2 330673 EOS30604 D57823 Hs. 92962 See23 (S. cerevisiae) homolog A 1.2 311814 EOS11745 AW377113 Hs. 119640 ESTs ; Moderately similar to zinc finger protein [H. sapiens] 1.2 335481 EOS35412 CH22_2833FG_570_10_LINK_EM : AC005500. GENSCAN. 460-4 CH22_FGENES.570_10 1.2 314775 EOS14706 Ail49880 Hs. 188809 ESTs 1.2 324961 EOS24892 AA613792 ESTcluster (notinUniGene) 1.2 313458 EOS13389 AA007259 Hs. 255853 ESTs 1.2 307074 EOS07005 Aìl50989 EST singleton (not in UniGene) with exon hit 1.2 337964 EOS37895 CH22_6410FG_LINK_EM : AC005500. GENSCAN. 100-9 CH22_EM : AC005500. GENSCAN. 100-9 1.2 326519 EOS26450 c19_hs gi#5867439#ref# gn 4 + 166004 166243 ex 4 5 CDSi 4.49 240 2534 CH. 19_hs gi#5867439 1.2 337366 EOS37297 CH22_5551FG_736_1_ CH22_FGENES. 736-1 1.2 322340 EOS22271 AF088076 EST cluster (not in UniGene) 1.2 307954 EOS07885 Al419692 EST singleton (not in UniGene) with exon hit 1.2 328615 EOS28546 c_7_hs gi#5868239#ref# gn 2 + 35214 35347 ex 3 4 CDSi 11.49 134 3651 CH. 07_hs gi#5868239 1.2 317787 EOS17718 AW339612 Hs. 249364 ESTs 1.2 335288 EOS35219 CH22_FGENES.CH22_2630FG_527_1_LINK_EM : AC005500. GENSCAN. 421-1 CH22_FGENES. 527_1 1.2 323175 EOS23106 A1827137 Hs. 184023 ESTs 1.2 330893 EOS30824 AA149620 Hs. 71999 ESTs 1.2 306810 EOS06741 A1057294 EST singleton (not in UniGene) with exon hit 1.2 338239 EOS38170 CH22_6833FG_LINK_EM : AC005500. GENSCAN. 264-5 CH22_EM : AC005500. GENSCAN. 264-5 1.2 332347 EOS32278 W60326 Hs. 221716 ESTs 1.2 309782 EOS09713 AW275156 Hs. 156110 Immunoglobulin kappa variable 1 D-8 1.2 322518 EOS22449 A1133446 EST cluster (not in UniGene) 1.2 301187 EOS01118 AA806542 EST cluster (not in UniGene) with exon hit 1.2 312129 EOS12060 AW300867 EST cluster (not in UniGene) 1.2 334714 EOS34645 CH22_2024FG_421_25_LINK_EM : AC005500. GENSCAN. 282-25 CH22_FGENES.421_25 1.2 316586 EOS16517 A1205077 Hs. 144689 ESTs 1. 2 320488 EOS20419 R31386 EST cluster (not in UniGene) 1.2 327458 EOS27389 c_2_hs gií6004455íren gn 3 + 173257173378 ex 5 7 CDSi 4.031221184 CH. 02_hs gií6004455 1.2 336707 EOS36638 CH22_4212FG_64_3_ CH22_FGENES. 64-3 1.2 313561 EOS13492 AA040155 EST cluster (not in UniGene) 1.2

330906 EOS30837 AA169498 Hs. 72804 ESTs 1. 2 330987 EOS30918 H40988 Hs. 131965 ESTs ; Weakly similar to I ! ! ! ALU SUBFAMILY J WARNING ENTRY ! I ! I [H. sapiens] 1.2 325041 EOS24972 A1809182 Hs. 130907 ESTs 1. 2 313225 EOS13156 AA502384 Hs. 151529 ESTs 1. 2 305295 EOS05226 AA687131 EST singleton (not in UniGene) with exon hit 1.2 306896 EOS06827 A1093383 EST singleton (not in UniGene) with exon hit 1. 2 326981 EOS26912 c21_hs gi#6588016#ref# gn 3 + 105091 106038 ex 1 1 CDSo 122.69 948 567 CH. 21_hs gi#6588016 332225 EOS32156 N33213 Hs. 100425 ESTs 1. 2 318802 EOS18733 R19443 Hs. 92414 ESTs 1.2 318413 EOS18344 AI138592 Hs. 144936 ESTs 1.2 312292 EOS12223 AW451893 Hs. 151124 ESTs 1.2 323753 EOS23684 AA327102 EST cluster (not in UniGene) 1.2 313582 EOS13513 AW207684 Hs. 13583 ESTs 1.2 317836 EOS17767 AA983913 Hs. 128929 ESTs 1.2 332868 EOS32799 CH22_86FG_28_8_LiNK_C20H1 2. GENSCAN. 18-8 CH22_FGENES.28_8 1.2 336924 EOS36855 CH22_4699FG_347_9_ CH22_FGENES. 347-9 1.2 327791 EOS27722 c_5_hs gi#5867977#ref# gn 1 + 2249122610 ex 6 7 CDSi 11.29120 658 CH. 05_hs 5867977 1.2 330717 EOS30648 AA233926 Hs. 23635 ESTs 1.2 322944 EOS22875 AA112573 EST cluster (not in UniGene) 1.2 312108 EOS12039 T82331 Hs. 127453 ESTs 1. 2 332570 EOS32501 AA401376 Hs. 26176 ESTs 1.2 330880 EOS30811 AA132420 Hs. 53542 KIAA0986 protein 1.2 310341 EOS10272 AW302773 EST cluster (not in UniGene) 1.2 334012 EOS33943 CH22_1290FG_313_3_LINK_EM: AC005500. GENSCAN. 169-3 CH22_FGENES.313_3 1.2 318230 EOS18161 AA558125 EST cluster (not in UniGene) 1.2 336071 EOS36002 CH22_3457FG_685_3_LINK_DJ32I10. GENSCAN. 21-6 CH22_FGENES.685_3 1.2 338510 EOS38441 CH22_7208FG_LINK_EM:AC005500. GENSCAN. 391-22 CH22_EM : AC005500. GENSCAN. 391-22 1.2 334487 EOS34418 CH22_1786FG_395_9_LINK.. EM : AC005500. GENSCAN. 258-10 CH22FGENES. #95_9 1.2 320661 EOS20592 AA864846 EST cluster (not in UniGene) 1.2 335200 EOS35131 CH22_2538FG_508_9_LINK_EM: AC005500. GENSCAN. 401-9 CH22_FGENES.508_9 1.2 333582 EOS33513 CH22_842FG_201_2_LìNK_EM : AC005500. GENSCAN. 72-3 CH22_FGENES. @01_2 1.2 320789 EOS20720 R78712 EST cluster (not in UniGene) 1.2 321185 EOS21116 H51659 Hs. 189854 ESTs 1.2 337740 EOS37671 CH22_6085FG_LINK_EM: AC000097. GENSCAN. 100-6 CH22EM : AC000097. GENSCAN. 100-6 1.2 315064 EOS14995 AA775208 Hs. 136423 ESTs 1.2 334883 EOS34814 CH22_2197FG_451_6_LINK_EM : AC005500. GENSCAN. 340-6 CH22_FGENES.451_6 1.2 331825 EOS31756 AA411144 Hs. 104768 ESTs 1.2 319141 EOS19072 F12377 EST cluster (not in UniGene) 1.1 333682 EOS33613 CH22_944FG_247_10_LINK_EM:AC005500. GENSCAN. 102-10 CH22_FGENES.247_10 1.1 336140 EOS36071 CH22_3530FG_705_2_LINK_DA59H18.GENSCAN. 10-2 CH22_FGENES.705_2 1.1 320727 EOS20658 U96044 EST cluster (not in UniGene) 1.1 323947 EOS23878 AA649842 Hs. 186667 ESTs 1.1 324746 EOS24677 AA603367 Hs. 222294 ESTs 1.1 306744 EOS06675 A1031882 EST singleton (not in UniGene) with exon hit 1.1 326517 EOS26448 c19_hs gi#5867439#ref# gn 1 + 44732 46356 ex 6 6 CDSI 148. 22 1625 2512 CH. 19_hs gil5867439 1.1 333597 EOS33528 CH22_858FG_211_5_LINK_EM : AC005500. GENSCAN. 79-5 CH22_FGENES.211_5 1.1 330135 EOS30066 c21_p2 gi#4456470#emb# gn 2 - 121583 121885 ex 2 2 CDSf 18.67 303 102 CH. 21_p2 gi#4456470 1.1 315118 EOS15049 AA564921 Hs. 143899 ESTs 1.1 302893 EOS02824 AL117539 Hs. 173515 Homo sapiens mRNA ; cDNA DKFZp586H021 (from clone DKFZp586H021) 1.1 337169 EOS37100 CH22_5189FG_563_1_ CH22_FGENES.563-1 1.1 336121 EOS36052 CH22_3510FG_701_6_LINK_DA59H18. GENSCAN. 8-6 CH22_FGENES.701_6 1.1 323332 EOS23263 A1829520 Hs. 227513 ESTs 1.1 320911 EOS20842 A1056872 Hs. 133386 ESTs 1.1 327990 EOS27921 c_6_hs gi#5868218#ref#gn 2 - 36225 36503 ex 1 2 COSI 16.35 279 1419 CH. 06_hs gií5ii68218 1.1 320425 EOS20356 C14069 Hs. 201627 ESTs ; Moderately similar to !!!! ALU SUBFAMILY SQ WARNING ENTRY !! ! ! [H. sapiens] 1. 1 327075 EOS27006 c21_hs gi#6531965#ref# gn 58 + 4041318 4041431 ex 4 4 CDSI 1.791141285 CH. 21_hs ! 6531965 1.1 314384 EOS14315 AA535840 Hs. 162203 ESTs ; Weakìysimilartoaltemaüveìysplicedproductusingexon13A [H. sapiens] 1, 1 338716 EOS38647 CH227502FGL) NK EM : AC005500. GENSCAN. 488-9 CH22_EM : AC005500. GENSCAN. 488-9 1.1 330886 EOS30817 AA135606 Hs. 189384 ESTs ; Weakly similar to ! ! ! ! ALU SUBFAMILY J WARNING ENTRY ! !!! [H. sapiens] 1.1 327331 EOS27262 c_1_hs gi#5867516#ref# gn 4-55606 55737 ex 2 6 CDSi 7.01132 2349 CH. 01_hs 5867516 1.1 326714 EOS26645 c20_hs gi#5867595#ref# gn 2 + 124490 124568 ex 5 6 CDSi 0.11791020 CH. @0_hs gi#5867595 1.1 316734 EOS16665 AW080237 Hs. 252884 ESTs 1.1 311660 EOS11591 A1978583 Hs. 232161 ESTs 1. 1 312757 EOS12688 A1285970 Hs. 183817 ESTs 1.1

331686 EOS31617 W88502 Hs. 182258 ESTs 337840 EOS37771 CH22_6223FG_LINK_EM AC005500. GENSCAN. 26-9 CH22 EM : AC005500. GENSCAN. 26-9 1. 1 332093 EOS32024 AA608794 Hs. 112592 ESTs 319595 EOS19526 H81361 Hs. 194485 ESTs 1. 1 315990 EOS15921 A1800041 Hs. 190555 ESTs 1. 1 322438 EOS22369 W44531 Hs. 167851 ESTs 1. 1 332965 EOS32896 CH22_189FG_50_3_LINK_EM: AC000097. GENSCAN. 3-5 CH22_FGENES.50_3 337182 EOS37113 CH22_5204FG_570_2_ CH22_FGENES.570-2 1.1 334948 EOS34879 CH22_2269FG_465_15_LINK_EM: AC005500. GENSCAN. 359-13 CH22_FGENES.465_15 325864 EOS25795 c16_hs gi#5867069#ref# gn 2 - 110834 110904 ex 3 3 CDSf 9.7671457 CH. 16_hs gi#5867069 1.1 337760 EOS37691 CH22_6110FG_LINK_EM : AC000097. GENSCAN. 116-8 CH22_EM : AC000097. GENSCAN. 116-8 1. 1 315422 EOS15353 AW135357 Hs. 192374 ESTs 1. 1 338889 EOS38820 CH22_7746FG_LINK_DJ32I10. GENSCAN. 7-1 CH22_DJ32I10. GENSCAN. 7-1 1. 1 332961 EOS32892 CH22_185FG_48_18_LINK_EM : AC000097. GENSCAN. 2-14 CH22_FGENES.48_18 314703 EOS14634 Api791249 EST cluster (not in UniGene) 1. 1 317791 EOS17722 A1801500 Hs. 128457 ESTs 1. 1 333680 EOS33611 CH22_942FG_247_7_LINK_EM : AC005500. GENSCAN. 102-7 CH22_FGENES. 247 7 1. 1 322419 EOS22350 AA248987 Hs. 14084 ESTs ; HighlysimilartozincRINGfingerproteinSAG [M. musculus] 1. 1 338124 EOS38055 CH22_6661 FG _ LINK_EM : AC005500. GENSCAN. 196-2 CH22 EM : AC005500. GENSCAN. 196-2 1. 1 308884 EOS08815 Api833131 Hs. 179100 ESTs 1. 1 333349 EOS33280 CH22_595FG_140_3_LINK_EM:AC005500. GENSCAN. 20-3 CH22_FGENES. 140_3 1. 1 313150 EOS13081 AA824410 Hs. 165003 ESTs 1. 1 339208 EOS39139 CH22_8146FG_LINK_FF113D11. GENSCAN. 6-3 CH22FF113D11. GENSCAN. 6-3 1. 1 335653 EOS35584 CH22_3013FG_590_4_LINK_EM : AC005500. GENSCAN. 484-4 CH22_FGENES. 590_4 1. 1 319524 EOS19455 AA682865 Hs. 194441 ESTs 1. 1 301576 EOS01507 AI682905 Hs. 146875 ESTs ; Weakly similar to ! ! !! ALU SUBFAMILY J WARNING ENTRY ! ! ! ! [H. sapiens] 1. 1 317598 EOS17529 AW206035 Hs. 192123 ESTs 1. 1 333473 EOS33404 CH22_724FG_162_3_LINK_EM : AC005500. GENSCAN. 42-10 CH22_FGENES.162_3 1.1 333949 EOS33880 CH22_1225FG_303_5_LINK_EM: AC005500. GENSCAN. 162-9 CH22_FGENES. 303_5 1. 1 339256 EOS39187 CH22_8207FG_LINK_BA354I12. GENSCAN. 7-11 CH22_BA354I12. GENSCAN. 7-11 1. 1 332884 EOS32815 CH22_104FG_33_5_LINK_C20H12. GENSCAN. 22-7 CH22_FGENES.33_5 314660 EOS14591 AA436007 Hs. 188780 ESTs 1. 1 333220 EOS33151 CH22_457FG_104_12_LINK_EM: AC000097. GENSCAN. 108-11 CH22_FGENES.104_12 1.1 308106 EOS08037 Al476803 EST singteton (not in UniGene) with exon hit 1. 1 320709 EOS20640 AA456660 Hs. 154165 ESTs 1. 1 307612 EOS07543 A1290787 EST singleton (not in UniGene) with exon hit 1. 1 330286 EOS30217 c_5_p2 gi#6671913#gb#A gn 2 - 31050 31171 ex 2 7 CDSi 8. 84 122 791 CH. 05_p2 gi#6671913 1.1 304495 EOS04426 AA446448 EST singleton (not in UniGene) with exon hit 1. 1 310583 EOS10514 AW205632 Hs. 211198 ESTs 1. 1 332896 EOS32827 CH22_117FG_35_10_LINK_C20H12.GENSCAN. 24-9 CH22_FGENES.35_10 1.1 337602 EOS37533 CH22 5895FG LINK C20H12.GENSCAN. 15-1 CH22_C20H12. GENSCAN. 15-1 1. 1 307626 EOS07557 A1300035 EST singleton (not in Un ! Gene) with axon hit 334696 EOS34627 CH22_2006FG_421_5_LINK_EM : AC005500. GENSCAN. 282-5 CH22_FGENES.421_5 1.1 318652 EOS18583 T53259 EST cluster (not in UniGene) 1. 1 337844 EOS37775 CH226229FGUNKEM : AC005500. GENSCAN. 30-9 CH22_EM : AC005500. GENSCAN. 30-9 1. 1 334823 EOS34754 CH22_2137FG_437_5_LINK_EM : AC005500. GENSCAN. 301-7 CH22_FGENES.437_5 1.1 333928 EOS33859 CH22_1201FG_299_2_LINK_EM : AC005500. GENSCAN. 158-5 CH22_FGENES.299_2 1.1 337503 EOS37434 CH22_5738FG_803 1 CH22 FGENES. 803-1 1. 1 323044 EOS22975 AA148725 Hs. 154190 ESTs 1. 1 329164 EOS29095 c_x_hs gi#5868691#ref# gn 1 + 62305 62517 ex 2 2 CDSI 17. 51 2131868 CH.X_hs gi#5868691 1.1 335468 EOS35399 CH22_2819FG_567_4_LINK_EM : AC005500. GENSCAN. 454-12 CH22_FGENES.567_4 1.1 338962 EOS38893 CH22_FGENES.7838FG__LINK_DJ32I10.GENSCAN. 23-39 CH22_DJ32I10. GENSCAN. 23-39 1. 1 323570 EOS23501 AL038623 Hs. 208752 ESTs ; Weakly similar to ! ! !! ALU SUBFAMILY SX WARNING ENTRY ! !!! [H. sapiens] 1. 1 333568 EOS33499 CH22 826FG 185_1_LiNK_EM : AC005500. GENSCAN. 64-1 CH22_FGENES.185_1 1.1 331865 EOS31796 AA425756 Hs. 98445 ESTs 1. 1 336246 EOS36177 CH22_3644FG_746_5_LINK_DA59H18. GENSCAN. 48-4 CH22_FGENES.746_5 1.1 337238 EOS37169 CH22_5343FG_641_3_ CH22_FGENES.641-3 1.1

