CA2371500A1 - Expression products of genes involved in diseases related to cholesterol metabolism - Google Patents

Abstract

The invention concerns nucleic acids expressed from genes located in the human genome in the 9q31-34 region of chromosome 9, likely to be involved in diseases genetically related to said chromosomal locus, in particular diseases of the plasmatic lipoprotein metabolism, more particularly the reverse transport of cholesterol. The invention also concerns polypeptides encoded by certain nucleic acids and antibodies specifically directed against such polypeptides, useful as diagnostic reagents. The invention further concerns vectors and recombinant host cells comprising said nucleic acids or fragments thereof.

Description

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2 Most apolipoproteins have regions helical amphipatics (apolipoprotein AI, A-II, A-IV, CI, C-II, C-III and E).
The density of the lipoprotein particles is inversely proportional to their size, their density reflecting the relative quantities low density non-polar lipids contained in the nucleus and high density surface proteins present.
Among the large lipoproteins we know the chylomicrons, secreted by enterocytes, in which apo B-48 is io majority, and VLDL, secreted by hepatocytes, which contain the apo B-100 protein.
The smallest classes of lipoproteins, LDL and HDL, contain mostly cholesterol esters in their nucleus.
The mature forms of these particles are not secreted directly ~ s from cells but are more particularly produced by metabolic pathways within the blood plasma.
LDL particles represent the end products of VLDL particle metabolism.
Some components of HDL particles are derived from 2o chylomicrons.
Thus, high density lipoproteins (HDL) are one of the four major classes of lipoproteins circulating in the plasma blood.
These lipoproteins are involved in different ways 2s metabolic such as lipid transport, acid formation bile ducts, steroidogenesis, cell proliferation and in addition interfere with plasma proteinase systems.
HDL are perfect free cholesterol acceptors and, in combination with cholesterol ester transfer proteins 30 (CETP), lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT), play a major role in reverse transport of cholesterol, i.e. transport of cholesterol in excess in peripheral cells to the liver for elimination from the body as bile acid.

3 HDL doesn't just transport cholesterol from cells peripheral to the liver but also distribute it to cells steroid-producing or peripheral cells depleted in cholesterol.
HDL precursors are secreted in discoid form at from the gut and liver, from which the spherical particles are formed through the formation of cholesterol esters which migrate to core of the lipoprotein particle.
The emerging particles of HDL contain apo AI and apo ~ o A-IV, while the nascent hepatic HDL particles are rich in apo AI, apo E and apo A-II.
The lipid part of these particles consists of phospholipids and small amounts of free cholesterol and triglyceride.
HDL has been shown to play a central role in transport of cholesterol from peripheral tissues to the liver.
Excess unesterified cholesterol from peripheral cells high in cholesterol is captured by HDL and undergoes esterification by LCAT action. These HDLs enriched with cholesterol esters are 2o captured by binding proteins or HDL receptors on the surface hepatocytes and deliver their cholesterol esters there.
The protective role of HDL in the reverse transport of cholesterol is confirmed by epidemiological studies demonstrating an inverse relationship between the cholesterol concentrations in these 25 HDL and the risk of developing coronary heart disease, or observations that HDL effectively accepts excess intracellular cholesterol from various cell types.
Atherogenic lipoproteins are ingested by macrophages or peripheral and degraded cells in lysosomes. The 3o cholesterol is released from lysosomes and. is re-esterified in the cytoplasmic compartment.
It has been shown in particular that HDLs rich in apo AI
stimulate cholesterol flow from macrophages or peripheral cells to the extracellular compartment, following a

4 interaction with HDL binding proteins on the surface of these cells.
Various diseases related to HDL deficiency have been described;
s including Tangier's disease, HDL deficiency and deficiency in LCAT.
The impairment involved in Tangier's disease is linked to a cellular deficit in the translocation of cellular cholesterol in which HDL precursors are degraded in lysosomes.
io Nevertheless, for Tangier's disease, the exact nature of the deficit has not not yet been precisely defined.
In Tangier's disease, this cell deficit leads to a disruption of lipoprotein metabolism. HDL not incorporating cholesterol from peripheral cells that cannot be ~ s metabolized properly, are quickly eliminated from the body. The HDL plasma concentration of these patients is therefore extremely reduced and HDL no longer ensures the return of cholesterol to the liver. This cholesterol accumulates in these peripheral cells and cause characteristic clinical manifestations such as 2o formation of orange tonsils. In addition, other disturbances lipoproteins like an overproduction of triglycerides as well as a increased synthesis and intracellular catabolism of phospholipids are observed.
Tangier's disease, the symptoms of which have been described 2s above, is classified among the family affections linked to metabolism HDL which are most commonly detected in patients affected by coronary heart disease.
Many studies have shown that a reduced level of HDL cholesterol is an excellent risk factor for screening ~ o coronary artery disease.
In this context, syndromes linked to HDL deficiencies have exhibited increased interest over the past decade in that they increase understanding of the role of HDL in atherogenesis.

J
Several mutations in the apo AI gene have been characterized.
These mutations are rare and can lead to an absence of production of apo AI.
Mutations in genes coding for lipoprotein lipase (LPL) or its activator apoC-II are associated with severe hypertriglyceridemias and highly HDL-c levels red u its.
Mutations in the gene coding for the enzyme lecithin:
cholesterol, acyltransferase (LCAT) are also associated with to severe HDL deficiency.
There is therefore a growing need in the state of the art identify genes involved in cholesterol metabolism and / or lipoproteins, and in particular genes associated with dysfunctions of reverse cholesterol transport from cells is peripheral to the liver.
Recently, a study of the segregation of different forms allelics of 343 microsatellite markers distributed throughout the genome and distant from each other on average 10.3 cM was performed.
2o The linkage study focused on a family well characterized over eleven generations, many of whose members are affected by Tangier's disease, the family comprising five lines of inbreeding.
25 This study made it possible to identify a region located in the locus 9q31 of human chromosome 9 statistically associated with the disorder (Rust S. et al., Nature Genetics, vol. 20, September 1998, pages 96-98).
However, the study by RUST et al. only defines a broad region of the genome whose alterations are likely to be 3o associated with Tangier's disease. It is simply stated that the region of locus 9q31-34 concerned contains ESTs but no gene known.
It has now been shown that a region of about 15 cm located in locus 9q31-34 in humans was associated, so ~ s general, to family deficiencies in HDL.

More particularly, it has been shown according to the invention that messenger RNA molecules were expressed from sequences located in the genome in a region of about 15 cM centered on the microsatellite marker D9S1784, identified as the marker s microsatellite giving the strongest genetic link to the deficiency family life in HDL and Tangier disease.
In addition, the region 9q31-34 considered potentially contains genes that may play a role in initiating or development of various diseases, such as ~ o - bone diseases such as myxoid chondrosarcomas, mental retardation related to chromosome 9 abnormalities (MRD);
- kidney diseases such as childhood nephrophtisia (NPH2);
- muscle diseases, such as muscular dystrophy of belts (LGMD2H);
ts - psychiatric illnesses like schizophrenia;
- digestive diseases such as Hirschprung's disease linked to RET
(SHSCR2).
Due to the location of positional candidate genes in this chromosomal interval, the messenger RNAs and the polypeptides zo correspondents, as isolated and characterized according to the invention, are potentially involved in some of the human pathologies described above, or even in other pathologies also genetically linked to this region of chromosome 9.
For some of the sequences included in these RNAs 2s messengers isolated and characterized by the applicant, a phase of putative open reading was determined and the protein sequence has been deduced from it. The corresponding polypeptides are potentially involved in a disorder linked to the metabolism of lipoproteins, more particularly linked to a deficit in reverse transport ~ o cholesterol.

DETAILED DESCRIPTION OF THE INVENTION
The present invention thus describes polynucleotides and s polypeptides whose alteration in sequence or expression is potentially associated with a deficit in the metabolism of plasma lipoproteins, more particularly to a deficit in the reverse transport of HDL.
The present invention also describes polynucleotides and to polypeptides whose alteration in sequence or expression is potentially associated with genetically linked diseases 9q31-34 of chromosome 9.
GENERAL DEFINITIONS
t5 The term "isolated" in the sense of the present invention designates a biological material (nucleic acid or protein) that has been removed from its original environment (the environment in which it is located naturally).
2o For example a polynucleotide present in the natural state in a plant or animal is not isolated. The same polynucleotide separated from adjacent nucleic acids into which it is naturally inserted in the genome of the plant or animal is considered "isolated".
Such a polynucleotide may be included in a vector and / or such a 25 polynucleotide can be included in a composition and remain nevertheless in the isolated state of the fact that the vector or the composition does not is not its natural environment.
The term "purified" does not require that the material be present in a form of absolute purity, exclusive of the presence of others ~ o compounds. Rather, it is a relative definition.
A polynucleotide is in the "purified" state after purification of the starting material or natural material of at least one order of ,. size, preferably 2 or 3 and preferably 4 or 5 orders of greatness.
3s For the purposes of this description, the expression "sequence nucleotide "may be used to designate either polynucleotide or a nucleic acid. The expression "sequence nucleotide "encompasses the genetic material itself and is therefore not not restricted to information regarding its sequence.
The terms "nucleic acid", "polynucleotide";
s "oligonucleotide" or "nucleotide sequence" include RNA, DNA, cDNA or hybrid sequences RNAlDNA of more than one nucleotide, indifferently in the simple form string or in the form of duplex.
The term "nucleotide" refers to both natural nucleotides io (A, T, G, C) as well as modified nucleotides which include, minus a modification such as (1) a purine analog, (2) a analog of a pyrimidine, or (3) a sugar analog, examples of such modified nucleotides being described for example in the application PCT No. WO 95/04 064.
i5 For the purposes of the present invention, a first polynucleotide is considered to be "complementary" to a second polynucleotide when each base of the first nucleotide is paired with the base complementary to the second polynucleotide whose orientation is reversed.
The complementary bases are A and T (or a and U), or C and G.
2o By "variant" of a nucleic acid according to the invention, is meant a nucleic acid that differs by one or more bases from the reference polynucleotide. A variant nucleic acid can be of natural origin, such as an allelic variant found naturally, or can also be an unnatural variant obtained for example by 2s mutagenesis techniques.
In general, the differences between the reference nucleic acid and variant nucleic acid is reduced so that the sequences nucleotides of the reference nucleic acid and the nucleic acid variant are very close and, in many regions, identical.
~ o Changes in nucleotides present in a nucleic acid variant can be silent, which means that they do not alter the amino acid sequences encoded by said variant nucleic acid.
However, nucleotide changes in an acid variant nucleic acid can also result in substitutions, ~~ additions, deletions in the polypeptide encoded by nucleic acid varying with respect to the peptides encoded by the nucleic acid of reference. In addition, changes in nucleotides in the regions coding can produce substitutions, conservative or not conservatives in the amino acid sequence.
Preferably, the variant nucleic acids according to the invention encode polypeptides which retain substantially the same biological function or activity that the nucleic acid polypeptide of benchmark or the ability to be recognized by directed antibodies against the polypeptides encoded by the original nucleic acid.
~ o Some variant nucleic acids will thus code for mutated forms of polypeptides whose systematic study will allow deduce activity structure relationships of the proteins in question. The knowledge of these mutations in relation to the disease studied is fundamental since it allows us to understand the molecular cause of ~ 5 pathology.
“Fragment” will be understood to mean a reference nucleic acid according to the invention, a nucleotide sequence of length reduced by report to the reference nucleic acid and comprising, on the part common, a nucleotide sequence identical to the nucleic acid of 2o reference.
Such a "fragment" of nucleic acid according to the invention can be the if necessary, included in a larger polynucleotide of which it is constitutive.
Such fragments include, or alternatively consist of, 2s of the oligonucleotides of length ranging from 8, 10, 12, 15, 18, 20 to 25, 30, 40, 50, 70, 80, 100, 200, 500, 1000 or 1500 consecutive nucleotides of a nucleic acid according to the invention.
By "variant" of a polypeptide according to the invention, is meant mainly a polypeptide whose amino acid sequence ~ o contains one or more substitutions, additions or deletions of at least an amino acid residue, relative to the amino acid sequence of reference polypeptide, it being understood that the substitutions amino acids can be indifferently conservative. or not conservatives.

By "fragment" of a polypeptide according to the invention, is meant a polypeptide whose amino acid sequence is shorter than that of the reference polypeptide and which comprises over the entire part common with these reference polypeptides, an acid sequence s identical amino.
Such fragments may, where appropriate, be included within of a larger polypeptide of which they are part.
Such fragments of a polypeptide according to the invention can have a length of 10, 15, 20, 30 to 40, 50, 100, 200 or 300 amino acids.
~ o The "percentage of identity" between two nucleotide sequences or amino acids, within the meaning of the present invention, can be determined by comparing two optimally aligned sequences, through a comparison window.
The part of the nucleotide or polypeptide sequence in the ~; comparison window can thus include additions or deletions (eg "gaps") with respect to the sequence of reference (which does not include these additions or deletions) of so as to obtain an optimal alignment of the two sequences.
The percentage is calculated by determining the number of positions ? o which an identical nucleic base or amino acid residue is observed for the two sequences (nucleic or peptide) compared, then by dividing the number of positions at which there is identity between the two bases or amino acid residues by the total number of positions in the comparison window, then multiplying the result by 100 2s in order to obtain the percentage of sequence identity.
Optimal sequence alignment for comparison can be carried out in a computerized manner using known algorithms contained in the WISCONSIN GENETICS Company package SOFTWARE PACKAGE, GENETICS COMPUTER GROUP (GCG), 575 ~ o Science Doctor, Madison, WISCONSIN.
By way of illustration, the percentage of sequence identity may be carried out using BLAST software (BLAST versions 1.4.9 of March 1996, BLAST 2Ø4 of February 1998 and BLAST 2Ø6 of September 1998), using only the default settings (S. F Altschul et al, ~ s J. Mol. Biol. 1990 215: 403-410, S. F Altschul et al, Nucleic Acids Res.

1997 25: 3389-3402). Blast searches for sequences similar / homologous to a reference "query" sequence, using of the algorithm of Altschul et al. The query sequence and the basics of data used can be peptide or nucleic, any s combination being possible.
By "high stringency hybridization conditions" within the meaning of present invention means the following conditions to 1- Membrane competition and PRE HYBRIDATION
- Mix: 40N1 salmon sperm DNA (10 mg / ml) + 40 NI human placental DNA (10mg / ml) ts - Denature for 5 min at 96 ° C, then immerse the mixture in ice.
- Remove the SSC 2X and pour 4 ml of formamide mix into the tube membranes containing membranes.
20 - Add the mixture of the two denatured DNAs.
- Incubation at 42 ° C for 5 to 6 hours, with rotation.
2- Competition of the labeled probe ~ o - Add to the labeled and purified probe 10 to 50 NI DNA Cot I, according to the amount of repeats.
- Denature 7 to 10 min at 95 ° C.
- Incubate at 65 ° C for 2 to 5 hours.

- Remove the pre-hybridization mix.
- Mix 40 NI salmon sperm DNA + 40 NI placental DNA
human ; denature 5 min at 96 ° C, then immerse in ice.
- Add 4 ml of formamide mix to the hybridization tube, the mixture ~ o of the two DNAs and the labeled probe / denatured Cot I DNA.
- Incubate 15 to 20 hours at 42 ° C, with rotation.
1 ~
4- Washes - Wash at room temperature in SSC 2X, to rinse.
- 2 times 5 minutes at room temperature SSC 2X and SDS 0.1% at 65 ° C.
- 2 times 15 minutes at 65 ° C SSC 1X and SDS 0.1% at 65 ° C.
? o Wrap the membranes in Saran and expose.
The hybridization conditions described above are adapted to hybridization under high stringency conditions of a molecule ? s nucleic acid varying in length from 20 nucleotides to several hundreds of nucleotides.
It goes without saying that the hybridization conditions described above can be adapted according to the length of the nucleic acid whose hybridization is sought or the type of labeling chosen, depending on ~ o techniques known to those skilled in the art.

Suitable hybridization conditions can for example be adapted according to the teaching contained in the work of HAMES
and HIGGINS (1985) or in the work by F. AUSUBEL et al (1999).
DETAIL OF NUCLEIC ACIDS AND POLYPEPTIDES ACCORDING TO
THE INVENTION
A brief description of the nucleic acid sequences and ~ o amino acid sequences according to the invention is represented in the Table I, following the examples.
Gene GS9002S31.
Nucleic acids) ~ s A messenger RNA corresponding to a transcript of the gene designated here under the number GS9002S31.
The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 1.
The sequence SEQ ID No. 1 has a length of 552 nucleotides.
2o No sequence identity was found during a search in the GenBank database (Version 110).
Expression analyzes of the transcript of sequence SEQ ID N ° 1 were carried out by RT PCR, as described in Example 1. These analyzes carried out using polyA + RNA from different tissues allowed 2s to show that the GS9002S31 gene was expressed in the fetal brain, the liver and the placenta.

Gene GS910331.
Nucleic acids) Two messenger RNA sequences have been isolated according to the invention corresponding to a transcript of the gene designated here under the number GS910331.
s The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 2.
The sequence SEQ ID No. 2 has a length of 1246 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 3.
~ o The sequence SEQ ID N ° 3 has a length of 3035 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110 and Version 115).
Expression analyzes of the transcript of sequence SEQ ID N ° 2 ts were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS310331 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern blot, using the sequence probes SEQ ID No. 82 and 20 83, revealed the presence of transcripts in the blot marketed by the Clontech company (Ref. N ° 7759-1).
The size of the transcripts detected with the sequence probe SEQ ID
No.
82 is 1.65 kb in the liver and heart respectively and 1.4 kb in the brain.
2s The size of the transcripts detected with the SEQ ID sequence probe No.
83 is 1.65 kb and 2.4 kb in the core and 1.65 kb respectively in the liver.
This gene is a candidate for a causal disease due to ~ o dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
s Gen GS914554 Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS94554.
to The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 4.
The sequence SEQ ID No. 4 has a length of 1479 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
~ s Expression analyzes of the transcript of sequence SEQ ID N ° 4 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS94554 gene was expressed in the fetal brain, the placenta and liver.
zo In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using respectively the sequence probe SEQ ID N ° 58, revealed the presence of transcripts in the blot marketed by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe 2s ID N ° 84 is respectively - 1.0, 1.3, 1.7 and 2.8 kb in the pancreas and the placenta;
- 1.0, 1.3 and 1.7 kb in the kidney, skeletal muscle, heart and liver;
- 1.7 kb in the brain and the lung.
~ o This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Gene GS914739.
Nucleic acids) Two messenger RNA sequences have been isolated according to the invention io corresponding to a transcript of the gene designated here under the No. GS14739.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N 5.
The sequence SEQ ID No. 5 has a length of 5169 nucleotides.
No sequence homology with the sequence SEQ ID N ° 5 ~ 5 was not found during a search in the database GenBank (Version 110).
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N 6.
The sequence SEQ ID No. 6 has a length of 7723 nucleotides.
zo This sequence includes an open reading frame (ORF) ranging from nucleotide at position 121 to the nucleotide at position 1517 of the sequence SEQ ID No. 6. The translation initiation codon begins at nucleotide at position 132 of the sequence SEQ ID No. 6. The sequence coding begins at the nucleotide at position 132 and ends at zs nucleotide in position 1517 of the sequence SEQ ID No. 6. The sequence SEQ ID No. 6 includes a polyadenylation sequence signal "ATTAAA" starting at the nucleotide at position 7686 of the sequence SEQ ID N ° 6. The Kozak motif by. "CCA CTC GCC ATG" sequence begins at the nucleotide in position 123 of the sequence SEQ ID No. 6.
~ o Two 100% sequence homologies were found during a search in the GenBank database (Version 115, N °
AF088031), respectively - of. nucleotide in position 1 to the nucleotide in position 146 of the s sequence SEQ ID No. 6; and - from the nucleotide in position 243 to the nucleotide in position 573 of the sequence SEQ ID N ° 6 Expression analyzes of the transcript of sequence SEQ ID N ° 5 were carried out by RT PCR, as described in Example 1. These ~ o analyzes carried out using polyA + RNA from different tissues allowed to show that the GS914739 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern blot, using the sequence probe SEQ ID No. 85, revealed the presence of transcripts in the blot marketed by the Company ~ s Clontech (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID N ° 85 is 1 kb in the heart, liver, skeletal muscle and the kidney.
2o This gene constitutes a candidate causative) of a disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
2s Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 6 The open reading frame of the nucleotide sequence SEQ ID
N ° 6 potentially codes for a polypeptide of 461 amino acids of 30 length constituting the sequence SEQ ID No. 129.

On the nucleotide regions 240-1481 and 1511-1675 of the sequence SEQ ID No. 129, an identity of approximately 30% was found with in the Genpept115, Swissprot38, trEMBL and PIR databases s following access number: AF035360 (homo), AF186461 (rattus), AF186460 (musspretus); AF196481 (homo sapiens ), AF196480 (musmusc) and with T09482 (male) and T09013 (mouse) (ring finger Fxy). Some homologies of sequence were also found with the numbers following access points: DA191 P20.2, A49656 and 149642.
The polypeptide of sequence SEQ ID No. 129 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to ~ s locus 9q31-34 of chromosome 9.
Gene S915574.
Nucleic acids) A messenger RNA corresponding to 2o a transcript of the gene designated here under the number GS915574.
The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 7.
The sequence SEQ ID No. 7 has a length of 1046 nucleotides.
No sequence identity was found during a 2s search in the GenBank database (Version 110).
Expression analyzes of the transcript of sequence SEQ ID N ° 7 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS915574 gene was expressed in the fetal brain, uterus, brain, heart, prostate, fetal liver, liver, placenta, the testicle and the kidney.
This gene is a candidate for a causal disease due to s dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Gene GS930321 Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS930321.
The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 8.
The sequence SEQ ID No. 8 has a length of 280 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
2o The analyzes of expression of the transcript of sequence SEQ ID N ° 8 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS930321 gene was expressed in the fetal brain, the liver and the heart.
This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies familial in HDL, or with a genetically linked locus disease 9q31-34 of chromosome 9.

Gene S931311.
Nucleic acids) s A messenger RNA corresponding to a transcript of the gene designated here under the number GS931311.
The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 9.
The sequence SEQ ID No. 9 has a length of 479 nucleotides.
to This sequence includes a partial open reading frame (ORF) ranging from the nucleotide at position 3 to the nucleotide at position 98 of the sequence No sequence identity was found during a search in the GenBank database (Version 110).
ts Expression analyzes of the transcript of sequence SEQ ID N ° 9 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS931311 gene was expressed in the fetal brain, liver, heart, placenta, testicle and kidney.
This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 2s 9q31-34 of chromosome 9.
Polypeptide encoded by the nucleic acid of sequence SEQ ID N ~ 9 The open framework for partial reading of the acid sequence nucleic acid SEQ ID N ° 9 potentially codes for a polypeptide of 32 amino acids of length constituting the sequence SEQ ID No. 130.
No significant homology with BLAST was found s with the sequences referenced in the Swissprot databases (version 36, last update of May 3, 1999) and PRODOM:
(peer domains obtained in Swissprot, version 34.2, November 1997).
The polypeptide of sequence SEQ ID No. 130 is susceptible o intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
~ s Gene S934660.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS934660.
The nucleic sequence of the cDNA corresponding to this transcript 2o constitutes the sequence SEQ ID No. 10.
The sequence SEQ ID No. 10 has a length of 2599 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
Expression analyzes of the transcript of sequence SEQ ID N ° 10 zs were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS934660 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern blot, using the sequence probe SEQ ID N ° 86, according to the protocol described in Example 1, revealed the presence of transcripts in the blot sold by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 86 is respectively s - 1 kb, 2 kb, 3 kb and 7.5 kb in the placenta;
- 2, 3 and 7.5 kb in the core;
- 7.5 kb in the kidney, pancreas, skeletal muscle, lung and the brain.
~ o This gene constitutes a causal positional candidate for a disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Gene GS938315.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS938315.
2o The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 11.
The sequence SEQ ID No. 11 has a length of 222 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
zs Expression analyzes of the transcript of sequence SEQ ID N ° 11 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS938315 gene was expressed in the fetal brain, liver, heart and kidney.
~ o This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease s 9q31-34 of chromosome 9.
Gene GS93953 Nucleic acids) ~ o It was isolated according to the invention two RNAs messengers corresponding to a transcript of the gene designated here under the number GS93953.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 12.
ts The sequence SEQ ID No. 12 has a length of 3422 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 13.
2o The sequence SEQ ID No. 13 has a length of 5791 nucleotides.
It includes a partial open reading frame (ORF) ranging from nucleotide at position 3 at the nucleotide at posüton 554 of the sequence SEQID NO 13.
Some sequence homologies have been found between the 2s sequence SEQ ID N ° 13 and the following access numbers of the base GenBank data (Version 116): AC013740.2, AC013783.2 and AF086175.1.
Expression analyzes of the transcript of sequence SEQ ID N ° 12 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS93953 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using the s sequence SEQ ID N ° 87, revealed the presence of transcripts in the blot sold by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 87 is 8 kb in the heart, brain, placenta, lung, the liver, skeletal muscle, kidney and pancreas.
~ o This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies familial in HDL, or a genetically-induced disease. linked to the locus ~ 5 9q31-34 of chromosome 9.
Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 13.
The partial open reading frame of the acid sequence 2o nucleic acid SEQ ID N ° 13 potentially codes for a polypeptide of 183 amino acids in length constituting the sequence SEQ ID No. 131.
45% homology was observed between region 6-162 of the sequence SEQ ID No. 131 and the sequence No. g3878571 (Z46381) of the Gen Bank database (Version 115) and the sequence n <°
25. EM: Q21453 M01 F1.4 PROTEIN from the trEMBL database (Version of August 1999).
The polypeptide of sequence SEQ ID No. 131 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments 2d in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Gene GS939874.
s) nucleic acids) Two messenger RNAs were isolated according to the invention corresponding to a transcript of the gene designated here under the number GS939874.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 14.
The sequence SEQ ID No. 14 has a length of 2615 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 15.
is The sequence SEQ ID No. 15 is 2551 nucleotides in length.
It includes an open reading frame going from the nucleotide in position 50 to the nucleotide at position 958 and a coding sequence ranging from nucleotide at position 67 to the nucleotide at position 958.
Homology of 99% identity on 2044 nucleotides of the 2o sequence SEQ ID No. 15 was observed with the sequence of the base of GenBank data (Version 116j with access number AK001355.
Expression analyzes of the transcript of sequence SEQ ID N ° 14 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed 2s to show that the GS939874 gene was expressed in the fetal brain, uterus, brain, heart, prostate, fetal liver, liver, placenta, the testicle and the kidney.
This gene is a causal positional candidate for a disease.
~ o due to dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
s Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 15.
The open reading frame of the nucleic acid of sequence SEQ
ID No. 15 potentially codes for a polypeptide of 291 acids amines of length constituting the sequence SEQ ID No. 132.
io Homology of 35% on 233 amino acids (14-246 of SEQ
ID No. 132) was found with the sequence referenced in the base of GenPept data (Version 115) under the number 85832945 (AL117195).
32% homology on 245 amino acids (30-274 of SEQ
ID No. 132) was found with the sequence referenced in the base of i5 GenPept data (Version 115) under n ° 85832942 (AL117195).
The polypeptide of sequence SEQ ID No. 132 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments 2o family in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Gene GS911370 Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS911370.
The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 16.
~ o The sequence SEQ ID No. 16 has a length of 775 nucleotides.

This sequence includes an open partial reading frame (ORF) going from the nucleotide in position 1 to the nucleotide in position 144 of the sequence SEQ ID N ° 16.
A nucleotide homology was found with the s following sequences ~ 96% homology on 229 bp (position 52-280 bp) with the GenBank sequence: gi ~ 1022224 ~ - Fragment Mse1 ~ o of Homo sapiens genomic DNA, containing an island CpG (clone 92e10, reverse reading of cpg92e10.rt1a) ~ 100% homology on 145 bp (position 1-144 bp) with the GenBank sequence: gi ~ 459833 ~ of human mRNA from ~ 5 beta unit of the Sec61 complex.
Expression analyzes of the transcript of sequence SEQ ID N ° 16 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed 2o to show that the GS911370 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using respectively the sequence probes SEQ ID Nos. 88 and 89, revealed the presence of transcribed in the blot marketed by the Clontech Company (Ref. N °
25 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 88 as well as with the sequence probe SEQ ID No. 89 is 7.4 kb in the pancreas.
~ o This gene constitutes a candidate causative) of a disease due to a dysfunction of the reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
s Polypepfide encoded by the nucleic acid of sequence SEQ ID No. 96 The open framework for partial reading of the acid sequence nucleic acid SEQ ID N ° 16 potentially codes for a polypeptide of 48 amino acids of length constituting the sequence SEQ ID No. 133.
~ o Homologies observed at the level of the protein sequence This potential ORF (48 aa) has an identity on 33 aa (position 16-48 aa) with the transport protein in beta unit of the complex Sec61 human whose sequences are sp ~ P38391 ~, gb ~ AAA19639.1 ~, PIR: (Non-redundant PIR sequences, version 57) ~ S ~ S42410 and 18652 Is p34.2 (1) respectively in the Swissprot databases (version 36, last update May 3, 1999)) Genpept: (translation of Genbank v110 and 111, last update May 7, 1999), PIR:
(NON-REDUNDANT PIR SEQUENCES, VERSION 57) no redundant and PRODOM: (homologous domains detected in 2o Swissprot, version 34.2, November 1997).
This identity is found in the various databases of protein data (PIR: (NON-REDUNDANT PIR SEQUENCES, VERSION 57), PRODOM: (homologous domains detected in Swissprot, version 34.2, November 1997)) and Genbank translations 2s and EMBL (TrEMBL (SP-TrEMBL, version 7, November 1998), Genpept:
(translation of Genbank v110 and 111, last update May 7 1999)).
Putative function The protein complex sec61 is a central component of ~ o cellular machinery for translocation of nascent proteins in the endoplasmic reticulum. The GS911370 gene could therefore be its homology with the beta subunit of the sec61 complex, a gene coding for a new component of this machinery. Through therefore its possible role in the translocation of proteins and by s consequence of the trafficking of proteins involved in the mechanism cholesterol efflux makes it a gene of interest in the study of deficit observed in Tangier / FHD patients.
The polypeptide of sequence SEQ ID No. 133 is thus susceptible to intervene in the regulation of cholesterol flow, and more io particularly Tangier disease or deficiencies family in HDL.
The polypeptide of sequence SEQ ID N133 is therefore susceptible to intervene in an important stage involved in transport reverse cholesterol by HDL.
is the polypeptide with sequence SEQ ID No. 133 is also likely to intervene in a disease genetically linked to the locus 9q31-34 of chromosome 9.
Gene GS913920.
2o Acid (nucleic sJ) A messenger RNA corresponding to a transcript of the gene designated here under the number GS913920.
A first sequence was isolated and characterized; it's about the nucleic acid sequence of the cDNA constituting the sequence SEQ ID No. 17.
z, The sequence SEQ ID No. 17 has a length of 491 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
~ o The analyzes of expression of the transcript of sequence SEQ ID N ° 17 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS913920 gene was expressed in the liver and, the heart.
From the sequence SEQ ID N ° 17, two primers nucleotides of sequences SEQ ID No. 102 and SEQ ID respectively s No. 103 have been synthesized. These nucleotide primers have enabled to amplify a cDNA of the GS913920 gene constituting the sequence SEQ ID
N ° 18.
Amplification reactions are carried out under the conditions following, applicable to all candidate genes according to the invention for which specific primers are described and implemented to isolate sequences of the transcript of interest Each PCR reaction is carried out with 400 NM of each dNTP, 0.5 NM of each primer, 2.5 mM of MgCl2, 50 ng of DNA or about 25 ng of cDNA and 2 units of Thermus aquaticus (Taq) DNA
i5 polymerase (Amplifier Taq Gold; Perkin Elmer) in the presence of its buffer.
The reactions are carried out in 96-well microplates, in 9700 thermal cyclers (Perkin Elmer). After a first denaturation at 94 ° C for 10 min, a program of 30 cycles is applied denaturation of 30 s. at 94 ° C, 30 s hybridization. at 64 ° C (2 cycles), 2o 61 ° C (2 cycles), 58 ° C (2 cycles) and 55 ° C (28 cycles), elongation of 1 min / kb at 72 ° C. The program ends with a 7 min extension to 72 ° C.
The nucleic sequence SEQ ID N ° 18 has a length of 293 2s nucleotides. It includes a partial open reading frame (ORF) going from the nucleotide in posüton 227 to the nucleotide in position 293.
This gene is a candidate for a causal disease due to dysfunction of, reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Polypepfide encoded by the nucleic acid of sequence SEQ ID NO 18 The open reading frame of the nucleic acid sequence SEQ ID N ° 18 potentially codes for a polypeptide of 22 amino acids of length constituting the sequence SEQ ID No. 134.
No significant homology with BLAST was found ~ o with the sequences referenced in the Genpept databases:
(translation of Genbank v115), TrEMBL (SP-TrEMBL, August version 1999), Swissprot (Version 38) and PIR: (SEQUENCES PIR NON
REDUNDANTES, Version 62-September 1999).
The polypptide of sequence SEQ ID No. 134 is susceptible is to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease or deficiencies family in HDL.
The polypeptide of sequence SEQ ID No. 134 is therefore susceptible to intervene in an important stage involved in transport 2o reverse cholesterol by HDL.
The polypeptide of sequence SEQ ID No. 134 is also likely to intervene in a disease genetically linked to the locus 9q31-34 of chromosome 9.
2s Gene GS91437.
Nucleic acids) Two messenger RNAs were isolated according to the invention corresponding to a transcript of the gene designated here under the number GS91437.
The first nucleic sequence of the cDNA corresponding to this 3o transcribed constitutes the sequence SEQ ID N ° 19.

The sequence SEQ ID No. 19 has a length of 2442 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 2 to the nucleotide in position 286 of the sequence SEQ ID N ° 19.
s No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 20.
The sequence SEQ ID No. 20 has a length of 4608 nucleotides.
~ o It includes a partial open reading frame (ORF) ranging from nucleotide at position 1 to the nucleotide at position 327.
The following sequence homologies have been found in the GenBank database (Version 116) with the sequence SEQ Id N °
~ s ~ 100% homology on 213 bps (positions [85-297]) with the positions [2807-2595] of sequence 87020279 (AK000294) Homo sapiens cDNA FLJ20287 fis, clone HEP04390 Length = 3043;
filed on 02-22-2000 in Genbank.
~ 88% on 219 bps (positions [82-300]) with the sequence 83850048 zo (AJ 004828) Mus musculus clone XX-BAC394, Length = 170351 ***
SEQUENCING IN PROGRESS ***, in unordered pieces;
Expression analyzes of the transcript of sequence SEQ ID N ° 19 were carried out by RT PCR, as described in Example 1. These 2 analyzes carried out using polyA + RNA from different tissues allowed to show that the GS91437 gene was expressed in the fetal brain, the liver, heart, prostate, placenta, uterus, testicle, kidney, skeletal muscle.
3o This gene constitutes a causal positional candidate for a disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 19 s The open framework for partial reading of the acid sequence nucleic acid SEQ ID N ° 19 potentially codes for a polypeptide of 95 amino acids of length constituting the sequence SEQ ID No. 135.
No significant homology with BLAST was found ~ o with the sequences referenced in the Swissprot databases (version 36, last update May 3, 1999), PRODOM:
(peer domains detected in Swissprot, versions 34.2 and 38,) Genpept: (translation of Genbank v110 and 111 as well as 115,), PIR:
(NON-REDUNDANT PIR SEQUENCES, VERSION 57), PDB:
~ s (PROTEIN DATA BANK, FEBRUARY 1999) and TrEMBL (SP-TrEMBL, version 7, November 1998).
The polypeptide of sequence SEQ ID No. 135 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments 2o family in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 20 2s The open reading frame (ORF) contained in the nucleic acid of sequence SEQ ID N ° 20 potentially codes for a polypeptide of 108 amino acids constituting the sequence SEQ ID No. 136.
No sequence homology was found with the bases Swissprot (Version 38), Genpept (Versiôn 115), PIR
~ o (Version 62, September 1999) and trEMBL (Version of August 1999).

The sequence polypeptide SEQ ID No. 136 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to s locus 9q31-34 of chromosome 9.
Gene GS91507.
Nucleic acids) ~ o It was isolated according to the invention two messenger RNAs corresponding to a transcript of the gene designated here under the n ° GS91507.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 21.
The sequence SEQ ID No. 21 has a length of 1627 nucleotides.
is This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 1 to the nucleotide in position 640 of the sequence SEQ ID N ° 21.
No sequence identity was found during a search in the GenBank database (Version 110).
zo The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 22.
The sequence SEQ ID No. 22 has a length of 2333 nucleotides.
It includes a complete open reading frame (ORF) ranging from nucleotide at position 368 to nucleotide at position 1348. The beginning of zs translation initiation codon is located on the nucleotide in position 371 of the sequence SEQ ID N ° 22. The coding sequence begins at the nucleotide at position 371 and ends at the nucleotide at position 1348.
~ o The sequence SEQ ID N ° 22 has homology with the following sequence referenced in the GenBank database (Version 116) next 99% nucleic identity on 2316 bp (position 115 to 2420 bp) with Homo sapiens cDNA FLJ20300 fis, clone HEP06465 (2331 b). Accession AK000307 s Expression analyzes of the transcript of sequence SEQ ID No. 21.
were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS91507 gene was expressed in the fetal brain.
io In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using the probe sequence SEQ ID N ° 90, revealed the presence of transcripts in the blot sold by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe t5 ID N ° 90 is respectively - 2 kb and 7.5 kb in the pancreas, the kidney, the skeletal muscle, the lung, placenta and brain.
This gene is a causal positional candidate for a disease.
2o due to a dysfunction of the reverse flow of cholesterol, and more particularly Tangier's disease or deficiencies family in HDL.
Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 27 2s The open reading frame of the nucleic acid sequence SEQ ID N ° 21 potentially codes for a polypeptide of 213 amino acids of length constituting the sequence SEQ ID No. 137.
Homologies observed at the level of the protein sequence:
This potential ORF of 213 aa has a domain with ~ o motif type homologies with different proteins such as ~ 29% homology on 155 aa (position 4-158 aa) with sequences from Swissprot (version 36, latest May 3, 1999 update) sp ~ Q10022 ~ and with PRODOM sequences: (homologous domains s detected in Swissprot, version 34.2, November 1997) 28705 p34.2 (1) YSX3 CAEEL - protein domain hypothetical (39KD) T28D9.3 located on the chromosome II.
~ 25% homology on 127 aa (position 6-132 aa) with 1o PIR sequences: (PIR SEQUENCES NO
REDUNDANT, VERSION 57) non-redundant: PIR:
(Non-redundant PIR sequences, version 57) ~ S ~ S66668 - protein induced by hydrogen peroxide (fragment of a mouse sequence).
In addition, homologies with translated coding sequences by Genbank and EMBL (TrEMBL (SP-TrEMBL, version 7, November 1998), Genpept: (translation of Genbank v110 and 111, last update day May 7, 1999)) would show annotations with proteins 2o potentials of "phosphatidic acid phosphatase" type ~ 34% homology over 200 aa (position 6-205 aa) with SP-TrEMBL sequences (SP-TrEMBL, version 7, November 1998): sp ~ P97544 ~ P97544 - protein 2s transmembrane of the endoplasmic reticulum.
~ 33% homology on 204 aa (position 6-209 aa) with Genpept sequences: (translation of Genbank v110 and 111, last update on May 7, 1999):
gi ~ 4105139 ~ - phosphatidic acid phosphatase-beta, type2; phosphatidate phosphohydrolase; phospholipid phosphatase in humans. ; and with sequences by Genpept: (translation of Genbank v110 and 111, last update on May 7, 1999): gi ~ 3047173 ~
s homolog of phosphatidic acid phosphohydrolase Human, and with gi ~ 2467300 ~ ~ - phosphatidic acid phosphatase 2b.
~ 31% homology on 203 aa (position 6-208 aa) with ~ o Genpept sequences: (translation of Genbank v110 and 111, last update on May 7, 1999):
gi ~ 1487873 ~~ - phosphatidic acid phosphatase mouse i5 ~ 31% homology on 203 aa (position 6-208 aa) with SP-TrEMBL sequences (SP-TrEMBL, version 7, November 1998): sp ~ Q61469 ~ Q61469 ~ - acid phosphatidic phosphatase 2A
2o Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 22.
The open reading frame of the SEQ nucleic acid sequence ID No. 22 potentially codes for a polypeptide of 325 amino acids of length constituting the sequence SEQ ID No. 138.
2s Homologies observed at the level of the protein sequence Homologies with Genbank translated coding sequences (Version 116) and EMBL (TrEMBL (Version of August 1999), Genpept [Version 115]) would show annotations with proteins potentials of the "phosphatidic acid phosphatase" type.

~ 30% homology on 316 aa (position 2-317 aa) with SP-trEMBL: sp ~ P97544 ~ P97544 ER TRANSMEMBRANE
PROTEIN
~ 30% homology on 320 aa (position 2-321 aa) with s Genpept116 gi ~ 4105139 ~ AF043329 type-2 phosphatidic acid phosphatase-beta; phosphatidate phosphohydrolase; phospholipid phosphatase [Homo sapiens] and with Genpept116: gi ~ 3047173 ~ AF01786 phosphatidic acid phosphohydrolase homolog [Homo ~ o sapiens] and with gi ~ 2467300 ~ AB000889 phosphatidic acid phosphatase 2b ~ 30% homology on 316 aa (2-317 aa) with Genpept116 gi 1684745 Y07783 transmembrane protein [Battus norvegicus] Length = 312 aa ~ s ~ 30% homology on 320 aa (position 2-317 aa) with SP-trEMBL EM: 014495 PHOSPHATIDIC ACID
PHOSPHATASE 2B. Length = 311 aa Putative function of the polypeptides of sequence SEQ ID N ° 137 and 138:
The GS91507 gene is of interest for the functional study of Tangier disease and FHD in the sense that it is both a 2s positional candidate and a gene coding for a new protein whose putative functions (phosphatidic acid phosphatase) could play a role in the intracellular signaling cascade linked to efflux HDL particle mediated intracellular cholesterol involved in Tangier's disease and family HDL deficiency (FHD).

WO 00/71710 PCTlFR0010142G

The polypeptides of sequence SEQ ID No. 137 and 138 is likely to be involved in regulating the flow of cholesterol, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to s locus 9q31-34 of chromosome 9.
Gene GS915231.
Nucleic acids) Two messenger RNAs were isolated according to the invention io corresponding to a transcript of the gene designated here under the number GS915231.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 23.
The sequence SEQ ID No. 23 has a length of 2764 nucleotides.
This sequence includes an open reading frame (ORF) ~ s partial from the nucleotide in position 3 to the nucleotide in position 1220 of the sequence SEQ ID N ° 23.
No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the cDNA corresponding to this zo transcribed constitutes the sequence SEQ ID N ° 24.
The sequence SEQ ID N ° 24 has a length of 3228 nucleotides It includes an open reading frame (ORF) ranging from the nucleotide to position 37 at the nucleotide at position 1304. The coding sequence begins at nucleotide at position 49 and ends at nucleotide at position zs 1304 of the sequence SEQ ID No. 24. The start of the initiation codon of the translation is located on the nucleotide at position 49. There is a signal polyadenylation starting on the nucleotide at position 3142 of the sequence SEQ ID N ° 24.
Sequence homologies have been observed between the ~ o sequence SEQ ID N ° 24 and the following sequences referenced in the GenBank database (Version 116) WO 00/71710 PCTlFR0010142G
~ 100% homology on 217 bps (positioris [2704-2920]) matching with positions [1-217] of sequence 84884337 (AL050130) Homo sapiens mRNA; cDNA DKFZp586H051 (from clone DKFZp586H051). Length = 1795; filed 18-FEB-2000; Direct s Submission; Submitted (15-MAY-1999) MIPS, Am Klopferspitz 18a, D-82152, Martinsried, GERMANY, ~ 4 fragments of homology: 100% on 393 bpd [2773-3165]; 100% on 153 bpd [913-1065]; 100% on 111 bpd [1083-1193]; 84% on 84 bps ~ o [2341-2424] with the sequence g6539402 (AC016904) Homo sapiens clone RP11-307P9, *** SEQUENCING IN PROGRESS ***, 36 unordered pieces. Length = 203456;
~ Different fragments of homology: 83% on 258 bps (529-786]; 89%
~ s on 66pdb [1195-1260]; 80% on 185pdb [91-275] with the sequence 85305227 (AF029260) Gallus gallus transcription factor ReIB (relb) mRNA, complete cds. Length = 2851 Expression analyzes of the transcript of sequence SEQ ID N ° 23 20 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS915231 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using the probe 2s sequence SEQ ID No. 91, revealed the presence of transcripts in the blot sold by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 91 is respectively - 1.3 kb, 2 kb, 4 kb, 4.4 kb and 7.5 kb in the heart, and the muscle ~ o skeletal WO 00/71710 PCTlFR0010142G

- 1.3 kb, 2 kb, 4 kb and 4.4 kb in the liver and the kidney;
- 1., 3 kb, 2 kb, 4.4 kb and 7.5 kb in the brain;
- 1.3 kb, 2 kb and 4.4 kb in the pancreas.
This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
io Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 23 The open framework for partial reading of the acid sequence nucleic acid SEQ ID N ° 23 potentially codes for a polypeptide of 406 amino acids in length constituting the sequence SEQ ID No. 139.
~ s Homologies observed at the level of the protein sequence ~ 51% homology with Genpept sequences:
(translation of Genbank v110 and 111, last update to May 7, 1999): gi: 2731377 is the translation 2o protein of the sequence gb ~ AAB93456.1 ~ (U28739) similar to alcohol dehydrogenase / ribitol dehydrogenase of C. elegans and sequences of SP-TrEMBL (SP-TrEMBL, version 7, November 1998): Q09979 on 401 aa (position 1-401 aa).
~ 30% homology on 164 aa (position 47-205 aa) with Protein Data Banks sequences: gi ~ 1827713 ~
corresponding to the protein 1AHI ~ A Chain A, 7 Alpha-Hydroxysteroid Dehydrogenase Complexed Wifh Nadh ~ o And 7-Oxo Glycochenodeoxycholic Acid and with WO 00/71710 PCTlFR0010142G

gi ~ 1827714 ~ corresponding to the protein 1AHI ~ B Chain 8, 7 Alpha-Hydroxysteroid Dehydrogenase Complexed Wifh Nadh And 7-Oxo Glycochenodeoxycholic Acid and - with gi ~ 1827715 ~ corresponding to the protein 1AHH ~ A
s Chain A, 7 Alpha-Hydroxysteroid Dehydrogenase Complexed With Nad + and with gi ~ 1827716 ~
corresponding to the protein 1AHH ~ B Chain 8, 7 Alpha-Hydroxysteroid Dehydrogenase Complexed With Nad +
and with gi ~ 1943533 ~ corresponding to the protein 1FMC ~ A
~ o Chain A, 7-Alpha-Hydroxysteroid Dehydrogenase Complex With Nadh And 7-Oxo Glycochenodeoxycholic Acid and with gi ~ 1943534 ~ corresponding to the protein 1 FMC ~ B Chain 8, 7-Alpha-Hydroxysteroid Dehydrogenase Complex With Nadh And 7-Oxo ~ s Glycochenodeoxycholic Acid ~ 29% homology on 131 aa (position 53-183 aa) with Protein Data Bank sequences: gi ~ 2624497 ~
corresponding to the protein Cis-Biphenyl-2,3-zo Dihydrodiol-2,3-Dehydrogenase from Pseudomonas Sp.
Lb400 ~ 27% homology on 194 aa (position 3-196 aa) with PIR base sequences: (PIR SEQUENCES NO
2s REDUNDANTES, VERSION 57): PIR: (PIR sequences non-redundant, version 57) ~ D69930 ~ corresponding to 3-oxoacyl-acyl-carrier protein reductase protein yoxD approval of - Bacillus subtilis and with Swissprot sequences (version 36, last update ~ o day of May 3, 1999): sp ~ P14802 ~ corresponding to the WO 00/71710 PCTlFR0010142G

protein YOXD_BACSU - hypothetical oxidoreductase present in the RTP-PELB region (ORF238) s ~ 52% homology on 44 aa (position 353-396 aa) with PRODOM sequences: (homologous domains detected in Swissprot, version 34.2, November 1997) (homologous domains detected in Swissprot (version 36, last update of May 3, 1999)): 2675 p34.2 (11) to NLTP (5) DHB4 (3) PX18 (2) corresponding to the protein NONSPECIFIC PRECURSOR ESTRADIOL BETA-DEHYDROGENASE 17-BETA = HYDROXYSTEROID
~ s ~ 27% homology over 167 aa (position 233-399 aa) with sequences from Swissprot (version 36, latest updated May 3, 1999): sp ~ P51659 ~ correspondent with the protein DHB4 HUMAN ESTRADIOL 17 BETA-DEHYDROGENASE 4 (EC 1.1.1.62) (17-BETA-HSD 4) ao (17-BETA-HYDROXYSTEROID DEHYDROGENASE 4) Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 24 The open reading frame (ORF) of the acid sequence nucleic acid SEQ ID N ° 24 potentially codes for a polypeptide of 2s 422 amino acids in length constituting the sequence SEQ ID No. 140.
The following sequence homologies have been found Homologies observed at the level of the protein sequence ~ 51% homology with Genpept: gi: 2731377 and SP
trEMBL: Q09979 on 416 aa (position 11-417 aa).
~ o Genpept: gi: 2731377 is the protein translation of the WO 00/71710 PCTlFR0010142G

gb sequence ~ AAB93456.1 ~ (U28739) similar to alcohol dehydrogenase / ribitol dehydrogenase from C. elegans ~ 30% homology on 164 aa (position 47-205 aa) with s Protein Data Bank: gi ~ 1827713 ~ corresponding to the protein 1AHI ~ A Chain A, 7 Alpha-Hydroxysteroid Dehydrogenase Complexed With Nadh And 7-Oxo Glycochenodeoxycholic Acid and with gi ~ 1827714 ~
corresponding to the protein 1AHI ~ B Chain B, 7 Alpha-io Hydroxysteroid Dehydrogenase Complexed With Nadh And 7-Oxo Glycochenodeoxycholic Acid and with gi ~ 1827715 ~ corresponding to the protein 1AHH ~ A Chain A, 7 Alpha-Hydroxysteroid Dehydrogenase Complexed With Nad + and with gi ~ 1827716 ~ corresponding to the is protein 1AHH ~ B Chain B, 7 Alpha-Hydroxysteroid Dehydrogenase Compléxed With Nad + and with gi ~ 1943533 ~ corresponding to 1â protein 1FMC ~ A Chain A, 7-Alpha-Hydroxysteroid Dehydrogenase Complex With Nadh And 7-Oxo Glycochenodeoxycholic Acid and zo with gi ~ 1943534 ~ corresponding to the protein 1FMC ~ B
Chain B, 7-Alpha-Hydroxysteroid Dehydrogenase Complex With Nadh And 7-Oxo Glycochenodeoxycholic Acid 2s ~ 29% homology on 131 aa (position 53-183 aa) with Protein Data Bank: gi ~ 2624497 ~ corresponding to the Cis-Biphenyl-2,3-Dihydrodiol-2,3- protein Dehydrogenase From Pseudomonas Sp. Lb400 WO 00/71710 PCTlFR0010142G
~ 27% homology on 202 aa (position 6-212 aa) with Non-redundant PIR: pir ~ D69930 ~ corresponding to the protein 3-oxoacyl- acyl-carrier protein reductase - yoxD homolog - Bacillus subtilis and with Swissprot:
s sp ~ P14802 ~ corresponding to the protein YOXD_BACSU
HYPOTHETICAL OXIDOREDUCTASE IN RTP-PELB
INTERGENIC REGION (EC 1.-.-.-) (ORF238) ~ 52% homology on 44 aa (position 353-396 aa) with io Prodom (homologous domains detected in Swissprot):
2675 p34.2 (11) NLTP (5) DHB4 (3) PX18 (2) corresponding to the LIPID-TRANSFER STEROL protein ~ 5 HYDROXYSTEROID
~ 27% homology on 183 aa (position 249-415 aa) with Swissprot: sp ~ P51659 ~ corresponding to the protein zo DEHYDROGENASE 4 (EC 1.1.1.62) (17-BETA-HSD 4) (17-BETA-HYDROXYSTEROID DEHYDROGENASE 4) ~ 44% homology on 272 AA (positions 12-280 AA) with the sequence g2072661 (Z95120) hypothetical 25 protein Rv3224 [Mycobacterium tuberculosis] Length =

~ Homology with NONSPECIFIC LIPID-TRANSFER
PROTEIN PRECURSOR (NSL-TP):

WO 00/71710 PCTlFR00101426 35% on 106 AA ([318-417]) with the sequence SP: NLTP BOVIN NONSPECIFIC LIPID-TRANSFER
PROTEIN (STEROL CARRIER PROTEIN 2) (SCP-2).
Length = 121 s and 30% on 133 AA [294-417J with the sequence SP: NLTP RAT NONSPECIFIC LIPID-TRANSFER
PROTEIN PRECURSOR (NSL-TP) (STEROL CARRIER
PROTEIN 2) (SCP-2) (STEROL CARRIER PROTEIN X) (SCP-X) (SCPX) .Length = 547 ~ o Putative function The ORF of 422 amino acids has homologies with different putative enzyme proteins involved in the mechanisms of dehydrogenation of sterols from several organisms: man, mouse, ~ s E. coli, S. cerevisiae, C. elegans. In addition, we were able to evidence of homology with a sequence of the SCP-2 protein involved in the intracellular transport of lipids. Therefore, the gene GS15231 codes for a protein of interest by virtue of its possible function in the defect of intracellular traffic of cholesterol in the patients 2o Tangier / FHD, which reinforces the interest of studying the GS15231 gene.
In addition, the gene 6515231 is, by its location, a candidate gene positions) for the study and characterization of the genetic defect observed in Tangier's disease or family defect in HDL.
The polypeptides of sequences SEQ ID Nos. 139 and 140 are 2s likely to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
~ o WO 00/71710 PCTlFR0010142G

Gene GS915528.
Nucleic acids) Two messenger RNAs were isolated according to the invention corresponding to a transcript of the gene designated here under the number GS915528.
s The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 25.
The sequence SEQ ID No. 25 has a length of 3106 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from nucleotide at position 1 to nucleotide at position 1272 ~ o of the sequence SEQ ID N ° 25 No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the CDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 26.
is The sequence SEQ ID No. 26 has a length of 3313 nucleotides.
It includes a partial open reading frame (ORF) ranging from nucleotide at position 3 to the nucleotide at position 1370, which corresponds also to the coding sequence. A polyadenylation signal begins at nucleotide at position 3280 of the sequence SEQ ID No. 26.
2o The sequence homologies of SEQ ID N ° 26 have been observed with sequences referenced in the database GenBank (Version 116) - 99% nucleic identity on 2755bp (position 119-2873) with 25 g7020444 AK000388 Homo sapiens cDNA FLJ20381 fis, clone KAIA2329 Length = 2970 bp - 99% nucleic identity with a BAC during sequencing g6514007 AC013568 Homo sapiens clone RP11-1 B9, WORKING
DRAFT SEQUENCE 10 unordered fragments WO 00/71710 PCTlFR0010142G

Expression analyzes of the transcript of sequence SEQ ID N ° 25 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS915528 gene was expressed in the fetal brain, s the liver, prostate, heart, placenta, uterus, testicle and brain.
In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using the probe sequence SEQ ID N ° 92, revealed the presence of transcripts in the blot to marketed by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 92 is respectively - 1.9 kb, 3.2 kb and 3.8 kb in the pancreas;
- 1 kb, 1.9 kb and 3.8 kb in the core;
t5 - 1 kb, 1.9 kb and 3.2 kb in the liver;
- 1 kb and 1.9 kb in the kidney;
- 1.9 kb in the skeletal muscle and the brain.
This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more 2o particularly Tangier's disease or deficiencies family in HDL.
Polypeptide encoded by the nucleic acid of sequence SEQ ID IVO 25 2s The open reading frame of the nucleic acid sequence SEQ ID N ° 25 potentially codes for a polypeptide of 424 amino acids of length constituting the sequence SEQ ID No. 141.
Homologies observed at the level of the protein sequence OJ

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This ORF of 424 aa has pattern type homologies with conserved domains of different tyrosine phosphatase proteins in different protein databases such as:.
~ 49% homology on 364 aa (position 3-366 aa) with s SP-TrEMBL sequences (SP-TrEMBL, version 7, November 1998): sp ~ P91433 ~ P91433 coded by cDNA
YK65E9.3 from C. elegans and with sequences of Genpept: (translation of Genbank v110 and 111, last updated May 7, 1999): gi ~ 1708767 ~ containing a io domain found in band 4.1, ezrin, moesin, radixin and talin in C. elegans ~ 44% homology on 322 aa (position 1-322 aa) on SP-TrEMBL sequences (SP-TrEMBL, version 7, i; November 1998): sp ~ 043491 X043491 PROTEIN 4.1-G
~ 43% homology on 227 aa (position 7-233 aa) with PRODOM sequences: (homologous domains detected in Swissprot, version 34.2, November 1997):
20 894 p34.2 (29) MOES (4) RADI (3) EZRI (3) corresponding to the protein tyrosine phosphatase domain of proteins involved in the membrane organization.
zs ~ 42% homology on 313 aa (position 9-321 aa) on Swissprot sequences (version 36, last update day of May 3, 1999): sp ~ P29074 ~ PTN4_HUMAN -human protein tyrosine phosphatase MEG1 (EC
3.1.3.48).

WO 00/71710 PCTlFR0010142G
s0 ~ 41% homology on 320 aa (position 7-326 aa) with PIR sequences: (PIR SEQUENCES NO
REDUNDANT, VERSION 57) non-redundant: PIR:
(Non-redundant PIR sequences, version 57) ~ S ~ JU0188 s - protein band 4.1 belonging to the superfamily of mouse tyrosine phosphatase protein. and Swissprot sequences (version 36, last update Day of May 3, 1999): sp ~ P52963 ~ NBL4 mouse - protein NBL4 and SP-TrEMBL sequences (SP-TrEMBL, to version 7, November 1998): sp ~ 057457 ~ protein similar to protein band 4.1 and sequences of Genpept: (translation of Genbank v110 and 111, last updated May 7, 1999): gi ~ 466548 ~ - NBL4 protein of mus musculus ~ 41% homology on 314 aa (position 9-322 aa) on Swissprot sequences (version 36, last update day of May 3, 1999): sp ~ P11171 ~ 41_HUMANPROTEIN
4.7 (BAND 4.1) (P4.1) Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 26 The open reading frame of the SEQ nucleic acid sequence ID No. 26 potentially codes for a polypeptide of 455 acids amines of length constituting the sequence SEQ ID No. 142.
2s Homologies observed at the level of the protein sequence This ORF of 455 aa has pattern type homologies with conserved domains of different tyrosine phosphatase proteins in different protein databases such as.

WO 00/71710 PCTlFR0010142G

~ 50% homology on 374 aa (position 24-397 aa) with SP-trEMBL: sp ~ P91433 ~ P91433 CODED FOR BY C.
ELEGANS CDNA YK65E9.3 and with Genpept115:
gi ~ 1708767 ~ 080955 containing a domain found in s band 4.1, ezrin, moesin, radixin and talin in c.
elegans ~ 45% homology on 333 aa (position 21-353 aa) on SP-trEMBL: sp ~ 043491 ~ 043491 PROTEIN 4.1-G.
~ 43% homology on 227 aa (position 7-233 aa) with Prodom: 894 p34.2 (29) MOES (4) RADI (3) EZRI (3) corresponding to PROTEIN PHOSPHATASE

~ 5 EZRIN RADIXIN MEMBRANE-ORGANIZING
~ 42% homology on 329 aa (position 24-352 aa) on Swissprot38: sp ~ P29074 ~ PTN4_HUMAN PROTEIN-TYROSINE PHOSPHATASE MEG1 (EC 3.1.3.48) (PTPASE-MEG1) (MEG).
~ 42% homology on 335 aa (position 23-357aa) with Non-redundant PIR: pir ~ S ~ JU0188 band 4.1 protein tyrosine phosphatase superfamily member protein de Zs mouse and Swissprot: sp ~ P52963 ~ NBL4 mouse NBL4 protein and SP-trEMBL: sp ~ 057457 ~ band 4.1-like protein 4 and Genpept: gi ~ 466548 ~ NBL4 mus musculus protein WO 00/71710 PCTlFR0010142G

~ 41% homology on 332 aa (position 22-353 aa) on Swissprot: sp ~ P11171 ~ 41_HUMAN PROTEIN 4.1 (BAND
4.1) (P4.1).
s Putative function The GS915528 gene is of interest for the functional study of Tangier disease and FHD in this sense. that it is both a positional candidate and a gene encoding a new protein including putative functions (tyrosine phosphatase) could play a role ~ o in the intracellular signaling cascade linked to the efflux of intracellular cholesterol mediated by HDL particles, involved in the Tangier disease and family HDL deficiency (FHD).
The polypeptides of sequences SEQ ID Nos. 141 and 142 are likely to be involved in regulating the flow of cholesterol, and more ts particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
2o Gene GS99817 Nucleic acids) Two messenger RNAs were isolated according to the invention corresponding to a transcript of the gene designated here under the number GS99817.
The first nucleic sequence of the cDNA corresponding to this 25 transcribed constitutes the sequence SEQ ID N ° 27.
The sequence SEQ ID No. 27 has a length of 1539 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 3 to the nucleotide in position 698 of the sequence SEQ ID N ° 27.

WO 00/71710 PCTlFR0010142G

No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 28.
s The sequence SEQ ID No. 28 is 3404 nucleotides in length.
It includes a partial open reading frame (ORF) ranging from nucleotide at position 1 to the nucleotide at position 792 of the sequence SEQ ID N ° 28.
Sequence homologies of SEQ ID NO: 28 have been ~ o found with sequences referenced in the database GenBank (Version 116) - 97% identity on 380 bp with a BAC END CIT-HSP-2166G6.TR
CIT-HSP Homo sapiens genomic clone 216666, genomic survey sequence Length = 380gi ~ 2975337 ~ gb ~ B93000.1 ~ B93000 [2975337]
~ s - 100% identity over 315 bp with a BAC END HS 2166 A2_D03 MR
CIT Approved Human Genomic Sperm Library D Homo sapiens genomic clone Plate = 2166 Col = 6 Row = G, genomic survey sequence Length =
316 gi ~ 3480271 ~ gb ~ AQ104915.1 ~ AQ104915 [3480271]
Expression analyzes of the transcript of sequence SEQ ID N ° 27 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS99817 gene was expressed in the fetal brain.
2s In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using the probe sequence SEQ ID N ° 93, revealed the presence of transcripts in the blot sold by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ~ o ID N ° 93 is respectively WO 00/71710 PCTlFR00lOla2G
her - 1.5 kb, 2 kb and 4.4 kb in the heart and the brain;
- .2 kb and 4.4 kb in the pancreas;
- 1.5 kb at 4.4 kb in the kidney and suqelettic muscle.
This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
io Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 27 The open reading frame of the SEQ nucleic acid sequence ID No. 27 potentially codes for a polypeptide of 232 amino acids in length constituting the sequence SEQ ID N ° 143.
~ s Homologies observed at the level of the protein sequence 27% homology on 211 aa (position 11-221 aa) with sequences deGenpept: (translation of Genbank v110 and 111, last update May 7, 1999): gi ~ 3876730 ~ and TrEMBL sequences (SP-TrEMBL, version 7, November 1998): sp ~ Q20021 ~ corresponding to the translation of 20 the sequence of a nematode cosmid F35C11.4 (Caenorhabditis elegans).
Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 28 The open reading frame of the SEQ nucleic acid sequence 2s ID N ° 28 potentially codes for a polypeptide of 263 acids amines of length constituting the sequence SEQ ID No. 144.
Homologies have been observed between the sequence SEQ ID No. 144 and the following sequences Homologies observed at the level of the protein sequence:

WO 00/71710 PCTlFR0010142G
28% homology on 255 aa (position 1-255 aa) with Genpept:
gi ~ 3876730 ~ and trEMBL: sp ~ Q20021 ~ corresponding to the translation the sequence of a nematode cosmid F35C11,4 - (Caenorhabditis elegans).

5 Putative function This gene is a candidate for the study of TangierlFHD disease in does chromosomal localization.
The polypeptides of sequences SEQ ID Nos. 143 and 144 are ~ o likely to be involved in regulating the flow of cholesterol, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
~ s Gene GS916229.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS916229.
zo The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 29.
The sequence SEQ ID No. 29 has a length of 792 nucleotides.
This sequence includes an open reading frame (ORF) ranging from the nucleotide in position 1 to the nucleotide in position 203 of the sequence z5 SEQ ID N ° 29.
No sequence identity was found during a search in the GenBank database (Version 110).
Expression analyzes of the transcript of sequence SEQ ID N ° 29 ~ o were carried out by RT PCR, as described in Example 1. These ~ 6 analyzes performed on polyA + RNA from different tissues allowed to show that the GS916229 gene was expressed in the fetal brain, liver, brain, heart, prostate, placenta, fetal liver, the uterus, the testicle and the kidney.
s This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease ~ 0 9q31-34 of chromosome 9.
Polypepfide encoded by the nucleic acid of sequence SEQ ID NO 29 The open reading frame of the nucleic acid sequence SEQ ID N ° 29 potentially codes for a polypeptide of 68 ~ s amino acids of length constituting the sequence SEQ ID No. 145.
No significant homology with BLAST was found with the sequences referenced in the Swissprot databases (version 36, last update of May 3, 1999) and PRODOM:
(peer domains detected in Swissprot, version 34.2, November 2, 1997).
The polypeptide of sequence SEQ ID No. 145 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments 2s family in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Gene GS92544 ~ o Nucleic acid (s)) WO 00/71710 PCTlFR0010142G

According to the invention, three corresponding messenger RNAs have been isolated.
respectively to one long transcript and two short transcripts of the gene designated here under the number GS92544.
The nucleic sequence of the cDNA corresponding to the long transcript s constitutes the sequence SEQ ID No. 30.
The sequence SEQ ID No. 30 has a length of 2733 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 1 to the nucleotide in position 2160 of the sequence SEQ ID N ° 30.
~ o The first nucleic sequence of the cDNA corresponding to the short transcript constitutes the sequence SEQ ID N ° 31.
The sequence SEQ ID No. 31 has a length of 2694 nucleotides.
This sequence includes an open reading frame (ORF) ~ s partial from the nucleotide in position 1 to the nucleotide in position 2121 of the sequence SEQ ID N ° 31.
No sequence identity was found during a search in the GenBank database (Version 110).
The second nucleic sequence of the cDNA corresponding to the 2o second short transcript constitutes the sequence SEQ ID N ° 32.
The sequence SEQ ID No. 32 has a length of 2765 nucleotides.
It includes a complete open reading frame ranging from the nucleotide in position 56 to the nucleotide in position 2287 of the sequence SEQ ID No.
32. The coding sequence begins at the nucleotide at position 410 and ends 2s ends at the nucleotide in position 2160 of the sequence SEQ ID No. 32 ..
The translation initiation codon begins on the nucleotide in position 410 of the sequence SEQ ID No. 32.
The sequence SEQ ID N ° 32 has homologies with the sequences referenced in the GenBank database (Version 30 116) following WO 00/71710 PCTlFR0010142G

~ 100% homology on 2419 bps (positions [485-2903]) matching with positions [1-2419] of sequence g6807990 (AL137432) Homo sapiens mRNA; cDNA DKFZp761 E1824 (from clone OKFZp761 E1824); partial cds, length = 2438 pdb, filed on 18-s FEB-2000, on Chromosome 9, and annotated "similar to CR2 receptor "
~ 97% homology on 157 bps (positions [1271-1427]) with the positions [431-277] of g3590696 (AQ192074) io HS 3228_B2_H11 T7 CIT Approved Human Genomic Sperm Library D Homo sapiens genomic clone Plate = 3228 Col = 22 Row = P, genomic survey sequence. Length = 513 ~ Several fragments of 99% to 100% identity with the sequence is gi ~ 6982613 ~ ~ AL138756: Homo sapiens chromosome 9 clone RP11-4O1 map q31.3-33.1, *** SEQUENCING IN PROGRESS ***, 41 unordered pieces ~ Several fragments of 100% identity with the sequence g7230026 20 (AC010824) Homo sapiens clone RP11-5A23, *** SEQUENCING IN
PROGRESS ***, 32 unordered pieces. Length = 162010 Expression analyzes of the long transcript and the short transcript were carried out by RT PCR, as described in Example 1. These 2 analyzes carried out using polyA + RNA from different tissues allowed to show that the GS92544 gene was expressed in the fetal brain.
In addition, an analysis of the expression of these transcripts by Northern blot, using respectively the SEQ ID sequence probes N ° 94, revealed the presence of transcripts in the blot sold over there ~ o Clontech Company (Ref. N ° 7759-1).