305089 EOS05020 AA642622 ESTsingteton (notinUniGene) withexonhit 1. 1 300097 EOS00028 A1916973 Hs. 213603 ESTs 1. 1 313134 EOS13065 N63406 Hs. 258697 ESTs 1. 1 337452 EOS37383 CH22_5665FG_775_1_ CH22_FGENES.775-1 1.1 325433 EOS25364 c12_hs gií5866936lrefi gn 4-480706 480826 ex 3 4 CDSi 1.99121818 CH. 12_hs gi#5866936 1.1 335999 EOS35930 CH22_3380FG_657_1_LINK_DJ246D7.GENSCAN. 11-1 CH22_FGENES.657_1 333580 EOS33511 CH22_840FG_199_2_LINK_EM : AC005500. GENSCAN. 71-2 CH22_FGENES.199_2 336836 EOS36767 CH22 4512FG_247 11 CH22_FGENES. 247-11 1. 1 334677 EOS34608 CH22_1986FG_418_30_LINK_EM:AC005500.GENSCAN.279-31 CH22_FGENES.418_30 1.1 329062 EOS28993 c_x_hs gi#5868690#ref# gn 3 - 58977 59094 ex 4 11 CDSI -6.19 118 627 CH. X_hs ! 5868590 1. 1 333671 EOS33602 CH22_932FG_245_5_LINK_EM : AC005500. GENSCAN. 100-12 CH22_FGENES.245_5 1.1 304941 EOS04872 AA612612 EST singleton (not in UniGene) with exon hit 1. 1 315772 EOS15703 AW515373 Hs. 158893 ESTs 1. 1 301281 EOS01212 AA843986 Hs. 190586 ESTs 1. 1 333520 EOS33451 CH22777FG1743LiNKEM : AC005500. GENSCAN. 53-6 CH22_FGENES.174_3 1.1 315203 EOS15134 A1559820 Hs. 199438 ESTs 1. 1 315927 EOS15858 AW025517 Hs. 133250 ESTs 1. 1 317161 EOS17092 AA972165 Hs. 150308 ESTs 1. 1 337692 EOS37623 CH22_6028FG_LINK_EM : AC000097. GENSCAN. 78-12 CH22EM : AC000097. GENSCAN. 78-12 1. 1 331472 EOS31403 N24830 yx70a02. sl Scares melanocyte 2NbHM Homo sapiens cDNA clone IMAGE : 267050 3'similar to gb#M87912#HUMALNE562 Human carcinoma cell-derived Alu RNA transcript, (rRNA); contains Alu repefifive element ;, mRNA sequence. 1. 1 336439 EOS36370 CH22_3859FG_827_4_LINK_DJ579N16.GENSCAN. 1-3 CH22_FGENES.827_4 1.1 326882 EOS26813 c20_hs gi#6682509#ref# gn 2-167988168179ex44 CDSf 18.69192 2238 CH. 20_hs gi#6682509 1.1 336977 EOS36908 CH22_4793FG_380_9_ CH22_FGENES.380-9 1.1 333983 EOS33914 CH22_1260FG_310_7_LINK_EM : AC005500. GENSCAN. 167-5 CH22_FGENES.310_7 1.1 328878 EOS28809 c_7_ hs gi#6552423#ref# gn 1 + 105580 105774 ex 67 CDSi 2.911956195 CH. 07 hsgií6552423 1. 1 330415 EOS30346 D83777 Hs. 75137 KIAA0193 gene product 1. 1 324824 EOS24755 A1826999 Hs. 224624 ESTs 1. 1 325815 EOS25746 c14_hs gi#662483#ref# gn 1 - 129273 130754 ex 11 CDSo 11.82 1482 2225 CH. 14_hs gi#6682483 1.1 300463 EOS00394 N52510 Hs. 186470 ESTs 1. 1 335708 EOS35639 CH22_3069FG_599_8_LINK_EM : AC005500. GENSCAN. 490-11 CH22_FGENES.599_8 1.1 324575 EOS24506 AW502257 EST cluster (not in UniGene) 1. 1 337951 EOS37882 CH22_6391FG_LINK_EM : AC005500. GENSCAN. 94-1 CH22_EM : AC005500. GENSCAN. 94-1 1. 1 335935 EOS35866 CH22_3313FG_646_6_LINK_DJ246D7.GENSCAN. 1-5 CH22_FGENES. 646_6 334914 EOS34845 CH22_2233FG_457_3_LINK_EM : AC005500. GENSCAN. 346-2 CH22_FGENES. 457 3 1. 1 309527 EOS09458 AW150648 Hs. 75621 protease inhibitor 1 (anti-elastase) ; alpha-l-antitrypsin 318901 EOS18832 AW368520 Hs. 24639 ESTs 320484 EOS20415 AA094436 Hs. 155712 follistatin-like 1 333665 EOS33596 CH22_926FG_244_1_LINK_EM : AC005500. GENSCAN. 99-1 CH22_FGENES.244_1 1.1 335860 EOS35791 CH22_3235FG_629-5_LINIK_EM:AC005500. GENSCAN. 519-4 CH22_FGENES.629_5 1.1 313339 EOS13270 AI682536 Hs. 163495 ESTs 1. 1 300149 EOS00080 AW448916 Hs. 149018 ESTs 1. 1 318112 EOS18043 A1028162 Hs. 132307 ESTs 1. 1 337807 EOS37738 CH22_6178FG_LINK_EM : AC005500. GENSCAN. 9-4 CH22_EM : AC005500. GENSCAN. 9-4 1. 1 336917 EOS36848 CH22_4688FG-346_4_ CH22_FGENES.346-4 1.1 337489 EOS37420 CH22 5722FG_799 2 CH22 FGENES. 799-2 1. 1 320112 EOS20043 T92107 Hs. 188489 ESTs 1. 1 332975 EOS32906 CH22_199FG_51_10_LINK_EM: AC000097. GENSCAN. 4-12 CH22_FGENES.51_10 1.1 327805 EOS27736 c_5_hs gi#58679868#ref# gn 2 + 19952 20019 ex 12 CDSf 9.47 68 988 CH. 05_hs gi#5867968 1.1 339215 EOS39146 CH22_8153FG_ 8153FGUNKFF113D11. GENSCAN. 6-10 CH22_FF113D11. GENSCAN. 6-10 1. 1 311965 EOS11896 T69279 EST cluster (not in UniGene) 1. 1 314043 EOS13974 AA827082 EST cluster (not in UniGene) 1. 1 333447 EOS33378 CH22 _697FG_154_5_LINK_EM : AC005500. GENSCAN. 35-6 CH22_FGENES.154_5 1. 1 333242 EOS33173 CH22_481FG_111_6_LINK_EM : AC000097. GENSCAN. 120-5 CH22_FGENES.111_6 1.1 338596 EOS38527 CH22J343FG_LINK_EM : AC005500. GENSCAN. 437-2 CH22_EM : AC005500. GENSCAN. 437-2 1. 1 329989 EOS29920 c16_p2 gi#4567166#gb#A gn 2+ 72861 73052 ex 1 3 CDSf 18.02192 590 CH. 16_p2 gi#4567166 1.1 315675 EOS15606 AA652272 Hs. 197320 ESTs 336722 EOS36653 CH22_4245FG_84_2 CH22_FGENES.84-2 1.1

334220 EOS34151 CH22_1503FG_359_4_LINK_EM : AC005500. GENSCAN. 217-7 CH22_FGENES.359_4 1.1 336703 EOS36634 CH22_4201FG_56-3_ CH22_FGENES.56-3 336397 EOS36328 CH22_3812FG_823_12_LINK_BA232E17. GENSCAN. 6-11 CH22_FGENES.823_12 1.1 316105 EOS16036 AW295687 Hs. 254420 ESTs 1. 1 334661 EOS34592 CH22_1969FG_418_9_LIK_EM : AC005500. GENSCAN. 279-13 CH22_FGENES.418_9 1.1 307783 EOS07714 AI347274 EST singleton (not in UniGene) with exon hit 1. 1 333997 EOS33928 CH22_1275G_310-22_LINK_EM : AC005500. GENSCAN. 167-21 CH22_FGENES.310_22 1.1 331903 EOS31834 AA436673 Hs. 29417 Homo sapiens mRNA ; cDNA DKFZp586B0323 (from clone DKZp586B0323) .1 328249 EOS28180 c_6_hs gi#6381891#ref# gn 2-96352 96527 ex 2 3 CDSi 6.19176 4550 CH. 06_hs gií6381891 1. 1 338251 EOS38182 CH22_6849FG_LINK_EM:AC005500. GENSCAN. 270-1 CH22_EM : AC005500. GENSCAN. 270-1 1. 1 323561 EOS23492 AA825426 Hs. 238832 ESTs ; Weakly similar to ! ! !! ALU SUBFAMILY J WARNING ENTRY ! !!! [H. sapiens] 1. 1 301464 EOS01395 AA991519 Hs. 253324 ESTs 1. 1 335916 EOS35847 CH22_3293FG_636_12_LINK_EM : AC005500. GENSCAN. 526-12 CH22_FGENES.636_12 1.1 321828 EOS21759 X56197 ESTcluster (notinUniGene) 1. 1 327413 EOS27344 c_2_hs gií5867750lren gn 3 + 101410 101508 ex 4 5 CDSi 4.34 99 587 CH. 02-hs gi#5867750 1.1 334474 EOS34405 CH22_1773FG_394_5_LINK_EM : AC005500. GENSCAN. 257-5 CH22_FGENES.394_5 336739 EOS36670 CH22_4291FG_117_3_ CH22_FGENES.117-3 1.1 316517 EOS16448 AI784315 Hs. 123163 ESTs 1. 1 325519 EOS25450 c12_hs gií6017036lren gn 5-186804186915 ex 1 3 CDSI 8. 36 112 2508 CH. 12_hs gi#6017036 1.1 333875 EOS33806 CH22_1145FG_291_11_LINK_EM : AC005500. GENSCAN. 149-6 CH22_FGENES.291_11 1.1 338221 EOS38152 CH22_679/FG_LINK-EM : AC005500. GENSCAN. 246-10 CH22_EM : AC005500. GENSCAN. 246-10 1. 1 336878 EOS36809 CH224617FG 318 5 CH22FGENES. 318-5 1. 1 337919 EOS37850 CH22_6388FG_LINK_EM: AC005500. GENSCAN. 66-5 CH22_EM : AC005500. GENSCAN. 66-5 1. 1 309828 EOS09759 AW293999 EST singleton (not in UniGene) with exon hit 1. 1 305259 EOS05190 AA679225 EST singleton (not in UniGene) with exon hit 1. 1 333922 EOS33853 CH22_1195FG_296-13_LINK_EM : AC005500. GENSCAN. 155-16 CH22_FGENES.296_13 1.1 322092 EOS22023 AF085833 EST cluster (not inUniGene) 1.1 313356 EOS13287 A1266254 Hs. 132929 ESTs 1. 1 318847 EOS18778 Z42908 Hs. 12308 ESTs 1. 1 337175 EOS37106 CH22_5195FG_567_1_ CH22_FGENES. S67-1 1. 1 336979 EOS36910 CH22_4802FG_385_4_ CH22_FGENES.385-4 1.1 312169 EOS12100 A1064824 Hs. 193385 ESTs 1. 1 336198 EOS36129 CH22_3595FG_719_2_LINK_DA59H18. GENSCAN. 21-2 CH22_FGENES.719_2 1.1 321948 EOS21879 AA309612 Hs. 118797 ubiquitin-conjugating enzyme E2D 3 (homologous to yeast UBC4/5) 1.1 324692 EOS24623 AA557952 EST cluster (not in UniGene) 330395 EOS30326 D10923 Hs. 137555 putative chemokine receptor ; GTP-binding protein 1. 1 333119 EOS33050 CH22347FG804UNKEM : AC000097. GENSCAN. 65-4 CH22_FGENES.80_4 1.1 316012 EOS15943 AA764950 Hs. 119898 ESTs 1. 1 300142 EOS00073 A1743419 Hs. 205707 ESTs 1. 1 317215 EOS17146 AW014242 Hs. 159998 ESTs 1. 1 329526 EOS29457 c10_p2 gi#3983506#gb#U gn 2 + 12251 12335 ex 33 CDSI 7. 37 75 178 CH. 10_p2 gi#3983506 317409 EOS17340 AA764968 Hs. 4864 KIAA0892 protein 1. 1 339230 EOS39161 CH22_8171FG_LINK-BA354i12. GENSCAN. 1-6 CH22_BA354I12. GENSCAN. 1-6 1. 1 311598 EOS11529 AW023595 Hs. 232048 ESTs 1. 1 339164 EOS39095 CH22_8091FG_LINK-DA59H18. GENSCAN. 69-4 CH22 DA59H18. GENSCAN. 69-4 1. 1 326725 EOS26656 c2_hs gií6552456lren gn 2-223005 223125 ex 5 6 CDS ! 6. 10 12 1038 CH. 20_hs gi#6552456 1.1 330952 EOS30883 H02855 Hs. 29567 ESTs 1. 1 334621 EOS34552 CH22_1928FG_412_4_LINK_EM : AC005500. GENSCAN. 275-4 CH22_FGENES.412_4 1.1 301685 EOS01616 W67730 EST cluster (not in UniGene) with exon hit 1. 1 308781 EOS08712 Al811707 ESTsingleton (notinLìniGene) withexonhit 1. 1 323413 EOS23344 AA248828 Hs. 225676 ESTs 1. 1 306723 EOS06654 A1026151 EST singleton (not in UniGene) with exon hit 1. 1 331258 EOS31189 Z41777 Hs. 27413 ESTs 1. 1 313028 EOS12959 AI35433 Hs. 190856 ESTs 1. 1 333002 EOS32933 CH22_226FG-59_3_LINK_EM: AC000097. GENSCAN. 21-3 CH22_FGENES.59_3 1.1 303011 EOS02942 AF090405 EST cluster (not in UniGene) with exon hit 1. 1 317687 EOS17618 AA972990 Hs. 127904 ESTs 1. 1 328779 EOS28710 c_7_hs gi#5868309#ref# gn 4 + 41570 41639 ex 1 5 CDSf 2.65705365 CH. 07_hs gi#5868309 1.1 338707 EOS38638 CH22_7487FG_LINK-EM: AC005500. GENSCAN. 482-2 CH22_EM : AC005500. GENSCAN. 482-2 1.1 337974 EOS37905 CH22_6427FG_LINK_EM : AC005500. GENSCAN. 106-3 CH22_EM : AC005500. GENSCAN. 106-3 1.1 332854 EOS32785 CH22_71FG_22_1_LINK_C20H12. GENSCAN. 15-2

CH22_FGENES.22_1 1.1 311225 EOS11156 AW451982 Hs. 248613 ESTs 1. 1 337094 EOS37025 CH22_5018FG_465_19_ CH22_FGENES.465-19 1.1 319357 EOS19288 F13425 Hs. 26229 ESTs 1. 1 332958 EOS32889 CH22_182FG_48-15_LINK-EM:AC000097.GENSCAN.2-11 CH22_FGENES.48_15 1.1 309634 EOS09565 AW193825 EST singleton (not in UniGene) with exon hit 1. 1 321171 EOS21102 AI769410 Hs. 221461 ESTs 1. 1 316440 EOS16371 AI954796 Hs.156135 ESTs 1.1 311665 EOS11596 AW294254 Hs. 223742 ESTs 1. 1 327548 EOS27479 c 3 hsgií5867797írengn2-8106781130ex37CDSi 6. 42 64 12 CH.03_hs gi#5867797. 1.1 314940 EOS14871 AW452768 Hs. 162045 ESTs 1. 1 326401 EOS26332 c19_hs gi[587355#ref# gn 1 + 35 15 35332 ex 9 11 CDSI 0. 41 168 788 CH. 19_hs gi#5867355 1.1 336347 EOS36278 CH22_3759FG_815_3_LINK_BA232E17. GENSCAN. 1-24 CH22_FGENES.815_3 1.1 322297 EOS22228 W76548 Hs. 136026 ESTs ; Moderately similarto ! ! I ! ALU SUBFAMILY SC WARNING ENTRY !!!! [H. sapiens] 1. 1 309977 EOS09908 AW451663 EST singleton (not in UniGene) with exon hit 1. 1 333466 EOS33397 CH22_717FG_161_2_LINK_EM:AC005500. GENSCAN. 42-2 CH22_FGENES.161_2 1.1 329170 EOS29101 c_x_hs gi#5868693#ref# gn 2 + 67924 68019 ex 6 8 CDSI 3.30961882 CH.X_hs gi#5868693 1.1 329479 EOS29410 c10_p2 gi#3983526#gb#A gn 3 - 7425 7561 ex 13 CDSI 4.33 137 22 CH. 10_p2 gi#3983626 1.1 326668 EOS26599 c20_hs gií6552455lren gn 1+ + 14676 146838 ex 11 11 CDSI 1.84113 767 CH.20_hs gi#6552455 1.1 319364 EOS19295 H06538 Hs. 12270 ESTs 1. 1 302988 EOS02919 W23986 Hs. 34578 aipha2 ; 3-sialyltransferase 1. 1 327687 EOS27618 c_4_hs gi#5867847#ref# gn 1 - 169293 169362 ex 2 3 CDSi-0. 28 70 782 CH. 04_hs gií5867847 1. 1 339413 EOS39344 CH22_8405FG_LINK_DJ579N16.GENSCAN.5-8 CH22_DJ579N16. GENSCAN. 5-8 1.1 306156 EOS06087 AA918274 Hs. 76067 heat shock 27kD protein 1 1. 1 320858 EOS20789 D59968 EST cluster (not in UniGene) 1. 1 325447 EOS25378 c12_h2 gi#6866941#ref# gn 3 - 72480 372621 ex 23 CDSI 9.161421026 CH. 12hsgif5866941 1. 1 322696 EOS22627 A1064724 Hs. 228468 ESTs 1. 1 329959 EOS29890 c16_p2 gi#5103803#gb#A gn 3 + 188050 188193 ex 8 8 CDSI 2.01 144 361 CH. 16_p2 gi#5103803 312628 EOS12559 AA632817 Hs. 190316 ESTs 1. 1 339305 EOS39236 CH22_8262FG_LINK_BA354I12. GENSCAN. 21-3 CH22_BA354I12. GENSCAN. 21-3 1. 1 311829 EOS11760 AìO78483 Hs. 134549 ESTs 1. 1 303270 EOS03201 AL120518 Hs. 105352 ESTs 1. 1 321226 EOS21157 AA311443 Hs. 251416 HomosapiensmRNA ; cDNADKFZp586E2317 (fromcloneDKFZp586E2317) 1. 1 335827 EOS35758 CH22_3200FG_620_1_LINK_EM : AC005500. GENSCAN. 51 2-1 CH22_FGENES.620_1 1.1 336677 EOS36608 CH22_4155FG_43-5_ CH22_FGENES.43-5 1.1 330081 EOS30012 c19_p2 gi#6015314#gb#A gn 1 - 5768 5835 ex 4 9 CDSI 2.88 68 162 CH. 19_p2 gi#6015314 1.1 339313 EOS39244 CH22_8272FG_LINK-BA354I12. GENSCAN. 22-11 CH22_BA354I12. GENSCAN. 22-11 1. 1 319936 EOS19867 W22152 EST cluster (not in UniGene) 1. 1 332858 EOS32789 CH22_76FG_24_1_LINK_C20H12.GENSCAN.16-6 CH22_FGENES.24_1 1.1 315630 EOS15561 AA648355 Hs. 185155 ESTs ; Weakly similar to echinoderm microtulbule -assoclaled protein_like EMAp2 [H. sapiens] 1. 1 332995 EOS32926 CH22-219FG_58_2_LINK_EM : AC000097. GENSCAN. 19-2 CH22_FGENES.58_2 1.1 333441 EOS33372 CH22 _691FG_151_5_LINK_EM : AC005500. GENSCAN. 32-5 CH22_FGENES.151_5 1.1 333496 EOS33427 CH22_748FG_168_6_LINK_EM : AC005500. GENSCAN. 47-5 CH22_FGENES.168_6 1.1 339188 EOS39119 CH22_8123FG_LINK_DA59H18. GENSCAN. 72-16 CH22_DAS59H1. GENSCAN. 72-16 1.1 336981 EOS36912 CH22 4818FG397 7 CH22FGENES. 397-7 1. 1 312142 EOS12073 AW298359 Hs. 221069 ESTs 1. 1 315779 EOS15710 AW015736 Hs. 211378 ESTs 1. 1 318596 EOS18527 AId70235 Hs. 172698 EST 1. 1 335701 EOS35632 CH22_3062FG_599_1_LINK_EM:AC005500. GENSCAN. 490-2 CH22_FGENES.599_1 1.1 319395 EOS19326 AW062570 Hs. 13809 ESTs 1. 1 304236 EOS04167 W93278 EST singleton (not in UniGene) with exon hit 1. 1 307264 EOS07195 A1202211 EST singleton (not in UniGene) with exon hit 1. 1 334066 EOS33997 CH22_1344FG_327_21_LINK_EM : AC005500. GENSCAN. 181-23 CH22_FGENES.32721 1. 1 327042 EOS26973 c21_hs gi#6531965#ref# gn 18-13808061381443 ex 15 CDSI 30.85 638 943 CH. 21_hs gií6531965 1. 1 326025 EOS25956 c17_hs gi#5867176#ref# gn 1 + 70854 70915 ex 6 8 CDSI-1. 46 62 127 CH. 17_hs gi#5867176 1.1 325609 EOS25540 c14_hs gi#5866996#ref3 gn 28 - 981751 981849 ex 1 10 CDSI 1.46 99101 CH. 14_hs gi#5866996 1.1 319983 EOS19914 T81429 EST cluster (not in UniGene) 1. 1 334298 EOS34229 CH22_1589FG_372_4_LINK_EM : AC005500. GENSCAN. 232-5 CH22_FGENES.372_4 1.1 323203 EOS23134 AA203135 Hs. 130186 ESTs 1. 1