WO 00/71710 PCTlFR0010142G

The size of the transcripts detected with the SEQ sequence probe ID No. 94 is 4 kb and 6 kb respectively in the placenta.
This gene constitutes a causal positional candidate for a disease due to s dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
~ o Polypeptides encoded by nucleic acids of sequences SEQ! D
NO 30 and 31 The open reading frame of the nucleic acid sequence SEQ ID N ° 30 (long transcript) potentially codes for a polypeptide of 720 amino acids in length constituting the sequence SEQ ID No. 146.
~ s The open reading frame for the nucleic acid sequence SEQ ID N ° 31 (short transcript) potentially codes for a polypeptide of 707 amino acids in length constituting the sequence SEQ ID No. 147.
Homologies observed at the level of the protein sequence:
This sequence has significant homologies of the positions zo 139-194 aa / 199 - 254 aa with conserved sushi.HMM domains the Pfam database (HMMER 2.0 (June 1998).
This ORF has an annotation in Genpept: (translation of Genbank v110 and 111, last update May 7, 1999) and TrEMBL
zs (SP-TrEMBL, version 7, November 1998) with the BIastX translation of many sequences such as ~ 42% homology on 115 aa (position 2-116 aa) with gi sequences ~ 340164 ~ human precursor to uromodulin and gi ~ 340166 ~ uromodulin [Homo sapiens]

WO 00/71710 PCTlFR00101426 on Genpept: (translation of Genbank v110 and 111, last updated May 7, 1999) ~ 37% homology on 141 a (position 2-142 aa) with s SP-TrEMBL sequences (SP-TrEMBL, version 7, November 1998): sp ~ P87363 ~ P87363 a frament of the FIBRILLIN-1.
~ 30% homology on 234 aa (position 7-240 aa) with ~ o Genpept sequences: (translation of Genbank v110 and 111, last updated on May 7, 1999):
gi ~ 306746 ~ and gi ~ 1335064 ~ human fibrillin.
~ 30% homology on 194 aa (position 8-201 aa) with i5 SP-TrEMBL sequences (SP-TrEMBL, version 7, November 1998): sp ~ 035806 ~ 035806 LATENT TGF-Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 32 Zo The open reading frame for the SEQ nucleic acid sequence ID No. 32 potentially codes for a 713 acid polypeptide amines of length constituting the sequence SEQ ID No. 148.
Homologies of the sequence SEQ ID No. 148 have been observed with sequences referenced in databases 2s data. The homologies are as follows ~ homology with Genpept: gi ~ 340164 ~ uromodulin precursor [Homo sapiens) and Genpept: gi ~ 340166 ~
uromodulin [Homo sapiens]
~ homology with SP-trEMBL: sp ~ P87363 ~ P87363 3o FIBRILLIN-1 (FRAGMENT).

WO 00/71710 PCTlFR00101426 ~ homology with Genpept: gi ~ 306746 ~ and gi ~ 1335064 ~
fibrillin [Homo sapiens]
~ homology with SP-trEMBL: sp ~ 035806 ~ 035806 s PROTEIN
~ homology with 8784994 (X81479) EMR1 [Homo sapiens] Length = 886 ~ homology with 84379069 (X94630) seven-span transmembrane protein [Homo sapiens]
~ o ~ Other homologies with proteins such as EMR1, CD97, fibulins, complement receptor ...
The sequence SEO ID N ° 148 has characteristic patterns such as than 3 EGF domains including 2 calcium binding, a tyrosine site ~ s phosphatase, a hydrophobic N-terminal domain; Many sites glycosylation; 2 camp phosphorylation sites; 2 Asp sites hydroxylation.
Putative function 2o By its homology with uromodulin, the gene product GS92544 is putatively a protein associated with the membrane like uromodulin which is a protein anchored by a glycosylphosphatidylinositol (GPI). These results based on studies of amino acid partial sequence homology suggest that the 2s product of the GS92544 gene could be associated with the membrane by a binding to membrane lipids and therefore could be associated with deficit efflux of cellular cholesterol seen in FHD patients or Tangier.
The polypeptides of sequences SEQ ID No. 146, 147 and 148 are ~ o. likely to be involved in regulating the flow of cholesterol, and more WO 00/71710 PCTlFR00101426 particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
s Gen GS930824 Nucleic acids) Two messenger RNAs were isolated according to the invention corresponding to a transcript of the gene designated here under the number GS930824.
The first nucleic sequence of the cDNA corresponding to this ~ o transcribed constitutes the sequence SEQ ID N ° 33.
The sequence SEQ ID No. 33 has a length of 4745 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 2 to the nucleotide in position 514 of the sequence SEQ ID N ° 33.
ts Homologies observed at the nucleotide sequence level:
90% homology with Genbank: AF115435, rat syntaxin 17 out of 510 bp (position 22-531 bp).
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 34.
zo The sequence SEQ ID No. 34 has a length of 5241 nucleotides.
It includes a complete open reading frame (ORF) ranging from nucleotide at position 57 to the nucleotide at position 1013 of the sequence SEQ ID N ° 34. The coding sequence begins at the nucleotide in position 105 and ends at the nucleotide at position 1013 of the sequence SEQ ID
zs N ° 34. The translation initiation codon begins on the nucleotide in position 105 of the sequence SEQ ID N ° 34.
The sequence SEQ ID N ° 34 has homologies with sequences referenced in the GenBank database (Version 116). These are the following homologies ~ o ~ 90% homology with Genbank: AF115435, rat syntaxin 17 on 510 bp (position 22-531 bp).

WO 00/71710 PCTlFR00101426 ~ 92% homology on 475 bps (positions [540-1036]) and 84% on 406 bps (positions [102-507]) with the sequence 84206160 AF115435) Rattus norvegicus syntaxin 17 mRNA, complete s cds.Length = 1678;
~ 98% homology on 431 bps (positions [1899-2329]) and 91% on 62 pdb (positions [1819-1880]) with the sequence 84652677 (AQ474416) CITBI-E1-258819.TF CITBI-E1 Homo sapiens genomic ~ o clone 258819, genomic survey sequence.Length = 525;
~ 99% homology on 331 bps (positions (6394-6724]) with the sequence 82929043 (B87911) RPC111-30N20.TP RPCI-11 Homo sapiens genomic clone RPCI-11-30N20, genomic survey ~ s sequence.Length = 425;
~ 99% homology on 2662 bps (positions [20-2681]) with the sequence 87020892 (AK000658) Homo sapiens cDNA FLJ20651 fis, clone KAT01814.Length = 2678; Submitted (15-FEB-2000) to the zo DDBJ / EMBL / GenBank databases, NEDO project.
Expression analyzes of the transcript of sequence SEQ ID N ° 33 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed zs to show that the GS930824 gene was expressed in the fetal brain, liver, brain, heart, prostate, placenta, fetal liver, the uterus, the testicle, kidney and skeletal muscle.
In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using respectively the ~ o SEQ ID No. 95 and 96 sequence probes, revealed the presence of WO 00/71710 PCTlFR0010142G

transcribed in the blot marketed by the Clontech Company (Ref. N °
7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 95 is respectively s - 1.1 kb, 1.6 kb, 2.6 kb, 4.9 kb. and 7 kb in the pancreas, kidney, skeletal muscle, liver, brain and heart;
- 1.6 kb, 2.6 kb, 4.9 kb. And 7 kb in the lung and the placenta.
The size of the transcripts detected with the SEQ sequence probe ~ o ID N ° 96 is respectively - 1.35 kb, 2.4 kb, 3.5 kb and 10 kb in the placenta;
- 1.35 kb and 2.4 kb in the pancreas, the kidney and the liver;
- 1.35 kb in the lung;
- 2.4 kb in the skeletal muscle, the brain and the heart.
~ s This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies family in HDL.
Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 33 The open reading frame of the nucleic acid sequence SEQ ID N ° 33 potentially codes for a polypeptide of 170 amino acids of length constituting the sequence SEQ ID No. 149.
2s No significant homology with BLAST was found with the sequences referenced in the Swissprot databases (version 36, last update of May 3, 1999) and PRODOM:
(peer domains detected in Swissprot, version 34.2, November 1997).
~ o Homologies observed at the level of the protein sequence:

WO 00/71710 PCTlFR00101426 72% homology with Genpept sequences: (translation of Genbank v11 D and 111, last update May 7, 1999): gi4206161 on 170 amino acids (position 1-170 aa) gi4206161 is the translation protein of the gene coding for syntaxin 17 of rat..Genpept:
s (translation of Genbank v110 and 111, last update on May 7 1999) Polypeptide coded by the nucleic acid of sequence SEQ ID N ° 34 The open reading frame of the sequence SEQ ID N ° 34 code ~ o potentially for a polypeptide of 318 amino acids constituting the sequence SEQ ID N ° 150.
The following homogies have been observed - 72% homology with Genpept: gi4206161 on 170 amino acids ~ s (position 1-170 aa). Genpept: gi4206161 is the protein translation of gene encoding rat syntaxin 17.
Protein homology on Genpept115, Trembl and PIR
- 75% homology on 302 AA (positions [105-1010)) with all the 20 length the translated sequence g4206161 (AF115435) syntaxin 17 [Beaten norvegicusJLength = 301; from the g4206161 The polypeptide of sequence SEQ ID No. 150 has a motif characteristic of a syntaxin between the nucleotides in positions 1 and ? s 243 of the open reading frame.
Putative function The polypeptides of sequence SEQ ID No. 149 and 150 are therefore related to a protein of the syntaxin family involved ~ o in intracellular vesicular transport. This underlying mechanism WO 00/71710 PCTlFR00101426 by specific addressing mediated by these proteins is of interest by compared to Tangier's disease / FHD which is described by a defect in the transport and translocation mechanism of cholesterol pools intracellular to acceptor HDL particles. The polypeptides of s sequence SEQ ID N ° 149 and 150 are therefore likely to intervene in an important step involved in the reverse transport of cholesterol by HDL.
The polypeptides of sequences SEQ ID Nos. 149 and 150 are also likely to be involved in a genetically engineered disease io linked to locus 9q31-34 of chromosome 9.
Gene GS93382.
Nucleic acids) A messenger RNA corresponding to ~ s a transcript of the gene designated here under the number GS93382.
The nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID N ° 35.
The sequence SEQ ID No. 35 has a length of 3014 nucleotides.
This sequence includes an open reading frame (ORF) partial zo going from the nucleotide in position 3 to the nucleotide in position 371 of the sequence SEQ ID N ° 35.
No sequence identity was found during a search in the GenBank database (Version 110).
2s Expression analyzes of the transcript of sequence SEQ ID N ° 35 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS93382 gene was expressed in the fetal brain.
In addition, an analysis of the expression of the transcript by Northern ~ o blot, according to the protocol described in Example 1, using the probe WO 00/71710 PCTlFR00101426 sequence SEQ ID N ° 97, revealed the presence of transcripts in the blot sold by the Clontech Company (Ref. N ° 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 97 is respectively s - 2 kb and 7.5 kb in the brain;
- 2 kb in the pancreas, kidney, skeletal muscle, liver and heart.
This gene constitutes a candidate causative) of a disease o due to a dysfunction of the reverse flow of cholesterol, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
is Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 35 The open reading frame of the nucleic acid sequence SEQ ID N ° 35 potentially codes for a polypeptide of 123 amino acids of length constituting the sequence SEQ ID No. 151.
No significant homology with BLAST was found 2o with the sequences referenced in the Swissprot databases (version 36, last update May 3, 1999), PRODOM:
(peer domains detected in Swissprot, version 34.2, November 1997), Genpept: (translation of Genbank v110 and 111, last updated May 7, 1999), Swissprot (version 36, last updated 2nd day of May 3, 1999), TrEMBL (SP-TrEMBL, version 7, November 1998), PIR: (NON-REDUNDANT PIR SEQUENCES, VERSION 57) and PDB:
(PROTEIN DATA BANK, FEBRUARY 1999).
The polypeptide of sequence SEQ ID No. 151 is susceptible to intervene in the regulation of cholesterol flow, and more 3o particularly Tangier's disease, in deficiencies WO 00/71710 PCTlFR00101426 in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
s GS946300 gene.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS946300.
The nucleic sequence of the cDNA corresponding to this transcript io constitutes the sequence SEQ ID N ° 36.
The sequence SEQ ID No. 36 has a length of 1575 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 3 to the nucleotide in position 176 of the sequence SEQ ID N ° 36.
~ s No sequence identity was found during a search in the GenBank database (Version 110).
Expression analyzes of the transcript of sequence SEQ ID N ° 36 were carried out by RT PCR, as described in Example 1. These zo analyzes carried out using polyA + RNA from different tissues allowed to show that the GS946300 gene was expressed in the fetal brain, liver, brain, heart, prostate, placenta, fetal liver, the uterus, the testicle and the kidney.
zs This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.

WO 00/71710 PCTlFR00101426 Polypeptide encoded by the nucleic acid of sequence SEQ ID ND 36 The open reading frame of the nucleic acid sequence SEO ID N ° 36 potentially codes for a 58 polypeptide amino acids of length constituting the sequence SEQ ID No. 152.
s No significant homology with BLAST was found with the sequences referenced in the Swissprot databases (version 36, last update of May 3, 1999) and PRODOM:
(peer domains detected in Swissprot, version 34.2, November 1997).
~ o The polypeptide of sequence SEQ ID N ° 152 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease or deficiencies family in HDL.
The polypeptide of sequence SEQ ID No. 152 is therefore susceptible ~ s to intervene in an important stage involved in transport reverse cholesterol by HDL.
Gene GS937345.
zo Nucleic acid (s)) Two corresponding messenger RNAs were isolated according to the invention respectively to a long transcript and a short transcript of the designated gene here under n ° GS937345.
A first nucleic sequence of the cDNA corresponding to the zs long transcript has been isolated and constitutes the sequence SEQ ID No. 37.
The sequence SEQ ID No. 37 has a length of 1607 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 2 to the nucleotide in position 109 of the sequence SEQ ID N ° 37.

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From the sequence SEQ ID No. 37, two primers of respective sequences SEQ ID N ° 104 and 105 have been synthesized and have allowed to amplify a cDNA from a polyA + mRNA library of different human tissues marketed by the company Clontech.
s The cDNA sequence amplified using the sequence primers SEQ ID N ° 104 and 105 constitutes the sequence SEQ ID N ° 38. The sequence SEQ ID No. 38 has a length of 1161 nucleotides.
Homologies have been found between the sequence SEQ ID N °
38 and sequences referenced in the GenBank database ~ o (Version 116). The homologies are as follows ~ 99% homology on 1096 bps (positions [1-1093]) matching with the positions [8-1102] of the sequence gi ~ 6841231 ~ gb ~ AF161409.1 ~ AF161409 [6841231] Homo sapiens is HSPC291 mRNA, partial cds. Length = 1102;
unpublished;
~ 99% on 1025 bps (positions (119-1148]) matching with positions [8-1030] of the sequence 2o gi ~ 6841235 ~ gb ~ AF161411.1 ~ AF161411 [6841235] Homo sapiens HSPC293 mRNA, partial cds. Length = 1045; unpublished;
~ 99% on 1161 bps (positions [1-1161]) matching with the positiosn 2s [43-1202] of the sequence gi ~ 7020861 ~ dbj ~ AK000637.1 ~ AK000637 [7020861] Homo sapiens cDNA FLJ20630 fis, clone KAT03874.Length = 1538; filed on 22-FEB-2000, NEDO project; unpublishèd.
~ o WO 00/71710 PCTlFR0010142G

~ 92% on 1003 bps (positions [1-1043]) and 94% on 38 bps (positions [1048-1085]) with the sequence gb ~ AC021286.2 ~ AC021286 [6899766] Homo sapiens clone RP11 . 9:22 p.m., WORKING DRAFT SEQUENCE, 19 unordered pieces.
Length = 175143;
The nucleic sequence of the cDNA corresponding to the short transcript constitutes the sequence SEQ ID N ° 39.
The sequence SEQ ID No. 39 has a length of 1332 nucleotides.
~ o No sequence identity was found for the respective sequences of the long transcript and the short transcript during a search in the GenBank database (Version 110).
~ s This gene constitutes a candidate) causative of a disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
zo Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 37 The open frame for partial reading of the long sequence transcript of nucleic acids SEQ ID N ° 37 potentially codes for a polypeptide of 36 amino acids in length constituting the sequence zs SEQ ID N ° 153.
Homologies observed at the nucleotide sequence level:
41% identity on 22 aa (position 6 to 29 aa) with sequences of Swissprot (version 36, last update May 3, 1999): sp ~ P23596 ~
PRTD ERVVCH Proteases secretion ATP- Binding protein PRTD.
~ o WO 00/71710 PCTlFR0010142G

This gene is a candidate for the study of Tangier disease / FHD of does chromosomal localization.
Gene GS99556 s) nucleic acids) Two corresponding messenger RNAs were isolated according to the invention respectively a long transcript and a short transcript of the designated gene here under n ° GS99556.
The nucleic sequence of the cDNA corresponding to the long transcript ~ o constitutes the sequence SEQ ID N ° 40.
The sequence SEQ ID No. 40 has a length of 10419 nucleotides.
This sequence includes an open reading frame (ORF) partial ranging from nucleotide at position 2 to nucleotide at position 1954 of the sequence SEQ ID N ° 40.
~ s The initiation codon (ATG) begins at the nucleotide at position 29 of the long transcript of sequence SEQ ID No. 40.
The nucleic sequence of the cDNA corresponding to the short transcript constitutes the sequence SEQ ID N ° 41.
2o The sequence SEQ ID No. 41 has a length of 1813 nucleotides.
2s No sequence identity was found during a search in the GenBank database (Version 110).
Expression analyzes of the transcript of sequence SEQ ID N ° 40 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed to show that the GS99556 gene was expressed in the fetal brain, the ~ o liver, brain, heart, prostate, placenta and fetal liver.

WO 00/71710 PCTlFR0010142G

In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using respectively the SEQ ID NO: 98 and SEQ ID NO: 99 sequence probes revealed the presence of transcripts in the blot marketed by the Clontech Company (Ref.
No.
s 7759-1).
The size of the transcripts detected with the SEQ sequence probe ID No. 98 is respectively - 2.6 kb, 4.2 kb, 5 kb and 10 kb in the brain;
- 2.6 kb and 5 kb in the liver, lung, placenta and heart;
~ o - 2.6 kb and 5 kb in the kidney;
- 2.6 kb in the skeletal muscle;
- 5 kb in the pancreas.
The size of the transcripts detected with the SEQ sequence probe ts ID N ° 99 is respectively - 2.2 kb in the liver;
- 2.4 kb and 4.4 kb in the heart;
- 9 kb in the brain, the placenta, the kidney, the pancreas and the lung.
? o The size of the transcripts detected with the SEQ sequence probe ID No. 100 is respectively - 5 kb and 7 kb in the placenta and the heart;
- 5 kb in the brain, the kidney and the pancreas.
2s This gene constitutes a causal positional candidate for a disease due to dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.

WO 00/71710 PCTlFR00lOla2G
7a Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 40 The open framework for partial reading of the acid sequence nucleic acid SEQ ID N ° 40 potentially codes for a polypeptide of s. 651 amino acids in length constituting the sequence SEQ ID No. 154.
Homologies observed at the level of the protein sequence This ORF has homologies with Genpept sequences:
(translation of Genbank v110 and 111, last update May 7 1999) and TrEMBL (SP-TrEMBL, version 7, November 1998) io (BIastX translation of the following sequences) ~ 32% homology on 403 aa in Genpept:
(translation of Genbank v110 and 111, last updated May 7, 1999) with gi ~ 4529890 ~
~ s NG22 [Homo sapiens]
~ 25% homology on 693 aa in Genpept:
(translation of Genbank v110 and 111, last updated May 7, 1999) with gi ~ 3986770 ~
20 NG22 [Mus musculus]
24% homology on 683 aa in Genpept: (translation by Genbank v110 and 111, last update on May 7, 1999) with gi ~ 1072187 ~
corresponding to the CEESB82F cDNA of C elegans -~ 24% homology on 683 aa with TrEMBL (SP-TrEMBL, version 7, November 1998) sp ~ Q20026 ~
coded by CEESB82F cDNA from C elegans ~ o Putative function WO 00/71710 PCTlFR0010142G
This gene is a candidate for the study of Tangier's disease / FHD of does chromosomal localization.
The polypeptide of sequence SEQ ID No. 154 is susceptible to intervene in the regulation of cholesterol flow, and more s particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
~ o Gene GS96663.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS96663. Six sequences nuclei representative of this transcript have been determined is the first partial nucleic sequence of the cDNA
corresponding to this transcript constitutes the sequence SEQ ID No. 42.
The sequence SEQ ID No. 42 has a length of 1377 nucleotides.
The second partial nucleic sequence of the cDNA
zo corresponding to this transcript constitutes the sequence SEQ ID No. 43.
The sequence SEQ ID No. 43 has a length of 452 nucleotides.
The third partial nucleic acid sequence of the cDNA
corresponding to this transcript constitutes the sequence SEQ ID N ° 44.
? s The sequence SEQ ID No. 44 has a length of 562 nucleotides.
The fourth partial nucleic sequence of the cDNA
corresponding to this transcript constitutes the sequence SEQ ID N ° 45.
The sequence SEQ ID No. 45 has a length of 1766 nucleotides.

WO 00/71710 PCTlFR00101426 No sequence identity was found during a search in the GenBank database (Version 110).
From sequence SEQ ID No. 42, two synthesized nucleotide primers, respectively the sequence primers s SEQ ID N ° 106 and 107.
From sequence SEQ ID No. 43, a synthesized nucleotide primer of sequence SEQ ID No. 108.
From sequence SEQ ID N ° 45, two synthesized nucleotide primers, respectively the sequence primers io SEQ ID N ° 109 and 110.
These primers have amplified a fifth and a sixth nucleotide sequence representative of the transcript of the GS96663 gene.
The fifth nucleic sequence corresponding to the transcript of gene GS96663 constitutes the sequence SEQ ID N ° 46. The sequence ts nucleic acid SEQ ID No. 46 has a length of 601 nucleotides.
The sixth nucleic sequence corresponding to the transcript of gene GS96663 constitutes the sequence SEQ ID N ° 47. The sequence SEQ
ID No. 47 has a length of 3706 nucleotides. It includes a frame 20 partial reading open from the nucleotide in position 1 to the nucleotide in position 3202 of the sequence SEQ ID N ° 47.
Homologies have been observed between the sequence SEQ ID
N ° 47 and sequences referenced in the GenBank database (Version 116). These homologies are as follows ~ 99% homology on 2423 bps (positions [1030-3451]) matching with positions [1-2419] of the sequence gi ~ 5102585 ~ emb ~ AL079279.1 ~ HST000009 [5102585] Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 248114. Length =
~ 0 2450; / chromosome = "9" / map = "D9S176-D9S279"; filed on 14-JUN-1999; Unpublished.

WO 00/71710 PCTlFR0010142G

~ 98% on 1623 bps (positions [1946-3559]) matching with positions [16-1638] of the sequence g3012351 (176197) Sequence 1 from patent US 5691147.Length ~ _ 1638 bpd; tabled 03-APR-1998; AUTHORS: Draetta, G. and s Gyuris, J. TITLE: CDK4 binding assay JOURNAL: Patent: US
5691147-A 1 25-NOV-1997;
~ Different fragments of homology from 99% to 100% on 2372 bpd ~ o (positions [1-2372]) and from 97% to 100% on 1160 bps (positions [2547-3706]) with the sequence gi ~ 7228016 ~ emb ~ AL158158.3 ~ AL158158 [7228016]; Homo sapiens chromosome 9 clone RP11-427L11 map q31.2-32, ***
SEQUENCING IN PROGRESS ***, 37 unordered pieces; dropped it off ~ s 08-MAR-2000;
Analysis of expression of the transcript of SEQ ID sequences N ° 42 to 47 were carried out by RT PCR, as described in The example 20 1. These analyzes carried out using polyA + RNA of different tissues have shown that the GSS96663 gene was expressed in fetal brain, liver, brain, heart, prostate, placenta, fetal liver, uterus, testis, kidney and skeletal muscle.
25 This gene is a causal positional candidate for a disease.
due to dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies family in HDL.

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Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 47 The open frame for partial reading of the acid sequence nucleic acid SEQ ID N ° 47 potentially codes for a polypeptide of 1066 amino acids in length which constitutes the sequence SEQ ID N °
s 155 ..
Homologies between the sequence SEQ ID N ° 155 and sequences listed in the databases. These homologies are the following ~ 27% homology on 1068 AA with sequences of ~ o type "complement receptor" CR1 (g30186; 8809019;
8451303; 8306680) and CR2 (818192; 8181940; 8599776) ~ 24% homology on approximately 1000 AA with is sequences "complement factor H"; sequences gi ~ 31965 ~ emb ~ CAA68704.1 ~ [31965] (Y00716) factor H
[Homo sapiens], PIR: NBHUH and PIR: NBMSH;
EM: Q14006 and EM: Q61408.
20 ~ 25% homology on 900 AA with the sequences of P-selectin and E-selectin: sequences sp ~ p16581 (lem2 human e-selectin precursor (endothelial leukocyte adhesion molecule 1) (elam-1) (leukocyte-endothelial cell adhesion molecule 2) (lecam2) (cd62e) 2s and sp ~ p16109 ~ 1em3 human p-selectin precursor (granule membrane protein 140) (gmp-140) (padgem) (cd62p) (leukocyte-endothelial cell adhesion molecule 3) (lecam3) and with non-redundant pir: pir ~ s ~ a30359 p-selectin precursor - human ..
~ o WO 00/71710 PCTlFR0010142G

~ 24% homology on 637 AA with the sequence g183391 (M25322) granule membrane protein-140 (GMP-140) precursor [domo sapiens], Length = 830 s ~ Homology with the trEMBL cell adhesion molecule:
sp ~ Q28290 ~ Q28290 CELL MOLECULE MEMBERSHIP
PRECURSOR (FRAGMENT).
io ~ Different fragments of homology from 25% to 29% on the sequence "apolipoprotein H precursor -human PIR: NBHU Length - 345; apolipoprotein H
precursor - human. with a homology of 29% on 256 AA.
~ s ~ Homology with membrane sequences cofacteur protein cofacteur "(PIR: S01896, PIR: 154479, PIR: A57278 and EM: P79138, EM: Q9ZOM4, EM: 019121) and EM: 062837 2o CD46 protein cofactor membrane.
~ Different fragments (from 400 to 500 AA) of homology of 25% to 27% with the PIR sequence: T16833 hypothetical 2s protein T07H6.5 - Caenorhabditis elegans found in genpept (g1255889 (U53344).
~ o Putative function WO 00/71710 PCTlFR0010142G
The GS96663 gene product, due to its amino acid homology with human P-selective and E-selective precursors, is related to this class of membrane proteins. His role in the efflux of intracellular cholesterol, mediated by proteins s membranes is not excluded as far as the gene is located in the genetic interval defined by positional cloning.
The polypeptide of sequence SEQ ID No. 155 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments to family in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Gene GS941675.
Acids) nucleic (s) ~ s A messenger RNA corresponding to a transcript of the gene designated here under the number GS941675. Two sequences nucleic acids are representative of this transcript:
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 48.
zo The sequence SEQ ID No. 48 has a length of 373 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 49.
The sequence SEQ ID No. 49 has a length of 459 nucleotides.
? s No sequence identity was found during a search in the GenBank database (Version 110).
The third nucleic sequence of the cDNA corresponding to this ~ o transcribed constitutes the sequence SEQ ID N ° 50.
The sequence SEQ ID N ° 50 has a length of 2575 nucleotides WO 00/71710 PCTlFR0010142G

Dice homologies between the sequence SEQ ID N ° 50 and sequences referenced in the GenBank database (Version 116) have been observed. These homologies are as follows s - 98% identity on 720 bp with a BAC END 86348761 AQ892571 HS 3143 A1 G01 T7C CIT Approved Human Genomic Sperm Library lenght 848pb This gene constitutes a candidate causative) of a disease to due to a dysfunction of the reverse flow of cholesterol, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
~ s Gene GS929341.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS929341. Two sequences Representative nucleics of this transcript have been determined.
2o The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 51.
The sequence SEQ ID No. 51 has a length of 231 nucleotides.
The second nucleic sequence of the cDNA corresponding to this 2s transcribed constitutes the sequence SEQ ID N ° 52.
The sequence SEQ ID No. 52 has a length of 344 nucleotides.
This sequence includes a partial open reading frame (ORF) ranging from the nucleotide at position 3 to the nucleotide at position 131 of the sequence SEQ ID No. 52.

WO 00/71710 PCTlFR0010142G

No identity with the sequences SEQ ID N ° 51 and 52 has been found during a search in the GenBank database (Version 110).
s The third nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 53.
The sequence SEQ ID No. 53 has a length of 402 nucleotides.
This sequence includes a partial open reading frame (ORF) ranging from the nucleotide at position 1 to the nucleotide at position 188 of the sequence to SEQ ID N ° 53.
No identity with the sequences SEQ ID N ° 51 to 53 has been found during a search in the GenBank database (Version 116).
ts Expression analyzes of the transcript of sequences SEQ ID
N ° 51 and 52 were carried out by RT PCR, as described in The example 1. These analyzes carried out using polyA + RNA from different tissues have showed that the GS929341 gene was expressed in the brain fetal, liver, brain, heart, prostate, placenta, liver fetal, 20 uterus, testis, kidney, skeletal muscle and lung.
This gene is a causal positional candidate for a disease.
due to dysfunction of reverse cholesterol flow, and more particularly Tangier's disease or deficiencies familial zs in HDL, or a disease genetically linked to the locus 9q31-34 of chromosome 9.
Polypeptide encoded by the nucleic acid of sequence SEQ ID NO 52 The open reading frame of the SEQ nucleic acid sequence ~ o ID N ° 52 potentially codes for a polypeptide of 43 amino acids of length constituting the sequence SEQ ID No. 156.

WO 00/71710 PCTlFR0010142G

No significant homology with BLAST was found with the sequences referenced in the Swissprot databases (version 36, last update of May 3, 1999) and PRODOM:
(homologous domains detected in Swissprot, version 34.2, s November 1997).
Polypeptide encoded by the nucleic acid of sequence SEQ ID No. 53 The open reading frame of the SEQ nucleic acid sequence ID No. 53 potentially codes for a polypeptide of 61 acids amines ~ o of length constituting the sequence SEQ ID N ° 157.
No significant homology with BLAST was found with the sequences referenced in the Swissprot databases (version 38), PIR (Version 62, September 1999), trEMBL (Version of August 1999) and Gen Pept (Version 115).
~ s The polypeptides of sequences SEQ ID N ° 156 and 157 are likely to be involved in regulating the flow of cholesterol, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Gene GS915742.
Nucleic acids) A messenger RNA corresponding to 2s a transcript of the gene designated here under the no. GS915742. Three sequences Representative nucleics of this transcript have been determined.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 54.
The sequence SEQ ID No. 54 has a length of 228 nucleotides.
~ o WO 00/71710 PCTlFR00lOla2G
her The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 55.
The sequence SEQ ID No. 55 has a length of 270 nucleotides. .
s The third nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 56.
The sequence SEQ ID No. 56 has a length of 1130 nucleotides.
No sequence identity was found during a search in the GenBank database (Versions 110 and 116).
io Analysis of expression of the transcript of SEQ ID sequences N ° 54 and 55 were carried out by RT PCR, as described in The example 1. These analyzes carried out using polyA + RNA from different tissues have showed that the GS915742 gene was expressed in the brain is fetal, liver, placenta and kidney.
This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more 2o particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
zs Gene GS913018.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS913018. Two sequences representative of this transcript are shown below.
~ o The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 57.

WO 00/71710 PCTlFR0010142G
The sequence SEQ ID No. 57 has a length of 463 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 58.
s The sequence SEQ ID No. 58 has a length of 289 nucleotides.
No sequence identity with the sequences SEQ ID N ° 57 and 58 were not found during a search in the database GenBank (Version 110).
From sequence SEQ ID No. 57, two synthesized nucleotide primers, respectively. sequence primers SEQID NO. 111 and 112.
From sequence SEQ ID No. 58, two synthesized nucleotide primers, respectively the sequence primers SEQID NO 113 and 114.
~ 5. The primers of sequences SEQ ID N ° 111 to 114 allowed to amplify a cDNA, from a polyA + mRNA library of different human tissues marketed by the Société Clontech a third nucleic sequence of the cDNA corresponding to the transcript of GS913018 gene.
The third nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 59.
The sequence SEQ ID No. 59 has a length of 1542 nucleotides.
Homologies were found on the sequence SEQ ID N °
2s 59, in particular different fragments of identity on the positions [735-1268] [1-357] [559-710] and [373-501] of the sequence SEQ ID N ° 59 with the sequence g6563616 (AC013740) Homo sapiens clone RP11-115J22, WORKING DRAFT SEQUENCE, 15 unordered pieces: Length = 180711, listed in GenBank (Version 116).

WO 00/71710 PCTlFR00101426 Analysis of expression of the transcript of SEQ ID sequences N ° 57 and 58 were carried out by RT PCR, as described in The example 1. These analyzes carried out using polyA + RNA from different tissues have showed that the GS913018 gene was expressed in the brain s fetal, liver, brain, heart, prostate, placenta, liver fetal, the uterus, testis and kidney.
This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more io particularly Tangier disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
~ s Gene GS911742.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS911742. Three sequence representative of this transcript have been determined.
2o The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 60.
The sequence SEQ ID No. 60 has a length of 1417 nucleotides.
The second nucleic sequence of the cDNA corresponding to this 2s transcribed constitutes the sequence SEQ ID N ° 61.
The sequence SEQ ID No. 61 has a length of 696 nucleotides.
No sequence identity with sequences SEQ ID N ° 60 and 61 was not found during a search in the database 3o GenBank (Version 110).

WO 00/71710 PCTlFR0010142G

The third nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 62.
The sequence SEQ ID No. 62 has a length of 2702 nucleotides.
This sequence includes a partial open reading frame (ORF) ranging from the nucleotide at position 1 to the nucleotide at position 792 of the sequence SEQ ID No. 62. The potential coding sequence begins at the nucleotide in position 49 and ends at the nucleotide at position 792 of the sequence SEQ ID N ° 62. The translation initiation codon begins at nucleotide in position 49 of the sequence SEQ ID N ° 62. This sequence includes 1o a Kozak motif of sequence "GC CGC GCC ATG C" which begins at nucleotide in position 41 of the sequence SEQ ID No. 62.
Homologies with the sequence SEQ ID No. 62 have been observed with sequences listed in the database GenBank (Version 116). These homologies are as follows IS
~ 98% homology on 1410 bps (positions [4-1413]) with the sequence gi ~ 5912095 ~ emb ~
AL117557.1 ~ HSM801083 [5912095] Homo sapiens mRNA; cDNA
DKFZp564D177 (from clone DKFZp564D177); partial cds. Length =
20 1431; filed 18-FEB-2000; Submitted (15-SEP-1999) MIPS, Am Klopferspitz 18a, D-82152 Martinsried, GERMANY, Bloecker, H., Boecher, M., Brandt, P., Wiemann, S.
2s ~ 97% homology on 10139 bps [1-1039] and 97% on 380 bps [1082-1458] and 90% on 51 bps [1506-1556] with the sequence gi ~ 6841247 ~ gb ~ AF161417.1 ~ AF161417 [6841247] Homo sapiens HSPC299 mRNA, partial cds. Length = 1659; filed on 01-FEB-2000; Direct Submission; Submitted (14-MAY-1999) Shanghai ~ o Institute of Hematology, Shanghai Second Medical University, Rui-Jin Hospital, 197 Rui-Jin Road II, WO 00/71710 PCTlFR0010142G

~ 98% homology on 1410 bps [4-1413] with the sequence 85912095 (AL117557) Homo sapiens mRNA; cDNA DKFZp564D177 (from clone DKFZp564D177); partial cds. Length = 1431; filed on 18-FEB-2000; Direct Submission; Submitted (15-SEP-1999) MIPS, Am s Klopferspitz 18a, D-82152; Martinsried, GERMANY, Bloecker, H., Boecher, M., Brandt, P., Mewes, HW, Gassenhuber, J. and Wiemann, S.
~ 93% on 911 bps (positions [1-911]) and 93% on 179 bps (positions ~ o [1395-1573]) and 81% on 131 bps (positions [992-1122]) with the sequence gi ~ 7023832 ~ dbj ~ AK002137.1 ~ AK002137 [7023832] Homo sapiens cDNA FLJ11275 fis, clone PLACE1009375. Length = 1564;
filed 22-FEB-2000; NEDO human cDNA sequencing project;
Unpublished ~ s ~ Different fragments of homology (from 90% to 100%) with the sequence 85932616 (AC009594) Homo sapiens chromosome 4 clone 363 G 01 map 4, *** SEQUENCING IN PROGRESS ***, 9 unordered pieces. Length = 150108;
Analysis of expression of the transcript of SEQ ID sequences N ° 60 and 61 were carried out by RT PCR, as described in The example 1. These analyzes carried out using polyA + RNA from different tissues have helped show that the GS911742 gene was expressed in the brain 2s fetal, liver, heart and placenta.
In addition, an analysis of the expression of the transcript by Northern blot, according to the protocol described in Example 1, using the sequence SEQ ID NO 101, revealed the presence of transcripts in the ~ o blot sold by the Clontech Company (Ref. N ° 7759-1).

WO 00/71710 PCTlFR0010142G

The size of the transcripts detected with the SEQ sequence probe ID No. 101 is 1.9 kb in the pancreas, kidney, muscle skeletal, the lung and the placenta.
s This gene is a candidate for a causative disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies family in HDL.
io Polypeptide encoded by the nucleic acid of sequence SEQ! D NO 62 The open frame for partial reading of the acid sequence nucleic acid SEQ ID No. 62 potentially codes for a polypeptide of 263 amino acids in length constituting the sequence SEQ ID No. 158.
Homologies observed at the level of the protein sequence is translated into six phases ~ 99% homology on 262 AA (position [4-789]) with the sequence 85912096 (AL117557) hypothetical protein [Homo sapiens] Length =
263; note = "similarity to NIPSNAP1"; filed 18-FEB-2000;
Direct Submission; Submitted (15-SEP-1999) MIPS, Am Klopferspitz 20 18a, D-82152, Martinsried, GERMANY, Bloecker, H., Boecher, M., Brandt, P :, Mewes, HW, Gassenhuber, J. and Wiemann, S, ~ Homologies with NISNAP2 and NISNAP2 sequences 27% homology on 179 AA with the sequence 82769254 zs (AJ001259) NIPSNAP2 protein [Homo sapiens] Length = 285 and 24%
of homology on 211 AA with the sequence 82769649 (AJ001258) NIPSNAP1 protein [Homo sapiens] Length = 284 ~ 27% homology on 179 AA with the sequence 83403167 ~ o (AF029786) GBAS [Homo sapiens]

WO 00/71710 PCTlFR0010142G
Length = 286. GBAS: guanine nucletide-binding protein, alpha-subunit (adenylate cyclase-stimulating G alpha protein).
This protein is described with a phosphorylation site and a - transmembrane region.
s "Guanine nucletide-binding proteins" have a modulator role or transducers in different signaling systems transmembrane.
21% identity with the protein YMQ1 ÇAEEL (Database ~ o Prodom, VERSION?) which has a simirality with the protein SNAP25 and 4-nitrophenylphosphatase.
The polypeptide of sequence SEQ ID No. 158 comprises glycosylation sites, phosphorylation sites such as is protein kinase cAMP- and cGMP-dependent phosphorylation sites and type II kinese casein.
2o Putative function The polypeptide of sequence SEQ ID No. 158 is therefore related by its motif found in PRODOM domain PD013981: (domains counterparts detected in Swissprot, version 34.2, November 1997) at a protein putatively involved in vesicular transport 2s intracellular. This mechanism underpins by a specific addressing mediated by these proteins is of interest in relation to TangierJFHD which is described by a defect in the transport mechanism and translocation of intracellular cholesterol pools to HDL acceptor particles. The polypeptide of sequence SEQ ID No. 158 is therefore likely to intervene in an important stage involved in reverse transport of cholesterol by HDL.
The polypeptide of sequence SEQ ID No. 158 is susceptible s to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
to Gene GS98601.
Nucleic acids) A messenger RNA corresponding to a transcript of the gene designated here under the number GS98601. Three sequences Representative nucleics of this transcript have been determined.
ts The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 63.
The sequence SEQ ID No. 63 has a length of 335 nucleotides.
No sequence identity was found during a search in the GenBank database (Version 110).
zo The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 64.
The sequence SEQ ID No. 64 has a length of 447 nucleotides.
No sequence identity was found during a 2s search in the GenBank database (Version 110).
The third nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 65.
The sequence SEQ ID No. 65 has a length of 2324 nucleotides.

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This sequence includes an open reading frame (ORF) partial ranging from the nucleotide in position 3 to the nucleotide in position 611 of the sequence SEQ ID N ° 65.
Homologies observed at the nucleotide sequence level s (307) ~ 99% homology on 514 bp (position 1508-2021 bp) with GenBank sequences: gi ~ 3483520 ~
corresponding to the cDNA clone ZB95F02 (Homo io sapiens) whose sequence is complete.
~ 98% homology on 170 bp (position 862-1031 bp) with GenBank sequences: gi ~ 1184671 ~ (region 3'TR partial mRNA encoding the protein ~ s inducible from Newcastle disease virus) Expression analyzes of the transcript of sequence SEQ ID N ° 45 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed 2o to show that the GS98601 gene was expressed in the brain, the placenta and uterus.
This gene is a causal positional candidate for disease caused by dysfunction of reverse cholesterol flow, and more 2 ~ particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.

WO 00/71710 PCTlFR0010142G

Polypepride encoded by the nucleic acid of sequence SEQ ID IVO 65 The open reading frame of the third acid sequence nucleic acid SEQ ID N ° 65 potentially codes for a polypeptide of 203 amino acids in length constituting the sequence SEQ ID No. 159.
s Homologies observed at the level of the protein sequence (307):
34% homology on 180 aa (position 3-182 aa) with sequences of Genpept: ~ (translation of Genbank v110 and 111, last update on May 7, 1999): gi ~ 3878571 ~ gnI ~ PID ~ e1348103 (Z46381) - low similarity with the yeast protein Ysy6 - (PIR: (PIR SEQUENCES NO
~ o REDUNDANTES, VERSION 57) access number JQ0912); IS cDNA
EMBL: D32318 is from this gene; IS EMBL cDNA: D33688 comes from this EST gene from EMBL cDNA: D34664 comes from this gene;
IS EMBL cDNA: D36574 comes from this gene and sequences from SP-TrEMBL (SP-TrEMBL, version 7, November 1998): sp ~ Q21453 ~
~ s corresponding to the protein M01 F1.4 of C elegans The polypeptide of sequence SEQ ID No. 159 is susceptible to intervene in the regulation of cholesterol flow, and more particularly Tangier's disease, in impairments zo familial in HDL, or in a disease genetically linked to locus 9q31-34 of chromosome 9.
Putative function This gene is a candidate by its chromosomal location for 2s Tangier / FHD pathologies.
Gene GS94852.
Nucleic acids) WO 00/71710 PCTlFR0010142G

A messenger RNA corresponding to a transcript of the gene designated here under the number GS94852. Three sequences Representative nucleics of this transcript have been determined.
The first nucleic sequence of the cDNA corresponding to this s transcribed constitutes the sequence SEQ ID N ° 66. .
The sequence SEQ ID No. 66 has a length of 447 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 67.
~ o The sequence SEQ ID N ° 67 has a length of 564 nucleotides.
From sequence SEQ ID No. 66, two synthesized nucleotide primers, respectively the sequence primers SEQ ID N ° 115 and 116.
is From the sequence SEQ ID N ° 67, two synthesized nucleotide primers, respectively the sequence primers SEQ ID N ° 117 and 118 .The primers of sequences SEQ ID. N ° 115 to 118 allowed amplify a cDNA from a bank of polyA + mRNAs of different 2o human tissue marketed by the Clontech Company a third cDNA nucleic sequence corresponding to the gene transcript GS94852.
The third nucleic sequence corresponding to the transcript of GS94852 gene constitutes the sequence SEQ ID No. 68.
2s The sequence SEQ ID No. 68 has a length of 604 nucleotides.
No sequence identity with the sequences SEQ ID N ° 66 to 68 was not found during a search in the database GenBank (Versions 110 and 116).
'JO

WO 00/71710 PCTlFR0010142G
Expression analyzes of the transcript of sequence SEQ ID N ° 67 were carried out by RT PCR, as described in Example 1. These analyzes performed on polyA + RNA from different tissues allowed de-show that the GS94852 gene was expressed in the liver and heart.
s This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease io 9q31-34 of chromosome 9.
Gene S935135.
Acids) nucleic (s) A messenger RNA corresponding to ts is a transcript of the gene designated here under the number GS935135. Three sequences Representative nucleics of this transcript have been determined.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 69.
The sequence SEQ ID No. 69 has a length of 482 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 70. '' The sequence SEQ ID No. 70 has a length of 402 nucleotides.
No sequence identity was found with the 2s sequences SEQ ID N ° 69 and 70 during a search in the database GenBank data (Version 110).
We synthesized a first nucleotide primer of sequence SEQ ID N ° 119 from the sequence SEQ ID N ° 69 and a second ~ o nucleotide primer of sequence SEQ ID N 120 from the WO 00/71710 PCTlFR00101426 sequence SEQ ID N ° 70. These primers made it possible to amplify a third nucleic acid sequence representative of the gene transcript GS935135 constituting the sequence SEQ ID N ° 71.
The nucleic sequence SEQ ID N ° 71 has a length of 758 s nucleotides.
Homologies were found with sequences listed in the GenBank database (Version 116). These homologies are as follows ~ 80 to 85% homology on 3 fragments (156 + 197 + 93 bpd) with the sequence 82168141 (gi ~ 2168141 ~ emb ~ Z93019.1 ~ HS49C23 [2168141) Human DNA
sequence from PAC 49C23 on chromosome X contains malate dehydrogenase pseudogene and STS. Length = 153078 is ~ 81% to 90% homology on 4 fragments (144 + gg + 197 + 137 bpd) with the sequence 82828782 (gi ~ 2828782 ~ gb ~ AC002319.1 ~ AC002319 [2828782)) Homo sapiens zo chromosome 9q34, clone 70C11, complete sequence. Length =

2s Expression analyzes of the transcript of sequence SEQ ID No. 69 or 70 were carried out by RT PCR, as described in Example 1.
These analyzes carried out using polyA + RNA from different tissues have showed that the GS935135 gene was expressed in the brain fetal, liver, brain, prostate, placenta, fetal liver, the uterus, the ~ o testicle and kidney.

WO 00/71710 PCTlFR0010142G

This gene is a causal positional candidate for disease caused by reverse cholesterol flow dysfunction, and more particularly Tangier's disease or even loss of life in HDL, or a genetically linked locus disease s 9q31-34 of chromosome 9.
Gene GS914669.
Nucleic acids) io A messenger RNA corresponding to a transcript of the gene designated here under the number GS914669. Three sequences Representative nucleics of this transcript have been determined.
The first nucleic sequence of the cDNA corresponding to this ~ s transcribed constitutes the sequence SEQ ID N ° 72.
The sequence SEQ ID No. 72 has a length of 673 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 73.
zo The sequence SEQ ID No. 73 has a length of 554 nucleotides.
No sequence identity with the sequences SEQ ID N ° 72 and 73 were not found during a search in the database GenBank (Version 110).
zs From the sequence SEQ ID No. 72, two synthesized nucleotide primers, respectively the sequence primers SEQ ID N ° 121 and 122.
From sequence SEQ ID No. 73, two synthesized nucleotide primers, respectively the sequence primers ~ o SEQ ID N ° 123 and 124.

WO 00/71710 PCTlFR0010142G

The primers of sequences SEQ ID N ° 121 to 124 made it possible to amplify a cDNA, from a bank of polyA + mRNA of different tissues humans marketed by the Clontech Company a third cDNA nucleic sequence corresponding to the gene transcript s GS914669. This sequence constitutes the sequence SEQ ID N ° 74. The sequence SEQ ID No. 74 has a length of 1794 nucleotides. She includes an open reading frame from the nucleotide at position 1 at the nucleotide in position 258 of the sequence SEQ ID No. 74 as well as a identically located coding sequence. This sequence includes io a polyadenylation site starting at the nucleotide at position 1751 of the SEQ ID No. 74.
Homologies with the sequence SEQ ID No. 74 have been found in the sequences listed in the database GenBank (Version 116). These homologies are as follows is 99% identity on 1000bp (792 to 1793bp) g6807977 AL137422 Homo sapiens mRNA; cDNA DKFZp761A1623 (from clone DKFZp761A1623);
partial cds Length = 1000 Identity with a BAC during sequencing AL137023 g6982086 2o Homo sapiens chromosome 9 clone RP11-403A22 map q34.13-34.3, ***
SEQUENCING IN PROGRESS ***, 19 unordered pieces. Length =

Expression analyzes of the transcript of sequence SEQ ID N ° 72 2s or 73 were carried out by RT PCR, as described in Example 1.
These analyzes carried out using polyA + RNA from different tissues have showed that the GS914669 gene was expressed in the brain fetal and heart.
3o This gene constitutes a candidate positioned) causal of a disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies WO 00/71710 PCTlFR0010142G

in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Polypeptide encoded by nucleic acid of sequence SEQ ID No. 74 s The open reading frame of the SEQ nucleic acid sequence ID No. 74 potentially codes for the polypeptide of sequence SEQ
ID
N ° 160 with a length of 85 amino acids.
No sequence homology was observed with the sequences listed in the Genpept databases (Version io 115), Svrvissprot (Version 38), trEMBL (Version of August 1999) and PIR
(Version 62 of September 1999).
Gene GS913839.
Nucleic acids) ~ s A messenger RNA corresponding to a transcript of the gene designated here under the number GS913839. Three sequences Representative nucleics of this transcript have been determined.
The first nucleic sequence of the cDNA corresponding to this Zo transcribed constitutes the sequence SEQ ID N ° 75.
The sequence SEQ ID No. 75 has a length of 507 nucleotides.
The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID N ° 76.
2s The sequence SEQ ID No. 76 has a length of 415 nucleotides.
No sequence identity with sequences SEQ ID N ° 75 and 76 was not found during a search in the database GenBank (Version 110).

WO 00/71710 PCTlFR0010142G

From the sequence SEQ ID No. 75, a synthesized nucleotide primer of sequence SEQ ID No. 125.
From the sequence SEQ ID N ° .76, a synthesized nucleotide primer of sequence SEQ ID N ° 1126 s. The primers of sequences SEQ ID N ° 125 and 126 allowed amplify a cDNA from a bank of polyA + mRNAs of different human tissue marketed by the Clontech Company a third cDNA nucleic sequence corresponding to the gene transcript GS94852. This sequence constitutes the sequence SEQ ID N ° 77.
The sequence SEQ ID N ° 77 has a length of 1318 nucleotides.
Homologies of the sequence SEQ ID No. 77 have been observed with sequences listed in the database GenBank (Version 116). These homologies are as follows ~ s ~ 99% homology on 1320 bps (positions [1-1318)) with the sequence 86006243 (AC011096) Homo sapiens clone 2_D_21, ***
SEQUENCING IN PROGRESS ***, 15 unordered pieces.Length =
135130;
~ 99% homology on 1320 bps (positions [1-1318]) with the sequence 87263520 (AL161631) Homo sapiens chromosome 9 clone RP11 70K10, *** SEQUENCING IN PROGRESS ***, 45 unordered pieces.
zs Length = 100562;
Expression analyzes of the transcript of sequence SEQ ID No. 75 or 76 were carried out by RT PCR, as described in Example 1.
~ o These analyzes carried out using polyA + RNA from different tissues have WO 00/71710 PCTlFR0010142G

helped show that the GS913839 gene was expressed in the brain fetal and liver.
This gene is a causal positional candidate for a disease.
s due to a dysfunction in the reverse flow of cholesterol; and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
~ o Gene GS912639.
Acids) nucleic (s) A messenger RNA corresponding to a transcript of the gene designated here under the number GS912639. Three sequences ~ s nucleic acid representative of this transcript have been determined.
The first nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID No. 78.
The sequence SEQ ID No. 78 has a length of 530 nucleotides.
zo The second nucleic sequence of the cDNA corresponding to this transcribed constitutes the sequence SEQ ID No. 79.
The sequence SEQ ID No. 79 has a length of 495 nucleotides.
No sequence identity with the sequences SEQ ID N ° 78 and 79 was not found during a search in the database 2s GenBank (Version 110).
From sequence SEQ ID No. 78, a synthesized nucleotide primer of sequence SEQ ID No. 127.
From sequence SEQ ID No. 79, a synthesized nucleotide primer of sequence SEQ ID N ° 128 WO 00/71710 PCTlFR0010142G

The primers of sequences SEQ ID N ° 127 and 128 allowed amplify a cDNA from a bank of polyA + mRNAs of different human tissue marketed by the Clontech Company a third cDNA nucleic sequence corresponding to the gene transcript s GS912639. This sequence constitutes the sequence SEQ ID N ° 80.
The sequence SEQ ID No. 80 has a length of 594 nucleotides.
1o Sequences of sequence of sEQ ID No. 80 have been found with sequences referenced in the database GenBank (Version 116). These homologies are as follows ~ 99% homology on 522 bps (positions [204-725]) with the sequence g2603415 (gi ~ 2603415 ~ gb ~
851178.1 ~ B51178 [2603415]) CIT978SK-95K15.TV CIT978SK Homo sapiens genomic clone 95K15, genomic survey sequence.Length = 524;
~ 99% homology on 501 bps (positions [204-704]) with the sequence g2866378 (gi ~ 2866378 ~ gb ~ B79355.1 ~ B79355 [2866378]) CIT978SK-95K15.TV.1 CIT978SK Homo sapiens genomic clone 95K15, genomic survey sequence.Length = 529;
~ 94% homology on 309 bps (positions [205-513]) with the sequence g2602442 (i ~ 2602442 ~ gb ~ B50205.1 ~
B50205 [2602442]) CIT978SK-96F5.TV CIT978SK Homo sapiens genomic clone 96F5, genomic survey sequence.Length = 309;
Expression analyzes of the transcript of sequence SEQ ID No. 78 or 79 were carried out by RT PCR, as described in Example 1.
These analyzes carried out using polyA + RNA from different tissues have showed that the GS912639 gene was expressed in the liver.
~ o WO 00/71710 PCTlFR0010142G

This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease s 9q31-34 of chromosome 9.
Gene GS933630.
Nucleic acids A messenger RNA corresponding to ~ o a transcript of the gene designated here under the n ° GS933630. A sequence Representative nucleic acid of this transcript has been determined.
This nucleic sequence of the cDNA corresponding to this transcript constitutes the sequence SEQ ID No. 81.
The sequence SEQ ID No. 81 has a length of 582 nucleotides.
is No homology was observed with the sequences referenced in the GenBank database (Version 116).
This gene is a candidate for a causal disease due to reverse cholesterol flow dysfunction, and more zo particularly Tangier's disease or deficiencies in HDL, or a genetically linked locus disease 9q31-34 of chromosome 9.
Characteristics of the invention 2s The invention thus relates to a nucleic acid encoding a protein having an amino acid sequence chosen from the group amino acid sequences SEQ ID NO: 129 to SEQ ID NO: 160 or a peptide fragment or a variant thereof or an acid ~ o nucleic acid of complementary sequence.

WO 00/71710 PCTlFR00lOla2G
loa In general, the nucleic acids according to the invention are present in an isolated or purified form.
The invention also relates to a nucleic acid comprising at least eight consecutive nucleotides of a polynucleotide selected from the group consisting of the nucleotide sequences SEQ ID N ° 1 to SEQ ID
N ° 81 and SEQ ID N ° 82 to SEQ ID N ° 101, or an acid nucleic acid complementary sequence.
The invention also relates to a nucleic acid comprising at least ~ o minus 20, 30, 40, 50, 100 or 150 consecutive nucleotides of a polynucleotide selected from the group consisting of sequences nucleotides SEQ ID N ° 1 to SEQ ID N ° 81 and SEQ ID N ° 82 to SEQ ID
No. 101, or a nucleic acid of complementary sequence.
According to another aspect, the invention also relates to an acid is nucleic acid having at least 90% nucleotide identity with an acid nucleic acid chosen from the group consisting of nucleotide sequences SEQ ID N ° 1 to SEQ ID N ° 81 and SEQ ID N ° 82 to SEQ ID
N ° 101, advantageously 80%, preferably 95, 99%, 99.5%, and so entirely preferred 99.8% identity in nucleotides with an acid 2o nucleic acid chosen from the group consisting of nucleotide sequences SEQ ID N ° 1 to SEQ ID N ° 81 and SEQ ID N ° 82 to SEQ ID
No. 101, or a nucleic acid of complementary sequence.
According to yet another aspect, the invention relates to an acid nucleic acid hybridizing, under strong hybridization conditions 2s stringency, with a nucleic acid as defined above, and more particularly a nucleic acid chosen from the group consisting of nucleotide sequences SEQ ID N ° 1 to SEQ ID N ° 81 and SEQ ID
N ° 82 to SEQ ID No. 101, or a nucleic acid of complementary sequence.
~ o As described in detail above, each of the nucleotide sequences SEQ ID No. 1 to SEQ ID No. 81 constitute CDNA whose nucleotide sequence is found in the transcripts of genes potentially involved in conditions related to a dysfunction of lipoprotein metabolism, especially the ~ s reverse transport of cholesterol.

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For some of these nucleic acids, a reading phase has been determined, which codes for a polypeptide of which one alteration in the amino acid sequence or in the expression is potentially associated with any of these conditions, which indicates that s nucleotide sequences including open reading phases constitute nucleic acids of potential interest therapeutic.
Consequently, the subject of the invention is also an acid nucleic acid having at least 80% nucleotide identity with a ~ o polynucleotide comprising, or alternatively consisting of, a framework of full or partial open reading, as defined above herein description.
The above nucleic acids which include, totally or partially, the coding region of the transcripts of is sequences SEQ ID N ° 1 to SEQ ID N ° 81 can be expressed in a desired host cell, when these nucleic acids are placed under the control of suitable expression signals.
Such expression signals can be indifferently the expression signals contained in the regulatory regions of each 2o corresponding genes or, on the contrary, made up of sequences exogenous regulatory nucleic acids.
Such a nucleic acid placed under the control of a sequence functional regulator in the desired host cell may also be inserted into a vector for expression.
2s NUCLEOTIDE PROBES AND PRIMERS
The nucleic acid fragments derived from any one nucleotide sequences SEQ ID No. 1 to SEQ ID No. 81 are useful ~ o for the detection of the presence of at least one copy of a sequence nucleotide chosen from the sequences SEQ ID N ° 1 to SEQ ID
N ° 81 or a fragment or a variant of. the latter in a sample.
The nucleotide probes or primers according to the invention 3s include at least eight consecutive nucleotides of a nucleic acid WO 00/71710 PCTlFR00101426 chosen from the group consisting of sequences SEQ ID N ° 1 to SEQ ID
No. 81, or a nucleic acid of complementary sequence.
Preferably, nucleotide probes or primers according to the invention will have a length of 10, 12, 15, 18 or 20 to 25, 35, 40, 50, s 70, 80, 100, 200, 500, 1000, 1500 consecutive nucleotides of an acid nucleic acid according to the invention, in particular a nucleic acid of nucleotide sequence chosen from sequences SEQ ID N ° 1 to SEQ
ID No. 81 or a nucleic acid of complementary sequence.
Alternatively, a nucleotide probe or primer depending on ~ o The invention will consist and / or include fragments with a length of 12, 15, 18, 20, 25, 35, 40, 50, 100, 200, 500, 1000, 1500 nucleotides sequences of a nucleic acid according to the invention, more particularly of a nucleic acid chosen from the sequences SEQ ID N ° 1 to SEQ ID
No. 81, or a nucleic acid of complementary sequence.
~ s The definition of a probe and a nucleotide primer according to the invention therefore encompasses oligonucleotides which hybridize, in the high stringency hybridization conditions defined above, with a nucleic acid chosen from the sequences SEQ ID N ° 1 to SEQ ID
N ° 81 or with a sequence complementary to these.
2o Preferred probes and primers according to the invention comprise all or part of a polynucleotide chosen from the sequences nucleotides SEQ ID N ° 82 to 101, or nucleic acids of complementary sequence, or among the sequences nucleotides SEQ ID N ° 102 to 128, or nucleic acids of 2s complementary sequence.
A primer or a nucleotide probe according to the invention can be prepared by any suitable method well known to those skilled in the art profession, including by cloning and restriction enzyme action or again by direct chemical synthesis using techniques such as ~ o phosphodiester method of NARANG et al. (1979) or BROWN and al. (1979), the diethylphosphoramidite method of BEAUCAGE and al. (1980) or technique. on solid support described in the EU patent No. EP 0 707 592.
Each of the nucleic acids according to the invention, including the 3s oligonucleotide probes and primers described above, can be WO 00/71710 PCTlFR0010142G

marked, if desired, by incorporating a marker detectable by spectroscopic, photochemical, biochemical means, immunochemical or chemical.
For example, such markers may consist of s radioactive isotopes (32p, ssP,, sH, ssS,), fluorescent molecules (5 bromodeoxyuridine, fluorescein, acetylaminofluorene, digoxigenin) or still ligands such as biotin.
The labeling of the probes is preferably done by incorporation of molecules labeled within polynucleotides by extension ~ o primers, or by addition on the ends 5 'or 3' Examples of non-radioactive labeling of acid fragments nucleic acids are described in particular in French patent No. FR 78 109 75 or in the articles of URDEA et al. (1988) or SANCHEZ-PESCADOR et al. (1988).
Advantageously, the probes according to the invention can have structural characteristics of .nature to allow a signal amplification, such as the probes described by URDEA et al.
(1991) or in European patent n ° EP-0 225 807 (CHIRON).
The oligonucleotide probes according to the invention can be 2o used in particular in Southern type hybridizations to DNA
genomics or in hybridizations to messenger RNA
corresponding when the expression of the corresponding transcript is sought in a sample.
The probes according to the invention can also be used for the 2s detection of PCR amplification products or for the detection of mismatches.
Nucleotide probes or primers according to the invention can be immobilized on a solid support. Such solid supports are well known to those skilled in the art and include surfaces of the 3o wells of microtiter plates, polystyrene beds, beds magnetic, nitrocellulose bands, or microparticles such as latex particles.
Consequently, the present invention also relates to a method for detecting the presence of a nucleic acid as described above in a sample, said method comprising the steps of WO 00/71710 PCTlFR0010142G

1) contact one or more nucleotide probes according to the invention with the sample to be tested;
2) detect the complex possibly formed between the one or more probes and the nucleic acid present in the sample.
According to a particular embodiment of the detection method according to the invention, the oligonucleotide probe (s) are immobilized on a support.
In another aspect, the oligonucleotide probes io include a detectable marker.
The invention further relates to a kit or kit for the detection of the presence of a nucleic acid according to the invention in a sample, said kit comprising a) one or more nucleotide probes as described above ~ s above;
b) where appropriate, the reagents necessary for the reaction hybridization.
According to a first aspect, the detection kit or kit is zo characterized in that the probe or probes are immobilized on a support.
According to a second aspect, the detection kit or kit is characterized in that the oligonucleotide probes comprise a detectable marker.
According to a particular embodiment of the detection kit described 2s above, such a kit will include a plurality of probes oligonucleotides according to the invention which can be used to detect target sequences of interest or alternatively detect mutations in coding regions or non-coding regions nucleic acids according to the invention, more particularly acids ~ o nucleic acid of sequences SEQ ID N ° 1 to SEQ ID N ° 81 or the acids nucleic acid of complementary sequence.
Preferred probes would include some or all of the polynucleotides of sequences SEQ ID No. 82 to SEQ ID No. 101.
Thus, the probes according to the invention immobilized on a support ~ s can be ordered in matrices such as "DNA chips". Of WO 00/71710 PCTlFR0010142G

such ordered matrices have been described in particular in the patent US No. 5,143,854, in PCT applications No. WO 90/150 70 and 92/10092.
Support matrices on which probes The nucleotides were immobilized at a high density are by example described in US Pat. Nos. 5,412,087 and in the application PCT No. WO 95/11995.
The nucleotide primers according to the invention can be used to amplify any of the nucleic acids according to the invention, and more particularly all or part of a nucleic acid of sequences SEQ ID N ° 1 to SEQ ID N ° 81, or a variant of this one.
Another object of the invention relates to a method for amplification of a nucleic acid according to the invention, and more particularly a nucleic acid of sequences SEQ ID N ° 1 to SEQ ID
is No. 81 or a fragment or variant thereof contained in a sample, said method comprising the steps of a) contacting the sample in which the presence of target nucleic acid is suspected with a pair of primers nucleotides whose hybridization position is localized respectively 2o on the 5 ′ side and on the 3 ′ side of the target nucleic acid region of which amplification is sought, in the presence of the reagents necessary for the amplification reaction; and b) detection of the amplified nucleic acids.
zs To implement the amplification process as defined above above, we will advantageously use any of the nucleotide primers described above.
The invention further relates to a kit or kit for amplification of a nucleic acid according to the invention, and more ~ o particularly all or part of a nucleic acid with sequences SEQ
ID N ° 1 to SEQ ID N ° 81, said kit or kit comprising a) a pair of nucleotide primers in accordance with the invention, whose hybridization position is located respectively on the 5 'side and on the 3 'side of the target nucleic acid whose amplification is sought;

WO 00/71710 PCTlFR0010142G

b) where appropriate, the reagents necessary for the reaction amplification.
Such a kit or amplification kit will include s advantageously at least one pair of nucleotide primers such as described above.
Recombinant vectors The invention also relates to a recombinanl vector to comprising a nucleic acid according to the invention.
Advantageously, such a recombinant vector will include a nucleic acid chosen from the following nucleic acids a) a nucleic acid coding for a protein having a amino acid sequence chosen from the group of sequences SEQ
~ s ID No. 129 to SEQ ID No. 160 or a peptide fragment or a varying from the latter;
b) a nucleic acid comprising a polynucleotide chosen from the group consisting of the sequences SEQ ID No. 1 to SEQ ID No. 81, or a fragment or a variant thereof;
2o c) a nucleic acid having at least 80% identity in nucleotides with a nucleic acid selected from the group consisting of sequences SEQ ID N ° 1 to SEQ ID N ° 81 or a fragment or a variant of this last ;
d) a hybridizing nucleic acid, under hybridization conditions 25 of high stringency, with a nucleic acid of sequences SEQ ID No. 1 to SEQ ID No. 81, or a fragment or variant thereof.
By "vector" in the sense of the present invention will be understood a circular or linear DNA or RNA molecule which is equally ~ o in the form of single strand or double strand.
According to a first embodiment, a recombinant vector according to the invention is used in order to amplify the nucleic acid which is there inserted after transformation or transfection of the desired cell host.
According to a second embodiment, these are vectors ~ s of expression comprising, in addition to a nucleic acid conforming to WO 00/71710 PCTlFR0010142G

the invention, regulatory sequences making it possible to direct the transcription and / or translation.
According to an advantageous embodiment, a recombinant vector according to the invention will include in particular the following elements s (1) elements regulating the expression of acid nucleic acid to be inserted, such as promoters and enhancers;
(2) the coding sequence included in the nucleic acid according to the invention to be inserted into such a vector, said sequence coding being placed in phase with the regulation signals described ~ o to (1); and (3) initiation and termination sequences of transcription appropriate.
In addition, the recombinant vectors according to the invention may ~ s include one or more origins of replication in cellular hosts in which their amplification or expression is sought, markers or selection markers.
By way of examples, the bacterial promoters may be the Lacl promoters, LacZ, RNA polymerase promoters from 2o bacteriophage T3 or T7, PR or PL promoters of phage lambda.
Promoters for eukaryotic cells will include the HSV virus thymidine kinase promoter or the promoter of mouse metallothionein-L.
Generally, for the choice of a suitable promoter, 2s those skilled in the art can advantageously refer to the work of SAMBROOK et al. (1989) cited above or to the techniques described by FULLER et al. (1996).
The preferred bacterial vectors according to the invention are by example the vectors pBR322 (ATCC37017) or also vectors such 3o as pAA223-3 (Pharmacia, Uppsala, Sweden), and pGEM1 (Promega Biotech, Madison, WI, USA).
Mention may also be made of other commercial vectors such as '' the vectors pQE70, pQE60, pQE9 (Qiagen), psiX174, pBluescript SA, pNHBA, pNH16A, pNH18A, pNH46A, pWLNEO, pSV2CAT, pOG44, ~ s pXTI, pSG (Stratagene).