305700 EOS05631 AA815428 EST singleton (not in UniGene) with exon hit 1. 1 313304 EOS13235 AI334078 Hs. 152438 ESTs 1. 1 310716 EOS10647 A1589618 Hs. 192413 ESTs 1. 1 327049 EOS26980 c21_s gi#6531965#ref# gn 24 - 1924026 1924110 ex 26 CDSI 9. 43 85 1012 CH. 21 hsgií6531965 1. 1 313749 EOS13680 AW450376 Hs. 130803 ESTs 1. 1 307041 EOS06972 AI144243 EST singleton (not in UniGene) with exon hit 1. 1 322394 EOS22325 AF077208 EST cluster (not in UniGene) 1.1 326416 EOS26347 c19_hs gil5867362íren gn 3-45283 45375 ex 3 3 CDSf 5.65 93 923 CH. 19_hs gi#5867362 1.1 333947 EOS33878 CH22_1221FG_303_1_LINK_EM : AC005500. GENSCAN. 162-5 CH22_FGENES.303_1 1.1 324609 EOS24540 AW299534 EST cluster (not in UniGene) 1.1 330057 EOS29988 c17_p2 gi#678962#gb#A gn 3 + 75145 75287 ex 3 3 CDSI-2. 56143150 CH. 17_p2 gi#6478962 1.1 337603 EOS37534 CH225896FGUNXC20H12. GENSCAN. 16-2 CH22_C20H12. GENSCAN. 16-2 1. 1 332913 EOS32844 CH22_134FG _36_18_LINK_C20H12, GENSCAN. 28-17 CH22_FGENES.36_18 1.1 310026 EOS09957 T24895 Hs. 100691 ESTs 1. 1 330153 EOS30084 c21_p2 gi#4325335#gb#A gn 2 + 14695 147475 ex 2 2 CDSI 25.45 525 233 CH. 21_p2 gi#4325335 1.1 334118 EOS34049 CH22_1396FG_330_19_LINK_EM : AC005500. GENSCAN. 185-20 CH22_FGENES.330_19 1.1 324795 EOS24726 AI494481 Hs. 141579 ESTs 1. 1 332530 EOS32461 M31682 Hs. 1735 inhibin; beta B (activin AB beta polypepude) 332048 EOS31979 AA496019 Hs. 201591 ESTs 1. 1 334532 EOS34463 CH22_1834FG_402_13_LINK_EM : AC005500.GENSCAN. 266-13 CH22_FGENES.402_13 1.1 329762 EOS29693 c14_p2 gi ! 6048280) en) bt gn 3 +127744127878 ex 2 4 CDS ! 11. 661351054 CH. 14_p2 gi#6048280 1.1 332909 EOS32840 CH22_130FG_36_13_LINK-C20H12. GENSCAN. 28-10 CH22_FGENES.36_13 1.1 321253 EOS21184 A1699484 EST ctuster (not in UniGene) 1. 1 336572 EOS36503 CH22_4007FG_843_12_LINK_DJ579N16. GENSCAN. 15-13 CH22_FGENES.843_12 1.1 328768 EOS28699 c_7_hs gi#6017031#ref# gn 5-223741224238 ex 1 1 CDSo 30.00 498 5285 CH. 07_hs gi#6017031 1.1 334335 EOS34266 CH22_1627FG_375_12_LINK_EM : AC005500. GENSCAN. 235-12 CH22_FGENES.375_12 1.1 334063 EOS33994 CH22_1341FG_32_17_LINK_EM : AC005500. GENSCAN. 181-20 CH22_FGENES. 32717 1. 1 333011 EOS32942 CH22_235FG_61_3_LINK_EM : AC000097. GENSCAN. 23-3 CH22_FGENES.61_3 304677 EOS04608 AA548071 EST singleton (not in UniGene) with exon hit 1. 1 313948 EOS13879 AW452823 Hs. 135268 ESTs 1. 1 334358 EOS34289 CH22_1652FG_378_1_LINK_EM : AC005500. GENSCAN. 239-1 CH22_FGENES.378-1 1.1 328479 EOS28410 c_7_hs gi#5868449#ref# gn 1-331 560 ex 1 31 CDS ! 18.51 230 2100 CH. 07_hs gi#5868449 1.1 335813 EOS35744 CH22_3185FG_618_1_LINK_EM:AC005500. GENSCAN. 510-1 CH22_FGENES.618_1 1.1 312430 EOS12361 AW139117 Hs. 117494 ESTs 1. 1 324783 EOS24714 AA640770 EST cluster (not in Un ! Gene) 337776 EOS37707 CH22_6132FG_LìNK_EM : AC000097. GENSCAN. 119-18 CH22_EM : AC000097. GENSCAN. 119-1 8 1. 1 327205 EOS27136 c_1_hs gi#5867447#ref# gn 5 + 167335 167576 ex 9 9 CDSI 15. 50 242 259 CH. 01_hs gi#5867447 1.1 315198 EOS15129 AI741506 Hs. 186753 ESTs ; Weakly similar toll !! ALU SUBFAMILY J WARNING ENTRY !!!! [H. sapiens] 1. 1 336135 EOS36066 CH22_3525FG_704_3_LINK_DA59H18. GENSCAN. 9-5 CH22_FGENES.704_3 1.1 318558 EOS18489 AW402677 Hs. 90372 ESTs 1. 1 328152 EOS28083 c_6_hs gi#5868060#ref# gn 1-73981 74203 ex 18 CDSI 31.69 223 3411 CH. 06_hs gi#5868060 1.1 330211 EOS30142 c_5_p2 gi#6013592#gb#A gn 1 + 59158 59215 ex 2 4 CDS ! 4.20 58184 CH. 05_p2 gi#6013592 1.1 339280 EOS39211 CH22_8234FG_LINK_BA354I12. GENSCAN. 14-12 CH22_BA354I12.GENSCAN.14-12 1.1 332045 EOS31976 AA491253 Hs. 155045 bromodomain adjacent to zinc finger domain ; 2A 313597 EOS13528 AW162263 Hs. 249990 ESTs 1. 1 329503 EOS29434 c10_p2 gi#3983517#gb#U gn 2 - 1801 1937 ex 14 CDSI 4.33 137 101 CH. 10_p2 gi#3983517 1.1 333488 EOS33419 CH22_740FG_167_3_LINK_EM : AC005500. GENSCAN. 46-10 CH22_FGENES.167_3 1.1 311960 EOS11891 AW440133 Hs. 189690 ESTs 1. 1 320590 EOS20521 U67058 Hs. 168102 Human proteinase activated receptor-2 mRNA ; 3'UTR 1. 1 334047 EOS33978 CH22_1325FG_326_5_LINK_EM : AC005500. GENSCAN. 175-5 CH22_FGENES.326_5 1.1 304782 EOS04713 AA582081 EST singleton (not in UniGene) with exon hit. 1. 1 324231 EOS24162 W60827 EST cluster (not in UniGene) 1. 1 327212 EOS27143 c_1_hs gi#5867463#ref# gn 1 - 42308 42424 ex 5 13 CDSI 6.58117325 CH. 01_hs gi#5867463 1.1 335857 EOS35788 CH22_3232FG_629_1_LINK_EM : AC005500. GENSCAN. 519-1 CH22_FGENES.629_1 1.1 317775 EOS17706 AA974603 Hs. 181123 ESTs 1. 1 331053 EOS30984 N70242 Hs. 183146 ESTs 1. 1

335940 EOS35871 CH22_3318FG_646_13_LINK_DJ246D7. GENSCAN. 1-12 CH22_FGENES.646_13 1.1 322568 EOS22499 W87342 Hs. 209652 ESTs 314091 EOS14022 AI253112 Hs. 133540 ESTs 313570 EOS13501 AA041455 Hs. 209312 ESTs 300967 EOS00898 AA565209 Hs. 190216 ESTs 314544 EOS14475 AA399018 Hs. 250835 ESTs 1. 1 328321 EOS28252 c_7_hs gi#5868373#ref# gn 7 - 1029614 1029673 ex 1 3 CDSI - 2.40 60 448 CH, 07_hs gi#5868373 1.1 310979 EOS10910 AW445166 Hs. 170802 ESTs 1. 1 310730 EOS10661 A1939421 Hs. 160900 ESTs 1. 1 318471 EOS18402 AW137725 Hs. 146874 ESTs 1. 1 315533 EOS15464 AW206191 Hs. 152774 ESTs 1. 1 325751 EOS25682 c14_hs gi#6682474#ref# gn 4 + 130437130520 ex 6 7 CDSi 0.22 841666 CH. 14_hs gi#6682474 1.1 318780 EOS18711 R90906 Hs. 113307 ESTs 1. 1 313271 EOS13202 AW444819 Hs. 144851 ESTs ; Weakly similar to C09F5. 2 [C. elegans] 1. 1 304546 EOS04477 AA486074 EST singleton (not in UniGene) with exon hit 1. 1 330618 EOS30549 X55990 Hs. 73839 ribonuclease ; RNase A family ; 3 (eosinophi) catonicprotein) 1. 1 332931 EOS32862 CH22_152FG_38_5_LINK_C20H12. GENSCAN. 29-5 CH22_FGENES.38_5 1.1 336602 EOS36533 CH22 _4047FG_372_4_LINK_EM: AC005500. GENSCAN. 232-4 CH22_FGENES.372_4 1.1 311185 EOS11116 A1638294 Hs. 224665 ESTs 1. 1 337585 EOS37516 CH22_5873FG_LINK_C20H12 GENSCAN. 5-3 CH22 C20H12. GENSCAN. 5-3 1.1 310249 EOS10180 AW071751 Hs. 13179 ESTs ; Moderately similar to ! !!! ALU SUBFAMILY SQ WARNING ENTRY !!! ! [H. sapiens] 1. 1 314578 EOS14509 AA410183 Hs. 137475 ESTs 1. 1 310750 EOS10681 A1373163 Hs. 170333 ESTs 333968 EOS33899 CH22_1245FG_307_4_LINK_EM : AC005500. GENSCAN. 165-5 CH22_FGENES.307_4 1.1 316133 EOS16064 A1187742 Hs. 125562 ESTs 1. 1 308337 EOS08268 AI608947 EST singleion (not in UniGene) with exon hit 1.1 326160 EOS26091 c17_hs gi#5867254#ref# gn 6 - 112000 112137 ex 2 4 CDSi 8.01 1381952 CH. 17_hs gi#5867254 1.1 336023 EOS35954 CH22_3406FG_669_12_LINK_DJ3210. GENSCAN. 9-17 CH22_FGENES.669_12 1.1 323479 EOS23410 AA278246 EST cluster (not in UniGene) 1. 1 336090 EOS36021 CH22_3477FG_689_2_LINK_DJ32110. GENSCAN. 23-20 CH22_FGENES.689_2 1.1 311192 EOS11123 AW237220 Hs. 211130 ESTs 1. 1 335081 EOS35012 CH22_2409FG_488_4_LINK_EM : AC005500. GENSCAN. 384-6 CH22_FGENES.488_4 1.1 309519 EOS09450 AW148940 Hs. 248647 EST 1. 1 321172 EOS21103 H49160 Hs. 133472 ESTs 1. 1 301976 EOS01907 T97905 ESTcìuster (notinUniGene) withexonhit 1. 1 323012 EOS22943 A1832201 Hs. 211469 ESTs 1. 1 319528 EOS19459 R08673 Hs. 177514 ESTs 1. 1 329838 EOS29769 c14_p2 gi#6672062#emb# gn 2 + 33990 34098 ex 3 4 CDS ! 9.11109 2222 CH. 14_p2 gií6672062 1. 1 302623 EOS02554 AB019571 EST cluster (not in UniGene) with exon hit 1.1 334433 EOS34364 CH22_1731FG_385_8_LINK_EM : AC005500. GENSCAN. 249-6 CH2_FGENES.385_8 1.1 304747 EOS04678 AA577816 EST singleton (not in UniGene) with exon hit 1. 1 333270 EOS33201 CH2_513FG_121_1_LINK_EM : AC005500. GENSCAN. 4-11 CH2_FGENES.121_1 1.1 307054 EOS06985 AI148181 Hs. 176835 EST 1. 1 320764 EOS20695 R73070 Hs. 246927 ESTs 1. 1 321523 EOS21454 H78472 Hs. 191325 ESTs, Weaklysimi ! artocDNAESTyk414c9. 3comesfromthisgene [C. elegans] 1. 1 322114 EOS22045 AA643791 Hs. 191740 ESTs 1. 1 303582 EOS03513 AA377444 EST cluster (not in UniGene) with exon hit 1. 1 322924 EOS22855 AA669253 Hs. 193971 ESTs 1. 1 311179 EOS11110 A1880843 Hs. 223333 ESTs 318601 EOS18532 T39921 EST cluster (not in UniGene) 1. 1 309791 EOS09722 AW276176 Hs. 73742 dbosomat protein ; large ; PO 333882 EOS33813 CH2_1153FG_292_4_LINK_EM : AC005500. GENSCAN. 150-4 CH2_FGENES.292_4 1.1 337645 EOS37576 CH2_5960FG_LINK_EM : AC000097. GENSCAN. 10-8 CH2_EM : AC000097. GENSCAN. 10-8 1.1 335623 EOS35554 CH2_2983FG_58_2_LINK_EM : AC005500. GENSCAN. 478-2 CH2_FGENES. 584_2 1. 1 314745 EOS14676 AA564489 Hs. 137526 ESTs 1. 1 330790 EOS30721 T48536 Hs. 105807 ESTs 1. 1 332071 EOS32002 AA598594 Hs. 112475 ESTs 1. 1 312005 EOS11936 T78450 Hs. 13941 ESTs 1. 1 330694 EOS30625 AA019806 Hs. 108447 spinocerebellar ataxia 7 (olivopontocerebellar atrophy with retinal degeneration) 1.1 330739 EOS30670 AA293477 Hs. 227591 ESTs 1. 1 303042 EOS02973 AF129532 EST cluster (not in UniGene) with exon hit 1. 1 323091 EOS23022 AW014094 Hs. 210761 ESTs 1. 1 328820 EOS28751 c_7_hs gi#5868330#ref# gn 1 + 90446 90602 ex 3 4 CDSi 10.20 157 5634 CH. 07_hs gi#5868330 1.1 300472 EOS00403 T90622 Hs. 82609 hydroxymethylbilane synthase 310645 EOS10576 AI420742 Hs. 163502 ESTs 1. 1 332238 EOS32169 N53480 Hs. 108622 ESTs 1. 1 300966 EOS00897 AA564740 Hs. 258401 ESTs 1. 1 330437 EOS30368 HG2730-HT2827 Fibrinogen, A Alpha PolypepUde, Alt. Splice 2, E 1. 1