WO 00/71710 PCTlFR0010142G

They can also be baculovirus type vectors such as vector pVL1392 / 1393 (Pharmingen) used to transfect cells of the line Sf9 (ATCC N ° CRL 1711) derived from Spodoptera frugiperda.
s It can also be adenoviral vectors such as adenovirus human type 2 or 5.
A recombinant vector according to the invention can also be a retroviral vector or an adeno-associated vector (AAV). Such adeno-associated vectors are for example described by FLOTTE et al.
io (1992), SAMULSKI et al. (1989), or even McLAUGHLIN BA et al.
(1996).
Recombinant host cells ts The invention also relates to a recombinant host cell comprising a nucleic acid according to the invention, and more particularly a nucleic acid of sequences SEQ ID N ° 1 to SEQ ID
No. 81 or a nucleic acid comprising all or part of the coding region of these.
2o According to another aspect, the invention also relates to a recombinant host cell comprising a recombinant vector as above above described.
The preferred host cells according to the invention are for example the following a) prokaryotic host cells: Escherichia coli strains (strain DH5-a), Bacilius subtilis, Salmonelia typhimurium, or strains of species such as Pseudomonas, Sfrepfomyces and Staphylococus;
~ o b) eukaryotic host cells: HeLa cells (ATCC N ° CCL2), Cv 1 cells (ATCC N ° CCL70), COS cells (ATCC N ° CRL 1650), Sf-9 cells (ATCC No. CRL 1711), CHO cells (ATCC No. CCL-61) or still 3T3 cells (ATCC No. CRL-6361).
3s WO 00/71710 PCTlFR0010142G

According to another aspect, the invention relates to a polypeptide comprising an amino acid sequence chosen from the group consisting of the peptides of sequences SEQ ID No. 129 to SEQ ID No. 160, or a peptide fragment or a variant thereof.
s The invention also relates to a polypeptide comprising at least 15 consecutive amino acids of a chosen amino acid sequence in the group consisting of peptides of sequence SEQ ID No. 129 to SEQ ID No. 160, or a peptide fragment or a variant thereof latest The invention also relates to a polypeptide comprising ~ o an amino acid sequence having at least 80% identity in amino acids with an amino acid sequence chosen from the group consisting of peptides of sequence .SEQ ID No. 129 to SEQ ID
No. 160, or a peptide fragment or a variant thereof.
Advantageously, part of the invention is a polypeptide having ~ s at least 85%, 90%, 95% or 99% amino acid identity with a amino acid sequence selected from the group consisting of peptides of sequences SEQ ID No. 129 to SEQ ID No. 160, or a fragment peptide or a variant thereof.
2o Preferably, polypeptides according to the invention will have a length from 15, 18 or 20 to 25, 35, 40, 50, 70, 80, 100 or 200 acids consecutive amines of a nucleic acid according to the invention, in particular a polypeptide of amino acid sequence chosen from sequences SEQ ID N ° 129 to SEQ ID N ° 160.
Alternatively, a polypeptide according to the invention will consist and / or will include fragments of length 15, 18, 20, 25, 35, 40, 50, 100 or 200 consecutive amino acids of a polypeptide according to the invention, more particularly of a polypeptide chosen from the sequences SEQ
~ o ID N ° 129 to SEQ ID N ° 160.
In general, the polypeptides according to the present invention come in an isolated or purified form.

WO 00/71710 PCTlFR00lOla2G
lla The invention also relates to a polypeptide comprising amino acid modifications of 1, 2, 3, 4, 5, 10 to 20 substitutions, additions or deletions of an amino acid with respect to the sequence in amino acids of a polypeptide of sequences SEQ ID No. 129 to SEQ ID
s No. 160, or a fragment or a variant thereof.
The invention also relates to a process for the production of one of the polypeptides of sequences SEQ ID No. 129 to SEQ ID
N ° 160 or a peptide fragment or a variant thereof, said method comprising the steps of ~ oa) insert a nucleic acid encoding said polypeptide into an appropriate vector;
b) cultivating, in an appropriate culture medium, a host cell previously transformed or transfected with the recombinant vector from step a);
is c) recover the conditioned culture medium or lyse the cell host, for example by sonication or by osmotic shock;
d) separate and purify from said culture medium or alternatively starting from the cell lysates obtained in step c), said polypeptide;
e) where appropriate, characterize the recombinant polypeptide produced.
The peptides according to the invention can be characterized by fixation on an immunoaffinity chromatography column on which the antibodies directed against this polypeptide or against a fragment or a variant of the latter have been immobilized beforehand.
2s According to another aspect, a recombinant polypeptide according to the invention can be purified by passage over an appropriate series of chromatography columns, according to methods known to man of art and described for example in F. Ausubel et al (1999).
A polypeptide according to the invention can also be prepared by ~ o classical techniques of chemical synthesis either homogeneous solution or solid phase.
By way of illustration, a polypeptide according to the invention could be prepared by the technique or in a homogeneous solution described by HOUBENWEYL (1974) or the phase synthesis technique 35 solid described by MERRIFIELD (1965a; 1965b).

WO 00/71710 PCTlFR0010142G

Also part of the invention are so-called polypeptides.
"homologs" to any of the polypeptides of sequences amino acids SEQ ID No. 129 to SEQ ID No. 160, or their fragments or variants.
s Such homologous polypeptides have acid sequences amines having one or more amino acid substitutions by an equivalent amino acid, relative to the reference polypeptides.
By equivalent amino acid according to the present invention, for example replacement of a residue in the L form with a io residue in form D or the replacement of an acid glutamic (E) with pyro-glutamic acid according to well techniques known to those skilled in the art. As an illustration, the peptide synthesis containing at least one residue in form D is described by KOCH
(1977).
~ s According to another aspect, are also considered as equivalent amino acids two amino acids belonging to the same class, i.e. two amino acids acidic, basic, non-polar or still unloaded polar.
The invention also includes polypeptides comprising 2o at least one non-peptide bond such as a retro-inverso bond (NHCO), a carba bond (CHzCH2) or even a bond ketomethylene (CO-CH2).
Preferably, the polypeptides according to the invention comprising a or more additions, deletions, substitutions of at least one acid 2s amino will retain their ability to be recognized by antibodies raised against unmodified polypeptides.
Antibody ~ o The polypeptides according to the invention, in particular the polypeptides of amino acid sequences SEQ ID No. 129 to SEQ ID No. 160 or the fragments and variants thereof as well as the peptides counterparts can be used for the preparation of antibodies.

WO 00/71710 PCTlFR00101426 By "antibody" within the meaning of the present invention, is meant including polyclonal or monoclonal antibodies or fragments (for example fragments F (ab) '2, Fab) or all polypeptide comprising a domain of the initial antibody recognizing s the target polypeptide or fragment of the polypeptide according to the invention.
Monoclonal antibodies can be prepared from of hybridomas according to the technique described by KOHLER and MILSTEIN
(1975).
~ o The present invention also relates to directed antibodies against a polypeptide as described above or a fragment or a variant of the latter, as produced in the trioma technique or still the hybridoma technique described by KOZBOR et al. (1983).
is The invention also relates to simple antibody fragments Fv chain (ScFv) as described in US Patent No. 4,946,778 or again by MARTINEAU et al. (1998).
The antibodies according to the invention also include antibody fragments obtained using RIDDER phage libraries 2o et al., (1995) or humanized antibodies REIMANN et al.
(1997); LEGER et al., (1997).
The antibody preparations according to the invention are useful in immunoassay tests to identify the presence and / or quantity of antigens present in a sample.
2s An antibody according to the invention may also comprise a isotopic or non-isotopic detectable marker, for example fluorescent or be coupled to a molecule such as biotin, according to techniques well known to those skilled in the art.
Thus, the reference also relates to a method for detecting the ~ o presence of a polypeptide according to the invention in a sample, said method comprising the steps of a) bringing the test sample into contact with an antibody such as described above; '' b) detecting the antigen / antibody complex formed.
~ s WO 00/71710 PCTlFR0010142G

The invention also relates to a kit or kit diagnostic or for detecting the presence of a polypeptide according to the invention in a sample, said kit comprising a) an antibody as defined above;
s ~ b) a reagent allowing the detection of complexes antigen / antibody formed.
Method for screening a molecule or binding substance on a polypepfide according to the invention.
~ o A polypeptide according to the invention can be used to screen for molecules attaching to it.
The binding of the polypeptide with the molecule or substance can activate (agonist molecule) or inhibit (antagonist molecule) activity of said polypeptide.
is Such molecules capable of binding to any one of polypeptides according to the invention include antibodies, oligonucleotides, other proteins and generally small molecules of all kinds.
In such a screening test, one can simply zo evidence of the binding of the candidate molecule to polypeptides, one of the two partners being labeled with a detectable compound (polypeptide of interest or candidate molecule), the visualization of the complex candidate polypeptide / molecule then being visualized by detection of the detectable marker, after elimination of the candidate molecules not 2s linked specifically.
For example, a screening test for a candidate molecule able to bind to a polypeptide according to the invention can advantageously understand a first step during which the polypeptide of interest or the candidate molecule is immobilized on a ~ o support, a second stage during which the second partner (candidate molecule or polypeptide of interest) is placed in the presence of the first compound previously immobilized on the support, a third stage during which one or more washes are carried out in suitable conditions for the removal of unbound compounds 35 specifically, and finally a fourth stage during which the WO 00/71710 PCTlFR0010142G

complex possibly formed between the polypeptide of interest and the candidate molecule is detected.
In the embodiment of the screening test according to which. the candidate molecule is immobilized beforehand on a support, then s bringing the polypeptide of interest according to the invention into contact, detecting of the complex formed by the candidate molecule and the polypeptide of interest according to the invention can advantageously be carried out using a antibody as described above.
In another embodiment of the screening test according to which it is the polypeptide of interest according to the invention which is previously immobilized on a support, the candidate molecule will advantageously marked with a detectable marker prior to its implementation contact with the immobilized polypeptide of interest.
Such a detectable marker can be radioactive or non-radioactive, ~ s for example fluorescent or correspond to a ligand for a third partner used for detection as a biotin molecule.
Consequently, the subject of the invention is also a method for screening an interacting molecule or candidate substance 2o with a polypeptide according to the invention, said method comprising the stages of a) bringing a polypeptide in accordance with the invention into contact with the candidate substance or molecule to be tested;
b) detecting any complexes formed between said 2s polypeptide and said candidate substance or molecule.
The invention also relates to a kit or kit for screening of an interacting candidate molecule or substance with a polypeptide according to the invention, said kit comprising ~ oa) a polypeptide according to the invention;
b) if necessary, the means necessary to detect the complex formed between said polypeptide and the molecule or substance candidate.

WO 00/71710 PCTlFR0010142G

The present invention is further illustrated, without however being limited, by the following examples EXAMPLES
s EXAMPLE 1 Tissue Distribution of the Transcripts According to the Invention The expression profile of the polynucleotides according to the present invention is determined according to Northern blot analysis protocols ~ o and reverse transcription coupled to PCR described in particular by Sambrook et al (ref. CSN Sambrook, J., Fritsch, EF, and Maniatis, T.
(1989). "Molecular Cloning: A Laboratory Manual," 2 "d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.).
~ s For example, in the case of an analysis by reverse transcription, a pair of primers synthesized from any one of nucleotide sequences of the transcripts SEQ ID N ° 1 to SEQ ID N ° 81 East used to detect the corresponding cDNA.
2o The polymerase chain reaction (PCR) is carried out on cDNA templates corresponding to polyA + mRNAs (Clontech) transcribed. Reverse transcription into cDNA is performed with the enzyme SUPERSCRIPT II (GibcoBRL, Life Technologies) according to conditions described by the manufacturer.
? s The polymer chain reaction is carried out according to standard conditions, in 20 NI of reaction mixture with 25 ng of the cDNA preparation. The reaction mixture is composed of 400 NM of each of the dNTPs, of 2 units of Thermus aquaticus (Taq) DNA
polymerizes (Taq Gold Amplifier; Perkin Elmer), 0.5 NM each 3o primer, 2.5 mM MgCl2, and PCR buffer. Thirty four cycles of PCR (30 s denaturation at 94 ° C, 30 s hybridization decomposed WO 00/71710 PCTlFR0010142G

as follows during the 34 cycles: 64 ° C 2 cycles, 61 ° C 2 cycles, 58 ° C 2 cycles and 55 ° C 28 cycles and one minute elongation per kilobase at 72 ° C) are carried out after a first denaturation step at 94 ° C
for 10 min in a Perkin Elmer 9700 thermocycler. Reactions s of PCR are visualized on agarose gel by electrophoresis. The cDNA fragments obtained can be used as probes for Northern blot analysis and can also be used for exact determination of the polynucleotide sequence.
~ o In the case of a Northern Blot analysis, a cDNA probe produced as described above is marked with 32P thanks to the system High Prime DNA label (Boehringer) according to the instructions indicated by the manufacturer. After labeling, the probe is purified on a Sephadex G50 microcolumn (Pharmacia) according to the instructions ~ s indicated by the manufacturer. The labeled and purified probe is then used for the detection of mRNA expression in different tissues.
Northern blot containing RNA samples from different human tissue ((Multiple Tissue Northern, MTN, Clontech) Blot 2, reference 77759-1) is hybridized with the labeled probe.
20. The protocol followed for hybridizations and washes can be either directly the one described by the manufacturer (User manual PT1200-1) either an adaptation of this protocol using the known methods of those skilled in the art and described for example in F. AUSUBEL et al (1999).
We can thus vary for example the temperatures of 2s prehybridization and hybridization in the presence of formamide.
For example we could use the following protocol 1- Competition of membranes and pre-hybridization:
~ o - Mix: 40p1 DNA sperm of salmon (10mg / ml) + 40 p1 human placental DNA (10mg / ml) WO 00/71710 PCTlFR0010142G

- Denature for 5 min at 96 ° C, then immerse the mixture in ice.
- Remove the SSC 2X and pour 4 ml of formamide mix into the tube s of hybridization containing the membranes.
- Add the mixture of the two denatured DNAs 1o - Incubation at 42 ° C for 5 to 6 hours, with rotation.
2- Competition of the marked probe - Add to the labeled and purified probe 10 to 50 NI DNA Cot I, depending on the amount of repeats.
- Denature 7 to 10 min at 95 ° C.
- Incubate at 65 ° C for 2 to 5 hours.

- Remove the pre-hybridization mix.
- Mix 40 NI salmon sperm DNA + 40 NI placental DNA
2s human; denature 5 min at 96 ° C, then immerse in ice.
- Add 4 ml of formamide mix to the hybridization tube, the mixture of the two DNAs and the denatured Cot I / DNA labeled probe.
- Incubate 15 to 20 hours at 42 ° C, with rotation.
4- Washes - Wash at room temperature in SSC 2X, to rinse.
- 2 times 5 minutes at room temperature SSC 2X and SDS 0.1% at 65 ° C.
- 2 times 15 minutes at 65 ° C SSC 1X and SDS 0.1% at 65 ° C.
After hybridization and washing, the blot is analyzed after one night exposure to a phosphor screen revealed using the Storm (Molecular Dynamics, Sunnyvale, CA).

WO 00/71710 PCTlFR0010142G

Example 2: Obtaining complete cDNA fragments corresponding to the transcripts according to the invention - Different approaches can be used to isolate the cDNA
s corresponding to one of the particular clones among the sequences SEQ ID
N ° 1 to SEQ ID N ° 81.
For example, a complete clone can be directly isolated by hybridization by screening a cDNA library using a probe polynucleotide specific for the sequence of the gene of interest.
~ o In particular a specific probe of 30-40 nucleotides is synthesized using an Applied brand synthesizer Biosystem / Perkin Elmer according to the chosen sequence.
The oligonucleotide obtained is radiolabelled, for example with 32P-y ATP using T4 polynucleotide kinase and is purified according to ~ s usual methods (eg Maniatis et al. Molecular cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring, NY 1982 or even F. Ausubel et al. (Current Protocols in Molecular Biology, J. Wiley and Sounds Eds, 1999).
zo The bank of clones containing the cDNA that we want to screen is spread on culture medium in Petri dish (1.5% agar) containing the appropriate antibiotics according to the usual methods mentioned above (F. Ausubel et al.). The colonies thus produced after incubation are transferred to nitrocellulose filters and screened using the probe 2s radiolabelled nucleotide, according to the usual methods and the colonies hybridizing with the probe are isolated and subcloned.
The DNA of the clones thus identified is prepared and analyzed by sequencing. The clones containing the fragments corresponding to ~ o the complete cDNA are purified and reclouged in the vector pcDNA3 according to WO 00/71710 PCTlFR0010142G

protocols known to those skilled in the art and presented for example in F. Ausubel et al (1999).
Different methods are known for identifying the ends s 5 'and 3' of cDNA corresponding to the genes described in the present request. These methods include but are not limited to cloning by hybridization, to cloning using protocols similar or identical to the 3 'or 5' RACE-PCR (Rapid Amplification of cDNA End-PCR) which are well known to those skilled in the art.
io For example, we could use the kit marketed by the company Clontech (Marathon ReadyTM cDNA kit, protocol referenced PT1156-1) or alternatively a method similar to 5'RACE is available to characterize the missing 5 'end of a cDNA (Fromont-Racine is et al. Nucleic Acid Res. 21 (7): 1683-1684 (1993)). In short, a RNA oligonucleotide is ligated to the 5 'end of a population of mRNA. After transcription in cDNA, a set of primers specific for the 5 'ligated adapter and a sequence located 3 'to the gene of interest is used in PCR to amplify ? o the 5 'portion of the cDNA sought. The amplified fragment is then used to reconstruct the complete cDNA.
Example 3 Analysis of the Gene Expression Profile for the Disease 2s of Tanaier Verification of the loss of expression of the candidate gene causing the Tangier cell phenotype may be determined by hydridation of these sequences with probes corresponding to WO 00/71710 PCTlFR0010142G
12a MRNA from fibroblasts from subjects with or without the disease, according to the methods described below 1. Preparation of the total RNAs of the poly (A) + mRNAs and of d_e probes cDNA
Total RNAs are obtained from cell cultures of fibroblasts from normal subjects or with Tangier's disease by the guanidine isothiocyanate method (Chomczynski & Sacchi, 1987). Poly (A) + mRNAs are obtained by affinity chromatography ~ o on oligo (dT) -cellulose columns (Sambrook et al., 1989) and the cDNAs used as probes are obtained by RT-PCR (DeRisi et al., 1997) with oligonucleotides labeled with a fluorescent product (Amersham Pharmacia Biotech; CyDyeT "").
~ s 2. Hydridation and detection of expression levels Glass membranes containing the sequences presented in this patent application, corresponding to the Tangier gene are hydrated with cDNA probes, obtained from fibroblasts 20 (lyer et al., 1999). Use of the Amersham / molecular system Dynamics (Avalanche MicroscannerT "") allows the quantification of expressions of sequence products on the healthy cell type or affected.
2s Example 4: Construction of the expression vector in mammalian cells The gene of interest can be expressed in cells of mammals. A typical eukaryotic expression vector contains a ~ o promoter which allows the initiation of transcription of mRNA, a WO 00/71710 PCTlFR0010142G

protein coding sequence and the signals required for termination of transcription and for polyadenylation of the transcript. II
also contains additional signals such as enhancers, .la sequence (de) Kozak and sequences necessary for splicing s mRNA. Efficient transcription is obtained with early elements and late SV40 virus promoters, retroviral LTRs or early promoter of the CMV virus. However cellular elements as the promoter of the active can also be employed. Of many expression vectors can be used to highlight ~ o works the present invention as the vector pcDNA3.
Example 5: Production of the polypeptides The polypeptide corresponding to the partial transcript of the GS gene t5 N ° XX or the full cDNA described in Example 2 (cloning of cDNA
complete) can be easily produced in an expression system bacterial, insect cell using baculovirus vectors or in mammalian cells with or without the vectors vaccinia virus. All methods are widely used today 2o described and known to those skilled in the art. We will find for example a detailed description in F. Ausubel et al. (1999).
Example 6: Production of an antibody derived from a polypeptide Antibodies in the present invention can be prepared by different methods (Current Protocols In Molecular Biology Volume 1 edited by Frederick M. Ausubel, Roger Brent, Robert E.
Kingston, David D. Moore, JG Seidman, John A. Smith, Kevin Struhl -~ o Massachusetts General Hospital Hanrard Medical School, chapter 11).

WO 00/71710 PCTlFR00101426 For example, cells expressing a polypeptide of the present invention are injected into an animal in order to induce the production of serum containing the antibodies. In one of the methods described, proteins are prepared and purified to avoid contamination.
s Such a preparation is then introduced into the animal for the purpose of produce higher activity polyclonal antisera.
In the preferred method, the antibodies of the present invention are monoclonal antibodies. Such monoclonal antibodies can be prepared using (a hybridoma technique. (Këhler and io al, Nature 256: 495 (1975); Kdhler et al, Eur. J. Immunol. 6: 511 (1976);
Kijhler et al, Eur. J. Immunol. 6: 292 (1976); Hammeling et al., In Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, NY, pp. 563-681 51981). In general, such methods involve immunizing the animal (preferably a mouse) with a polypeptide or, better ~ s again, with a cell expressing the polypeptide. These cells can be cultured in a suitable tissue culture medium.
However, it is preferable to cultivate the cells in an Eagle medium.
(Modified Earle) supplemented with 10% fetal bovine serum (inactivated at 56 ° C) and added with approximately 10 g / I of non-essential amino acids, of 20 1000 U / ml of penicillin and approximately 100 Ng / ml of streptomycin.
The splenocytes of these mice are extracted and fused with a adequate myeloma cell line. However, it is better to use the parental myeloma cell line (SP20) available at ATCC. After merger; the resulting hybridoma cells are 2s selectively maintained in HAT medium then cloned by limiting dilution as described by Wands et al. (Gastroenterology 80: 225-232 (1981)).
The hybridoma cells obtained after such a selection are tested to identify clones secreting antibodies capable of attach to the polypeptide.
~ o On the other hand, other antibodies capable of binding to the polypeptide can be produced in a 2 step procedure WO 00/71710 PCTlFR0010142G

using anti-idiotypic antibodies such a method is based on the fact that the antibodies are antigens themselves and consequence it is possible to obtain an antibody recognizing a other antibody. According to this method, the specific antibodies of the s proteins are used to immunize an animal, preferably a mouse. The splenocytes of this animal are then used to produce hybridoma cells, and these are screened to identify clones that produce an antibody whose ability to bind to specific protein-antibody complex may be blocked by io polypeptide. These antibodies can be used to immunize a animal to induce the formation of more antibodies specific to the protein.
It would be appreciated if Fab and F (ab ') 2 and the other fragments of antibodies of the present invention can be used according to the ~ s methods described here. Such fragments are typically produced by proteolytic cleavage using enzymes such as Papain (for produce the Fab fragments) or Pepsin (to produce the fragments F (ab ') 2). Otherwise, the secret fragments recognizing the protein can be produced by applying recombinant DNA technology zo or synthetic chemistry.
For the in vivo use of antibodies in humans it would be better to use chimeric monoclonal antibodies "humanized". Such antibodies can be produced using genetic constructs derived from hybridoma cells producing the 2s monoclonal antibodies described above. Methods to produce chimeric antibodies are known to those skilled in the art. (For review, see: Morrison, Science 229: 1202 (1985); Oi et al., Biotechnique 4: 214 (1986); Cabilly et al., US patent no. 4,816,567; Taniguchi et al., EP
171496; Morrison et al., EP 173494; Neuberger et al., WO 8601533;
~ o Robinson et al., WO 8702671; Boulianne et al; Nature 312: 643 (1984); Neuberger et al., Nature 314: 268 (1985)).

WO 00/71710 PCTlFR0010142G

EXAMPLE 7 Correction of the Cell Phenotype of the Disease Tanaier Tangier's disease is characterized by catabolism accelerated high density lipoprotein particles (HDL) and a accumulation of cholesterol in the tissues. In particular, fibroblasts of Tangier disease patients have a capacity reduced to eliminate their cholesterol content by the efflux process cholesterol provided by apolipoprotein AI (apoA-I), a major protein HDL (Francis et al., 1995). This characteristic corresponding to loss of function is also found in other cells fibroblastics from patients with familial HDL deficiency (Marcil and is al., 1999).
Correction of the Tangier fibroblast phenotype may be ensured by the transfection of complete cDNAs corresponding to proposed sequences, in said cells. CDNA is inserted into a 2o expression vector which is then transfected according to the methods described below 1. Preparation of fibroblast cultures of normal subjects and subjects with Tangier's disease 25 Primary fibroblasts of human skin are obtained by culture of skin biopsy from the forearm. These biopsies are performed on patients with the disease of Tangier having the clinical and biochemical particularities of "homozygous", that is to say orange tonsils, 3o plasma concentrations of apoA-I and HDL-cholesterol lower than WO 00/71710 PCTlFR0010142G

Fifth percentile. Normal fibroblast lines are obtained from the American Type Culture Collection (Rockville, MD). Fibroblasts are grown in an EMMEM (Eagle-modified minimium essential) environment medium; GIBCO) supplemented with 10% fetal calf serum, s 2 mM glutamine, 100 IU / ml of penicillin and 100 Ng / ml of steptomycin (medium designated by EMMEM10). With a view to carrying out the study of cholesterol efflux, these cells are pre-loaded with cholesterol by 24 hour incubation with 50pg / ml of cholesterol in the medium described above without calf serum but containing 2 ml of albumin to bovine (BSA, fraction V), 2. Study of the cholesterol efflux Fibroblasts preloaded with confluent cholesterol on 24-well plates are incubated in EMMEM10 medium and 1 NCilml of ~ s 1,2 3H-cholesterol (50 Ci / mmol; Dupont; Wilmington, DE) for 48 hours. About 100,000 shots per minute are obtained per well or 1000 shots per minute per Ng of cellular protein. The cells are washed three times with EMMEM / BSA medium, and incubated with this medium for 24 hours before transferring the gene of interest and starting 20 efflux by adding 10 Ng / ml of proteoliposome containing apoA-I in EMMEM / BSA environment. These proteoliposomes are prepared by sonication phosphatidylcholine and purified human apoA-I (Jouas, 1986). The cell transfection is carried out by the precipitation technique of calcium phosphate (Sambrook et al., 1989). After the efflux period, 2s in general 20 hours, the medium is collected, centrifuged (1000 g, 5 min), and radioactivity determined by liquid scintillation counting. The residual radioactivity in cells is also determined at night after extraction of the lipids in isopropanol. Percentage of efflux is calculated by dividing the radioactivity measured in the supernatant by the ~ o sum of the radioactivities measured, in the supernatant and the extract internal control is carried out by transfection of a gene WO 00/71710 PCTlFR0010142G

marker and 24 hour incubation with EMMEM / BSA medium without proteoliposome containing apoA-I. The efflux of cellular cholesterol from normal fibroblasts transfected with a control gene correspond to 6 ~ 2% while that obtained from fibroblasts s with Tangier's disease and transfected with this control gene is less than 1%. In contrast, the transfection of fibroblasts with Tangier disease with a plasmid corresponding to the genes proposed in this case would restore the ability of these cells to eliminate their excess cholesterol to a level corresponding to that of io normal fibroblasts.
EXAMPLE 8 Isolation of the Aenome Clones Corresponding to a polynucleotide Isolation of genomic clones corresponding to a transcript is is carried out by screening the BAC library of human genomic DNA
(for example that provided by Mel Simon, CaITech., ref: Kim et al.
Genomics (1996), 34: 213-218)) by PCR with specific primers of the cDNA sequence corresponding to the sequences of the transcripts SEQ ID N ° 1 to SEQ ID N ° 81 according to the invention, according to the method described 2o in Example 1.
Example 9: Determination of polymorphism / mutation of one of the genes corresponding to the transcripts according to the invention Detection of polymorphisms and or mutations in 2s sequences of transcripts can be performed according to different protocols.
The method of choice is direct sequencing.
In the case of a transcript where the structure of the corresponding gene is unknown or partially known it is necessary to determine precisely its intron-exon structure as well as the genomic sequence o the corresponding gene. It is therefore firstly a question of isolating the or the BAC clones of genomic DNA corresponding to the transcript studied according to the method described in Example 8, to sequence the insert of the corresponding clone (s) and determine the intron structure exon by comparing the sequence of cDNA to that of genomic DNA
got.
The mutation detection technique by direct sequencing consists in comparing the genomic sequences of the corresponding gene with cDNA SEQ ID N ° 1 to SEQ ID N ° 81 obtained from at least individuals (4 individuals affected by the pathology studied and 4 individuals io not affected). Sequence divergences constitute polymorphisms. All those modifying the amino acid sequence of wild protein are mutations that can affect the function of said protein which is worth considering more particularly in the casltemoin association studies described in is Example 8.
Example 10 Identification of the Causal Gene by the Causal Mutation or a transcriptional difference Among the mutations identified according to the method described in ? o Example 9, all those associated with the sick phenotype are likely to be causal. The validation of these results is done in sequencing the gene in all affected individuals and their relatives (whose DNA is available).
On the other hand, the realization of Northern blot nu RT_PrR ~ Am., M
? s method described in Example 1, starting from RNA specific to individuals achieved and not achieved can detect significant variations in level of expression of the gene studied, in particular an absence of gene transcription. .

WO 00/71710 PCTlFR0010142G

TABLE I
BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
SquenceDsignation #

1 corresponding cDNA in GS9002S31 at 2 1 'cDNA corresponding to the GS910331 gene 3 2 cDNA corresponding to the GS910331 gene 4 corresponding cDNAs GS914554 at 1 cDNA corresponding to the GS914739 gene

6 2 cDNA corresponding to gene GS914739

7 corresponding cDNAs GS915574 at

8 corresponding ADNC GS930321 at

9 corresponding cDNA in GS931311 at Corresponding cDNA G5934660 at 11 corresponding cDNAs GS938315 at 12 1 cDNA corresponding to the GS93953 gene 13 2 cDNA corresponding to the GS93953 gene 14 1 "cDNA corresponding to gneGS939874 2 cDNAs corresponding to gneGS939874 16 corresponding cDNAs GS911370 at 17 1 "ADNC corresponding to gneGS913920 18 2 cDNA corresponding to gneGS913920 19 1 cDNA corresponding to gneGS91437 2 cDNAs corresponding to gneGS91437 21 1 ~ 'ADiVc corresponding to the GS91507 gene 2.2 2 corresponding cDNA
to gen GS91507 23 1 'cDNA corresponding to gneGS915231 24 2 corresponding cDNA
at gneGS915231 1 "cDNA corresponding to gene GS915528 26 2 corresponding cDNA
to GS915528 27 1 cDNA corresponding to the GS99817 gene WO 00/717

10 PCTlFR0010142G

TABLE I (continued 1) BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
SquenceDsignation #

28 2 DNA corresponding to savings GS99817 29 gene cDNA
correspondent GS916229 at 30 1 'corresponding to CDNA gene 31 2 DNA corresponding to savings GS92544 32 3 DNA corresponding to saving GS92544 33 the DNA corresponding to GS930284 gene 34 2 DNA corresponding to savings GS930284 35 gene cDNA
correspondent GS93382 at 36 gene cDNA
GS946300 correspondent at 37 1'ADNccor? -Espondantaugne GS937345 38 2 DNA corresponding to savings GS937345 39 3 DNA corresponding to savings GS937345 40 1 ~ DNA corresponding to saving GS99556 41 2 DNA corresponding to savings GS99556 42 1 ~ DNA corresponding to saving GS96663 43 2 DNA corresponding to savings GS96663 44 3 DNA corresponding to savings GS96663 45 4 DNA corresponding to savings GS96663 46 5 DNA corresponding to savings GS96663 47 6 DNA corresponding to savings GS96663 48 1 "DNA corresponding to savings GS941675 49 2 DNA corresponding to savings GS941675 50 3 DNA corresponding to savings GS941675 51 the DNA corresponding to the savings GS929341 52 2 DNA corresponding to savings GS929341 TABLE I (continued 2) BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
SquenceDsignation #
~

53 3 DNA corresponding to gene GS929341 54 1 "cDNA
corresponding at gene 55 2 DNA corresponding to gene GS915742 56 3 DNA corresponding to gene GS915742 57 1 DNA corresponding to gene GS913018 58 2 DNA corresponding to gene GS913018 59 3 DNA corresponding to gene GS913018 60 the DNA corresponding to the GS911742 gene 61 2 DNA corresponding to gene GS911742 62 3 DNA corresponding to gene GS911742 63 1C DNA corresponding to gene GS98601 64 2 DNA corresponding to gene GS98601 65 3 DNA corresponding to gene GS98601 66 DNAs corresponding to gene GS94852 67 2 DNA corresponding to gene GS94852 68 3 DNA corresponding to gene GS94852 69 1C ~ ADNC corresponding to gene GS935135 70 2 DNA corresponding to gene GS935135 71 3 DNA corresponding to gene GS935135 72 1 DNA corresponding to gene GS914669 '' 73 2 ADNC corresponding to gene GS914669 74 3 corresponding DNA GS914669 to gene 75 1 DNA corresponding to gene GS913839 '' 76 2 cDNA
corresponding at gene CDNA
corresponding at gene 78 1 DNA corresponding to gene GS912639 CDNA
corresponding at gene TABLE I (continued 3 BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
SquenceDsignation #

80 3 corresponding to GS912639 CDNA gene co 81 corresponding cDNA gneGS 933630 at 82 SEQID NO2 frequency probe 83 SEQID NO2 frequency probe 84 SEQID NO4 frequency probe 85 SEQID NO5 frequency probe 86 SEQID NO10 frequency probe 87 SEQID NO12 frequency probe 88 Sequence probe SEQID No16 89 SEQID NO16 sequence probe 90 SEQID NO21 frequency probe 91 SEQID NO23 frequency probe 92 SEQID NO25 frequency probe 93 SEQID NO27 frequency probe 94 SEQID NO30 frequency probe 95 Sequence probe SEQID NO33 96 SEQID NO33 frequency probe 97 SEQID NO35 frequency probe 98 SEQID NO40 frequency probe 99 SEQID NO40 sequence probe 100 SEQID NO40 probe 101 SEQID NO60 sequence probe 102 Lead in SEQ
ID
NO

103 Prime in SEQ
ID
NO

104 Prime in SEQ
ID
NO

105 Prime in SEQ
ID
NO

106 Prime in SEQ
ID
NO

TABLE I (continued 4) BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
SquenceDsignation #

107 Start in ID NO 42 SEQ

108 Start in ID NO 43 SEQ

109 Start in ID NO 45 SEQ

110 Start in ID NO 45 SEQ

111 Start in ID NO 57 SEQ

112 Primer in ID NO 57 SEQ

113 Start in ID NO 58 SEQ

114 Start in ID NO 58 SEQ

115 Start in ID NO 66 SEQ

116 Start in ID NO 66 SEQ

117 Primer. In ID NO 67 SEQ

118 Start in ID NO 67 SEQ

119 Start in ID NO 69 SEQ

120 Primer in ID NO 70 SEQ

121 Start in ID NO 72 SEQ

122 Start in ID NO 72 SEQ

123 Start in ID NO 73 SEQ

124 Start in ID NO 73 SEQ

125 Start in ID NO 75 SEQ

126 Start in ID NO 76 SEQ

127 Start in SEQ ID NO

128 Start in SEQ ID NO

129 Polypeptide by the sequence SEQ ID NO
cod 6 130 Polypeptide by the sequence SEQ ID NO
cod 9 131 I Polypeptide by the sequence SEQ ID NO
cod 13 WO 00/71710 PCTlFR0010142G

TABLE I (continued 5) BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
No. of Squence Designation 132 Polypeptidecod by sequence SEQIDNO 15 133 Polypeptidecod by sequence SEQIDNO 16 134 Polypeptidecod by sequence SEQIDNO 18 135 Polypeptidecod by sequence SEQIDNO 19 136 Polypeptidecod by sequence SEQIDNO 20 137 Polypeptidecod by sequence SEQIDNO 21 138 Polypeptidecod by sequence SEQIDNO 22 139 Polypeptidecod by sequence SEQIDNO 23 140 Polypeptidecod by sequence SEQIDNO 24 141 Polypeptidecod by sequence SEQIDNO 25 142 Polypeptidecod by 1 sequence SEQIDNO 26 143 Polypeptidecod by 1 sequence SEQIDN027 144 Polypeptidecod by 1 sequence SEQIDNO 28 145 Polypeptidecod by sequence SEQIDN029 146 Polypeptidecod by sequence SEQIDNO 30 147 Polypeptidecod by sequence SEQIDNO 31 148 Polypeptidecod by sequence SEQIDNO 32 149 Polypeptidecod by sequence SEQIDNO 33 150 Polypeptidecod by sequence SEQIDNO 34 151 Polypeptidecod by sequence SEQIDNO 35 152 Polypeptidecod by sequence SEQIDNO 36 153 Polypeptidecod by sequence SEQIDNO 37 154 Polypeptidecod by sequence SEQIDNO 40 155 Polypeptidecod by sequence SEQIDNO 47 156 Polypeptidecod by sequence SEQIDNO 52_ WO 00/71710 PCTlFR0010142G

TABLE I (continued 6) BRIEF DESCRIPTION OF THE SEQUENCES ACCORDING TO THE INVENTION
No. of Squence Designation 157 Polypeptidecod parla squence.SEQ ID NO

158 Polypeptidecod parla sequence SEQ ID NO

159 Polypeptidecod parla squenceSEQ ID NO

160 IPolypeptidecod by the sequence SEQ ID NO

WO 00/71710 PCTlFR0010142G

REFERENCES:
~ BUSH et al., 1997, J. Chromatogr., 777: 311-328.
s ~ FLOTTE et al., 1992, Am. J. ResPIR: (PIR sequences not redundant, version 57). Cell Mol. Biol., 7: 349-356.
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~ KOCH Y., 1977, Biochem. Biophys. Res. Commun., 74: 488-491.
~ KOHLER G. and MILSTEIN C., 1975, Nature, 256: 495.
~ o ~ KOZBOR et al., 1983, Hybridoma, 2 (1): 7-16.
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~ REIMANN KA, et al. 1997, AIDS Res Hum Retroviruses. 13 (11): 933-943.
is ~ Ausubel et al., 1989, Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, NY
~ Beaucage et al., Tefrahedron Leff 1981, 22: 1859-1862 ~ Brown EL, Belagaje R, Ryan MJ, Khorana HG, Methods Enzymol 1979; 68: 109-151 20 ~ Bush et al., 1997, J. Chromatogr., 777: 311-328.
~ Flotte et al., 1992, Am. J. Respir Cell Mol. Biol., 7: 349-356.
~ Fuller SA et al., 1996, Immunology in Currenf Protocols in Molecular Biology, Ausubel et al.
~ Hames BD and Higgins SJ, 1985, "Nucleic acid hybridization: a 2s practical approach ", Hames and Higgins Ed., IRL Press, Oxford.