302292 EOS02223 AF067797 EST cluster (not in UniGene) with exon hit 1. 1 330138 EOS30069 c21_p2 gi) 4210430 ; embi gn 1-22334 22460 ex 3 3 CDSf 16.56127105 CH. 21_p2 gi#4210430 1.1 332952 EOS32883 CH2_176FG_48_8_LINK_EM:AC000097. GENSCAN. 2-4 CH2_FGENES.48_8 1.1 319901 EOS19832 T77136 Hs. 8765 RNA helicase-related protein 321166 EOS21097 AA411263 Hs. 128783 ESTs 1. 1 336227 EOS36158 CH2_3625FG_730_2_LINK_DA59H18.GENSCAN.36-2 CH2_FGENES.730_2 1.1 302332 EOS02263 Api833168 Hs. 184507 Homo sapiens Chromosome 16 BAC done CIT987SK-A-328A3 1. 1 313800 EOS13731 AW296132 Hs. 166674 ESTs 1. 1 339356 EOS39287 CH2_8326FG_LINK_BA354112. GENSCAN. 31-1 CH2_BA354112. GENSCAN. 31-1 1.1 324512 EOS24443 AW502125 EST cluster (not in Un ! Gene) 319235 EOS19166 F11330 Hs. 177633 ESTs 1. 1 320352 EOS20283 Y13323 Hs. 145296 disintegrinprotease 1. 1 338316 EOS38247 CH2_6944FG_LINK_EM : AC005500. GENSCAN. 304-2 CH2_EM : AC005500. GENSCAN. 304-2 1. 1 333964 EOS33895 CH2_1241FG_305_2_LINK_EM : AC005500. GENSCAN. 164-2 CH2_FGENES.305_2 1.1 312758 EOS12689 AA721107 Hs. 202604 ESTs 1. 1 338178 EOS38109 CH2_6726FG_LINK_EM : AC005500. GENSCAN. 219-6 CH22_EM : AC005500. GENSCAN. 219-6 1.1 315199 EOS15130 AA877996 Hs. 125376 ESTs 1. 1 312321 EOS12252 R66210 Hs. 186937 ESTs 1. 1 338765 EOS38696 CH22 7588FG LINK_EM : AC005500. GENSCAN. 518-1 CH2_EM : AC005500. GENSCAN. 518-1 1. 1 330547 EOS30478 U32989 Hs. 183671 tryptophan 2 ; 3-dioxygenase 315368 EOS15299 AW291563 Hs. 152495 ESTs 1. 1 328691 EOS28622 c_7_hs gi#6588001#ref# gn 7-579598 579664 ex 2 3 CDSi 12.78 67 4326 CH. 07_hs gi#6588001 1.1 329179 EOS29110 c_x_hs gi#5868704#ref# gn 2 + 181639 181815 ex 3 4 CDSi 0.32 177 1939 CH.Xhsgi) 5868704 1. 1 327072 EOS27003 c21_hs gi#6531965#ref# gn 55 - 3796429 3797197 ex 4 4 CDSf 9.33 7691270 CH. 21_hs gi#6531965 1.1 312056 EOS11987 T83748 Hs. 189712 ESTs 1. 1 339128 EOS39059 CH2_8046FG_LINK_DA59H18.GEN SCAN. 55-2 CH2_DA59H18. GENSCAN. 55-2 1.1 307646 EOS07577 AI302236 EST singleton (not in UniGene) with exon hit 1.1 319198 EOS19129 F07354 EST cluster (not in Un ! Gene) 338556 EOS38487 CH2_7283FG_LINK_EM : AC005500. GENSCAN. 417-8 CH2_EM : AC005500. GENSCAN, 417-8 1.1 306143 EOS06074 AA916314 EST singleton (not in UniGene) with exon hit 1. 1 332384 EOS32315 M11433 Hs. 101850 reM-binding protein 1; cellular 325100 EOS25031 T10265 Hs. 116122 ESTs ; Weakly similar to coded for by C. elegans cDNA yk30b3. 5 [C. elegans] 1. 1 309839 EOS09770 AW296076 EST singleton (not in UniGene) with exon hit 1. 1 312180 EOS12111 AI248285 Hs. 118348 ESTs 1. 1 330385 EOS30316 AA449749 Hs. 31386 ESTs ; Highly similar to secreted apoptosis related protein 1 [H. sapiens] 315882 EOS15813 A1831297 Hs. 123310 ESTs 1. 1 325843 EOS25774 c16_hs gi#6552453#ref# gn 1-7126 7232 ex 13 CDSI 1.87107182 CH. 16_hs gi#6552453 1.1 330783 EOS30714 D60050 Hs. 34812 ESTs 1. 1 317224 EOS17155 D56760 Hs. 8122 ESTs 1. 1 316042 EOS15973 AW297979 Hs. 170698 ESTs 1. 1 333524 EOS33455 CH2_781FG_175_10_LINK_EM : AC005500. GENSCAN. 53-15 CH2_FGENES.175_10 1.1 302357 EOS02288 X03178 Hs. 198246 group-specific component (vitamin D binding protein) 1. 1 309830 EOS09761 AW294725 EST singleton (not in UniGene) with exon hit 1. 1 321489 EOS21420 AW392474 Hs. 172759 ESTS ; Moderately similar to !!! ! ALU SUBFAMILY SQ WARNING ENTRY"" [H. sapiens] 1. 1 312304 EOS12235 AA491949 Hs. 183359 ESTs 1. 1 322026 EOS21957 AA233527 Hs. 213289 low density lipoprotein receptor (familial hypercholesterolemia)

TABLE 1A Table 1A shows the accession numbers for those primekeys in Table 1 which lack a unigeneID. Listed for each probeset is the gene cluster (CAT) number from which the oligonucleotides were designed. Gene clusters were compiled using sequences derived from Genbank ESTs and mRNAs. These sequences were clustered based on sequence similarity using Clustering and Alignment Tools (DoubleTwist, Oakland California). The Genbank accession numbers for sequences comprising each cluster are listed in the"Accession" column.

Pkey : Unique Eos probeset identifier number CAT number: Gene cluster number Accession: Genbank accession numbers Pkey CAT number Accession 300611 337193_1 N75450 AA877636 AW137945 W05248 AA514763 AW972399 A1758397 AW195051 301187 434061_1 AW976692 AA806542 AA745856 301254 463589_1 AI049624 AA814705 AW404856 BE078289 BE078292 301266 468223_1 AA829774 AI082020 301454 534162_2 AI751738 AA977930 301615 5613_2 W39477 AK002047 NM_015515 T58707 AA386214 C19007 AA295466 T49621 T47323 301661 7974_1 AK001735 AF227906 AI815558 AW238991 AL133051 AW272417 A1083492 A1816503 AW888717 AA333166 AI925832 BE048352 BE048415 Api141922 AW805674 AW805578 AA633581 AA424632 R71439 AW020988 AW976735 AA883247 W37208 A1091039 AW317020 BE221788 AA502917 AW009024 Api141417 BE349081 AI421443 AI080490 AI003921 AI373690 AI379240 AA424587 AA740607 AA972391 AA620797 AW271656 AA400517 AI370902 AI680616 AA757270 AA909500 N32107 R43738 AI270464 AI870568 AI085139 AA225666 Z41046 Al767739 Al270546 N56779 301685 326972_1 W67730 Z44630 AA490699 W67596 W76661 R21207 301804 61_1 AK001468 AA190315 AA374980 AW961179 AA307782 AA315295 AA347194 AW953073 AW368190 AW368192 AA280772 AA251247 N85676 AI215522 AI216389 N87835 R12261 R57094 AI660045 AA347193 R16712 AW119006 N55905 N87768 AW900167 AI341261 AI818674 D20285 AI475165 AA300756 R40626 AI122827 AA133250 AI952488 AA970372 AA889845 AW069517 A1524385 AA190314 AI673359 AA971105 AI351088 AI872789 AI919056 AI611216 AK001472 BE568761 AA581004 301976 128835_1 T97905 AA101672 302245 9482_1 H18835 R47363 AI460004 N31660 AA454774 AA551759 AI417040 AA694490 AA633315 AI344661 AA708532 AA878567 Al802702 AI913465 AW001160 AA932133 AI092908 AA026974 AW628573 AA592910 H18836 AI274428 C00675 AK000048 BE313619 302292 27735_1 AF067797 AB013456 NM_001169 AI791955 AW843925 AI732659 AA577625 AW083143 AW138645 302476 31932_3 AF182294 NM_016200 AL046942 AI354410 AI697029 AI859557 AW188855 AW105437 Api358735 AW000959 AI491813 AW023693 302623 9705_1 AW836724 BE243668 AB019571 H43803 302626 10441_1 AK001553 AK001951 AB021870 NM_016282 F01168 AA211870 AA078889 AA312979 AL138385 R70844 AA165658 AA007279 AA194688 H65871 AA476639 F01095 AA300170 R39487 AA649126 AA193643 AA418300 BE173477 N84408 AW024465 AA406255 BE173412 BE173583 BE173470 AW069288 AA372937 BE504414 AA209472 AI262833 AI628359 AI458075 AI476266 AA397706 AI768605 AW243125 A1056436 AA838326 AA810651 AI472025 N35912 AA165622 AI985532 Al139528 M626087 W16998 AI632833 AW130827 AW662551 AA731459 AW780188 Al653447 Al694970 M810662 AI199987 AI587402 AI492972 H65872 AI805624 AW194835 AW994874 R70790 AA836506 N53285 F00181 R83595 AI290941 AW936750 AW936703 AW936623 AW936785 AW936691 AW936668 AW936713 AW936788 AW936744 AW936613 AW936614 AW936665 AW936702 AW936647 AW936643 AW936712 AW936791 AW936624 AW936672 AW936754 AW936696 AW936802 AW936792 AW936589 AW936692 AW936645 AW936746 AW936801 AW936748 AW936661 AW936612 AW936697 AW936704 AW936695 AW936626 AW936794 AW936629 AW936577 AW936798 T35617 AA375943 R29459 AW936717 AA342108 AW963351 Z24876 AW936708 AW374110 AW936586 W20080 AW936752 W31803 AA093709 AA431256 AW803610 AA424959 W76607 AA432267 W72009 R70817 AW778851 AA890563 AA194632 Al089644 AI373864 AA890333 AI745574 AI095714 AI567507 AI280712 AW864083 AW468991 N48087 AA860500 AA279471 AA993680 AA676504 AI360949 AI052134 AI038657 AI439836 AA629147 AA651840 AA435925 AA854457 AW796472 AA838729 AA193407 AA302403 AW958003 AA342107 AA639258 AI435811 AA410342 N25790 M156454 Al539628 A1275854 N58849 Al858171 AW338576 W15321 AA418342 AA780577 W04701 AA630452 AW769154 Al274286 N23736 BE465020 AI554346 AI920804 AA969728 AW193440 AI368697 AA115096 AA564981 AA630461 N91475 BE464381 AA913741 AA757161 Z24907 C00067 AA649290 AI245223 AA363098 AI520754 AA887983 AI273015 AW878871 AW878981 AA480455 AA709267 AW959521 AW959523 N90014 N32441 F00193 AA115095 AA147583 W19813 AI333349 AI197937 R39488AW750110 302655 41899_1 AJ227892 AA338715 BE074475 BE074469 BE074474 AW006182 AW572953 AI831725 Al762923 Al341466 AW449335 BE551686 AI692895 AI040410 AI276881 AI891008 302758 24028_3 AK001841 H40087 H11121 AW408676 N99603 AA984563 H92041 H11226 302882 458_60 AW403330 AF062097

302977 47403_3 AW263124 AI925166 AW105732 AA804479 BE621436 AF086399 W79085 W74440 AW992181 AA389686 AA314311 AA173955 AA677564 D59895 D60771 Al887733 C14814 AW162193 D81894 AA732538 AW150919 AA748064 AA769465 AA708143 BE327613 AA092726 AI692476 T35673 Z33600 AA134036 Al671394 Al267461 AW362795 AI769759 AA909042 AA130042 AW156938 AI753129 AI246205 AI823883 AI752836 D60770 Al336386 Al584003 AW627976 AI348676 D59894 AI969795 AW073259 A1400534 A1081318 Al082427 BE550515 302980 47495_1 AI925740 AF086489 W93435 W93345 AA337166 AW966214 AA336257 T11355 AW842435 303011 41689_1 AF090405 AF090407 AF090406 303037 35681_1 AF118395 NM_014317 AW376657 AW848189 AI261617 AI963829 AW848591 AW848598 AW376696 AW848523 AW848450 AW848655 AW848183 AW848550 AW376675 AI632752 AI590245 AI431824 AI857990 AI953341 AA888092 AW364968 AI188545 AI217741 AW275906 AI311481 AI991404 AI364963 AA628392 AA927982 AW150563 AA503063 AW079470 AW512180 AA889371 AW390132 AW609052 AW390112 AW581780 303042 5058_1 AW505345 AF129532 AF126028 AA852108 BE169359 R83701 Z43904 BE613543 AA283163 AA905463 AW067849 R13544 R12337 R14020 H98970 AI474918 N56139 AL135669 AW067702 AW372065 AW631389 AA083416 AA287511 AA602923 AA488914 All 67215 AW946829 R82855 AI948792 AA371333 AW953883 AW956152 C02539 AA298280 AI932587 AA022742 AI983021 AA195252 N58991 R78733 AW083996 H39614 AI365249 AW615389 A1927744 A1089971 N52205 AA083417 BE326666 BE349514 AI743785 AI640148 AI378211 AW181881 AI949484 W31374 AW628233 AA418406 AW068010 AI708085 AI092696 AI089823 AI277828 AA022660 AI440527 AW054937 AW474104 AI017436 AI159819 AI356716 AW473140 AW316518 N34522 AI675092 AI866697 AA864593 AW511185 AA488844 AA904975 N49111 Z39951 R37265 A1141362 T25856 R20664 F03163 Al767927 M805942 D79905 A1914645 AW190553 AI934213 AI458796 AA195385 R82854 W31965 303072 4654_1 AI56678 AF157833 NM_012133 AI202415 AK002086 AF207598 AI214562 AI202184 AI865579 AA603481 AA483808 AA909166 AA774034 AW748102 AW176026 AW351472 BE164787 AA970983 BE622521 BE389817 AW366336 AW366328 AW366327 AW366329 AW366335 AW366337 BE269711 T11249 T11264 BE253295 BE256412 BE250882 BE255440 BE257663 303149 97393_1 AW963315 AA312995 AA037152 AA088607 AA064770 BE088067 303306 11887 1 AB037732 AW503898 AA215297 BE547488 AW177355 AA046224 AA361664 AA773328 AW512704 Al283330 Al307357 AI138263 AA046116 A1219874 AA315431 AW169999 AA492006 AW298002 AA043140 AA131781 AA292383 AA031721 AA027867 R31381 AW023352 686186AW467416AA493914AA483019AA483081 AA040871 AA558288AW070397 AW572828 AA693439 AW206584 AA761354 AA907254 AI671019 BE221791 AI915828 AA744724 AA027815 AA131769 AA031641 AA837286 AA737401 Al765196 AW086076 AW873024 AI567164 AA744556 AA888910 AI572276 303443 224022_1 AA320525 AW025411 AI684617 AI653685 303502 325188_1 BE174240 AA488528 AL042253 303582 647662_1 AA377444 AI458965 303610 226089_1 BE247299 AA323288 AW966142 AA334916 AL046572 BE145095 AW751265 303642 284260_1 AW299459 AA417112 303777 244977_1 AA348491 BE246984 AW505247 303839 1770217_1 Z45939 T54414 T06550 303874 5013_1 AL050333 F08138 Z43325 H13393 AA258921 AA224232 BE439918 AL050018 AW363692 AA236615 AA746291 Z19312 AA428674 Z28579 T32527 AW952956 R59046 AA403173 AA403171 AW023058 AA461143 BE149531 AA428185 AI382812 H42659 AA406086 L48858 AW630177 Z24777 AW675297 AI393859 AI743022 AI669354 AW803015 AA401255 AI952901 AW043840 AI808787 AI140662 AA194627 AI140997 AA007454 AA007318 AI469859 AI540581 C06482 Al277356 Al458423 AA460839 AA861452 AN80197 AA630781 AA845367 Af125582 AA411705 AA970524 AA699910 AW804640 AW805007 AA724226 Al128207 Al696852 AW673064 AA748404 AW771788 AW088185 A1026976 Al537560 M224233 T24024 T50208 A1827319 R17235 T11904 Al816830 R41845 AA639828 Z41214 AA258158 H06057 F02752 303886 81595_1 AW365963 BE141537 BE141535 BE141538 T19123 R57434143870 AA298099 AA298004 AW963314 Al627790 AA298160 BE501485 AW271198 AA195563 AA195584 H28868 AA004370 Z42582 R21338 303929 AW470753 304084 T91986 304143 30606_-14 R88737 304165 H73265 304183 H91161 304236 W93278 304350 AA186871 304439 AA398882 304495 AA446448 304518 AA461438 304521 AA464716 304546 14011_1 AF113676 X01683 K01396 M11465 NM_000295 K02212 J02619 AB004044 H60588 T72131 T74637 T70970 T73183 T62154 R93629 H50855 H80585 H78044 T69186 R95698 H59327 T54018 H83071 R99626 H89864 H91798 T72841 T71108 T72812 T54005 T50896 H56102 W01486 W01669 AA137076 H90340 T61854 T61840 N93360 T61844 N53576 T55852 X02920 H56350 T58720 H56351 R92748 H56914 H59279 H50665 H56928 T69144 H80448 R91066 H77829 R92479 T55014 T52174 T67613 AA845231 H95664 V00496 M26123 AA484470 Al114833 T58716 T64752 T50876 T67858 H48675 T51161 T70409 T61715 T72289 H51854 H72171 T50834 H81483 T72132 T58792 T51179 T72833 R29662 T60563 W23562 H94193 T55017 T74830 H78469 H90811 T61303 H75867 T71527 T68360 R91065 R91079 T71172 H52923 T50871 T86567 H94691 T69226 AV649730 T46850 T56587 T46849 T60552 BE043578 BE042051 T72296 T61001 T58918 T52107 H82324 H47453 R06725 D16856 T48282 T52250 R92117 AI287339 H73203 AA318670 D17206 H66626 T69268 H73485 R93078 H73533 R87097 T71529 AA885254 AA486074 R94242 H74033 T73643 D12131 AV655901 AA345387 W07278 AW371443 AW371484 AW371427 AW371435 AW371467 AW371474 AW371471 AW371453 AW371448 AW371468 AW371486 AW371521 AW371463 AW371485 AW371460 T55283 H58030 H68955 AA360298 H73996 T58919 N94213 T50911 H51045 T56077 T72988 T71819 H60101 T72439 T68079 T73548 D11609 T61008 H67597 N49781173190 H50843 T73140 H61124 AV657376 N39304 AW075086 AI247165 H73123 H60258 AA343450 X17122 AW470706 AA336649 AW392737 H75576 N76963 T64227 AI803294 W73727 AV649563 Al307406 AW075080 D11525 A1032826 304547 AA486189 304636 AA524031 304677 2822_15 AF119850 A1133021 BE561919 BE617370 BE621149 BE561526 BE616541 BE561473 BE618997 BE549320 BE515105 AA471325 BE616284 BE559668 BE547034 BE548383 BE299097 BE545965 BE614687 BE615783 BE561441 BE562777

BE515345 BE614972 BE560948 BE561499 BE615787 BE267297 BE545452 BE300347 BE514432 BE615122 BE561421 BE560145 BE618939 BE544951 BE395272 BE619057 BE396645 BE563309 BE544527 BE408111 BE615925 BE254022 BE549220 BE562856 BE279501 BE616173 AA486917 BE560738 BE547802 BE548127 BE561779 BE314412 BE542474 BE249907 R35879 BE561536 BE544036 BE549153 BE560885 BE545111 BE256731 BE548221 BE619339 AA130747 BE259251 BE294371 BE546522 BE548227 BE612845 BE543601 N87541 H45619 BE547387 BE259822 W28818 BE542131 BE547778 BE292868 AW580223 BE513458 T60201 AW364101 BE293099 BE296447 BE270504 AW794068 BE266461 BE617287 BE277701 BE265741 BE267576 BE293068 BE265316 BE253499 BE261049 BE513754 BE252038 AA652484 BE255820 BE171777 BE393701 BE253247 BE564673 BE261164 AA308384 BE314208 BE293686 BE393327 BE263931 BE019750 AW937098 BE315499 AA079590 AA247598 BE387154 AW601680 AA152060 BE253235 BE258730 BE076040 BE549252 W05061 NM_001404 X63526 BE314801 BE397574 AA353735 BE622279 BE561832 BE256022 BE297838 BE542783 AA346189 Z11S31 AA159202 N27603 H68019 BE616749 BE249954 AA206881 BE619172 AL079889 T50884 T73176 H84175 N42762 AA190934 AA199914 BE541310 BE267209 BE304598 BE256955 BE257013 AA213850 BE546575 BE410825 BE257518 BE304451 BE392426 BE249978 AW938636 BE280611 BE269434 AA018801 BE249981 AA356501 BE546691 BE543217 BE535759 BE548149 BE274370 BE298124 BE621502 BE548075 BE562746 BE383394 BE262657 BE544530 BE619215 Api904614 BE546044 BE256949 BE560570 BE538936 BE548558 BE269263 BE296993 BE260919 AW862760 AA011045 BE563467 BE396985 AA934616 BE378952 AA100761 BE251832 BE254887 BE545870 BE396771 BE543862 BE538869 BE266240 BE542730 BE383556 BE502067 BE552014 AW602866 BE261720 AA016106 BE258671 BE281263 AW882888 W56843 AA090219 AW883193 BE618734 BE539981 BE616532 AA338063 BE618675 M55409 BE267147 BE545495 BE622854 BE618741 BE299535 BE512709 BE619549 BE621826 BE619650 BE271084 BE304968 BE620704 F00658 BE278020 BE543196 AA359668 AW959325 BE296029 BE256156 BE613346 BE617836 BE304900 AI142782 BE619732 BE621566 BE396956 AW887816 BE168703 Api219282 BE613404 BE088705 AI379660 AI620510 AA659784 W79449 Al767892 AA908586 AW863561 AI142797 BE278846 AA299822 AW954154 AA826854 W32788 AW801176 BE257998 BE569129 AA167694 H95000 AI431695 AA613987 T53824 BE514817 AA227510 AA877445 AW882770 AA507451 AW820977 BE174939 AI200307 AI445023 AI569411 AA548618 AA724243 AA653140 AA522801 AW578153 AA177136 AW192960 R76536 AA548071 AW969645 N86444 Api273891 R49511 AA860967 AA916058 AA826867 H25586 BE548884 AI911255 AA199842 AA115835 AA976259 H69325 AA055300 AI474601 W60531 A1719943 H26633 H67377 AW410942 AA133585 AA069276 BE260996 AA668262 AA172175 AW973378 AA084253 AA989530 A1250640 BE168951 BE564839 AW440725 BE564468 AA070688 BE315049 AA224349 F31228 AW517818 AA523027 AA190811 AA161089 AA088923 AI468923 AA129110 AA205266 AI220801 AA181780 AA121359 AA483551 AA501345 AA081217 AA865545 AA151850 AA604041 AA583670 AA807148 AA056615 AA486229 AA206889 R43764 AA187051 N88700 T49757 AW247901 AA582333 AW194553 AW387155 AA086260 AW166834 AA535771 AA001541 A1275743 AW589611 BE539505 Al472623 M724240 Al270077 R26806 AA018915 AW979353 Al702378 AW591470 AW015803 AW265338 F27619 F37352 304679 AA548741 304747 AA577816 304782 AA582081 304813 AA584540 304852 27797_1 NM_005534 U05875 BE244633 AW163768 AW163746 Api879080 U05877 BE274096 BE390182 BE409310 BE302866 AA303965 W31129 AA496185 F07599 Z43842 R24838 N29198 AW877047 AW877121 AW877125 AW363656 AW877123 AA377595 BE207637 W20297 AA315151 W35239 T89516 AA058408 AW408191 W23815 AA448929 Al793330 M173035 AI567425 C02282 AW602173 R73773 A1870491 AA287175 A1140367 AI025534 AA370611 AI824138 AI300591 AI300537 H04055 AA039282 Al921705 M738464 M376968 AW474501 AW157734 AW190741 AW474549 AI590825 BE302836 AA128344 AW151252 Api813665 AW514266 W78209 AI368371 AI419996 AA834439 AA085743 AA779622 AW264599 BE313816 AA470375 AA572697 AI970559 Al445034 N91836 Al160431 W72709 AI248975 AA757418 AI719633 BE300540 AI811310 AI368446 AI619458 AI186860 AA037665 AI126764 AI985833 AA579211 AI126755 AI140467 AA470989 AI188863 AA913322 AA825360 AA848066 AA683483 BE206448 AW008445 AA741327 A1022347 AA740593 AW117190 AI906053 AA843509 AI39173 AI733305 AI492747 N50093 AA862085 D20407 A1094789 AA449440 AA719906 T89696 AA838546 A1140848 AA503840 AI580923 AA828526 AI970569 AA993118 AA082836 AA825533 AA699833 AI263685 AA922853 AI160301 AI078729 AA570145 BE046096 AI371141 AI436611 AI186016 AI088757 AI141470 AI187126 AI342299 AI373836 AI827816 AI201090 AA970120 AA551892 AA287086 AW841869 AI492741 AI073355 AI192343 AI344429 AI879541 AI423770 N94310 A1051206 A1344504 AA854553 Al126700 M775124 AW572702 W19288 AA748746 Api344385 H38212 AI130719 AA626341 AW771310 AW019997 AW771346 AI922093 AA775114 R44542 AA703616 Api362485 AW072333 AI186652 AW675704 AI636453 AA709431 R43128 AA588595 AA832391 AI865833 R73681 AA515501 AW235701 N94608 Api798771 BE045450 Al369476 Al886680AW197390 Z39908 H03368 AI766761 T28478 AI424369 F03847 N90677 F32611 BE041313 AI420363 AW009689 AI933460 AA614856 AI401046 AA056737 AI620906 AI797411 AA039629 BE243267 W23784 Api311585 W70312 AA081965 AA643695 AA541686 AI249750 AW298157 AA939276 N63266 AW000886 AA678042 F19175 AI499969 AI924421 T25501 Z20802 AI972829 AI826621 AW891571 Z20801 W26292 AW190699 AI640652 AA970137 W77882 A1567514 A1570317 D45596 AA905904 304941 AA612612 304948 AA613107 304987 AA618044 304998 AA621203 305081 AA641638 305089 AA642622 305211 AA668563 305257 AA679005 305259 AA679225 305271 33276_16 T81656 AI174932 T82847 T19334 BE563893 BE563101 BE407270 BE386893 AW075527 BE616551 AI879322 AI929728 Al557023 M657885 Al207449 H74068 AA135820 BE560404 BE250148 BE619362 BE612714 BE276295 X55715 NM_001005 T71701 BE513229 BE385149 BE387298 R27196 T55650 AI546980 BE276020 AA483994 AI525170 BE384198 AA158297 BE206964 AA259269 H51936 S42658 AA187098 AA186388 AA205135 AA533926 BE083862 BE563679 N88835 AA096117 AA225077 BE543870 U14991 U14992 U14990 W40297 W17363 AA377786 AA199796 H14178 H74025 W05492 AA187571 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AA242817 AA258359 AW027603 AI935204 AI500360 AI569741 BE551058 AW275536 A1457854 AI142093 AW028288 AI286002 AI279114 AI364121 AI341323 AI190436 AW002607 AI242488 AI338122 AI368600 AI340276 AI417994 AI190234 AI275527 AI934886 AI498274 AI813630 AI075339 AI087976 AI459251 AI989477 AW004046 A1992190 AI885279 AI479475 AI698030 AI473294 AI951648 AI699587 AI660602 AI873018 AW613987 AI808297 AW270159 AW572955 AW195908 AW469034 AW197100 AA855164 AW611688 AI143033 AI910560 AA418374 AW341092 AI871169 AI937136 AI204003 AA775707 AW590759 AW593350 AW572981 AI197905 AI660941 AI733469 AW237017 AI808587 AI984962 AA4185254 AI828104 AA625231 AI832151 H84232 AI240215 AI911775 AI219668 AI336801 AA232630 AI343741 W69129 N93602 AA768883 W04386 AI086277 AA983433 W07646 AA458584 N86625 Al384055 Al928089 W25479 AA242952 AI763303 Al225039 Al740896 M953758 W69240 AA558331 A1760593 AA558712 AW992121 AW992157 W69115 BE328596 Al953190 W95311 AI950195 AI739605 AI857262 W69185 AA884588 AI198104 AI127451 AA905932 AA723310 AI936623 AA732940 AI332918 AI221396 AI336095 AI200067 AI824853 D55893 D52697 D56205 AA232764 T53299 H84555 AA076539 AA158347 BE298430 AL134493 AW732398 AW750740 AW578208 N36572 AA453861 AA252914 AA234197 AW576988 AW577034 AA025199 AW577052 AW385538 AW576996 AW577021 T83230 AA421529 AI928492 AA909038 AA507060 AA654561 AA064597 AW001594 AW469192 AI368002 AI142435 AW379382 W93438 AA076387 AI802344 A1097013 AA987215 AA635282 W93349 A1017818 AA421564 AA158348 Al140004 AA506259 AW473184 AA236350 Al138669 H96873 AA974889 AA643735 AA995463 AA995471 AA809555 AA253225 AI298682 AI572515 T53300 AA064596 AA193589 AA025118 Al669682 M610638 T90774 Al972332 Al280776 T27980 AW136058 BE000428 AI378691 AA961520 BE049142 AI311424 AA283211 AI344071 AI34407 AI344097 AI582410 AL036314 AW798038 AI905228 C15325 AA380386 AW958417 AW630531 BE538239 T70488 AA088296 T34175 T31626 D54331 D53142 AA029415 AW946823 A1914128 AA355446 T34322 BE006559 M85677 AA034335 T31463 AW804007 AA256591 D55128 AI535884 D55192 N23605 T31802 AA326899 AW999156 AA355201 AW999306 A1091590 BE172021 AA029490 BE000255 AW339939 AW150093 Al872098 Al274876 T06303 AA857909 N23606M922714 Al914104AI285281 AW999919 AI339803 A1081354 AA972184 A1049566 AW151583 AI682455 AA088257 AI217050 BE551774 AI277033 AI252627 AA910406 AI369422 H46634 AI873113 AA033710 AW078579 AI636452 N23010 A375263 AA256592 T05786 AA884195 AA406145 AA907807 AA482840 AI637691 AA654523 AA911495 T06601 AW594370 AW016524 C15324 AA622519 AA340191 AA174168 C13992 T69433 T96576 AW166622 T96575 323011 139750_1 AA580288 AA315655 AA133031 AA377748 323166 162676_1 AA291001 AA188974 AA290616 323216 6526_1 AA332145 AA331790 AW962563 AA86819 L13837 T34468 AA055882 AA096148 AA092327 H57062 R59098 R11247 F07659 Z44949 AF131829 L13835 T79889 AA252451 N28984 H85260 AL046384 AW995631 R58386 A1061651 AW376050 AW379789 W90347 AA450157 A1799939 AA461340 W02347 AA233095 N39675 AA659441 AW995284 W17060 R32252

A1042599 AL046385 AI970370 AA744764 AI249761 AI628106 R32668 Al863011 A1923998 A1186798 N26601 Api141864 N34992 Al377031 N23934 AI683466 BE219548 AA622032 AW089867 AA243717 N79547 R59099 AW241293 AI917545 AW103697 A1383179 AW517527 AW163642 W90348 AW381409 R1195 AA461166 AA836624 AA280285 AW242055 L13836 N89647 L13834 AI358605 AA452023 AI868391 H57063 AW075868 N20590 Z40695 R37603 R28484 AA251913 F03914 AA055772 N43752 323243 140566_2 W47525 AA134047 BE391212 AA330333 AA376355 BE304871 BE167342 H87402 AA631722 W45724 AA715517 A1925438 AI8048949 AW241617 AW403807 AI653435 AA134038 AW747874 A1922327 A) 814967 AM35895 AA228865 AW504076 AA225008 AW673858 C03914 323244 647858_1 AW675572 A1248270 T85161 AL133848 T70731 T69747 323333 62251_1 AV651680 AA228883 AA367341 AW962458 AA628024 AW172426 AI767785 AAE13012 AW963323 323430 63341_1 AW062479 AW062488 AW062491 AW062480 AW938564 AW062478 AA322408 AA324351 AW938595 AW938598 BE162389 AW176556 AW938599 AW838792 AW938566 BE162305 BE162377 AW938570 AW062459 AW176555 AW938562 AW938568 AA251701 BE162320 AW938597 323465 193343_1 AA287406 AA261844 AA261845 AA287355 AA810895 323479 194627_1 AA278426 AW292815 AA278703 323538 217887_1 AW247696 BE265140 AW403615 AL037647 AA312336 323632 333100_1 AL041844 AL040002 AL039950 323731 226193_1 AA323414 AW664013 AI809377 AI276041 AW296883 AI798340 323753 12462_4 AK002161 AA327102 Al056868 Al743901 Al139018 Al199114 Al076003 323835 506747_1 AL042005 AL042006 AA911481 323898 243407_1 AF347566 AF346521 AI111169 324048 267284_1 AA378739 AW964174 AA570564 A1076833 AW265063 AW006805 AA480656 AW004789 324231 975669_1 W60827 AL079968 AL047234 324430 312113_1 AA464018 AA464079 AA468142 324432 3124877_1 AA464510 AA631257 AI740516 AI739132 AW972467 Api741376 AW068935 Al467852 Al752240 Al123717 Al754551 AW205510 AW044211 AW028889 AW198033 Al538632 M513096 324456 1155396_1 AW500954 AW501111 AW501394 324512 1156071_1 AW502122 AW502125 AW501663 AW501720 324575 65704_1 AW502257AI014241 AA100360 BE298534 324609 33046_1 AW299534 AW299896 AA504765 AA505099 AA505100 AA584753 AW136415 AA768306 324620 69834_1 BE397649 H14413 BE397689 BE514098 H53372 AA448021 R57944 AI307272 BE259369 H72331 BE251092 T27364 AA001666 AA044433 AA875998 AW075405 AW338356 AA001667 AW300173 AW514944 AW468914 AA604673 AA702749 AA805550 AA447621 AA934104 AI373527 AA604794 AI911203 AI500644 AI291383 AA731133 BE350633 AA044604 H95689 H14366 AV660983 AA912893 A1369587 AI382271 AA917508 AW138391 BE622560 324662 560496_1 AI376331 AI819150 AI097038 AI351100 AW504689 324670 72231_1 AW503713 AA352950 AA044972 BE618246 AA335047 AW96269 324692 315987_1 AA557952 AA67593 AA618150 324715 290035_2 AAI739168 AA426249 AI199636 AW505198 AW977291 AA824583 AA883419 AA724079 Al015524 Al377728 AW293682 AI928140 AA731438 AI092404 AI085630 AA731340 324728 210991 2 T85872 T48305 324783 389615_1 AA640770AI683112AA913009 324848 371388_1 AA602539 D59262 AI684171 N46711 AW021857 D19768 324961 376239_1 AA613792 AW182329 T05304 AW858385 324988 22162-1 AK001379 AK001411 AW795711 T06997 AA287540 AA354538 AW957773 AI632268 AI651003 AI689650 AI809332 AW304483 AI805269 AA278506 AA862381 AA287875 AW628545 A1085761 AW025965 AI658615 AW628879 AW139496 AI214278 AA902745 AA991679 BE540102 A593658 AI745602 AA744687 AI285441 AA807089 AI218314 AA721449 A1202987 AA432129 A1285502 A1281462 AA731319 BE082573 325071 1562044_1 H09693 H09699 T09229 325176 700767_1 T194142 AI351168 T52843 BE241963

TABLE IB Table 1B shows the genomic positioning for those primekeys in Table 1 that lack unigene ID's and accession numbers. For each predicted exon, the genomic sequence source used for prediction is listed. Nucleotide locations of each predicted exon are also listed.

Pkey: Unique number corresponding to an Eos probeset Ref : Sequence source. The 7 digit numbers in this column are Genbank identifier (GI) numbers "Dunham I. et al."refers to the publication entitled "The DNA sequence of human chromosome 22."Dunham I. et al., Nature (1999) 402: 489-495.

Strand: Indicates DNA strand from which exons were predicted.

NLposition : Indicates nucleotide positions of predicted exons.