WO 00/71710 PCTlFR00lOla2G
lao ~ Higgins et al., 1996, Methods Enzymol. 266: 383-402.
~ Houbenweyl, 1974, in Meuthode der Organischen Chemie, E. Wunsch Ed., Volume 15-I and 15-II, ~ Koch Y., 1977, Biochem. Biophys. Res. Commun., 74: 488-491 ~ Kohler G. and Milstein C., 1975, Nature, 256: 495.
~ Kozbor et al., 1983, Hybridoma, 2 (1): 7-16.
~ Leger OJ, et al., 1997, Hum Antibodies, 8 (1): 3-16 ~ Martineau P, Jones P, Winter G, 1998, J Mol Biol, 280 (1): 117-127 ~
~ McLaughlin BA et al., 1996, Am. J. Hum. Genet., 59: 561-569.
~ o ~ Merrifield RB, 1965a, Nature, 207 (996): 522-523.
~ Merrifield RB., 1965b, Science, 150 (693): 178-185.
~ Narang SA, Hsiung HM, Brousseau R, Mefhods Enzymol 1979; 68: 90-~ Reimann KA, et al., 1997, AIDS Res Hum Retroviruses. 13 (11): 933-is 943 ~ Ridder R, Schmitz R, Legay F, Gram H, 1995, Biotechnology (NY) 13 (3): 255-260 ~ Rust S. et al., Nature Genetics, vol. 20, September 1998, pages 96-98 ~ Samulski et al., 1989, J. Virol., 63: 3822-3828.
20 ~ Sanchez-Pescador R., 1988, J. Clin. Microbiol., 26 (10): 1934-1938 ~
~ Urdea MS, 1988, Nucleic Acids Research, 11: 4937-4957 ~ Urdea MS et al., 1991, NucIeicAcids Symp Ser., 24: 197-200.
~ Chomczynski, P., & Sacchi, N. (1987) Anal Biochem 762, 156-9.
~ DeRisi, J., lyer, V., 8 ~ Brown, P. (1997) Science 278, 680-6.

WO 00/71710 PCTlFR00lOla2G
lal ~ Francis, GA, Knopp, RH, & Oram, JF (1995) Journal of Clinicat Investigation 96, 78-87.
~ lyer, V., Eisen, M., Ross, D., Schuler, G., Moore, T., Lee, J., Trent, J., s ~ Staudt, L., Hudson, JJ, Boguski, M., Lashkari, D., Shalon, D., Botstein, ~, & Brown, P. (1999) Science 283, 83-7.
~ Jonas, A. (1986) Reconsfitufion ôf High Density Lipoprotein, Vol.
128, Academic Press, London.
~ Marcil, M., Yu, L., Krimbou, L., Boucher, B., Oram, J., Cohn, J., &
Genest, JJ (1999) Arterioscler Thromb Vasc Biol 19, 159-69.
~ Remaley, AT, Schumacher, UK, Stonik, JA, Farsi, BD, ts Nazih, H., 8 ~
Brewer, HB (1997) Arteriosclerosis Thrombosis and Vascular Biology 17, 1813-1821.
~ Sambrook, J., Fritsch, EF, & Maniatis, T. (1989) Molecular Cloning, 2o a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
~ F. Ausubel et al. Current Protocols in Molecular Biology, J. Wiley and Sounds Eds, 1999 ~ Fromont-Racine et al. Nucleic Acid Res. 21 (7): 1683-1684 (1993) 2s Current Protocols In Molecular Biology Volume 1 edited by Frederick M.
Ausubel, Roger Brent, Robert E. Kingston, David D. Moore, JG
Seidman, John A. Smith, Kevin Struhl - Massachusetts General Hospital Harvard Medical School, chapter 11 WO 00/71710 PCTlFR00lOla2G
1 to 2 ~ K6hler et al, Nature 256: 495 (1975) ~ K ~ hler et al, Eur. J. Immunol. 6: 511 (1976) K ~ hler et al, Eur. J. Immunol. 6: 292 (1976).
~ Hammeling et al., In: Monoclonal Antibodies and T-Cell Hybridomas, s Elsevier, NY, pp. 563-681 51981) ~ Wands et al. (Gastroenterology 80: 225-232 (1981) ~ Morrison, Science 229: 1202 (1985) ~ Oi et al., Biotechnique 4: 214 (1986) ~ Cabilly et al., US patent n ° 4,816,567 io ~ Taniguchi et al., EP 171496 ~ Morrison et al., EP 173494 ~ Neuberger et al., WO 8601533 ~ Robinson et al., WO 8702671;
~ Boulianne et al; Nature 312: 643 (1984) ~ s ~ Neuberger et al., Nature 314: 268 (1985) LIST OF SEQUENCES
<110> AVENTIS PHARMA SA
<120> Products of expression of genes involved in diseases genetically linked to locus 9q31-34.
<130> Extension FR61610K - AVENTIS
<140>
<141>
<160> 160 <170> PatentIn Ver. 2.1 <210> 1 <211> 552 <212> DNA
<213> Homo sapiens <400> 1 gggtaaatag ttgtgaacat aactattgtg aatactatgt tatatgttat agttgtgaat 60 gtaaatagta ttcacaattg tgaatacaat gtaaatagct ttcacaattg tgaatacaat 120 gtaagtagct atgtaaatag tgaatacaat gtaaatagct atgtaaatag ttgttatgct 180 gattagggaa taatgagaag gaaaaaaagt atacatattc agtacagatg cagtcatctt 240 tttttcccct cgaacatttt tgatccacaa ttggttgaat ccacagatgg ggaacacaca 300 gtcttggtaa atttaaccaa caaggagggt aaacgcatcc caacagggaa ggtaaactgc 360 acatccatca gtacctcttn gaggggcatcat actggtttat aggcttcaat tacagtggac 420 tatnttccag gantaatggg ccttttagtt tttccccnga angnttaant tggnggnttg 480 ccntttgttt ggantgagnt tantcnaacn tattgangta atttttaaag gggntttcat 540 aacagaaggc ct 552 <210> 2 <211> 1246 <212> DNA
<213> Homo sapiens <400> 2 tagtggaatc agtaaggctt ggcagttgac cttgtttgtt ggagagaagg gataagattt 60 taaagctaca tgtctgaaag aatgatgctg ctgattgaaa taaaggaaga aaggatgcat 120 ttcgggctcc aacctgtcct aggaaggcct agacctcaaa caccaacacc tccatgcatt 180 tcctctttgg ctactatgtc ttttccctga cttctgcctc tccagctctc tgggctgctg 240 cttccacctg ttcatctgac ttagaccctc cctgctgggt ccttgttcac ctactcattt 300 ggtgcttcgt ctgccatcag tacctccatt gcagctggtg ggatgtcagt caccatctct 360 tatatttgct tcccactaga aagatcaaga gaagttattt ctttcccttg cgctccaatt 420 tttctctaga cagttggtat ccacaatttt aaaaaatgtt ccatgttgta taaacaagca 480 WO 00/71710 - PCTlFR0010142G
-r ttcgctgaga ggggctgtta atacacatcg tgcccctttt ataaaaattc atgcatggaa 540 tcctacatta ttatgcatca aaatctccag aaatgtctta ggatttttgc agggagaata 600 ttaaatgcat tgttttgctt tgttttgaag agactagatg tgcagaggaa gagaggtggc 660 atggtgggag ggtacatttg agttgtcaac agtctctgca gtgtcaggtc aattacatca 720 gcacttggac tggaccaggg aaaggaatga ttctgcttcc tgggaatgtc agaaggacct 780 gatgattata tttggcaaag ccaggaggag tggctttgaa tgtcattgct aagaattaca 840 ctttgagtag catttctgga tgtctgagct tttcaaatga tacttctttt ctgctgtggc 900 tttcctttct gttggactgg ttcccagagg gtcctcttgt ttgtccttgc cctcgctttt 960 atatcagttc atgttttctc ttctgtcatc ttccttccca gcgctgtttc tccaccccct 1020 cctgctgcac tcacaacagc ttcccctctc ctgtttagag gtggaagcat gtaagaatgc 1080 gtttgagggg gatgcttgcc aaaggacagc atattcaaca tctggtatca acaaggtaat 1140 gtttaacctt agactagcca aactagtgat gacctgcttc catgctgcat ctgctgcttt 1200 ttgtgttgat gggactcaga aatcatgaga aaggtcttca gtgatc 1246 <210> 3 <211> 3035 <212> DNA
<213> Homo sapiens <400> 3 aactgagcaa agattgcctt tgcttcacct attgacacat ttaagaacct.cgttttatag 60 agagtacgga gtggggtctg agattctaca tttcttacaa gttcctggtt tatgccagtt 120 ctgtttgtct ggtcaccaca cttctgaata gcaaggtttc agaggactct atgaagtttt 180 tatttctcaa aaatttggct taggtacatc tttacataca gtggtgctag atattattct 240 ttcagaactt aaccatgcaa caatgcagaa gaatacaaaa aatgcttgca cacagtagtg 300 tattttaatg gaactataaa agcattgaac tgattcctaa ctttacatat aaaggataat 360 taaaccagca gcctaaagca ccttgctcta ctgttaatgg tacttatgag tttataacag 420 tagcttccaa ccttggctat gcattagaaa cagcatttta taaatgatta gtcccactgc 480 gtcccatttc cacaggattc tgattcaatt tacctgggct ggggccttgt cctctatatt 540 tttcagaagc tttacagggg attatgatgc ataattggga ttgagaatna ctgatgtagc 600 attcacaact gtgtctcatt ttattcttaa tcccatgagg ccatgcagaa ggaaggaaat 660 gatgctcaga gaagaaccac ctggtgtcaa gcagatagct agccgaatgg caaagcagaa 720 cctcaatccc agatttcttg actccaaaat atgtagtcca aactgcctgc ccttgtccca 780 ttccttgagc tctatcatga attggtttta tcctgagagt cagatcacat tacagggtac 840 ttgtttcagt gtctccattt gtgagcaagt atatcacaat tcatttcact tttgagcagt 900 ttcttacccg aggtagaaat gcaataacca tttcttggta ggtggtgtag gggatagaca 960 ggtaaatatt aagacacagt tcatcatccc ccaccttggc aaattacgga cacagcccag 1020 tagggagtat aagggttgta cacagctatc atgcgcttga tcagtgcatg tcttcaaagt 1080 gcacttgtac ctcagcagag agctaagaag catgaaggaa gtcttcatgg aggagatggc 1140 actggagcta agtcttcaga gtcggcattt tggcaggtgg agattgggaa accagaggaa 1200 cttcactaga tgcaaggtcc tgttgaagat tcaaggtaat gagacacata attgagaggg 1260 agtgacagca tggggaattt ctgagtttgg gcagtaatgt gatcagaact gtactccagg 1320 aagaagagta gaagaaagaa ctgagtggag agaagactgg agtaggggat acgtaggagg 1380 gtttgtccct ggttaggatg agatgatagc aggacccaga agaggttgca gtaaaaccaa 1440 gagagacagc cgggtgcggt ggctcacgcc tgtaatccca gcacattggg aggccaaggc 1500 gggtggatca cctgaggtca ggagttcgcg agcagcctgg ccaacatggt gaaaccccgt 1560 ctatactaaa aatacaaaaa gatagccaga cgtggtggca ggcgcctgta atcctagcta 1620 WO 00/71710 PCTlFR0010142G

cttgggaggc tgaggcaaga gaattgcttg aacccaggag gtggacgttg tagtgagcca 1680 agatcacacc attgcactcc agcctgggta acaagagtga aactccgtct ccaaacaaac 1740 aaacaaacaa acaaacccac gagggagatc agtgtgaagg gcattgccaa agtggaatca 1800 gtaaggcttg gcagttgacc ttgtttgttg gagagaaggg ataagatttt aaagctacat 1860 gtctgaaaga atgatgctgc tgattgaaat aaaggaagaa aggatgcatt tcgggctcca 1920 acctgtccta ggaaggccta gacctcaaac accaacacct ccatgcattt cctctttggc 1980 tactatgtct tttccctgac ttctgcctct ccagctctct gggctgctgc ttccacctgt 2040 tcatctgact tagaccctcc ctgctgggtc cttgttcacc tactcatttg gtgcttcgtc 2100 tgccatcagt acctccattg cagctggtgg gatgtcagtc accatctctt atatttgctt 2160 cccactagaa agatcaagag aagttatttc tttcccttgc gctccaattt ttctctagac 2220 agttggtatc cacaatttta aaaaatgttc catgttgtat aaacaagcat tcgctgagag 2280 gggctgttaa tacacatcgt gcccctttta taaaaattca tgcatggaat cctacattat 2340 tatgcatcaa aatctccaga aatgtcttag gatttttgca gggagaatat taaatgcatt 2400 gttttgcttt gttttgaaga gactagatgt gcagaggaag agaggtggca tggtgggagg 2460 gtacatttga gttgtcaaca gtctctgcag tgtcaggtca attacatcag cacttggact 2520 ggaccaggga aaggaatgat tctgcttcct gggaatgtca gaaggacctg atgattatat 2580 ttggcaaagc caggaggagt ggctttgaat gtcattgcta agaattacac tttgagtagc 2640 atttctggat gtctgagctt ttcaaatgat acttcttttc tgctgtggct ttcctttctg 2700 ttggactggt tcccagaggg tcctcttgtt tgtccttgcc ctcgctttta tatcagttca 2760 tgttttctct tctgtcatct tccttcccag cgctgtttct ccaccccctc ctgctgcact 2820 cacaacagct tcccctctcc tgtttagagg tggaagcatg taagaatgcg tttgaggggg 2880 atgcttgcca aaggacagca tattcaacat ctggtatcaa caaggtaatg .tttaacctta 2940 gactagccaa actagtgatg acctgcttcc atgctgcatc tgctgctttt tgtgttgatg 3000 ggactcagaa atcatgagaa aggtcttcag tgatc 3035 <210> 4 <211> 1479 <212> DNA
<213> Homo sapiens <400> 4 gtctgcagaa ttcgcccttg ctgccaccta tgtaccagct attccagatg accaagccct 60 gctagaataa agactgactt ttcattgtga cctctgaagg atgtgcagct cagctttcac 120 ctatccccac gttcacccaa gccaaaaaga agaattgttc attcaaactg gaaatgatct 180 ccagcttgga aatgagactc ctcatgagct tattctaaga tcagagtctg aaaattattt 240 tctcaaaagt tacaaataaa tgtcttttaa cagtactgtc agactagtga ccaacaagtt 300 actttatgag gatggatgat gatattagag ttcaagcaat tgtccagttt gtttcgatgc 360 cacagtttgc ttttaaattc ccatagtgag cttccatctt gagacccact caacacagaa 420 ggattacata aaggttgatc acccacgctc tacagatgaa caaattgaga cccagagatg 480 ctaaactgct ctgcaggtca caaacctgaa cagcagcata gccaaaatgg gaacg-gagct 540 cttctgactt caagcccctg cacttttttc ttaaccacat taattttatg aatatctatg 600 tggtcaaagt ctcttttgta aaatctgagt ataagctgaa ctagatcatg tctctgtaag 660 ctaagatggc agaaacacat tgtcatgtta gtttggagga gcaaacagat ataagtatgt 720 gttgtaatgt tatagtgagc tgttatgtat cccccagcaa tgtccaaagt gatcagagct 780 actagatgac ttattacaat gttcagatcc cactccttca ttcctcctct ctcagtgacc 840 tgtctacccc caagctttag aactgagctc tctccaactt agaactcatt agagtttgtt 900 gcattagtga ttggatctcc tcatgaaagt tttttgacca atgacagtag agccccttta 960 WO 00/71710 PCTlFR0010142G

agctagccag gcccaagata gggaagcact gctggtttac atttctgctc tttctaattc 1020 agttgtctat tgcatgcaga catcccctgc ccgacttctc cattatggaa ggctaaggcc 1080 atccttcctt gtccagtttc tctacctaca cactaacatg ccttttcccc atggagtgaa 1140 ctctgccagt tgtctttgga cattttctgc agatgcaggc tcagttctgc tcttttgttc 1200 ccacccactt ctagatcttc ctccatttaa tcccttattc ttataaggag tctaattttt 1260 gtgtattgtc cttgâttâgg gcagctgaca gctttacacc aaagctgaag tctctcactt 1320 aatcctaagc aaggggctag ggagaactaa gatatccttc ccatatcaag ggatataggt 1380 tactagaagg gtggaggtct cttaacaggc tcactcacct ttcagagttt aaattatggt 1440 caggcttaag aagctctctc ttgtgactga gtgtattgc 1479 <210> 5 <211> 5169 <212> DNA
<213> Homo sapiens <400> 5 cagttctttt cattccatca ctttaggtga tgggtaagat ttttgaaagc cttatatttt 60 ttgattttgt tgtctagttt aatcctacct ttaatagttg tgtttggtaa aattcccact 120 tgaatgtgac actgataata attatgctga tttttagcat ctcttatagg aatcaaagtt 180 tattaaagtt acatagagga ttgaaaaatg tatatcactc aatttttatc taagaaggat 240 aggttataaa gggaggtacc taaatactca aataatgtat atattctttt.tcataacata 300 tggaatgctt taagcaattg ttttgaaaaa aatctgcgta tctttgactt aattggcaca 360 tgactttttc aagcagccat tcattcagag gtttgttttc tctcagtcct tttgctacat 420 tcactttctt ttcaaagaaa tgttaattat tacaaaaatt gacatagata tctttcccaa 480 acttggggta aaacccatgg ttatgtggaa cataactgtt cttaaaaagt caattataat 540 ttgtaactca catcctttga gctaaactaa attaaaatta cagtatttaa taattctttg 600 ggcattttta agaggtctga atttgtattt ttcttcattt ttgaaacttt acatttgttg 660 actttttttc attctcattt aaaatatatt gtgctatgat aaccaacctt cttccaagga 720 gtgaccatta ctgcctacat ttgcgttgct ttctacatag agacttgtat aatagtatta 780 atagtagctc attctctcta aaaatttact gcccactgag aggatgtttt gtttccttga 840 taaaacaaat gtaaatgagg aattttattt gaattggaat attgtttttc tagaggacat 900 tcatatctgc actattatct gatgacatgt tggtaatttt aaagactgca aggcagttta 960 gagaatgaag taaaccaata gatactcttt tgattctcca aagaaatata attttggttt 1020 ttgttcctca gagagagttt gaaagaaatt ttcagatgtt ctgttcccta tagagggcct 1080 attccaggat ctaaatgaat gggaatttat aattcctttc atagactcaa acctgaaagc 1140 agaaattttt agtagttgag ttgctttaag tgaattttaa caaatatgac acagaaaagg 1200 tcagatgctg ttgtataaaa ttttttacta gtgtgtctta tataattctt tcttctcatt 1260 aattcagtgc ctttttcctc taagcatact cttggtccat gccccatgca gtgtcaactg 1320 atgtttaagc tacagagcat tgttgtagtg gtgagggccc tctgttgcag gggcatgggg 1380 aaatgcatat attaatcagg ggctggagga gtatacatga ttcttgtgtt catgttgtca 1440 tttgaaactc ttcacataaa attttctaat attcatttgg aaaacctctc cactggagag 1500 gtttcatctc tgagaggttt tgtaataata gtgtaagttc agtaaatcca gtccaaattc 1560 tcatcacatg tattatttga tactaaattt tcaattatta cttcaaaata agagtctgag 1620 gatttcttct tactggcgtt cttaaaggtc tctaaaatta aagaacaaga tgtggttttt 1680 tgtttaagac gtttttagtt tatttgttgt taagttaaac tggagaaagt ttgtcatcct 1740 cattttcaaa ctgaaaacta atcaaatata gtgcctattt agtctcaaaa taaggtaact 1800 attaacttga ttatactata taatattctc aattacattt gaatttaaaa atattgagct 1860 WO 00/71710 PCTlFR0010142G
cttgattaca atttaataca ttgtaaaaag tattaaatcc tttgaaacat cttttgttgc 1920 ttatttagtt tttgtttcta caggtcaaac atgattgctt tctataaaag aaatgcttga 1980 gaggttgact ataatggata tgtcacaggt ataaaacagt tgttttctaa aaacatgcat 2040 ttagtatggc attctctttt agcaactgaa ttcccaacga gttttattaa gctggatatc 2100 gaaatgaagg agctgcctta agcactttag aaaaagaatt tttttacaat tcattttgac 2160 tctcatggct gaccatgtca ttatgtcttt aaattttggt aaatatgtag ataccaagca 2220 ttaataacta atgcacacag aaatttaata tacagcaatt ctttgaatgt tccaggtgta 2280 cgtaaactaa ctgaaagtat taaggacatg cctgtctata catgggtttc attgatggta 2340 tctgtatcat cttgacaaat cgtgaactgc tgctgtatgg ctagactttg cctatttact 2400 ctgttatgca aacagtaatt tttccctatg ttatgaagag agacatattg gcttgcttta 2460 atttacttat ttatgaaatt aaagcatgaa taatatgtat aatttgaatt ttttgtgact 2520 gatccttggc agtataaatg ataaaagtaa atgtaatgga atcttttaat taggctaaga 2580 tatgctattt cataacttat gtagaatgat ttttatctat atactttgtc cataaaatta 2640 taattgttta tgtaatttta ttgtttctta tggaaacaat tggaaaagta tatggaaaat 2700 gattatttca aagaatattt atttaaagag ggaagtgtag acttcttact gtaaaatatg 2760 tgattccagg cttaagaaat tgattatatt ttaaaataat tattttttta aaaacgtaat 2820 ttgtttttaa aagatgagtc tccattcatt ggctaatcca tacagcaaat atttgagtgt 2880 ttgtgatatg gcagtaaaaa tgtgattact ttgtatatac attaaccaaa accagtgaag 2940 tttgatggac tgtgcataga gttttgcagc ttttgagtag tgtgacagag tttgcctctt 3000 aaaattgttt tgctaataag tcagaagttt aaaatgtgtt atagtttgct aaaaaaaaat 3060 caaattaact gcatataaaa tggttcactt ttatatagtc acatgtaatg ggcctgaaaa 3120 agtttcttct ttgattatgt agttactcta gatacattct tttagggaag tgtatggtca 3180 acatatattt actcagtata cagataacca caaagttgtt atttttaacc aaaatataca 3240 tttcataatg ttggcactgg agtattataa gagatcatga atgtttcctt aattatcatg 3300 gcaagattac ctcacgttca gtatagttta gttttgtgtg tatcttacag tatgcatgtt 3360 ctgaaattat ttgtgatcct gatatgtcac atataatagc tttgttacct ggagtatttg 3420 attaacctaa acagtttaag cattttgaat tagttggagt ttaaatggat tacatttggt 3480 gtatattgtc ttcattgaaa agatattgtt ggatatgcca catcagagtt agcattgact 3540 tataaataaa taccagaatt taccagagta cacttttctc ttcagatgac tcaattatta 3600 aataaaagaa tatttcttat ttctgggtca atataaggta ctgacttctg atgcataatc 3660 acttaagcta tgtgagttta aactggtatc ttttcttagt ggtacccatt caatgtaagc 3720 tggtccatgg gaatggacat gaagaggatt tcacagtatg tagagcagaa ggcacgtgaa 3780 tgtgtttgct ttggcttgga gcttattaag ttttgactac ggttaaaata agtcaaatag 3840 taagtggtaa aacacatttt tgttagtatt ggaactttct ggagaacata agggctatga 3900 gaatgcatat atatattttt taacatttcc tatatatcta aggtaccaaa gcactgagtc 3960 taatttacct attaagggag actctttaaa atcaacttta taactaattc atactataag 4020 acagataata gctaaagttt tggaataatt tatattaaaa gccgcaagtc ttaaaaatcc 4080 ctggatatga cataaaaagg attttggctt cttttttgaa gtatttaaaa ttaatcacct 4140 tagctctacc atatactaga tctgtgaccg ctacacaaat tgtttatcat ctttgggtct 4200 ctattgcctt ctttataaaa taagtgtaag ttgttcagcc tgcctcacag ggctgttgtg 4260 aggaaataaa atgaaatgga gtatgtgaaa ttgcttcagc aacagcaaag tgctacgtaa 4320 atgtaaagtg ttgtttttag ctaataatgg atttaagtgt ttggataatt gtagatgcat 4380 ttactttgat aaagcgtgtg cttaaagtgg tatcaccagt gatttctaac atgattttaa 4440 aaaaataaaa ccccaattaa aatgttcttt aatattcatt taatttgtgc atgacttgtg 4500 gcctttttgt attttctcaa gcctattact ctagagctgt aaaagctctt gcacagcatt 4560 gttgtgtcag tgtagaatag tggcataaat aaatgaatta agctacattt ccatgcaggc 4620 atttgcactt tgaagttagg gctgcccagt gccacatgca aagagtgtat ttggtctaaa 4680 cagttctttc caaacaacca aatggctggg cagcttgttg tcacggataa atgatataaa 4740 WO 00/71710 PCTlFR0010142G
G
atgtaaccac tgaacatttg acaactttgt tgcattatca tttttaaaaa aagatgaagc 4800 atttcaaaat cttgttaacc tggttatctc ttggtatctc tcctgacata tttgttttgc 4860 tttaaattgg attaaatggt ttacaggtta tctgaatcta cagatttagt atgtctatta 4920 tctggacatg attttgctat gcagttgtga taataaaaat tctaattcct caggtttggc 4980 cttttaagtt atggctgaag acctttaatg atacttatga tgcactcagt gccatacaat 5040 agtgttttaa gaagcacatg gcctcatttt ccttagaaac aagacaaagc ctttttaaaa 5100 tgtttttttt tcactttaaa atagggtatt caaagtggag taacgtgtat tttgaaatga 5160 ttttgtgtt <210> 6 <211> 7723 <212> DNA
<213> Homo sapiens <400> 6 gtggggccgg gcggtgccgg tgcgggctgg ggcagtgcag tgagtagcgg tcttggggtg 60 tgcgatctcg ctgagcctcc tcacacggtt cgtcgtctcg ggttcgagcc cagtgggctt 120 agccactcgc catggactcc cagaaatact gctttaagga gaatgaaaac gttacagttg 180 ataaagcctg ttttctgatc tctaacatca ctattggacc agagtctatt aacttgcagc 240 aggaagctct acagaggatc atttcaactc tggcaaataa aaatgatgaa attcagaact 300 ttattgatac actacatcat acactaaaag gagttcagga aaattcgtcc .aacatactct 360 cagagttaga tgaagaattt gatagtttat actctatact ggatgaagta aaagaaagta 420 tgattaactg tatcaagcag gaacaagctc gtaaatccca agagttacag agtcagatta 480 gtcaatgtaa taatgccctg gagaactctg aagaactatt agaatttgca acaaggtcat 540 tagatataaa ggaacctgaa gaattttcaa aggctgccag acagatcaag gatagagtca 600 caatggcttc agcctttcgc ctttctttga aaccaaaggt cagtgacaac atgactcatt 660 taatggtgga tttctcacag gaaagacaga tgctgcaaac tttgaagttt ttgccagtcc 720 ccaaagctcc agagatagat ccagtagagt gtttggtggc agataactct gtaacagtgg 780 cttggagaat gccagaagaa gataataaga ttgaccattt tatactggaa cataggaaga 840 ctaattttga tggacttcca cgtgtaaagg atgagcgatg ctgggagata attgataata 900 ttaagggtac tgaatataca ctatcaggct taaaatttga ttcaaagtat atgaatttca 960 gagtgcgagc ttgtaacaag gctgtggctg gagagtattc tgatccagtg actctagaga 1020 ccaaagcact taacttcaat ttggataact cctcatccca tttgaacctg aaagttgaag 1080 atacatgtgt agagtgggat cctactggag gaaaaggtca agaaagtaaa attaaaggaa 1140 aagagaacaa gggcagtgtc catgttactt cactgaagaa acatacaaga agtggtacac 1200 catccccaaa acgaacatct gtaggctcca ggccaccagc agtaagaggc agtagagatc 1260 gttttactgg agaatcatac acagtgctgg gagacactgc tattgaaagt ggacaacatt 1320 attgggaggt caaggcccag aaggattgta aatcctacag tgtgggagta gcatacaaaa 1380 cgttggggaa atttgaccaa ttgggaaaga caaacactag ttggtgtatc catgtcaaca 1440 actggctaca aaacacattt gcagcaaagc ataataataa agtcaaagct ttggatgtta 1500 ctgttctgaa aaaataggtg tattttgtga ttttgatggg ggtcaacttt cattctatga 1560 tgcaaattct aaacagttgc tatattcctt taagacaaaa tttactcagc cagtactacc 1620 tggtttcatg gtatggtgtg gtggactttc tttgagtact gggatgcagg ttccaagtgc 1680 tgtgagaaca cttcagaaaa gtgaaaatgg aatgactggt tcagctagca gcctgaacaa 1740 tgttgttact caatagtgtc tactcagaat acgtttaccc tccgtcttga ttaggtggcc 1800 ttttctgtgc agttactaat cacaggaatt tggtagtagt gaaaatcagg tttgctgtgt 1860 tctgctttga ggcctggaat cttttatcat taaacaccta gtacgaagca tttgcaggaa 1920 WO 00/71710 PCTlFR0010142G