Pkey Ref Strand Nt_position 332792 Dunham, I. et. al. Plus 73381-73768 332908 Dunham, I. et. al. Plus 1934283-1934366 332909 Dunham, I. et. al. Plus 1946582-1946735 332913 Dunham, I. et. al. Plus 1963539-1963843 332952 Dunham, I. et. al. Plus 2472864-2473012 332958 Dunham, I. et. al. Plus 2516164-2516310 332961 Dunham, I. et. al. Plus 2521424-2521555 332975 Dunham, I. et. al. Plus 2599641-2599702 332991 Dunham, I. et. al. Plus 2686938-2687372 333119 Dunham, I. et. al. Plus 3288316-3288640 333131 Dunham, I. et. al. Plus 3350064-3350170 333139 Dunham, I. et. al. Plus 3369495-3369571 333156 Dunham, I. et. al. Plus 3617584-3617790 333222 Dunham, I. et. al. Plus 3979706-3979803 333254 Dunham, I. et. al. Plus 2521424-2521555 333348 Dunham, I. et. al. Plus 4711908-4712181 333349 Dunham, I. et. al. Plus 4713940-4714084 333366 Dunham, 1. etal. Plus 4798273-4798469 333384 Dunham, I. et. al. Plus 4907535-4907610 333385 Dunham, I. et. al. Plus 4907928-4908032 333391 Dunham, I. et.al. Plus 4916697-4916780 333488 Dunham, I. et. al. Plus 5396233-5396310 333520 Dunham, I. et. al. Plus 5586133-5586296 333524 Dunham, I. et. al. Plus 5612620-5612780 333532 Dunham, I. et. al. Plus 5622804-5622937 333580 Dunham, I. et. al. Plus 6142935-6143145 333585 Dunham, I. et. al. Plus 6234778-6234894 333597 Dunham, I. et. al. Plus 6331421-6331536 333619 Dunham, I. et. al. Plus 6562799-6562926 333671 Dunham, I. et.al. Plus 7038849-7039193 333680 Dunham, I. et. al. Plus 7071730-7071794 333682 Dunham, I. et. al. Plus 7076641-7076760 333763 Dunham, I. et. et.al. Plus 7692491-7692630 333764 Dunham, I. et. al. Plus 7693573-7693716 333769 Dunham, I. et. al. Plus 7696625-7696707 333770 Dunham, I. et. al. Plus 7700384-7700476 333849 Dunham, I. et. al. Plus 8018323-8018472 333875 Dunham, I. et. al. Plus 8135505-8136179 333882 Dunham, I. et. al. Plus 8153002-8153169 333922 Dunham, I. et. al. Plus 8381385-8381444 333928 Dunham, I. et. al. Plus 8468844-8469015 333947 Dunham, I. et. al. Plus 8579888-8579966 333949 Dunham, I. et. al. Plus 8589634-8589791 333968 Dunham, I. et. al. Plus 8681004-8681241 333983 Dunham, I. et. al. Plus 8813593-8813668 333995 Dunham, I. et. al. Plus 8855296-8855424 <BR> <BR> 333997 Dunham, I. et. al. Plus 8866668-8867255 334003 Dunham, I. et. al. Plus 8892882-8892970 334012 Dunham, I. et. al. Plus 9007456-9010221 334047 Dunham, I. et. al. Plus 9428152-9428211 334063 Dunham, I. et. al. Plus 9731991-9732085 334066 Dunham, I. et. al. Plus 9739568-9739680 334078 Dunham, I. et. al. Plus 9809783-9809863 334118 Dunham, I. et. al. Plus 10344273-10344384

334122 Dunham, I. et. al. Plus 10411792-10411901 334150 Dunham, I. et. al. Plus 10529221-10529854 <BR> <BR> 334220 Dunham, l. et. al. Plus 12718720-12718857 33428 Dunham, I. et. al. Plus 13424763-13425914 334324 Dunham, I. et. al. Plus 13539210-13539323 334335 Dunham, I. et. al. Plus 13608488-13608705 334433 Dunham, I. et. al. Plus 14273261-14273429 334532 Dunham, I. et. al. Plus 14792798-14792901 334561 Dunham, I. et. al. Plus 14987299-14987447 334616 Dunham, I. et. al. Plus 15176123-15176470 334628 Dunham, I. et. al. Plus 15310346-15310415 334630 Dunham, I. et. al. Plus 15322614-15322744 334631 Dunham, I. et. al. Plus 15325949-15326116 334661 Dunham, I. et. al. Plus 15477716-15477786 334677 Dunham, I. et. al. Plus 15517449-15517560 334696 Dunham, I. et. al. Plus 15665919-15666002 334714 Dunham, I. et. al. Plus 15760702-15760767 334718 Dunham, I. et. al. Plus 15775491-15775599 334720 Dunham, I. et. al. Plus 15792931-15793085 334727 Dunham, I. et. al. Plus 15942616-15942750 334739 Dunham, I. et. al. Plus 16004120-16004225 334740 Dunham, I. et. al. Plus 16009324-16009547 334769 Dunham, I. et. al. Plus 16170704-16170876 <BR> <BR> 334872 Dunham, I. et. al. Plus 19162417-19162565 334876 Dunham, I. et. al. Plus 19185336-19185400 334883 Dunham, I. et. al. Plus 19223107-19223253 334891 Dunham, I. et.al. Plus 19299770-19299944 334900 Dunham, I. et. al. Plus 19315678-19315743 334902 Dunham, I. et. al. Plus 19317083-19317195 334914 Dunham, I. et. al. Plus 19495158-19495275 334916 Dunham, I. et. al. Plus 19572924-19573846 335044 Dunham, I. et. al. Plus 20842088-20842682 335081 Dunham, I. et. al. Plus 21113871-21113937 335158 Dunham, I. et. al. Plus 21569610-21569666 335164 Dunham, I. et. al. Plus 21585912-21586014 335166 Dunham, I. et.al. Plus 21587100-21587213 335170 Dunham, I. et. al. Plus 21623383-21623967 335188 Dunham, I. et. al. Plus 21669118-21669328 335189 Dunham, I. et. al. Plus 21673403-21673472 335200 Dunham, I. et. al. Plus 21743499-21743881 335211 Dunham, I. et. al. Plus 21774611-21774680 335219 Dunham, 1. et. al. Plus 21875591-21875688 335221 Dunham, I. et. al. Plus 21882840-21882968 335225 Dunham, I. et. al. Plus 21890315-21890448 335255 Dunham, I. et. al. Plus 22032258-22032661 335287 Dunham, I. et. al. Plus 22299047-22299299 335361 Dunham, I. et. al. Plus 22807292-22807445 335364 Dunham, I. et. al. Plus 22833430-22833586 335369 Dunham, I. et. al. Plus 22843392-22843506 <BR> <BR> 335468 Dunham, I. et. al. Plus 23787245-23787367 335481 Dunham, I. et. al. Plus 24082522-24084870 335488 Dunham, I. et. al. Plus 24118744-24118839 335496 Dunham, I. et. al. Plus 24164386-24164545 335497 Dunham, I. et. al. Plus 24167666-24167869 335499 Dunham, I. et.al. Plus 24176698-24176869 <BR> <BR> 335504 Dunham, I. et. al. Plus 24182110-24182199 335599 Dunham, I. et. al. Plus 25043628-25043775 335623 Dunham, I. et. al. Plus 25138489-25138547 335653 Dunham, I. et. al. Plus 25329710-25329802 335687 Dunham, I. et. al. Plus 25445952-25446064 335690 Dunham, I. et. al. Plus 25455442-25455625 335692 Dunham, I. et. al. Plus 25468557-25468725 335697 Dunham, I. et. al. Plus 25481456-25481649 <BR> <BR> 335701 Dunham, I. et. al. Plus 25513366-25513807 335708 Dunham, I. et. al. Plus 25541777-25541907 335739 Dunham, I. et. al. Plus 25698550-25698826 335742 Dunham, I. et. al. Plus 25712654-25712771 336003 Dunham, I. et. al. Plus 28406289-28406759 336015 Dunham, I. et. al. Plus 28640586-28640673 336016 Dunham, I. et.al. Plus 28646816-28646947 336018 Dunham, I. et. al. Plus 28660880-28660978 336019 Dunham, I. et. al. Plus 28663992-28664102 336020 Dunham, I. et. al. Plus 28683778-28683851 336021 Dunham, I. et. al. Plus 28686482-28686559 336023 Dunham, I. et. al. Plus 28698240-28698343

336071 Dunham, I. et. al. Plus 29264457-29264684 336090 Dunham, I. et. al. Plus 29413020-29413162 336107 Dunham, I. et. al. Plus 29987731-29987869 336121 Dunham, I. et. al. Plus 30048054-30048129 336124 Dunham, I. et. al. Plus 30053441-30053500 336132 Dunham, I. et. al. Plus 30107247-30107412 336135 Dunham, I. et. al. Plus 30123235-30123335 336194 Dunham, I. et. al. Plus 30443138-30443282 336235 Dunham, I. et. al. Plus 31122315-31122623 336367 Dunham, I. et. al. Plus 33942937-33943058 336379 Dunham, I. et. al. Plus 33995071-33995243 336439 Dunham, I. et. al, Plus 34186130-34186215 336502 Dunham, I. et. al. Plus 34268953-34269083 336572 Dunham, I. et. al. Plus 34446383-34446496 336602 Dunham, I. et.al. Plus 13424060-13424582 336721 Dunham, I. et. al. Plus 3371522-3371586 336739 Dunham, I. et. al. Plus 2599641-2599702 336766 Dunham, I. et. al. Plus 4905608-4905684 336833 Dunham, I. et. al. Plus 6856506-6856634 336836 Dunham, I. et. al. Plus 7077262-7077326 336878 Dunham, I. et. al. Plus 9200300-9200399 336880 Dunham, I. et. al. Plus 9250034-9250123 336902 Dunham, I. et. al. Plus 10385555-10386053 336917 Dunham, I. et. al. Plus 11228329-11228403 336919 Dunham, I. et. al. Plus 11351181-11351274 336924 Dunham, I. et. al. Plus 11525273-11525527 <BR> <BR> 336946 Dunham, I. et. al. Plus 12337073-12337258 336953 Dunham, I. et. al. Plus 12988791-12988889 336979 Dunham, I. et. al. Plus 14270748-14270816 337169 Dunham, I. et. al. Plus 23529987-23530214 337175 Dunham, I. et. al. Plus 23782209-23782374 337182 Dunham, I. et. al. Plus 23934889-23934962 337238 Dunham, I. et. al. Plus 27141465-27141776 337303 Dunham, I. et.al. Plus 2918849-29128974 337489 Dunham, I. et. al. Plus 33295724-33295872 337503 Dunham, I. et. al. Plus 33385583-33385857 337504 Dunham, I. et. al. Plus 33386053-33386236 337570 Dunham, I. et. al. Plus 359309-359459 337585 Dunham, I. et. al. Plus 951744-952008 337629 Dunham, I. et. al. Plus 2017380-2017517 337670 Dunham, I. et. al. Plus 3110593-3110760 337674 Dunham, I. et. al. Plus 3332616-3332697 337692 Dunham, I. et. al. Plus 3575105-3575299 337740 Dunham, I. et. al. Plus 3870165-3870223 337755 Dunham, I. et.al. Plus 3971764-3971900 337807 Dunham, I. et.al. Plus 4444885-4444981 337844 Dunham, I. et. al. Plus 4993372-4993603 337902 Dunham, I. et. al. Plus 5682218-5682307 337904 Dunham, I. et. al. Plus 5685819-5686012 337919 Dunham, I. et. al. Plus 6035207-6035326 337951 Dunham, I. et. al. Plus 6766321-6766382 337958 Dunham, I. et. al. Plus 6969162-6969270 337964 Dunham, I. et. al. Plus 7032720-7032802 338008 Dunham, I. et. al. Plus 7697068-7697236 338053 Dunham, I. et.al. Plus 8412742-8412823 338057 Dunham, I. et. al. Plus 8526397-8526522 338059 Dunham, I. et. al. Plus 8540638-8540712 338120 Dunham, I. et. al. Plus 10765673-10765820 338124 Dunham, I. et. al. Plus 10860311-10860471 338178 Dunham, I. et. al. Plus 12800037-12800181 338196 Dunham, I. et. al. Plus 13629317-13629466 338204 Dunham, I. et. al. Plus 13870980-13871152 338239 Dunham, I. et. al. Plus 14669918-14670016 338249 Dunham, I. et. al. Plus 14870864-14870944 338250 Dunham, I. et.al. Plus 14874504-14874575 338251 Dunham, I. et. al. Plus 14963460-14963521 338260 Dunham, I. et. al. Plus 15458919-15459257 338282 Dunham, I. et. al. Plus 16240812-16241002 338316 Dunham, I. et. al. Plus 17089711-17089988 338364 Dunham, I. et. al. Plus 18210049-18210226 338374 Dunham, I. et. al. Plus 18371200-18371282 338454 Dunham, I. et. al. Plus 20180035-20180113 338494 Dunham, I. et. al. Plus 21181818-21182009 338596 Dunham, I. et. al. Plus 23078273-23078348 338622 Dunham, I. et. al. Plus 23546552-23546749

338702 Dunham, I. et. al. Plus 25219632-25219739 338707 Dunham, I. et. al. Plus 25266346-25266417 338716 Dunham, I. et. al. Plus 25472519-25472686 <BR> <BR> 338765 Dunham, I. et. al. Plus 26657278-26657346 338852 Dunham, I. et. al. Plus 28086911-28086971 338862 Dunham, I. et. al. Plus 28230332-28230444 338962 Dunham, I. et. al. Plus 29581892-29582020 33897 Dunham, I. et.al. Plus 30092658-30092730 339164 Dunham, I. et. al. Plus 32207441-32207802 339305 Dunham, I. et. al. Plus 33334676-33334864 339313 Dunham, I. et. al. Plus 33383457-33383585 339319 Dunham, I. et. al. Plus 33410900-33410972 339323 Dunham, I. et. al. Plus 33418663-33418829 339356 Dunham, I. et. al. Plus 33573387-33573517 339358 Dunham, I. et. al. Plus 33577760-33577922 339361 Dunham, I. et. al. Plus 33580121-33580251 339413 Dunham, I. et. al. Plus 34268734-34268875 339418 Dunham, I. et. al. Plus 34353362-34353421 339436 Dunham, I. et al. Plus 34546469-34546834 332813 Dunham, I. et. al. Minus 318840-318777 332854 Dunham, I. et. al. Minus 1283611-1283053 332858 Dunham, I. et. al. Minus 1339607-1339397 332863 Dunham, I. et. al. Minus 1389980-1389884 332868 Dunham, I. et. al. Minus 1413234-1413078 332884 Dunham, I. et. al. Minus 1573063-1572923 332886 Dunham, I. et. al. Minus 1574863-1574660 332896 Dunham, I. et. al. Minus 1631641-1631422 332929 Dunham, I. et.al. Plus Minus 2020758-2020664 332930 Dunham, I. et. al. Minus 2022565-2022497 332931 Dunham, I. et. al. Minus 2023651-2023562 332932 Dunham, I. et. al. Minus 2035348-2035282 332965 Dunham, I. et. al. Minus 2537457-2537396 332995 Dunham, I. et. al. Minus 2708847-2708685 333002 Dunham, I. et. al. Minus 2537457-2537396 333011 Dunham, I. et. al. Minus 2769669-2769571 333029 Dunham, I. et. al. Minus 2885241-2885175 333033 Dunham, I. et. al. Minus 2889900-2889699 333110 Dunham, I. et. al. Minus 3244892-3244779 333126 Dunham, I. et. al. Minus 3324305-3324184 <BR> <BR> 333217 Dunham, I. et. al. Minus 3967830-3967716 333220 Dunham, I. et. al. Minus 3969363-3968789 333242 Dunham, I. et. al. Minus 4104544-4104259 333243 Dunham, I. et. al. Minus 4104961-4104728 333259 Dunham, I. et. al. Minus 4306769-4306639 333270 Dunham, I. et. al. Minus 4373573-4373219 333278 Dunham, I. et.al. Minus 4414616-4414389 333279 Dunham, I. et. al. Minus 4415252-4414844 333358 Dunham, I. et. al. Minus 4732336-4732236 333408 Dunham, I. et. al. Minus4936879-4936661 333441 Dunham, I. et. al. Minus 2708847-2708685 333444 Dunham, I. et. al. Minus 5070077-5069643 <BR> <BR> 333447 Dunham, I. et al. Minus 2537457-2537396 333466 Dunham, I. et. al. Minus 2708847-2708685 333473 Dunham, I. et. al. Minus 2537457-2537396 333496 Dunham, I. et.al. Minus 5404643-5404523 333511 Dunham, I. et. al. Minus 5557881-5557718 333542 Dunham, I. et. al. Minus 5861529-5861341 333568 Dunham, I. et. al. Minus 5965072-5964999 333582 Dunham, I. et. al. Minus 6158522-6158322 333655 Dunham, I. et. al. Minus 6975471-6975215 333673 Dunham, I. et. al. Minus 7054704-7054602 333734 Dunham, I. et. al. Minus 7535394-7535309 333964 Dunham, I. et. al. Minus 8626045-8625966 334156 Dunham, I. et. al. Minus 10580883-10580765 334172 Dunham, I. et. al. Minus 11644142-11644008 334183 Dunham, I. et. al. Minus 11832582-11832508 334184 Dunham, I. et. al. Minus 11833848-11833757 334223 Dunham, I. et. al.. Minus 12734365-12734269 334270 Dunham, I. et. al. Minus 13249131-13249007 334288 Dunham, I. et. al. Minus 13295104-13294969 334303 Dunham, I. et. al. Minus 13454331-13454217 334358 Dunham, I. et. al. Minus 13724372-13724201 334370 Dunham, I. et. al. Minus 13782655-13782493 334472 Dunham, I. et. al. Minus 14391308-14391169 334474 Dunham, I. et.al. Minus 14391920-14291809