cctactgtgc agtatcatag aggcaagcag ataccaagca aaaaactgat gattgaagag 1980 taaatggggg aaaaggcagt gtttaattaa cataaaaact catttttgta tttcttggat 2040 tactttgact attctaatgt ttaattacat atggtaaccc taaggcctgg ggagaaaagc 2100 ttttaaatct tgccttcttt cttctgtact ttgtcttttt aaaatctcat tactatctat 2160 tatttagttc taacacagaa gctttaaaaa tacatagtca tccaaggttt tctaaaaatt 2220 gaaatcatat gttgggaatg gtaaaaaggt tttcaaatgg tttatttttc ctcttttata 2280 aataagtttt acaaaatttt cctcttttgt ttattgacta gattgtatat aattttcttt 2340 tttccaaaat attgtgataa gaaatttcta gacacaacag cttaaaatca cccaaatttc 2400 agttctttac ctaactgcac taacaatggc aaggggggta ttctttatat gttgccttgt 2460 ttaactacag ttcttttcat tccatcactt taggtgatgg gtaagatttt tgaaagcctt 2520 atattttttg attttgttgt ctagtttaat cctaccttta atagttgtgt ttggtaaaat 2580 tcccacttga atgtgacact gataataatt atgctgattt ttagcatctc ttataggaat 2640 caaagtttat taaagttaca tagaggattg aaaaatgtat atcactcaat ttttatctaa 2700 gaaggatagg ttataaaggg aggtacctaa atactcaaat aatgtatata ttctttttca 2760 taacatatgg aatgctttaa gcaattgttt tgaaaaaaat ctgcgtatct ttgacttaat 2820 tggcacatga ctttttcaag cagccattca ttcagaggtt tgttttctct cagtcctttt 2880 gctacattca ctttcttttc aaagaaatgt taattattac aaaaattgac atagatatct 2940 ttcccaaact tggggtaaaa cccatggtta tgtggaacat aactgttctt aaaaagtcaa 3000 ttataatttg taactcacat cctttgagct aaactaaatt aaaattacag tatttaataa 3060 ttctttgggc atttttaaga ggtctgaatt tgtatttttc ttcatttttg aaactttaca 3120 tttgttgact ttttttcatt ctcatttaaa atatattgtg ctatgataac caaccttctt 3180 ccaaggagtg accattactg cctacatttg cgttgctttc tacatagaga cttgtataat 3240 agtattaata gtagctcatt ctctctaaaa atttactgcc cactgagagg atgttttgtt 3300 tccttgataa aacaaatgta aatgaggaat tttatttgaa ttggaatatt gtttttctag 3360 aggacattca tatctgcact attatctgat gacatgttgg taattttaaa gactgcaagg 3420 cagtttagag aatgaagtaa accaatagat actcttttga ttctccaaag aaatataatt 3480 ttggtttttg ttcctcagag agagtttgaa agaaattttc agatgttctg ttccctatag 3540 agggcctatt ccaggatcta aatgaatggg aatttataat tcctttcata gactcaaacc 3600 tgaaagcaga aatttttagt agttgagttg ctttaagtga attttaacaa atatgacaca 3660 gaaaaggtca gatgctgttg tataaaattt tttactagtg tgtcttatat aattctttct 3720 tctcattaat tcagtgcctt tttcctctaa gcatactctt ggtccatgcc ccatgcagtg 3780 tcaactgatg tttaagctac agagcattgt tgtagtggtg agggccctct gttgcagggg 3840 catggggaaa tgcatatatt aatcaggggc tggaggagta tacatgattc ttgtgttcat 3900 gttgtcattt gaaactcttc acataaaatt ttctaatatt catttggaaa acctctccac 3960 tggagaggtt tcatctctga gaggttttgt aataatagtg taagttcagt aaatccagtc 4020 caaattctca tcacatgtat tatttgatac taaattttca attattactt caaaataaga 4080 gtctgaggat ttcttcttac tggcgttctt aaaggtctct aaaattaaag aacaagatgt 4140 ggttttttgt ttaagacgtt tttagtttat ttgttgttaa gttaaactgg agaaagtttg 4200 tcatcctcat tttcaaactg aaaactaatc aaatatagtg cctatttagt ctcaaaataa 4260 ggtaactatt aacttgatta tactatataa tattctcaat tacatttgaa tttaaaaata 4320 ttgagctctt gattacaatt taatacattg taaaaagtat taaatccttt gaaacatctt 4380 ttgttgctta tttagttttt gtttctacag gtcaaacatg attgctttct ataaaagaaa 4440 tgcttgagag gttgactata atggatatgt cacaggtata aaacagttgt tttctaaaaa 4500 catgcattta gtatggcatt ctcttttagc aactgaattc ccaacgagtt ttattaagct 4560 ggatatcgaa atgaaggagc tgccttaagc actttagaaa aagaattttt ttacaattca 4620 ttttgactct catggctgac catgtcatta tgtctttaaa ttttggtaaa tatgtagata 4680 ccaagcatta ataactaatg cacacagaaa tttaatatac agcaattctt tgaatgttcc 4740 aggtgtacgt aaactaactg aaagtattaa ggacatgcct gtctatacat gggtttcatt 4800 WO 00/71710 PCTlFR0010142G
s gatggtatct gtatcatctt gacaaatcgt gaactgctgc tgtatggcta gactttgcct 4860 atttactctg ttatgcaaac agtaattttt ccctatgtta tgaagagaga catattggct 4920 tgctttaatt tacttattta tgaaattaaa gcatgaataa tatgtataat ttgaattttt 4980 tgtgactgat ccttggcagt ataaatgata aaagtaaatg taatggaatc ttttaattag 5040 gctaagatat gctatttcat aacttatgta gaatgatttt tatctatata ctttgtccat 5100 aaaattataa ttgtttatgt aattttattg tttcttatgg aaacaattgg aaaagtatat 516b ggaaaatgat tatttcaaag aatatttatt taaagaggga agtgtagact tcttactgta 5220 aaatatgtga ttccaggctt aagaaattga ttatatttta aaataattat ttttttaaaa 5280 acgtaatttg tttttaaaag atgagtctcc attcattggc taatccatac agcaaatatt 5340 tgagtgtttg tgatatggca gtaaaaatgt gattactttg tatgtacatt aaccaaaacc 5400 agtgaagttt gatggactgt gcatagagtt ttgcagcttt tgagtagtgt gacagagttt 5460 gcctcttaaa attgttttgc taataagtca gaagtttaaa atgtgttata gtttgctaaa 5520 aaaaaatcaa attaactgca tataaaatgg ttcactttta tatagtcaca tgtaatgggc 5580 ctgaaaaagt ttcttctttg attatgtagt tactctagat acattctttt agggaagtgt 5640 atggtcaaca tatatttact cagtatacag ataaccacaa agttgttatt tttaaccaaa 5700 atatacattt cataatgttg gcactggagt attataagag atcatgaatg tttccttaat 5760 tatcatggca agattacctc acgttcagta tagtttagtt ttgtgtgtat cttacagtat 5820 gcatgttctg aaattatttg tgatcctgat atgtcacata taatagcttt gttacctgga 5880 gtatttgatt aacctaaaca gtttaagcat tttgaattag ttggagttta aatggattac 594'0 atttggtgta tattgtcttc attgaaaaga tattgttgga tatgccacat cagagttagc 600D
attgacttat aaataaatac cagaatttac cagagtacac ttttctcttc agatgactca 6060 attattaaat aaaagaatat ttcttatttc tgggtcaata taaggtactg acttctgatg 6120 cataatcact.taagctatgt gagtttaaac tggtatcttt tcttâgtggt acccattcaa 6180 tgtaagctgg tccatgggaa tggacatgaa gaggatttca cagtatgtag agcagaaggc 6240 acgtgaatgt gtttgctttg gcttggagct tattaagttt tgactacggt taaaataagt 6300 caaatagtaa gtggtaaaac acatttttgt tagtattgga actttctgga gaacataagg 6360 gctatgagaa tgcatatata tattttttaa catttcctat atatctaagg taccaaagca 6420 ctgagtctaa tttacctatt aagggagact ctttaaaatc aactttataa ctaattcata 6480 ctataagaca gataatagct aaagttttgg aataatttat attaaaagcc gcaagtctta 6540 aaaatccctg gatatgacat aaaaaggatt ttggcttctt ttttgaagta tttaaaatta 6600 atcaccttag ctctaccata tactagatct gtgaccgcta cacaaattgt ttatcatctt 6660 tgggtctcta ttgccttctt tataaaataa gtgtaagttg ttcagcctgc ctcacagggc 6720 tgttgtgagg aaataaaatg aaatggagta tgtgaaattg cttcagcaac agcaaagtgc 6780 tacgtaaatg taaagtgttg tttttagcta ataatggatt taagtgtttg gataattgta 6840 gatgcattta ctttgataaa gcgtgtgctt aaagtggtat caccagtgat ttctaacatg 6900 attttaaaaa aataaaaccc caattaaaat gttctttaat attcatttaa tttgtgcatg 6960 acttgtggcc tttttgtatt ttctcaagcc tattactcta gagctgtaaa agctcttgca 7020 cagcattgtt gtgtcagtgt agaatagtgg cataaataaa tgaattaagc tacatttcca 7080 tgcaggcatt tgcactttga agttagggct gcccagtgcc acatgcaaag agtgtatttg 7140 gtctaaacag ttctttccaa acaaccaaat ggctgggcag cttgttgtca cggataaatg 7200 atataaaatg taaccactga acatttgaca actttgttgc attatcattt ttaaaaaaag 7260 atgaagcatt tcaaaatctt gttaacctgg ttatctcttg gtatctctcc tgacatattt 7320 gttttgcttt aaattggatt aaatggttta caggttatct gaatctacag atttagtatg 7380 tctattatct ggacatgatt ttgctatgca gttgtgataa taaaaattct aattcctcag 7440 gtttggcctt ttaagttatg gctgaagacc tttaatgata cttatgatgc actcagtgcc 7500 atacaatagt gttttaagaa gcacatggcc tcattttcct tagaaacaag acaaagcctt 7560 tttaaaatgt ttttttttca ctttaaaata gggtattcaa agtggagtaa cgtgtatttt 7620 gaaatgattt tgtgttctat atagaatgtc ccagttaaga ttttacagaa gcacctggaa 7680 WO 00/71710 PCTlFR0010142G

tatctcatta aaaatttaaa aactcttaaa aaaaaaaaaa aaa 7723 <210> 7 <211> 1046 <212> DNA -<213> Homo sapiens <400> 7 ccttcagtgc tcagaggagc agacacagtt gctcactctc cactcaaagt tggtccaggc 60 cttgtgctaa ttaaaggagg aagcactgct gtagcgcaga aggaaaaggc cagtcctcca 120 cctgttcagc atgataatgc agctcccctg tggtaagggt tggtcggact acaatatctt 180 tgtgactttg atgaaagcat ctgcagttat aatgtggcaa agaaaaggat aattccagaa 240 tttcccattt ccatcatttg agcttgaaat atctgaatag atatttacaa aaccttgtga 300 agaagtcacc ttatttctca tgtttctaat gaacatatat aaacttctca tttccagctc 360 taggataagc aaacagcaaa aaattaccaa tgaaaagtta ggagttcaaa agaagtagtc 420 tgaactagat agattagatg tcatcctgtg aaataggttt accacatgat agggaagaac 48D
tttcaaacag tacagggtct attttcagtt attcactatg aaatgagaac atttcacagt 540 tgttaaaggt tgctttcaga agaaaagccc aactgatgaa tgtttttaaa aatgcactat 600 tgagagcgaa caacagactg gatgccataa ttttatagtc aagtttggga caagttttaa 660 gaaactgtgt tacaattcag agaaaagaca gttggtgagc atattaagag atatagggaa 72D
cagatttaga tgatccaata tgcttattat cagaattcca gaaaaaggca, tgaaatcata 780 aagaagacag aataccaggc aaaattaatg aaaaaatatt aatccaaaca catataataa 840 aaagtatcaa tttcaagaat aaaagaatta tataagcatt taacacacat aaacattggt 9D0 tacctgtaaa aggtgaaaaa aaaaaacagg ttcagatttt ctgcttaaat atcaaagggc 960 aaatggaaca tttttacgat cacctaaaat tcttgaaata ggccaagatt tttcatatac 1020 aaaggcaaca gccttcttgc cocoa 1046 <210> 8 <211> 280 <212> DNA
<213> Homo sapiens <400> 8 gggagaggag gcagaggcca gatcctgaaa aactcttcag tggtggactg aggtgcctgg 60 acttcagagg cgacaggagg gtagtgaggt ttctggagca ggctggtcaa agtcagcagc 120 acccttgttt gatatccatc ccattccctc accccacatc tacctgggac ttgcttctct 180 gaccctcctg ctgtggcaag atcctgattg tcccaggtgc acatggctct acttcctgac 240 tgctcatcct cacgcagtcc tcagccctct atgacccccc 2gD
<210> 9 <211> 479 <212> DNA
<213> Homo sapiens <400> 9 WO 00/71710 PCTlFR0010142G
aaatcaagaa catcattctc tcggtatctt tatggagcaa aatgtttatg gtagagacag 60 gtgaccttgc agctagccta accacattct ccaagtgtta attagatggt gcaatattca 120 catagaccta gagtccactg actatgaaag gctctgacct ttttgcggct tctttaccag 180 gagtgtataa tcttcctagt tcctaaatct ttctaagaga acctgactac ctccaggtct 240 agagggagca gccccttcac tatataacca atttccctga ctgcacatat ggtaattcca 300 tctatggtga ataatgaatc cattctaggc caaatagata ctcttatgca gagcccagct 360 gggacagtca cgtgcaagga gaaaagagaa agccagactg cagacatagc taatgcaaag 420 gcacggagat acagactaca caaactagaa gaaacgtaga gtaagctgct ttgtctctt 479 <210> 10 <211> 2599 <212> DNA
<213> Homo sapiens <400> 10 gaaatccagg ggaccaatgc attttatcac taaaactatt tttatataat tttaagaata 60 taccaaaagt tgtctgattt aaagttgtaa tacatgattt ctcactttca tgtaaggtta 120 tccacttttg ctgaagatat tttttattga atcaaagatt gagttacaat tatacttttc 180 ttacctaagt ggataaaatg tacttttgat gaatcaggga atttttttaa agttggagtt 240 tagttctaaa ttgactttac gtattactgc agttaattcc ttttttggct agggatggtt 300 tgataaacca caattggctg atattgaaaa tgaaagaaac ttaaaaggtg ggatggatca 360 tgattactgt cgataactgc agataaattt gattagagta ataattttgt catttaaaaa 420 cacagttgtt tatactgccc atcctaggat gctcaccttc caagattcaa cgtggctaaa 480 acatcttctg gtaaattgtg cgtccatatt cattttgtca gtagccagga gaaatgggga 540 tgggggaaat acgacttagt gaggcataga catccctggt ccatcctttc tgtctccagc 600 tgtttcttgg aacctgctct cctgcttgct ggtccctgac gcagagaccg ttgcctcccc 660 cacagccgtt tgactgaagg ctgctctgga gacctagagt aaaacggctg atggaagttg 720 tgggacccac ttccatttcc ttcagtcatt agaggtggaa gggaggggtc tccaagtttg 780 gagattgagc agatgaggct tgggatgccc ctgctttgac ttcagccatg gatgaggagt 840 gggatggcag caaggtggct cctgtggcag tggagttgtg ccagaaacag tggccagttg 900 tatcgcctat aagacagggt aaggtctgaa gagctgagcc tgtaattctg ctgtaataat 960 gatagtgctc aagaagtgcc ttgagttggt gtacagtgcc atggccatca agaatcccag 1020 atttcaggtt ttattacaaa atgtaagtgg tcacttggcg attttgtagt acatgcatga 1080 gttacctttt ttctctatgt ctgagaactg tcagattaaa acaagatggc aaagagatcg 1140 ttagagtgca caacaaaatc actatcccat tagacacatc atcaaaagct tatttttatt 1200 cttgcactgg aagaatcgta agtcaactgt ttcttgacca tggcagtgtt ctggctccaa 1260 atggtagtga ttccaaataa tggttctgtt aacactttgg cagaaaatgc cagctcagat 1320 attttgagat actaaggatt atctttggac atgtactgca gcttcttgtc tctgttttgg 1380 attactggaa tacccatggg ccctctcaag agtgctggac ttctaggaca ttaagatgat 1440 tgtcagtaca ttaaactttt caatcccatt atgcaatctt gtttgtaaat gtaaacttct 1500 aaaaatatgg ttaataacat tcaacctgtt tattacaact taaaaggaac ttcagtgaat 1560 ttgtttttat tttttaacaa gatttgtgaa ctgaatatca tgaaccatgt tttgataccc 1620 ctttttcacg ttgtgccaac ggaatagggt gtttgatatt tcttcatatg ttaaggagat 1680 gcttcaaaat gtcaattgct ttaaacttaa attacctctc aagagaccaa ggtacattta 1740 cctcattgtg tatataatgt ttaatatttg tcagagcatt ctccaggttt gcagttttat 1800 ttctataaag tatgggtatt atgttgctca gttactcaaa tggtactgta ttgtttatat 1860 ttgtacccca aataacatcg tctgtacttt ctgttttctg tattgtattt gtgcaggatt 1920 WO 00/71710 PCTlFR0010142G
II
ctttaggctt tatcagtgta atctctgcct tttaagatat gtacagaaaa tgtccatata 1980 aatttccatt gaagtcgaat gatactgaga agcctgtaaa gaggagaaaa aaacataagc 2040 tgtgtttccc cataagtttt tttaaattgt atattgtatt tgtagtaata ttccaaaaga 2100 atgtaaatag gaaatagaag agtgatgctt atgttaagtc ctaacactac agtagaagaa 2160 tggaagcagt gcaaataaat tacatttttc ccaagtgcca gtggcatatt ttaaaataaa 2220 gtgtatacgt tggaâtgagt catgccatat gtagttgctg tagatggcaa ctagaacctt 228'0 tgagttacaa gagtctttag aagttttcta accctgccta gtgcaagtta caatattata 2340 gcgtgttcgg ggagtgccct cctgtctgca ggtgtgtctc tgtgcctggg ggcttttctc 2400 cacatgctta ggggtgtggg tcttccattg gggcatgatg gacctgtcta caggtgatct 2460 ctgttgcctt tgggtcagca catttgttag tctcctgggg gtgaaaactt ggcttacaag 2520 agaactggaa aaatgatgag atgtggtccc caaacccttg attgactctg gggaggggct 2580 ttgtgaatag gattgctct 2599 <210> 11 <211> 222 <212> DNA
<213> Homo sapiens <400> 11 gtaggagaga agtatggcta cctttcactt ccaaagccaa tggtaagtag aagaattatg 60 tacattgcag aatgttttta ttcagaattc aaattatgct cttgttgcct gttgctgctc 120 ccctctacca caaataattg acatgacaga aaaaagttag gatattaatg ttgacttcag 180 agttgttatt ctgggtagca atctagttgt ggcttacact ct 222 <210> 12 <211> 3422 <212> DNA
<213> Homo sapiens <400> 12 gaagtcactg ataattataa ttagtttaaa tttattctta cactacttaa gaaaaatttc 60 atttagaaaa ggctaccatg agatcttttg actatatgga gtagactgca tacagatctc 120 tttatttcta ttatgaatat tttagcgatt ataatcagct attccactga gtattagatt 180 tggtcactaa gtaactcatg tttttcttta gtcaatcatt cattcattca ctaaaacatt 240 tgttgagagt tggctaaact ctagattctg tgccaggcac tgtacagggt gatggagatc 300 actcataaga aggcctcttg ctcttagcca gatcatatgt aatactaaat ttaaattttt 360 tgcattaaaa ggctaaaaaa tcatttgttt ttgttaatta tatactggtt gatttataga 420 tgtaattagc acatattcat aagagacaaa tatatacaat gagttactat acatatacaa 480 agtgatttta gctgtataaa gtgatattgc aaaaaactac agctaatgtt tcttgctggg 540 taattattag cataaatatc aggttcttag aggtctttaa gagaatactt tagagctacc 600 aaaattagca gcagtgatgt aatatcaccc tgaaatacca ggagcagagg tgccccagag 660 tgcttcacag ctatgatcag gaaacttgac ctgccccatt gctacagcaa cggcataagg 720 actaggaagg tccactagct ggggaggtct tggaaccctc cgagcc ~ gaa agaagcattc 780 cagcatgatt cctcagatgc aatgaggaag gtttacagaa ttttcacagg gcaacagaga 840 tcaagtggta tgaaaaggta ggagttttaa gctcaagtct caaagataac ctacctttac 900 attctcagtc agaatttgac ccagaaagag gaagtttctt caggaacaga ccgtacgttg 960 WO 00/71710 PCTlFR0010142G

atgaagtaga agtcatttca gtaaaaacgg agtacagaac ttggtcataa tatcttgcat 1020 tttatagatt tattaaagat tagtttcaag ttcacattcg ctattcagtt gtaaaccgaa 1080 tggatgggag gggagaaaat acaagctctc cacacaggta tgctcctctc ttttctgaga 1140 gagaaggcat gggattttca gcataaattc catgttatgt gagtgctgtt tgagttctga 1200 agttcctatc aatatctgtt cctgcaagtg atctctgtaa gaccacctta catgctggtc 1260 ttagttattg ttaaaattgc aaggtttctt cacaccctct ttgataagaa gtgtttagct 1320 ggcagagctt tcccttgact tctgagtcta gtgtgggttg gcccatgaca gtgggaagaa 1380 atccaacatg ttacatggag accttgtatg taaacaaact ctgtagcctt tgaaagtgga 1440 actgcttttt acagttaaag ggctgctaaa tggcttgcag atgagatctt ctggctcacc 1500 ttgatcttca catgaaccca ttgtgaccta tctggatttc ctagga ~ ctg tagtttccat 1560 ttgggttata ttagtgcctc aggaatgtgt cactactggt caagcaatac tcagaaattc 1620 aggctgtgag gggttagatt agaggaaagt aatttaggtg agctatccag agctttcaac 1680 ctcagggttt ataggaaaaa aaaacaaaat acaaaaaccc ttaggacttc tcatactcta 1740 gccctgacct tgcagtctcc tctgaggggc ctcctaagac ccttaaaata atattacaat 1800 aggactttga gtgtgcattt cacatgtgga aatacctctg gctagcatta cttccaaatg 1860 ctagttccag ctaaaaacaa gtacttttta ttagtttctt gtctttcaac attctgccat 1920 caaaatatat tcattttatt aacttaccga ttattgggaa cctgcaaaaa aaaaaaaaaa 1980 aacacacatg ctgtctgcag ccactgtttg gttatttttg atagtttaag agaattataa 2040 atcaagttgt tctgtctact agagtcagaa attctgtgct agaatgggac ttctaaaatt 2100 aggtggtcct gtcactttct agagaaagac ccaaattcat aggtttaagt ggcttgtctg 2160 acatacacat acagccagtt agtaacagaa ttcagaatag aatagagttc ttttttttct 2220 gtcagtccgt tgttctactt ctctttcctt ttcttcatgg ttgagcagct tttggcaaaa 2280 tgtgttccat atagcagtag ttccaagaga tgttaataga tgtaagaaaa aaagtgtgtg 2340 tgtgttgggg gtgggggatt gcatggtcaa ttaaaatgaa ggaatgctga gtttgtttcc 2400 ttactgtagg acttctaaga gttttgaaca tgctattaca cattgtgaat ttataaaagg 2460 ggacaaacac tgtttgacct tagactgcac tccccttctt tattcctcag agcatctcaa 2520 aggactacag ggtcctttga gaaacatggc ccttgatcaa gtttacaact ctttgagaag 2580 acatccctaa tggaaatact gaatggcaga tctattactg tggtaccatg tagtgtgtaa 2640 taaatcttga agtccagaaa gcaagtatat ttgctgttta gagctatact taaggtatag 2700 agattctttt ccacctgtgg tgtgtaaaat cagtattgtg tttaattttg caggtttttc 2760 aaggatcaac taatgtgcaa atacagtggt gatatattga tattacâttt taataatgct 2820 tttgtatggc actttatagt tttcagacac cttttgtaac agccctgtga gacagacaat 2880 attatcctta ttgtacagat gggggggctc tggaggctct gaaaagtttt tggtgatatt 2940 cccctaagtt tataccacaa aatgatggag ccagaattta gttgcagaac ttctgactcc 3000 aagtccagag ttctttacta gacatctggt ttcttactag ctttttgcta gctttttatt 3060 ttacagtgaa aagtatggaa gcaaatcctg ataattttgg cttattatca aatatcattt 3120 attttttatt gcagagaccc agcagatgta actctcattg tagccatccc aaagaaaacc 3180 cttctttgcc ctttgcagtg ccacttattt aggtaactga agtgtatttc cagtacaatt 3240 tgattttgaa ctaagatttg atatagagtt gtaattgctt acataactct ttgaaaatgt 3300 atcatccctg ggttctcagg tgaaggaggc aattcaaaag taaaaaagaa tattcgaata 3360 caataaatac cctctgttct cacacaaatg ctgtttctta gctaacttgc tttgacaacc 3420 your <210> 13 <211> 5791 <212> DNA
<213> Homo sapiens WO 00/71710 PCTlFR0010142G

<400> 13 ctaatattat tggccagtct gtggaagaag ctatcagagg ggtgtttgat gcttccctca 60 aaatggctgg cttctatgga ttgtatacct ggctgactca tactatgttt ggcatcaata 120 ttgtcttcat accatcagca ttagcagcaa tccttggagc agtgccattc ctggggacat 180 actgggcagc agtacctgca gttcttgacc tgtggctgac acaagggtta ggatgcaagg 240 ccattttact gttgattttt catctcttgc caacatactt tgtagatact gcaatctact 300 ctgacatatc aggaggtggc catccttacc tgacaggctt ggcagtggcc ggtggagcat 360 actacctagg cctggaagga gcaatcatcg gtcctattct tctctgcata cttgtggttg 420 cttccaatat ctatagtgcc atgctagtga gtcccacgaa ttcagttccc acgccaaacc 480 agaccccatg gcctgctcag cctcagcgga ctttccgtga catttctgaa gatctgaaat 540 cttcagtagg ttgatgtggt ttcctctgca gtgatttttc taggaagttc aaatttgaca 600 gcgagttcag ctcagctgtg gccntctgcc cttccagctg tgcctagcaa gcaaaaccca 660 ggaaagaagc agaagcctcc tggccttaca tacagaatgc ctggacaaga gagaacttgc 720 tgcgggctgc tttgtatttt aaaacacagc ttgagagttc agagttggtg gtttgctcac 780 ttaactgttg ttaagatggc ttgaaaagtt tcattttata cactggtacc ctggcttgaa 840 atttttccac tttggttatc tatgttacta tattatatat ttataaagtt attttaagaa 900 ctctaaacta cctgctgtta aaagaataga tggtgtaatt ttttcctggt ttaagaaatg 960 tattgttaaa cttttctaag acagtcactt ttcaaggaag agggctttca cttttgagtg 1020 tgtagttgag tgagcaggaa aaatgaatct tctacccttc tcccacaatg tattatacgc 1080 tctttaagaa ataataaatc ataagtataa gggtggggtg gcttatttga tgttcagttt 1140 tatattataa ccctgggaga tacaaagact gaagctcttc ctcctcttcc ttttctcttc 1200 acgcttcttt acactattgc caaattataa aacttggctg accacgttga agtgaaatac 1260 ttattaagct gctatgaatg gtaacagtat gataaaattc atgctgttat taggttttct 1320 ccttccaggt ggttgaagtg aaaaatctca ggtgtagcaa tactctgatt tgttaaatgt 1380 atccgtttca ttatttggaa ctctgccaat aagttagttt tcagcagaat tttgtattta 1440 tgtagtattt tcccatctct tagcacagtg ccttgcacat gactctaaat gaatgcttgt 1500 tgaattgaat tgcagcttta aaaatatctc agatatcaca ataaccagca tagtgcttta 1560 cattttacaa agtccttttg cacatactat ttcacaagta catcacatca gctttcatat 1620 agctttatat tattttacat cagttttaca ctgatggaga agctaaggtt cagaaaagtg 1680 accaactcaa agtcgtaaag tgtagtagga tttggcctca gatctttgac tccgttgtgt 1740 gcagattctg ctgtattagt gttccttcta aatattgtat gcagttttcc cagtgttang 1800 agattggtgt tgctatccat ttgttgtgaa tgaagacttg tcctatagta catgacaggg 1860 ctgagagtgg actgtagttc ttagctgaac cctttctact gtttaaaaca atcatcaggc 1920 ctatcctctg ctcccagggg aatgtgggag agaaaagggt tcttggccag gctgtaggtg 1980 gtggctcaca tctgtaatcc cagcactttg gaaggctgag gtgggtggat tgcttgagcc 2040 cagggatttg agatcagcct aggcaacatg gcaaaacccc atctctacaa aaaaaaaaaa 2100 aaaaaaaaaa aaattagctg ggcacggtgg tgtggctata gtctgagcta ctcaggaggc 2160 tgatgtatga ggatcacctg agtccaggag gtcgaggctg cagtgagcca agatggcgcc 2220 actgcactcc agcctgggtg agagagtgag acactgtccc aaggaaaaaa aaaagtgttg 2280 gggggtagtt cttaagcgtt gaagatttcc tttttggaaa gtatttaaag gtagaaatat 2340 taataatttt tcctaaaaca tctccctaag aagtcactga taattataat tagtttaaat 2400 ttattcttac actacttaag aaaaatttca tttagaaaag gctaccatga gatcttttga 2460 ctatatggag tagactgcat acagatctct ttatttctat tatgaatatt ttagcgatta 2520 taatcagcta ttccactgag tattagattt ggtcactaag taactcatgt ttttctttag 2580 tcaatcattc attcattcac taaaacattt gttgagagtt ggctaaactc tagattctgt 2640 gccaggcact gtacagggtg atggagatca ctcataagaa ggcctcttgc tcttagccag 2700 atcatatgta atactaaatt taaatttttt gcattaaaag gctaaaaaat catttgtttt 2760 WO 00/71710 PCTlFR00lOla2G
ia tgttaattat atactggttg atttatagat gtaattagca catattcata agagacaaat 2820 atatacaatg agttactata catatacaaa gtgattttag ctgtataaag tgatattgca 2880 aaaaactaca gctaatgttt cttgctgggt aattattagc ataaatatca ggttcttaga 2940 ggtctttaag agaatacttt agagctacca aaattagcag cagtgatgta atatcaccct 3000 gaaataccag gagcagaggt gccccagagt gcttcacagc tatgatcagg aaacttgacc 3060 tgccccattg ctacagcaac ggcataagga ctaggaaggt ccactagctg gggaggtctt 3120 ggaaccctcc gagccagaaa gaagcattcc agcatgattc ctcagatgca atgaggaagg 3180 tttacagaat tttcacaggg caacagagat caagtggtat gaaaaggtag gagttttaag 3240 ctcaagtctc aaagataacc tacctttaca ttctcagtca gaatttgacc cagaaagagg 3300 aagtttcttc aggaacagac cgtacgttga tgaagtagaa gtcatttcag taaaaacgga 3360 gtacagaact tggtcataat atcttgcatt ttatagattt attaaagatt agtttcaagt 3420 tcacattcgc tattcagttg taaaccgaat ggatgggagg ggagaaaata caagctctcc 3480 acacaggtat gctcctctct tttctgagag agaaggcatg ggattttcag cataaattcc 3540 atgttatgtg agtgctgttt gagttctgaa gttcctatca atatctgttc ctgcaagtga 3600 tctctgtaag accaccttac atgctggtct tagttattgt taaaattgca aggtttcttc 3660 acaccctctt tgataagaag tgtttagctg gcagagcttt cccttgactt ctgagtctag 3720 tgtgggttgg cccatgacag tgggaagaaa tccaaca.tgt tacatggaga ccttgtatgt 3780 aaacaaactc tgtagccttt gaaagtggaa ctgcttttta cagttaaagg gctgctaaat 3840 ggcttgcaga tgagatcttc tggctcacct tgatcttcac atgaacccat tgtgacctat 3900 ctggatttcc taggacctgt agtttccatt tgggttatat tagtgcctca ggaatgtgtc 3960 actactggtc aagcaatact cagaaattca ggctgtgagg ggttagatta gaggaaagta 4020 atttaggtga gctatccaga gctttcaacc tcagggttta taggaaaaaa aaacaaaata 4080 caaaaaccct taggacttct catactctag ccctgacctt gcagtctcct ctgaggggcc 4140 tcctaagacc cttaaaataa tattacaata ggactttgag tgtgcatttc acatgtggaa 4200 atacctctgg ctagcattac ttccaaatgc tagttccagc taaaaacaag tactttttat 4260 tagtttcttg tctttcaaca ttctgccatc aaaatatatt cattttatta acttaccgat 4320 tattgggaac ctgcaaaaaa aaaaaaaaaa acacacatgc tgtctgcagc cactgtttgg 4380 ttatttttga tagtttaaga gaattataaa tcaagttgtt ctgtctacta gagtcagaaa 4440 ttctgtgcta gaatgggact tctaaaatta ggtggtcctg tcactttcta gagaaagacc 4500 caaattcata ggtttaagtg gcttgtctga catacacata cagccagtta gtaacagaat 4560 tcagaataga atagagttct tttttttctg tcagtccgtt gttctacttc tctttccttt 4620 tcttcatggt tgagcagctt ttggcaaaat gtgttccata tagcagtagt tccaagagat 4680 gttaatagat gtaagaaaaa aagtgtgtgt gtgttggggg tgggggattg catggtcaat 4740 taaaatgaag gaatgctgag tttgtttcct tactgtagga cttctaagag ttttgaacat 4800 gctattacac attgtgaatt tataaaaggg gacaaacact gtttgacctt agactgcact 4860 ccccttcttt attcctcaga gcatctcaaa ggactacagg gtcctttgag aaacatggcc 4920 cttgatcaag tttacaactc tttgagaaga catccctaat ggaaatactg aatggcagat 4980 ctattactgt ggtaccatgt agtgtgtaat aaatcttgaa gtccagaaag caagtatatt 5040 tgctgtttag agctatactt aaggtataga gattcttttc cacctgtggt gtgtaaaatc 5100 agtattgtgt ttaattttgc aggtttttca aggatcaact aatgtgcaaa tacagtggtg 5160 atatattgat attacatttt aataatgctt ttgtatggca ctttatagtt ttcagacacc 5220 ttttgtaaca gccctgtgag acagacaata ttatccttat tgtacagatg ggggggctct 5280 ggaggctctg aaaagttttt ggtgatattc ccctaagttt ataccacaaa atgatggagc 5340 cagaatttag ttgcagaact tctgactcca agtccagagt tctttactag acatctggtt 5400 tcttactagc tttttgctag ctttttattt tacagtgaaa agtatggaag caaatcctga 5460 taattttggc ttattatcaa atatcattta ttttttattg cagagaccca gcagatgtaa 5520 ctctcattgt agccatccca aagaaaaccc ttctttgccc tttgcagtgc cacttattta 5580 ggtaactgaa gtgtatttcc agtacaattt gattttgaac taagatttga tatagagttg 5640 WO 00/71710 PCTlFR0010142G
taattgctta cataactctt tgaaaatgta tcatccctgg gttctcaggt gaaggaggca 5700 attcaaaagt aaaaaagaat attcgaatac aataaatacc ctctgttctc acacaaatgc 5760 tgtttcttag ctaacttgct ttgacaacct a 5791 <210> 14 <211> 2615 <212> DNA
<213> Homo sapiens <400> 14 acccaaactt caaaactggt caataattaa caatgtatta attttgaaaa gtttttaact 60 gtaagagtat caaatataat acagagctct taaatactta aagctttctg tcacaatatt 120 aaaaataaaa cttcttagca ttccaagact atgaaaagtg ccccctccca attttttaag 180 caagtaatag tatctgctgg tgtttatatt tgttaaaaat ttaaaataac aacaacaaaa 240 aaaaaacttc taacttgaat gtgatgtgac ttgagtactt ctaaaccatc gaaaatacct 300 gatacgggga gtaggttcat ggttttggta aaagaaacta tgtcacagag ttttaatatt 360 ataactggac ttctaaatca taaagtaaga aaattaacat catttagtat cttttcttgt 420 ttgtttttta ttttgctaag aaggaaccag attttatatc atcattcttc atctaaatgg 480 actgccatat gaagttctgg tttctctgtt tcttcttggt tagctggtta ctaccaaatg 540 cctaaggaca attctcagag catttccaca tgaaggtgat tagttttcat ttaataaaat 600 taataacaca ttacatgtag atgaaaatat aacaaaacca tacgaaagct tgtcagagat 660 attcaactag aaaactaaaa cagtagccac tagaaaaaag acatagtgga aaaatttttg 720 aacggatatg ctttttgttg aataattaca gtaattacta ccaatatatt cagaccaaca 780 aagattagaa agaacatgca aaatgctgag aaaatttctc ctacaattaa aacaaatgtg 840 tttttatgag agagaaaaaa ataagtcaag ctcctaaaat gaaaattaca aaacatagga 900 ttaacaattt attaaaaatt acacccttga tttttttgag gccaaaaaaa gtagtttttt 960 taaaacaagg gcatgaaaaa gacttcagat taagactcat actctgttct aaatgaaaag 1020 tagtaaaact acttctagta gaaaatacct gctatggaaa aaaaatttca gatattttcc 1080 atttgatgta ggtattaata aaaaatatga tgtttatatc taaaatataa actagcaatt 1140 tattttcatt tataatataa agtgttttag gaaaagttta ctcttctcag tgttcaaaat 1200 aaaataggaa ttgttctcca tacctagcaa ttttaatgat aatgtcaagt aaaaatttaa 1260 ttctgctgaa ctaaagctca aatagattca aattttaaaa atatgaaaaa tctacatttt 1320 taaaagctta aaatttttgt tactttgcaa tgacagatct gctttttcta acatttaaaa 1380 aattttgtct tcttttatta atataaaact attcaaataa tcacaacaga atctcttata 1440 ccggtaaagc ataatcacat gatacactcg taacactcta caaatacaat ccagaaaggg 1500 gaagtctccc tcaaacaaag aatttctttc tttctgtcac ctccattcca tatatatagt 1560 cttcatttca catcacatac atagaaaaat tagcacaata taacaggtag ataagaaaaa 1620 aaatttttgg ccttgtagag ctcatcacgt aaatttattc attcttctta gtatgtttct 1680 ttttaacatt atctgaggca acatctaccg gctttgaggc caatgaccca acgccattgg 1740 aaggtgactt tgcttcactt ttcttctcac atgatgaaaa cggctgctgc cagccaaata 1800 gcatccaact caatgtatcc tcaaaaggag caaatgtcat agtagaagtc tgtgtagtca 1860 tcatggttat ctttgtggcc acaataaaga tggtataaag gaacataaga ttatgctttg 1920 atattgccag atgctgggtg tgctggaatg tgaagataac tgaccccagc agggttacct 1980 tggcagggta tgacatcttc agccattcat caccttctgg tttccaatct ccttttacca 2040 acctctcaaa attcgttata atggtaccac ctgcacctcg ggcccatcca atagctatca 2100 tgactatcca gccatttttg taatagctat tagcatgtgt gactccacct actattttcc 2160 aagttctggt cacttccttc attcccgaag ccagtagttg aacaggtaga tatgaatagc 2220 WO 00/71710 PCTlFR0010142G
IG
cctgggaaac taggtcatgc gggcaaaaaa atgtaatata ccagattgaa gatgccagta 2280 atatgttagt gtggtttgca agaaacttca atggaggctc tgcaagcagt agacaggata 2340 aaattcctcc accaaaacag tggagcatag cagtaaacca gcttgaaata ggattcttcc 2400 atgccaatgc agctgctccc ggctgacgtt tcaccgccat cactgacact agatagtgcg 2460 cgatgtcaaa aaagggaaac atggacgtgc gggagaaggc cagagccaac tcgtcccatg 2520 gagaatccat aacgaccacc gaccgcggca accgaagcag ccgcggctac tggttccccg 2580 cgctcgcgcg gtgaggagta ggagagggca cagcc 2615 <210> 15 <211> 2551 <212> DNA
<213> Homo sapiens <400> 15 ggctgtgccc tctcctactc ctcaccgcgc gagcgcgggg aaccagtagc cgcggctgct 60 tcggttgccg cggtcggtgg tcgttatgga ttctccatgg gacgagttgg ctctggcctt 120 ctcccgcacg tccatgtttc ccttttttga catcgcgcac tatctagtgt cagtgatggc 180 ggtgaaacgt cagccgggag cagctgcatt ggcatggaag aatcctattt caagctggtt 240 tactgctatg ctccactgtt ttggtggagg aattttatcc tgtctactgc ttgcagagcc 300 tccattgaag tttcttgcaa accacactaa catattactg gcatcttcaa tctggtatat 360 tacatttttt tgcccgcatg acctagtttc ccagggctat tcatatctac ctgttcaact 420 actggcttcg ggaatgaagg aagtgaccag aacttggaaa atagtaggtg gagtcacaca 480 tgctaatagc tattacaaaa atggctggat agtcatgata gctattggat gggcccgagg 540 tgcaggtggt accattataa cgaattttga gaggttggta aaaggagatt ggaaaccaga 600 aggtgatgaa tggctgaaga tgtcataccc tgccaaggta accctgctgg ggtcagttat 660 cttcacattc cagcacaccc agcatctggc aatatcaaag cataatctta tgttccttta 720 taccatcttt attgtggcca caaagataac catgatgact acacagactt ctactatgac 780 atttgctcct tttgaggata cattgagttg gatgctattt ggctggcagc agccgttttc 840 atcatgtgag aagaaaagtg aagcaaagtc accttccaat ggcgttgggt cattggcctc 900 aaagccggta gatgttgcct cagataatgt taaaaagaaa catactaaga agaatgaata 960 aatttacgtg atgagctcta caaggccaaa aatttttttt cttatctacc tgttatattg 1020 tgctaatttt tctatgtatg tgatgtgaaa tgaagactat atatatggaa tggaggtgac 1080 agaaagaaag aaattctttg tttgagggag acttcccctt tctggattgt atttgtagag 1140 tgttacgagt gtatcatgtg attatgcttt accggtataa gagattctgt tgtgattatt 1200 tgaatagttt tatattaata aaagaagaca aaatttttta aatgttagaa aaagcagatc 1260 tgtcattgca aagtaacaaa aattttaagc ttttaaaaat gtagattttt catattttta 1320 aaatttgaat ctatttgagc tttagttcag cagaattaaa tttttacttg acattatcat 1380 taaaattgct aggtatggag aacaattcct attttatttt gaacactgag aagagtaaac 1440 ttttcctaaa acactttata ttataaatga aaataaattg ctagtttata ttttagatat 1500 aaacatcata ttttttatta atacctacat caaatggaaa atatctgaaa ttttttttcc 1560 atagcaggta ttttctacta gaagtagttt tactactttt catttagaac agagtatgag 1620 tcttaatctg aagtcttttt catgcccttg ttttaaaaaa actacttttt ttggcctcaa 1680 aaaaatcaag ggtgtaattt ttaataaatt gttaatccta tgttttgtaa ttttcatttt 1740 aggagcttga cttatttttt tctctctcat aaaaacacat ttgttttaat tgtaggagaa 1800 attttctcag cattttgcat gttctttcta atctttgttg gtctgaatat attggtagta 1860 attactgtaa ttattcaaca aaaagcatat ccgttcaaaa atttttccac tatgtctttt 1920 ttctagtggc tactgtttta gttttctagt tgaatatctc tgacaagctt tcgtatggtt 1980 WO 00/71710 PCTlFR0010142G