334487 Dunham, I. et. al. Minus 14432191-14432132 334500 Dunham, I. et. al. Minus 14486730-14486621 334537 Dunham, I. et. al. Minus 14827542-14827354 334621 Dunham, I. et. al. Minus 15190418-15190299 334648 Dunham, I. et. al. Minus 15363301-15363222 334764 Dunham, I. et. al. Minus 16151208-16151104 334783 Dunham, I. et. al. Minus 16293336-16293226 334784 Dunham, I. et. al. Minus 16294548-16294360 <BR> <BR> 334786 Dunham, I. et. al. Minus 16297434-16297275 334789 Dunham, I. et.al. Minus 16306095-16305996 334806 Dunham, I. et. al. Minus 16433227-16433125 334823 Dunham, I. et. al. Minus 16851360-16851189 334850 Dunham, I. et. al. Minus 17660892-17660787 334924 Dunham, I. et. al. Minus 19744615-19744229 334939 Dunham, I. et. al. Minus 20131162-20131054 334943 Dunham, I. et. al. Minus 20135064-20134903 334948 Dunham, I. et. al. Minus 20141727-20141583 334970 Dunham, I. et. al. Minus 20195886-20195554 334991 Dunham,. I. et. al. Minus 20341858-20341773 334993 Dunham, I. et. al. Minus 20354277-20354174 335062 Dunham, I. et. al. Minus 20921289-20921087 335207 Dunham, I. et. al. Minus 21763011-21762880 335288 Dunham, I. et. al. Minus 22304275-22303770 <BR> <BR> 335289 Dunham, I. etal. Minus 22305950-22305708 335293 Dunham, I. et. al. Minus 22316408-22316275 335332 Dunham, I. et. al. Minus 22557778-22557557 335389 Dunham, I. et. al. Minus 23043682-23043558 335478 Dunham, I. et. al. Minus 23924778-23924329 35524 Dunham, I. et. al. Minus 24237218-24236208 335547 Dunham, I. et. al. Minus 24658526-24658460 335671 Dunham, I. et. al. Minus 25358629-25358533 335682 Dunham, I. et. al. Minus 25421215-25421093 335684 Dunham, I. et. al. Minus 25425165-25425096 335698 Dunham, I. et. al. Minus 25493029-25492767 335755 Dunham, I. et. al. Minus 25763806-25763747 335756 Dunham, I. et. al. Minus 25764330-25764251 335773 Dunham, I. et. al. Minus 25880858-25880661 335813 Dunham, I. et. al. Minus 26318734-26318649 335815 Dunham, I. et. al. Minus 26320518-26320421 335817 Dunham, I. et.al. Minus 26321875-26321750 335827 Dunham, I. et. al. Minus 26380557-26380472 335829 Dunham, I. et. al. Minus 26382348-26382251 335826 Dunham, I. et. al. Minus 26397823-26397694 335857 Dunham, I. et. al. Minus 26677208-26677096 335860 Dunham, I. et. al. Minus 26684908-26684800 335871 Dunham, I. et. al. Minus 26734972-26734892 335896 Dunham, I. et.al. Minus 26977639-26977558 335897 Dunham, I. et. al. Minus 26978293-26978142 335903 Dunham, I. et. al. minus 26985739-26985580 335914 Dunham, I. et al. Minus 27024197-27023994 335916 Dunham, I. et. al. Minus 27027028-27026912 <BR> <BR> 335935 Dunham, I. et. al. Minus 27360288-27360058 335940 Dunham, I. et. al. Minus 27420194-27420000 335999 Dunham, I. et. al. Minus 28033986-28033848 336045 Dunham, I. et. al. Minus 29044217-29044140 336140 Dunham, I. et. al. Minus 30134204-30133980 336182 Dunham, I. et.al. Minus 30371411-30371339 336198 Dunham, I. et. al. Minus 30459668-30459460 336227 Dunham, I. et. al. Minus 30902014-30901946 336246 Dunham, I. et. al. Minus 31425669-31425253 336262 Dunham, I. et. al. Minus 31833610-31833533 336292 Dunham, I. et. al. Minus 32818035-32817927 336347 Dunham, I. et. al. Minus 33843218-33843104 336397 Dunham, I. et.al. Minus 34021504-34021389 336434 Dunham, I. et. al. Minus 34073056-34072952 336662 Dunham, I. et. al. Minus 2158060-2157993 336675 Dunham, I. et. al. Minus 2020758-2020664 336676 Dunham, I. et. al. Minus 2022565-2022497 336677 Dunham, I. et. al. Minus 2023651-2023562 336678 Dunham, I. et. al. Minus 2035348-2035282 336684 Dunham, 1. et. al. Minus 2158060-2157993 336703 Dunham, I. et. al. Minus 5071373-5071278 336707 Dunham, I. et. al. Minus 2820219-2820111 336722 Dunham, I. et. al. Minus 3377722-3377590 336778 Dunham, I. et. al. Minus 5071373-5071278

336846 Dunham, I. et. al. Minus 7566306-7566238 336977 Dunham, I. et. al. Minus 14110003-14109910 336981 Dunham, I. et. al. Minus 14478638-14478472 337056 Dunham, I. et. al. Minus 17975104-17974976 337094 Dunham, I. et. al. Minus 20146915-20146778 337102 Dunham, I. et. al. Minus 20581738-20581628 337161 Dunham, I. et. al. Minus 23473450-23473375 337366 Dunham, I. et. al. Minus 30961904-30961787 337422 Dunham, I. et. al. Minus 32030671-32030417 337452 Dunham, I. et. al. Minus 32415187-32415117 337534 Dunham, I. et. al. Minus 34193847-34193769 337595 Dunham, I. et. al. Minus 1020506-1020210 337602 Dunham, I. et. al. Minus 1282987-1282741 337603 Dunham, I. et. al. Minus 1299296-1299194 337645 Dunham, I. et. al. Minus 5141462-5141329 337760 Dunham, I. et. al. Minus 4008389-4008037 337772 Dunham, I. et. al. Minus 4061918-4061782 337776 Dunham, I. et. al. Minus 4084555-4084460 337840 Dunham, I. et. al. Minus 4940540-4940409 337908 Dunham, I. et. al. Minus 5697187-5697071 337937 Dunham, I. et. al. Minus 6556005-6555907 337974 Dunham, I. et. al. Minus 7153401-7153085 337986 Dunham, I. et. al. Minus 7296008-7295951 338000 Dunham, I. et. al. Minus 7530875-7530793 338221 Dunham, I. et. al. Minus 14183649-14183568 <BR> <BR> 338510 Dunham, I. eLal. Minus 21339584-21339508 338535 Dunham, I. et. al. Minus 21799696-21799274 338546 Dunham, I. et. al. Minus 22012448-22012383 <BR> <BR> 338556 Dunham, I. et. al. Minus 22179326-22179234 338561 Dunham, I. et. al. Minus 22311966-22311856 338668 Dunham, I. et. al. Minus 24500606-24500442 338689 Dunham, I. et. al. Minus 24893073-24892972 338727 Dunham, I. et. al. Minus 25926788-25926580 338759 Dunham, I. et. al. Minus 26582475-26582199 338763 Dunham, I. et. al. Minus 26628148-26628009 338779 Dunham, I. et. al. Minus 27030151-27029795 338876 Dunham, I. et. al. Minus 28364326-28364071 338889 Dunham, I. et. al. Minus 28477552-28477412 339028 Dunham, I. et. al. Minus 30574122-30573937 339044 Dunham, I. et. al. Minus 30721853-30721740 339128 Dunham, I. et. al. Minus 31692815-31692686 339188 Dunham, I. et. al. Minhus 32347554-32347250 339208 Dunham, 1. et. al. Minus 32491714-32491657 339215 Dunham, I. et. al. Minus 32502559-32502383 339230 Dunham, I. et. al. Minus 32729004-32728929 339256 Dunham, I. et. al. Minus 32926055-32925967 339280 Dunham, I. et. al. Minus 33114230-33114010 339370 Dunham, I. et. al. Minus 33805912-33805797 337895 <BR> <BR> 329598 3962482 Plus 39924-40220<BR> <BR> <BR> <BR> 329563 3962490 Minus 410-635<BR> <BR> <BR> <BR> 329557 3962492 Minus 53197-53647 329539 3983503 Minus 1-326 329526 3983506 Plus 12251-12325 <BR> <BR> 329524 3983507 Minus 38025-38143<BR> <BR> <BR> 329502 3983517 Plus 75-338<BR> <BR> <BR> <BR> 329503 3983517 Minus 1801-1937<BR> <BR> <BR> <BR> 329499 3983518 Plus 33463-33789<BR> <BR> <BR> <BR> 329479 3983526 Minus 7425-7561<BR> <BR> <BR> <BR> 329625 4567169 Minus 85893-85984 325363 5866920 Plus 700446-700516 325366 5866920 Minus 920962-921713 <BR> <BR> 325433 5866936 Minus 480706-480826<BR> <BR> <BR> <BR> 325447 5866941 Minus 372480-372621 325481 5866957 Plus 47590-47672 325482 5866957 Plus 47957-48078 325472 6017034 Minus 289581-289657 <BR> <BR> 325513 6017035 Minus 34295-34490<BR> <BR> <BR> <BR> 325519 6017036 Minus 186804-186915<BR> <BR> <BR> <BR> 325587 6682462 Plus 126724-126967<BR> <BR> <BR> <BR> 325585 6682462 Plus 73476-73574<BR> <BR> <BR> 325594 5866992 Minus 470474-470566<BR> <BR> <BR> <BR> 325609 5866996 Minus 981751-981849 325622 5867000 Plus 69994-70075 <BR> <BR> 325751 6682474 Plus 130437-130520

325815 6682483 Minus 129273-130754 329762 6048280 Plus 127744-127878 <BR> <BR> 329789 6469354 Minus 118977-119036<BR> <BR> <BR> <BR> <BR> 329797 6523160 Minus 10616-10894<BR> <BR> <BR> <BR> <BR> 329838 6672062 Plus 33990-34098 325864 5867069 Minus 110834-110904 <BR> <BR> 325885 5867087 Plus 193212-193377<BR> <BR> <BR> <BR> <BR> 325892 5867088 Minus 10498-10652<BR> <BR> <BR> <BR> <BR> 325929 5867125 Minus 51715-51996<BR> <BR> <BR> <BR> <BR> 325843 6552453 Minus 7126-7232<BR> <BR> <BR> <BR> <BR> 329989 4567166 Plus 72861-73052<BR> <BR> <BR> <BR> 329960 5091594 Minus 1031-1162<BR> <BR> <BR> <BR> <BR> 329959 5103803 Plus 188050-188193 329936 6165200 Minus 82761-82920 <BR> <BR> 329919 6223624 Minus 103492-103681 330004 6623963 Minus 78872-78999 326025 5867176 Plus 70854-70915 <BR> <BR> 326054 5867184 Minus 146342-146469 326112 5867192 Plus 2151-2725 326165 5867208 Minus 62787-62929 326213 5867224 Minus 60751-60927 326219 5867226 Minus 264008-264274 <BR> <BR> 326160 5867254 Minus 112000-112137 326257 5867264 Plus 222712-222819 <BR> <BR> 330057 6478962 Plus 75145-75287<BR> <BR> <BR> <BR> <BR> 326359 5867293 Plus 9436-9494<BR> <BR> <BR> <BR> 326393 5867341 Plus 41702-41841<BR> <BR> <BR> <BR> <BR> 326399 5867353 Plus 6385-6536<BR> <BR> <BR> <BR> <BR> 326401 5867355 Plus 35165-35332<BR> <BR> <BR> <BR> <BR> 326416 5867362 Minus 45283-45375<BR> <BR> <BR> <BR> <BR> 326431 5867371 Plus 15855-15971<BR> <BR> <BR> <BR> <BR> 326460 5867400 Minus 142633-142935<BR> <BR> <BR> <BR> 326517 5867439 Plus 44732-46356<BR> <BR> <BR> <BR> <BR> 326519 5867439 Plus 166004-166243 326596 6138928 Plus 133386-133563 <BR> <BR> 330081 6015314 Minus 5768-5835<BR> <BR> <BR> <BR> 326714 5867595 Plus 124490-124568<BR> <BR> <BR> <BR> <BR> 326752 5867615 Minus 1214-1562<BR> <BR> <BR> <BR> <BR> 326757 6249610 Plus 74531-74597 326668 6552455 Plus 146726-146838 326720 6552456 Plus 84525-84677 326725 6552456 Minus 223005-223125 326862 6552465 Plus 107702-107782 <BR> <BR> 326882 6682509 Minus 167988-168179 326892 6682511 Plus 119424-119500 326996 5867660 Minus 63212-63404 327010 5867664 Plus 941057-941139 326919 6456782 Minus 40486-41046 327042 6531965 Minus 1380806-1381443 327049 6531965 Minus 1924026-1924110 327072 6531965 Minus 3796429-3797197 <BR> <BR> 327074 6531965 Plus 4039993-4040096 327075 6531965 Plus 4041318-4041431 326981 6588016 Plus 105091-106038 <BR> <BR> 327133 6682522 Plus 38069-38938<BR> <BR> <BR> <BR> <BR> 330137 4210430 Minus 21220-21377 330138 4210430 Minus 22334-22460 <BR> <BR> 330143 4210430 Plus 184737-184848<BR> <BR> <BR> <BR> <BR> 330153 4325335 Plus 146951-147475 330135 4456470 Minus 121583-121885 <BR> <BR> 327205 5867447 Plus 167335-167576<BR> <BR> <BR> <BR> <BR> 327212 5867463 Minus 4230842424<BR> <BR> <BR> <BR> <BR> 327287 5867479 Minus 62838-63024<BR> <BR> <BR> <BR> <BR> 327331 5867516 Minus 55606-55737 327364 6552412 Minus 115235-115396 <BR> <BR> 327413 5867750 Plus 101410-101508 327481 5867783 Plus 104472-104673 <BR> <BR> 327458 6004455 Plus 173257-173378<BR> <BR> <BR> <BR> <BR> 327516 6117815 Plus 199078-199216<BR> <BR> <BR> <BR> 327527 6381882 Minus 98950-99040<BR> <BR> <BR> <BR> <BR> 327548 5867797 Minus 81067-81130 327554 5867801 Minus 23092-23191 <BR> <BR> 327565 5867811 Plus 32516-32778 327600 6004462 Minus 2621-2862 <BR> <BR> 327687 5867847 Minus 169293-169362

330182 5123954 Plus 120156-120245 <BR> <BR> 327742 5867944 Minus 143307-143512<BR> <BR> <BR> <BR> 327805 5867968 Plus 19952-20019<BR> <BR> <BR> <BR> 327809 5867968 Plus 54610-54761<BR> <BR> <BR> <BR> 327814 5867968 Plus 69377-70566<BR> <BR> <BR> <BR> 327815 5867968 Plus 70804-71401<BR> <BR> <BR> 327791 5867977 Plus 22491-22610<BR> <BR> <BR> <BR> 327745 6531959 Minus 229066-229124<BR> <BR> <BR> <BR> 330211 6013592 Plus 59158-59215 330207 6013606 Minus 109912-110004 <BR> <BR> 330257 6671881 Minus 143228-143393<BR> <BR> <BR> <BR> 330262 6671884 Plus 67913-68053<BR> <BR> <BR> <BR> 330286 6671913 Minus 31050-31171 328105 5868020 Minus 301705-301784 328113 5868024 Minus 80378-80491 <BR> <BR> 328142 5868050 Minus 9656-9778<BR> <BR> <BR> <BR> 328152 5868060 Minus 73981-74203<BR> <BR> <BR> <BR> 328170 5868071 Plus 93170-93295 327910 5868162 Plus 21622-21748 327919 5868165 Plus 547701-547800 <BR> <BR> 327990 5868218 Minus 36225-36503<BR> <BR> <BR> <BR> 328249 6381891 Minus 96352-96527<BR> <BR> <BR> <BR> 328251 6381891 Plus 124444-124557<BR> <BR> <BR> <BR> 328253 6381894 Minus 4411-4509<BR> <BR> <BR> <BR> 328084 6469819 Minus 155366-155459<BR> <BR> <BR> <BR> 328274 5868219 Minus 31244-31439<BR> <BR> <BR> 328615 5868239 Plus 35214-35347<BR> <BR> <BR> <BR> 328632 5868247 Plus 76734-76853 328779 5868309 Plus 41570-41639 328783 5868309 Minus 73658-73822 <BR> <BR> 328801 5868321 Minus 44492-44609 328820 5868330 Plus 90446-90602 <BR> <BR> 328835 5868339 Plus 88053-88461 328290 5868363 Minus 127366-127496 <BR> <BR> 328321 5868373 Minus 1029614-1029673 328332 5868375 Plus 280154-280289 <BR> <BR> 328333 5868375 Plus 282506-282664<BR> <BR> <BR> <BR> 328349 5868383 Minus 260704-260804 328450 5868425 Minus 209192-209321 <BR> <BR> 328466 5868434 Minus 15643-15900<BR> <BR> <BR> <BR> 328479 5868449 Minus 331-560<BR> <BR> <BR> <BR> 328481 5868449 Minus 8987-9180<BR> <BR> <BR> <BR> 328546 5868487 Minus 17547-17722<BR> <BR> <BR> <BR> 328662 6004473 Plus 1184773-1184855 328767 6017031 Minus 35625-35723 328768 6017031 Minus 223741-224238 <BR> <BR> 328857 6381927 Minus 80557-81051<BR> <BR> <BR> <BR> 328878 6552423 Plus 105580-105774 328882 6552423 Minus 157669-157826 328690 6588001 Minus 571207-571274 328691 6588001 Minus 579598-579664 330307 4877982 Plus 107384-107559 <BR> <BR> 328903 5868514 Plus 23625-24468<BR> <BR> <BR> <BR> 328987 5868535 Minus 25705-25764<BR> <BR> <BR> <BR> 328998 5868538 Plus 40996-41104<BR> <BR> <BR> 329062 5868590 Minus 58977-59094<BR> <BR> <BR> <BR> 329086 5868604 Minus 35489-35588<BR> <BR> <BR> <BR> 329154 5868686 Minus 200851-201356<BR> <BR> <BR> <BR> 329156 5868686 Minus 202013-202341<BR> <BR> <BR> <BR> 329164 5868691 Plus 62305-62517<BR> <BR> <BR> <BR> 329170 5868693 Plus 67924-68019<BR> <BR> <BR> 329179 5868704 Plus 181639-181815 329193 5868716 Plus 168095-168181 329254 5868733 Plus 4133-4214 329369 5868842 Minus 121148-121516 <BR> <BR> 329367 5868842 Minus 87201-87587<BR> <BR> <BR> <BR> 329141 6017060 Plus 343924-343997<BR> <BR> <BR> 329347 6456785 Plus 18433-18897 329017 6682532 Minus 255591-255672 <BR> <BR> 329434 5868883 Minus 31124-31263

TABLE 2 DNA AND PROTEIN SEQUENCES FOR CBF9 AND BF08 Table 2 provides the nucleic acid and protein sequence of the CBF9 and BF08 genes as well as the Unigene and Exemplar accession numbers for CBF9 and BF08.

CBF9 DNA SEQUENCE Gene name : ESTs Unigene number: Hs. 157601 Probeset Accession &num : W07459 Nucleic Acid Accession # : AC005383 Coding Sequence: 328-2751 (underlined sequences correspond to start and stop codons) 1 11 21 31 41 51 GACAGTGTTC GCGGCTGCAC CGCTCGGAGG CTGGGTGACC CGCGTAGAAG TGAAGTACTT 60 TTTTATTTGC AGACCTGGGC CGATGCCGCT TTAAAAAACG CGAGGGGCTC TATGCACCTC 120 CCTGGCGGTA GTTCCTCCGA CCTCAGCCGG GTCGGGTCGT GCCGCCCTCT CCCAGGAGAG 180 ACAAACAGGT GTCCCACGTG GCAGCCGCGC CCCGGGCGCC CCTCCTGTGA TCCCGTAGCG 240 CCCCCTGGCC CGAGCCGCGC CCGGGTCTGT GAGTAGAGCC GCCCGGGCAC CGAGCGCTGG 300 TCGCCGCTCT CCTTCCGTTA TATCAACATG CCCCCTTTCC TGTTGCTGGA GGCCGTCTGT 360 GTTTTCCTGT TTTCCAGAGT GCCCCCATCT CTCCCTCTCC AGGAAGTCCA TGTAAGCAAA 420 GAAACCATCG GGAAGATTTC AGCTGCCAGC AAAATGATGT GGTGCTCGGC TGCAGTGGAC 480 ATCATGTTTC TGTTAGATGG GTCTAACAGC GTCGGGAAAG GGAGCTTTGA AAGGTCCAAG 540 CACTTTGCCA TCACAGTCTG TGACGGTCTG GACATCAGCC CCGAGAGGGT CAGAGTGGGA 600 GCATTCCAGT TCAGTTCCAC TCCTCATCTG GAATTCCCCT TGGATTCATT TTCAACCCAA 660 CAGGAAGTGA AGGCAAGAAT CAAGAGGATG GTTTTCAAAG GAGGGCGCAC GGAGACGGAA 720 CTTGCTCTGA AATACCTTCT GCACAGAGGG TTGCCTGGAG GCAGAAATGC TTCTGTGCCC 780 CAGATCCTCA TCATCGTCAC TGATGGGAAG TCCCAGGGGG ATGTGGCACT GCCATCCAAG 840 CAGCTGAAGG AAAGGGGTGT CACTGTGTTT GCTGTGGGGG TCAGGTTTCC CAGGTGGGAG 900 GAGCTGCATG CACTGGCCAG CGAGCCTAGA GGGCAGCACG TGCTGTTGGC TGAGCAGGTG 960 GAGGATGCCA CCAACGGCCT CTTCAGCACC CTCAGCAGCT CGGCCATCTG CTCCAGCGCC 1020 ACGCCAGACT GCAGGGTCGA GGCTCACCCC TGTGAGCACA GGACGCTGGA GATGGTCCGG 1080 GAGTTCGCTG GCAATGCCCC ATGCTGGAGA GGATCGCGGC GGACCCTTGC GGTGCTGGCT 1140 GCACACTGTC CCTTCTACAG CTGGAAGAGA GTGTTCCTAA CCCACCCTGC CACCTGCTAC 1200 AGGACCACCT GCCCAGGCCC CTGTGACTCG CAGCCCTGCC AGAATGGAGG CACATGTGTT 1260 CCAGAAGGAC TGGACGGCTA CCAGTGCCTC TGCCCGCTGG CCTTTGGAGG GGAGGCTAAC 1320 TGTGCCCTGA AGCTGAGCCT GGAATGCAGG GTCGACCTCC TCTTCCTGCT GGACAGCTCT 1380 GCGGGCACCA CTCTGGACGG CTTCCTGCGG GCCAAAGTCT TCGTGAAGCG GTTTGTGCGG 1440 GCCGTGCTGA GCGAGGACTC TCGGGCCCGA GTGGGTGTGG CCACATACAG CAGGGAGCTG 1500 CTGGTGGCGG TGCCTGTGGG GGAGTACCAG GATGTGCCTG ACCTGGTCTG GAGCCTCGAT 1560 GGCATTCCCT TCCGTGGTGG CCCCACCCTG ACGGGCAGTG CCTTGCGGCA GGCGGCAGAG 1620 CGTGGCTTCG GGAGCGCCAC CAGGACAGGC CAGGACCGGC CACGTAGAGT GGTGGTTTTG 1680 CTCACTGAGT CACACTCCGA GGATGAGGTT GCGGGCCCAG CGCGTCACGC AAGGGCGCGA 1740 GAGCTGCTCC TGCTGGGTGT AGGCAGTGAG GCCGTGCGGG CAGAGCTGGA GGAGATCACA 1800 GGCAGCCCAA AGCATGTGAT GGTCTACTCG GATCCTCAGG ATCTGTTCAA CCAAATCCCT 1860 GAGCTGCAGG GGAAGCTGTG CAGCCGGCAG CGGCCAGGGT GCCGGACACA AGCCCTGGAC 1920 CTCGTCTTCA TGTTGGACAC CTCTGCCTCA GTAGGGCCCG AGAATTTTGC TCAGATGCAG 1980 AGCTTTGTGA GAAGCTGTGC CCTCCAGTTT GAGGTGAACC CTGACGTGAC ACAGGTCGGC 2040 CTGGTGGTGT ATGGCAGCCA GGTGCAGACT GCCTTCGGGC TGGACACCAA ACCCACCCGG 2100 GCTGCGATGC TGCGGGCCAT TAGCCAGGCC CCCTACCTAG GTGGGGTGGG CTCAGCCGGC 2160 ACCGCCCTGC TGCACATCTA TGACAAAGTG ATGACCGTCC AGAGGGGTGC CCGGCCTGGT 2220 GTCCCCAAAG CTGTGGTGGT GCTCACAGGC GGGAGAGGCG CAGAGGATGC AGCCGTTCCT 2280 GCCCAGAAGC TGAGGAACAA TGGCATCTCT GTCTTGGTCG TGGGCGTGGG GCCTGTCCTA 2340 AGTGAGGGTC TGCGGAGGCT TGCAGGTCCC CGGGATTCCC TGATCCACGT GGCAGCTTAC 2400 GCCGACCTGC GGTACCACCA GGACGTGCTC ATTGAGTGGC TGTGTGGAGA AGCCAAGCAG 2460 CCAGTCAACC TCTGCAAACC CAGCCCGTGC ATGAATGAGG GCAGCTGCGT CCTGCAGAAT 2520 GGGAGCTACC GCTGCAAGTG TCGGGATGGC TGGGAGGGCC CCCACTGCGA GAACCGTGAG 2580 TGGAGCTCTT GCTCTGTATG TGTGAGCCAG GGATGGATTC TTGAGACGCC CCTGAGGCAC 2640 ATGGCTCCCG TGCAGGAGGG CAGCAGCCGT ACCCCTCCCA GCAACTACAG AGAAGGCCTG 2700 GGCACTGAAA TGGTGCCTAC CTTCTGGAAT GTCTGTGCCC CAGGTCCTTA GAATGTCTGC 2760 TTCCCGCCGT GGCCAGGACC ACTATTCTCA CTGAGGGAGG AGGATGTCCC AACTGCAGCC 2820

ATGCTGCTTA GAGACAAGAA AGCAGCTGAT GTCACCCACA AACGATGTTG TTGAAAAGTT 2880 TTGATGTGTA AGTAAATACC CACTTTCTGT ACCTGCTGTG CCTTGTTGAG GCTATGTCAT 2940 CTGCCACCTT TCCCTTGAGG ATAAACAAGG GGTCCTGAAG ACTTAAATTT AGCGGCCTGA 3000 CGTTCCTTTG CACACAATCA ATGCTCGCCA GAATGTTGTT GACACAGTAA TGCCCAGCAG 3060 AGGCCTTTAC TAGAGCATCC TTTGGACGGC GAAGGCCACG GCCTTTCAAG ATGGAAAGCA 3120 GCAGCTTTTC CACTTCCCCA GAGACATTCT GGATGCATTT GCATTGAGTC TGAAAGGGGG 3180 CTTGAGGGAC GTTTGTGACT TCTTGGCGAC TGCCTTTTGT GTGTGGAAGA GACTTGGAAA 3240 GGTCTCAGAC TGAATGTGAC CAATTAACCA GCTTGGTTGA TGATGGGGGA GGGGCTGAGT 3300 TGTGCATGGG CCCAGGTCTG GAGGGCCACG TAAAATCGTT CTGAGTCGTG AGCAGTGTCC 3360 ACCTTGAAGG TCTTC CBF9 Protein sequence Gene name: ESTs Unigene number: Hs. 157601 Protein Accession # : none found Signal sequence: 1-17 Transmembrane domains: none found VGW domains : 49-223 ; 341-518; 529-706 EGF domains: 298-333; 715-748 Cellular Localization: plasma membrane 1 11 21 31 41 51 MPPFLLLEAV CVFLFSRVPP SLPLQEVHVS KETIGKISAA SKMMWCSAAV DIMFLLDGSN 60 SVGKGSFERS KHFAITVCDG LDISPERVRV GAFQFSSTPH LEFPLDSFST QQEVKARIKR 120 MVFKGGRTET ELALKYLLHR GLPGGRNASV PQILIIVTDG KSQGDVALPS KQLKERGVTV 180 FAVGVRFPRW EELHALASEP RGQHVLLAEQ VEDATNGLFS TLSSSAICSS ATPDCRVEAH 240 PCEHRTLEMV REFAGNAPCW RGSRRTLAVL AAHCPFYSWK RVFLTHPATC YRTTCPGPCD 300 SQPCQNGGTC VPEGLDGYQC LCPLAFGGEA NCALKLSLEC RVDLLFLLDS SAGTTLDGFL 360 RAKVFVKRFV RAVLSEDSRA RVGVATYSRE LLVAVPVGEY QDVPDLVWSL DGIPFRGGPT 420 LTGSALRQAA ERGFGSATRT GQDRPRRWW LLTESHSEDE VAGPARHARA RELLLLGVGS 480 EAVRAELEEI TGSPKHVMVY SDPQDLFNQI PELQGKLCSR QRPGCRTQAL DLVFMLDTSA 540 SVGPENFAQM QSFVRSCALQ FEVNPDVTQV GLVVYGSQVQ TAFGLDTKPT RAAMLRAISQ 600 APYLGGVGSA GTALLHIYDK VMTVQRGARP GVPKAWVLT GGRGAEDAAV PAQKLRNNGI 660 SVLWGVGPV LSEGLRRLAG PRDSLIHVAA YADLRYHQDV LIEWLCGEAK QPVNLCKPSP 720 CMNEGSCVLQ NGSYRCKCRD GWEGPHCENR EWSSCSVCVS QGWILETPLR HMAPVQEGSS 780 RTPPSNYREG LGTEMVPTFW NVCAPGP BF08 DNA SEQUENCE Gene name: TMPRSS3a Unigene number: Hs. 298241 Probeset Accession # : AI538613 Nucleic Acid Accession # : AB038157 Coding sequence: 202-1566 (underlined sequences correspond to start and stop codons) 1 11 21 31 41 51 ACCGGGCACC GGACGGCTCG GGTACTTTCG TTCTTAATTA GGTCATGCCC GTGTGAGCCA 60 GGAAAGGGCT GTGTTTATGG GAAGCCAGTA ACACTGTGGC CTACTATCTC TTCCGTGGTG 120 CCATCTACAT TTTTGGGACT CGGGAATTAT GAGGTAGAGG TGGAGGCGGA GCCGGATGTC 180 AGAGGTCCTG AAATAGTCAC CATGGGGGAA AATGATCCGC CTGCTGTTGA AGCCCCCTTC 240 TCATTCCGAT CGCTTTTTGG CCTTGATGAT TTGAAAATAA GTCCTGTTGC ACCAGATGCA 300 GATGCTGTTG CTGCACAGAT CCTGTCACTG CTGCCATTGA AGTTTTTTCC AATCATCGTC 360 ATTGGGATCA TTGCATTGAT ATTAGCACTG GCCATTGGTC TGGGCATCCA CTTCGACTGC 420 TCAGGGAAGT ACAGATGTCG CTCATCCTTT AAGTGTATCG AGCTGATAGC TCGATGTGAC 480 GGAGTCTCGG ATTGCAAAGA CGGGGAGGAC GAGTACCGCT GTGTCCGGGT GGGTGGTCAG 540 AATGCCGTGC TCCAGGTGTT CACAGCTGCT TCGTGGAAGA CCATGTGCTC CGATGACTGG 600 AAGGGTCACT ACGCAAATGT TGCCTGTGCC CAACTGGGTT TCCCAAGCTA TGTGAGTTCA 660 GATAACCTCA GAGTGAGCTC GCTGGAGGGG CAGTTCCGGG AGGAGTTTGT GTCCATCGAT 720 CACCTCTTGC CAGATGACAA GGTGACTGCA TTACACCACT CAGTATATGT GAGGGAGGGA 780

TGTGCCTCTG GCCACGTGGT TACCTTGCAG TGCACAGCCT GTGGTCATAG AAGGGGCTAC 840 AGCTCACGCA TCGTGGGTGG AAACATGTCC TTGCTCTCGC AGTGGCCCTG GCAGGCCAGC 900 CTTCAGTTCC AGGGCTACCA CCTGTGCGGG GGCTCTGTCA TCACGCCCCT GTGGATCATC 960 ACTGCTGCAC ACTGTGTTTA TGACTTGTAC CTCCCCAAGT CATGGACCAT CCAGGTGGGT 1020 CTAGTTTCCC TGTTGGACAA TCCAGCCCCA TCCCACTTGG TGGAGAAGAT TGTCTACCAC 1080 AGCAAGTACA AGCCAAAGAG GCTGGGCAAT GACATCGCCC TTATGAAGCT GGCCGGGCCA 1140 CTCACGTTCA ATGAAATGAT CCAGCCTGTG TGCCTGCCCA ACTCTGAAGA GAACTTCCCC 1200 GATGGAAAAG TGTGCTGGAC GTCAGGATGG GGGGCCACAG AGGATGGAGC AGGTGACGCC 1260 TCCCCTGTCC TGAACCACGC GGCCGTCCCT TTGATTTCCA ACAAGATCTG CAACCACAGG 1320 GACGTGTACG GTGGCATCAT CTCCCCCTCC ATGCTCTGCG CGGGCTACCT GACGGGTGGC 1380 GTGGACAGCT GCCAGGGGGA CAGCGGGGGG CCCCTGGTGT GTCAAGAGAG GAGGCTGTGG 1440 AAGTTAGTGG GAGCGACCAG CTTTGGCATC GGCTGCGCAG AGGTGAACAA GCCTGGGGTG 1500 TACACCCGTG TCACCTCCTT CCTGGACTGG ATCCACGAGC AGATGGAGAG AGACCTAAAA 1560 ACCTGAAGAG GAAGGGGACA AGTAGCCACC TGAGTTCCTG AGGTGATGAA GACAGCCCGA 1620 TCCTCCCCTG GACTCCCGTG TAGGAACCTG CACACGAGCA GACACCCTTG GAGCTCTGAG 1680 TTCCGGCACC AGTAGCAGGC CCGAAAGAGG CACCCTTCCA TCTGATTCCA GCACAACCTT 1740 CAAGCTGCTT TTTGTTTTTT GTTTTTTTGA GGTGGAGTCT CGCTCTGTTG CCCAGGCTGG 1800 AGTGCAGTGG CGAAATCCCT GCTCACTGCA GCCTCCGCTT CCCTGGTTCA AGCGATTCTC 1860 TTGCCTCAGC TTCCCCAGTA GCTGGGACCA CAGGTGCCCG CCACCACACC CAACTAATTT 1920 TTGTATTTTT AGTAGAGACA GGGTTTCACC ATGTTGGCCA GGCTGCTCTC AAACCCCTGA 1980 CCTCAAATGA TGTGCCTGCT TCAGCCTCCC ACAGTGCTGG GATTACAGGC ATGGGCCACC 2040 ACGCCTAGCC TCACGCTCCT TTCTGATCTT CACTAAGAAC AAAAGAAGCA GCAACTTGCA 2100 AGGGCGGCCT TTCCCACTGG TCCATCTGGT TTTCTCTCCA GGGGTCTTGC AAAATTCCTG 2160 ACGAGATAAG CAGTTATGTG ACCTCACGTG CAAAGCCACC AACAGCCACT CAGAAAAGAC 2220 GCACCAGCCC AGAAGTGCAG AACTGCAGTC ACTGCACGTT TTCATCTCTA GGGACCAGAA 2280 CCAAACCCAC CCTTTCTACT TCCAAGACTT ATTTTCACAT GTGGGGAGGT TAATCTAGGA 2340 ATGACTCGTT TAAGGCCTAT TTTCATGATT TCTTTGTAGC ATTTGGTGCT TGACGTATTA 2400 TTGTCCTTTG ATTCCAAATA ATATGTTTCC TTCCCTCAAA AAAAAAAAAA AAAAAAAAAA 2460 AAAAAAAA BF08 Protein sequence: Gene name: TMPRSS3a Unigene number: Hs. 298241 Probeset Accession &num : AI538613 Protein Accession &num : BAB20077 Signal sequence: none found Transmembrane domains: 43-65, 239-261 Tryp_SPc domain: 216-444 Cellular Localization: not determined 1 11 21 31 41 51 I I I I I I MGENDPPAVE APFSFRSLFG LDDLKISPVA PDADAVAAQI LSLLPLKFFP IIVIGIIALI 60 LALAIGLGIH FDCSGKYRCR SSFKCIELIA RCDGVSDCKD GEDEYRCVRV GGQNAVLQVF 120 TAASWKTMCS DDWKGHYANV ACAQLGFPSY VSSDNLRVSS LEGQFREEFV SIDHLLPDDK 180 VTALHHSVYV REGCASGHVV TLQCTACGHR RGYSSRIVGG NMSLLSQWPW QASLQFQGYH 240 LCGGSVITPL WIITAAHCVY DLYLPKSWTI QVGLVSLLDN PAPSHLVEKI VYHSKYKPKR 300 LGNDIALMKL AGPLTFNEMI QPVCLPNSEE NFPDGKVCWT SGWGATEDGA GDASPVLNHA 360 AVPLISNKIC NHRDVYGGII SPSMLCAGYL TGGVDSCQGD SGGPLVCQER RLWKLVGATS 420 FGIGCAEVNK PGVYTRVTSF LDWIHEQMER DLKT