ttgttatatt ttcatctaca tgtaatgtgt tattaattttttattaatgaa aactaatcac 2040 cttcatgtgg aaatgctctg agaattgtcc ttaggcattt ggtagtaacc agctaaccaa 2100 gaagaaacag agaaaccaga acttcatatg gcagtccatt tagatgaaga atgatgatat 2160 aaaatctggt.tccttcttag caaaataaaa aacaaacaag aaaagatact aaatgatgtt 2220 aattttctta ctttatgatt tagaagtcca gttataatat taaaactctg tgacatagtt 2280 tcttttacca aaaccatgaa cctactcccc gtatcaggta ttttcgatgg tttagaagta 2340 ctcaagtcac atcacattca agttagaagt tttttttttg ttgttgttat tttaaatttt 2400 taacaaatat aaacaccagc agatactatt acttgcttaa aaaattggga gggggcactt 2460 ttcatagtct tggaatgcta agaagtttta tttttaatat tgtgacagaa agctttaagt 2520 atttaagagc tctgtattat atttgatact c 2551 <210> 16 <211> 775 <212> DNA-<213> Homo sapiens <400> 16 tctatccgtc cgcgtcagcg ccttgccacc ctcatctcca atatgcctgg tccgaccccc 60 agtggcacta acgtgggatc ctcagggcgc tctcccagca aagcagtggc cgcccgggcg 120 gcgggatcca ctgtccggca gaggtaagga accctgcagt tcgttcgctt ccagactcgg 180 agataggacc cagaacctcg ctgattctgg ggtggagacc ctagcatgtg aagattgaca 240 aaggcaaaat gagcttctag tgacgtggcc gtgggagtag ttaaaggcct tttgggagga 300 aggcgacatt ttttttctcg ttgctcagtt tagggcacta ctcttaaaaa aggaaagtta 360 acaaactgga atagagtcag agataacttt gagaaaaccg atgtcattaa actggtgtct 420 ctggacctga ggtttgcact cacatttcca tctggcggcc ccataagcaa tctgtcctac 480 agataactcg tcctacacaa aacttagtct cttttcagct cagctctctc actctcaatt 540 atatctcctt acttccatat ggcactgttg tacactcatt tactcagagc cagaaacgtc 600 agcgtcatct tggatttttc ttatgctctt tctctctcta gtcatatgcc agactttaaa 660 ctctgcttga aagctttctc ataagctctt tccttttccc tttctactgc tttgcatttg 720 ctacttaacc cttttcttca ggctgtttgc tttccagtcc atcgttcgct ctgct 775 <210> 17 <211> 491 <212> DNA
<213> Homo sapiens <400> 17 ccctcctttc ccaccagaca ctcccttaca ccatgcacat ttatttaatn atgtacttaa 60 ttcaaactta acacccaggc aacacttatc ctaaactatg tgctttcctt aagaagttcc 120 cagggctaat gtggaagaga aaaccaggcc tggnagatcc agtttcaaaa atnccagaga 180 ttacctcaaa ggccgtttgt caacaacccc agctattact gagatggagg ccaccatgct 240 ccnnggtggg accacggact caaggatagc cactggaaac aaggacacag aggaccttgt- 300 gcccaggcaa cactcccgca tgcctcccat tccaaggttc cctttttang cccctctctt 360 ccagccaaag ttgnaaatgg ggtttnttta nggcactagc cttgggntat ttttacccnn 420 tgnnngctnt ggnagggaan gtcantttcc tttcactgnn tctcaccttt gttacctggc 480 tttgcaagtg g 491 WO 00/71710 PCTlFR0010142G

<210> 18 <211> 293 <212> DNA
<213> Homo sapiens <400> 18 caccatgcac atttatttaa ttatgtactt attcaactta caccaggcac acttatctaa 60 ctatgtgctt tcttagaagt tccagggcta atgtggagag aaaccaggcc tggagatcca 120 gtttcaaaat tccagagatt acctcaaggc cgtttgtcaa caacccagct attactgaga 180 tgaggccacc atgctccagg tggaccacga ctcaagatag ccactgaaac aagacacaga 240 gaccttgtgc ccagcaacac tcccgcatgc ctcccattcc aaggttccct ttt 293 <210> 19 <211> 2442 <212> DNA
<213> Homo sapiens <400> 19 tatgtgggat tttagggcaa ggattttcaa cagtcaacag tactggaagc..tgaggcttca 60 gaacccaggt atggaaggca gggagtttga actatgctcc ttgcacagaa tgggaagcca 120 ggaaaatgca aatgtcaaac tatcctacag ggaagtctct ataaacctcc acagaactcc 180 cacaaaagac acacttaggg aaaaggtatg cagcccaaaa tatacaagtc tgttcaactt 240 gctccctaaa ataagggaga atgccgacac cgcaggaaaa aggagctaat ggaactaaca 300 agaactttaa agaaacacca ataaaccaag aacacgcgaa aatgacaaaa taccaaataa 360 aaatccaaaa tagaaacaaa tccaaaagaa aacaaaagtt gatgaaataa aatctcagta 420 ggaggattaa gtaaaagaat tagcaaattg aaagattttt aagagacgaa gacagaataa 480 aaagctccct atgtttaaaa ggagttttta gaagaaaata gaaacaatgg gggaagatgg 540 ttaaaaatta ataataactt tccagacttg aagaaaaaaa actgaatctt cacattacag 600 aagcacacta tgtctagggc aggataaata acaaatctac actaggacac atcctgatct 660 gcaacacact gaagataaag agagaacagt aaaaatatag attactacct gtaagattac 720 tacctacaaa ctaagagggc tcagactaac agcagatttt ttcattagtt aacactgagg 780 caaggagaca atagaacagt atcttcaagg cacagcagac agtactaaac aactcaactc 840 ggtcaaacct aactttctgg ccagcacttg tgaaatcaaa ggctccccag taatttgatt 900 agcactttca tcattttgta atcttataaa caccttctcc agtggggaag aaatagccca 960 aatgggaatt ttaggtacct aagacttcgg ctgccaactg tgcctaatat cctagtaatg 1020 ttaacctttc cagtacccag tatagaatac ccctacaact gggcatttta aacaggcaaa 1080 caagtattac acacacttaa ttttgttcat tccagccaca tgaagtcaaa ggatgtttct 1140 ctataagaaa ctacaataga tctttgaaac tttgcatgaa.gttgttttag gggccatact 1200 tcaagtgaca ggaaataaca aatagcaata cacacacatt tcattaagtg gggatcttat 1260 aaaatctcta gaaccctgag aagttccttg ctacttataa agccttttct tgacctgtca 1320 gacctaatgt ttgatgatgt ataagaaaac tatcgtcgaa tttatgttat gcataaattt 1380 tatagtatat ttaaagtgaa atacacaatt tttttctatg cacatactct tactggaaaa 1440 aatttgaatg ctgacaataa aatggctaag ttatggtaca tgcatgtaac agaatactat 1500 agagcagact gagcaaacta tggccacagg ccaaatccag cccatggtaa gtatttgtaa 1560 atagttttac tggaacacaa ttatactcat ttatttacat attatctatt gatgctttca 1620 WO 00/71710 PCTlFR0010142G

cactaccgtg gtagtgctga gtagccatga cagagaccta atggtctgca aaacctaaaa 1680 tatttactaa etaacccttt atagaaagaa ctttgctgaa ccctggtatg gagaaataaa 1740 aacgaatgaa atacagctga atgagtcaac ttcaatcaat ctcaaaagca atgctgagag 1800 aatcaaatca caaaaaatac atgcagtata attcccatta caaaaaatcc acaaatatgc 1860 aaaacaaacc tgatactgtt cacaaatgca cataaaacca tttttttttt taaggtaatg 1920 aagttgatca acaccaagtg atctggggca gaggggtacg tagaagacat ttaactgtgc 1980 agggtacatt aacagtatat gtgctgatga tattctatat ccgaacctgg ggttggttaa 2040 atggaggttc agtttataat taccttttaa actacataaa tgttttttta tacattcagt 2100 atatgtattt tcatgtcatt taaaagttca aaaaagacca aaaaggcaca tatcaaaaca 2160 ttaacagcag gtgacagaat atttgccaac ctgttagcag gttttaaaac cttctacaat 2220 gaacttttaa tgggcacaca aataagaaca caagcataaa atacttttta aaattaaagt 2280 aaaatcttcc caactacgct aaaagctcta gcctgaatat tttatatacg agcaaaagta 2340 ctaattaaaa gcactagcat cttagaagaa tttccttaaa tccaagattt taaaattccc 2400 actctggcta gctctaatga agctcaaaac aaaatacaaa gg 2442 <210> 20 <211> 4608 <212> DNA
<213> Homo sapiens <400> 20 ctcaaaacac actttccccc atgcccccgt cataaattca ttcttatgct aatactgcaa 60 agcctccggt accatgcttc ttaccgtgat attcttgatg atctgctgca ccaagatcgc 120 attggtcaac atatgagtcc tgaggggtgc atgctgaagc agcagtcgaa gcagctggcc 180 cacaacaggc agctcctcag gcccaactct gttcacccgc aggctctgca gcatcaacct 240 gaggactcga ggcaagagag ccaggatgga gacacagacc ccccacagct tgtccctaca 300 ataacagaga cagaaatgag tcagtgagca aatgcccaca ggaaaagccc cccttctata 360 ttcccccaaa gtgaaatgtc cttttaagga acatgttttc caataacatt taaactgaga 420 gccaaatcaa gaacgcaatc tcacttacaa tagccacaca cactaaatac ctaggaatac 480 atctaaccaa ggaggtgaaa gatctctaca agaaaaacta cagaacactg ctgagagaaa 540 tcacagatga cacagataaa tggaaaaaca ttccatgctc atgaattgga ataatcagta 600 ttgttaaaat ggccacactg ctcaaagcaa cctacagatt caactgtatt cctatcaaac 660 taccaacatc attcttcaca caattaaaaa aaaatattct aaaattcaca tggaaccaaa 720 aaagccagaa tggccaaagc aatcctaagc aaaaacaacc tgacttcaca gtacactaca 780 aggctacagt agccaaaaca gcatggtaat gatagagaac aacagacaga taaaccaatg 840 gaacagaaaa gagaacccag aaataaagcc acatacctac aactatctca tcttcaacta 900 aggtgacaaa aacaagcaac agggcaagga ttccctattc aataaatggt gctgggacaa 960 ttggctatcc ttttgtagaa gaataaaaat ggatccctat ctttcatcat atacaaaaaa 1020 ttaactcggc caggcgcggt ggctcacgcc tgtaatccca gcactttggg aggctgaggc 1080 aggtggatca cgaagtcaag aaatcaagac catcctggcc aacatggaga aaccccgtct 1140 ctactacaga tacaaaatta gccaggcatg gtggcacgcg cctgcagtcc cagctactcg 1200 ggaggctgag gcaggagaat tgcttgaatc cgggaggtgg aggttgtagt gagccgagat 1260 cacaccactg cattccagcc tggcaaaaga atgagactcc gtctcaaaaa aaaaattaac 1320 tcaagataga ttaagaattc attactaagt cctcaaaagc aattgcaaaa acaaaaaatg 1380 acaagtgggc cctaattaaa cttaagaaca agagaaacta tccacatttc aataaacatg 1440 gtgtttttca ctaacattta ggctaagagc caaatcaaga acatcattct ctcggtatct 1500 ttatggagca aaatgtttat ggtagagaca ggtgaccttg cagctagcct aaccacattc 1560 WO 00/71710 PCTlFR0010142G
tccaagtgtt aattagatgg tgcaatattc acatagacct agagtccact gactatgaaa 1620 ggctctgacc tttttgcagc ttctttacca ggagtgtata âtcttcctag ttcctaaatc 1680 tttctaagag aacctgacta cctccaggtc tagagggagc agccccttca ctatataacc 1740 aatttccctg actgcacata tggtaattcc atctatggtg aataatgaat ccattctagg 1800 ccaaatagat actcttatgc agagcccagc tgggacagtc acgtgcaagg agaaaagaga 1860 aagccagact gcagacatag ctaatgcaaa ggcacggaga tacagactac acaaactaga 1920 agaaacgtag agtaagctgc tttgtctctt gctaaatttc taattcctag cccttgggtt 1980 ttacaagtta ctcctgtaat aatcaaatat tttcattttc tacttttctt aatttgagtg 2040 gatttcaaat aaccacagac cttaaaaaaa aaagacagcc aagctcaagg ccagatgggt 2100 aaaacctcta ggtgaaagaa actataatga aattcatata aagatatcca acagtcataa 2160 aaactgtatg tgggatttta gggcaaggat tttcaacagt caacagtact ggaagctgag 2220 gcttcagaac ccaggtatgg aaggcaggga gtttgaacta tgctccttgc acagaatggg 2280 aagccaggaa aatgcaaatg tcaaactatc ctacagggaa gtctctataa acctccacag 2340 aactcccaca aaagacacac ttagggaaaa ggtatgcagc ccaaaatata caagtctgtt 2400 caacttgctc cctaaaataa gggagaatgc cgacaccgca ggaaaaagga gctaatggaa 2460 ctaacaagaa ctttaaagaa acaccaataa accaagaaca cgcgaaaatg acaaaatacc 2520 aaataaaaat ccaaaataga aacaaatcca aaagaaaaca aaagttgatg aaataaaatc 2580 tcagtaggag gattaagtaa aagaattagc aaattgaaag atttttaaga gacgaagaca 2640 gaataaaaag ctccctatgt ttaaaaggag tttttagaag aaaatagaaa caatggggga 2700 agatggttaa aaattaataa taactttcca gacttgaaga aaaaaaactg aatcttcaca 2760 ttacagaagc acactatgtc tagggcagga taaataacaa atctacacta ggacacatcc 2820 tgatctgcaa cacactgaag ataaagagag aacagtaaaa atatagatta .ctacctgtaa 2880 gattactacc tacaaactaa gagggctcag actaacagca gattttttca ttagttaaca 2940 ctgaggcaag gagacaatag aacagtatct tcaaggcaca gcagacagta ctaaacaact 3000 caactcggtc aaacctaact ttctggccag cacttgtgaa atcaaaggct ccccagtaat 3060 ttgattagca ctttcatcat tttgtaatct tataaacacc ttctccagtg gggaagaaat 3120 agcccaaatg ggaattttag gtacctaaga cttcggctgc caactgtgcc taatatccta 3180 gtaatgttaa cctttccagt acccagtata gaatacccct acaactgggc attttaaaca 3240 ggcaaacaag tattacacac acttaatttt gttcattcca gccacatgaa gtcaaaggat 3300 gtttctctat aagaaactac aatagatctt tgaaactttg catgaagttg ttttaggggc 3360 catacttcaa gtgacaggaa ataacaaata gcaatacaca cacatttcat taagtgggga 3420 tcttataaaa tctctagaac cctgagaagt tccttgctac ttataaagcc ttttcttgac 3480 ctgtcagacc taatgtttga tgatgtataa gaaaactatc gtcgaattta tgttatgcat 3540 aaattttata gtatatttaa agtgaaatac acaatttttt tctatgcaca tactcttact 3600 ggaaaaaatt tgaatgctga caataaaatg gctaagttat ggtacatgca tgtaacagaa 3660 tactatagag cagactgagc aaactatggc cacaggccaa atccagccca tggtaagtat 3720 ttgtaaatag ttttactgga acacaattat actcatttat ttacatatta tctattgatg 3780 ctttcacact accgtggtag tgctgagtag ccatgacaga gacctaatgg tctgcaaaac 3840 ctaaaatatt tactaactaa ccctttatag aaagaacttt gctgaaccct ggtatggaga 3900 aataaaaacg aatgaaatac agctgaatga gtcaacttca atcaatctca aaagcaatgc 3960 tgagagaatc aaatcacaaa aaatacatgc agtataattc ccattacaaa aaatccacaa 4020 atatgcaaaa caaacctgat actgttcaca aatgcacata aaaccatttt tttttttaag 4080 gtaatgaagt tgatcaacac caagtgatct ggggcagagg ggtacgtaga agacatttaa 4140 ctgtgcaggg tacattaaca gtatatgtgc tgatgatatt ctatatccga acctggggtt 4200 ggttaaatgg aggttcagtt tataattacc ttttaaacta cataaatgtt tttttataca 4260 ttcagtatat gtattttcat gtcatttaaa agttcaaaaa agaccaaaaa ggcacatatc 4320 aaaacattaa cagcaggtga cagaatattt gccaacctgt tagcaggttt taaaaccttc 4380 tacaatgaac ttttaatggg cacacaaata agaacacaag cataaaatac tttttaaaat 4440 WO 00/71710 PCTlFR0010142G

taaagtaaaa tcttcccaac tacgctaaaa gctctagcct gaatatttta tatacgagca 4500 aaagtactaa ttaaaagcac tagcatctta gaagaatttc cttaaatcca agattttaaa 4560 attcccactc tggctagctc taatgaagct caaaacaaaa tacaaagg 4608 <210> 21 <211> 1627 <212> DNA
<213> Homo sapiens <400> 21 gaatgctgtt acctgaaccc cttacttcga aggatcataa gattcacagg ggtgtttgca 60 tttggacttt ttgctactga catttttgta aacgccggac aagtggtcac tgggcactta 120 acgccatact tcctgactgt gtgcaagcca aactacacca gtgcagactg ccaagcgcac 180 caccagttta taaacaatgg gaacatttgt actggggacc tggaagtgat agaaaaggct 240 cggagatcct ttccctccaa acacgctgct ctgagcattt actccgcctt atatgccacg 300 atgtatatta caagcacaat caagacgaag agcagtcgac tggccaagcc ggtgctgtgc 360 ctcggaactc tctgcacagc cttcctgaca ggcctcaacc gggtctctga gtatcggaac 420 cactgctcgg acgtgattgc tggtttcatc ctgggcactg cagtggccct gtttctggga 480 atgtgtgtgg ttcataactt taaaggaacg caaggatctc cttccaaacc caagcctgag 540 gatccccgtg gagtacccct aatggctttc ccaaggatag aaagccctct ggaaacctta 600 agtgcacaga atcactctgc gtccatgacc gaagttacct gagacgactg atgtgtcaca 660 agctgttttt taaaatcatc.ttccaattct atacttcaaa acacacagtt gctcaatgtc 720 aaactgtgat gacaaatatt acgtttatct agttagaagc taatgttttg tacatttttt 780 gtatgaggaa gtgatgtagc ttgccctgat tttttttttt tttttggtca gctttaatat 840 atttatgcca gaattttaaa accaacaaaa ttttcttgtt caagcgtgca ttgaagaacc 900 acatttattc aatggttgac gttgttttgt gatatttgta cacaaatttt cttttctcag 960 ttttataaac acagaatata acaattcact ttaaactttt attaccacag ttgctgcctc 1020 ctccagaatt tttgaatttt aataaaaggc aaacttttga gctgcaggaa ggacaatgtt 1080 ggttaataat aaatctcaaa gtcaattgta gaaaaaaaat tgtcttcaaa aagaatgttg 1140 cactctgatc tcttaacaaa ttgttacgtt caaagtttaa agtgatatat taacaaagtc 1200 acctagttat acaaacaatt gtcagagaat tctggatttg gagggtattg gggttatatg 1260 attctttctt agataatggc ctctactaaa taactcaaga tctttctgga atgtcttctg 1320 gcaggcaggt gccactgtca gcttttctcc aaaaagcagc caacatcagc ctcccctgtc 1380 aactcaacag ttttgtatct catattatat ggactttata tgaaaatgaa tattttacag 1440 tttgcacagt attattttac agaaaaggaa tcagagaatc tacaacatag ggccccagaa 1500 caacagtttc actttgtggc ttttaattat tctagaattt taactgcatc tcatttttct 1560 agcatggtga gaactaatat gtaactcctt tgattgaagg agctcttttg tccgtaccta 1620 tcagaat 1627 <210> 22 <211> 2333 <212> DNA
<213> Homo sapiens <400> 22 attcaagaga gcaaggacaa ataatggtca aggaaggaag tcagggattg gtggctctgt 60 WO 00/71710 PCTlFR0010142G
actaagtgtc agcttcaaag ggagagacca gagcataaac agacaattct ctaggttgca 120 aattgggagg attaggaaca agtaagagag ttccatgcag gatggacaag aaaaaaaagt 180 tttataccaa aaattgtatt tcatggcatt agggcagtct actggggtaa ggcactatgc 240 agtactaggc aattagaatt ctattcacta gctatgtgca caagcggctc ctgacctggt 300 cattttggct gtaaaactat tcatgcctgg acagtttttg acggtgcagt cttgctatat 360 ggtgtgagaa atggctgtag gaaacaacac tcaacgaagt tattccatca tcccgtgttt 420 tatatttgtt gagcttgtca tcatggctgg gacagtgctg cttgcctact acttcgaatg 480 cactgacact tttcaggtgc atatccaagg attcttctgt caggacggag acttaatgaa 540 gccttaccca gggacagagg aagaaagctt catcacccct ctggtgctct attgtgtgct 600 ggctgccacc ccaactgcta ttatttttat tggtgagata tccatgtatt tcataaaatc 660 aacaagagaa tccctgattg ctcaggagaa aacaattctg accggagaat gctgttacct 720 gaacccctta cttcgaagga tcataagatt cacaggggtg tttgcatttg gactttttgc 780 tactgacatt tttgtaaacg ccggacaagt ggtcactggg cacttaacgc catacttcct 840 gactgtgtgc aagccaaact acaccagtgc agactgccaa gcgcaccacc agtttataaa 900 caatgggaac atttgtactg gggacctgga agtgatagaa aaggctcgga gatcctttcc 960 ctccaaacac gctgctctga gcatttactc cgccttatat gccacgatgt atattacaag 1020 cacaatcaag acgaagagca gtcgactggc caagccggtg ctgtgcctcg gaactctctg 1080 cacagccttc ctgacaggcc tcaaccgggt ctctgagtat cggaaccact gctcggacgt 1140 gattgctggt ttcatcctgg gcactgcagt ggccctgttt ctgggaatgt gtgtggttca 1200 taactttaaa ggaacgcaag gatctccttc caaacccaag cctgaggatc cccgtggagt 1260 acccctaatg gctttcccaa ggatagaaag ccctctggaa accttaagtg cacagaatca 1320 ctctgcgtcc atgaccgaag ttacctgaga cgactgatgt gtcacaagct gttttttaaa 1380 atcatcttcc aattctatac ttcaaaacac acagttgctc aatgtcaaac tgtgatgaca 1440 aatattacgt ttatctagtt agaagctaat gttttgtaca ttttttgtat gaggaagtga 1500 tgtagcttgc cctgattttt tttttttttt tggtcagctt taatatattt atgccagaat 1560 tttaaaacca acaaaatttt cttgttcaag cgtgcattga agaaccacat ttattcaatg 1620 gttgacgttg ttttgtgata tttgtacaca aattttcttt tctcagtttt ataaacacag 1680 aatataacaa ttcactttaa acttttatta ccacagttgc tgcctcctcc agaatttttg 1740 aattttaata aaaggcaaac ttttgagctg caggaaggac aatgttggtt aataataaat 1800 ctcaaagtca attgtagaaa aaaaattgtc ttcaaaaaga atgttgcact ctgatctctt 1860 aacaaattgt tacgttcaaa gtttaaagtg atatattaac aaagtcacct agttatacaa 1920 acaattgtca gagaattctg gatttggagg gtattggggt tatatgattc tttcttagat 1980 aatggcctct actaaataac tcaagatctt tctggaatgt cttctggcag gcaggtgcca 2040 ctgtcagctt ttctccaaaa agcagccaac atcagcctcc cctgtcaact caacagtttt 2100 gtatctcata ttatatggac tttatatgaa aatgaatatt ttacagtttg cacagtatta 2160 ttttacagaa aaggaatcag agaatctaca acatagggcc ccagaacaac agtttcactt 2220 tgtggctttt aattattcta gaattttaac tgcatctcat ttttctagca tggtgagaac 2280 taatatgtaa ctcctttgat tgaaggagct cttttgtccg tacctatcag aat 2333 <210> 23 <211> 2764 ' <212> DNA
<213> Homo sapiens <400> 23 cagtttttat cacaggtgca agccgtggca ttggcaaagc tattgcattg aaagcagcaa 60 aggatggagc aaatattgtt attgctgcaa agaccgccca gccacatcca aaacttctag 120 WO 00/71710 PCTlFR0010142G

gcacaatcta tactgctgct gaagaaattg aagcagttgg aggaaaggcc ttgccatgta 180 ttgttgatgt gagagatgaa cagcagatca gtgctgcagt ggagaaagcc atcaagaaat 240 ttggaggaat tgatattctg gtaaataatg ccagtgccat tagtttgacc aatacattgg 300 acacacctac caagagattg gatctgatga tgaacgtgaa caccagaggc acctaccttg 360 catctaaagc atgtattcct tatttgaaaa agagcaaagt tgctcatatc ctcaatatca 420 gtccaccact gaacctaaat ccagtttggt tcaaacagca ctgtgcttat accattgcta 480 agtatggtat gtctatgtat gtgcttggaa tggcagaaga atttaaaggt gaaattgcag 540 tcaatgcatt atggcctaaa acagccatac acactgctgc tatggatatg ctgggaggac 600 ctggtatcga aagccagtgt agaaaagttg atatcattgc agatgcagca tattccattt 660 tccaaaagcc aaaaagtttt actggcaact ttgtcattga tgaaaatatc ttaaaagaag 720 aaggaataga aaattttgac gtttatgcaa ttaaaccagg tcatcctttg caaccagatt 780 tcttcttaga tgaataccca gaagcagtta gcaagaaagt ggaatcâact ggtgctgttc 840 cagaattcaa agaagagaaa ctgcagctgc aaccaaaacc acgttctgga gctgtggaag 900 aaacatttag aattgttaag gactctctca gtgatgatgt tgttaaagcc actcaagcaa 960 tctatctgtt tgaactctcc ggtgaagatg gtggcacgtg gtttcttgat ctgaaaagca 1020 agggtgggaa tgtcggatat ggagagcctt ctgatcaggc agatgtggtg atgagtatga 1080 ctactgatga ctttgtaaaa atgttttcag ggaaactaaa accaacaatg gcattcatgt 1140 cagggaaatt gaagattaaa ggtaacatgg ccctagcaat caaattggag aagctaatga 1200 atcagatgaa tgccagactg tgaaggaaaa tataaaaaaa aagtcgactg ctatgctcaa 1260 aaagtaaaaa aagctcaaca gttaaaatct aatgtttgtt ttctttcctg ttatattata 1320 aggatatgca cgtttgttct ggaaaagata gaatttgtct ctaaaagact tgaaattgta 1380 attaaaatgg caagctaatc aaacataagc ttcattaagt gggattctaa gacagtctgt 1440 gtttttatat ttcaagggtt taaccctttg agccttacat ctcattcact gtctttctcc 1500 aagaaaagta ttttgggcgg acagtcagat caagcagtaa aattagctct ttcaaatctt 1560 cttgtcatgt aaaatgaagc tagtctgttt taaaattttt agttttggat tgtatactaa 1620 tgaaaatctt aatgatgttt ttgattttta tatacttatt ttaaagaaaa tcttatatag 1680 tacattttac aaaaattata aaaaatgaat tagtactggc gaggactaaa tgaaacaata 1740 atttttcatt ttgataacta gctttccagg tggacttagc cataggaaaa tattactaat 1800 gtaatttaac aaattgctgc atgtattcca tttaaaaata tgtttaaatt gtcctaaaac 1860 aaaataattt tctccctagg agtatgcatt tggctacagt gttttgaaac agaaacctta 1920 gaataggtca ttggtatggg ctgaactgtg tatcccccaa ttcatttgtt gaggtcctaa 1980 ctcccatttc ttttgaatgt gactgttcgg agatgaggcc tttaaagagg tgacttaagt 2040 tcaaaggagg ctgttagtct aatccaacat ggtgtccttt ggacataaga gataccagca 2100 atgtgtgcac agaacaaaga ccaggagagg acacagtgag aaggcagtta tctgcaagca 2160 aagagagagg cttcagaaga aacaaaatca ccagcacctt gatctttgac ttctaatctc 2220 cagaatagtg agaaataaat ttctgttgt, t aagccgtcca ctgtgggagg ccgacgcagg 2280 aggattgctt gaggccagga gttcaaggcc agcctggaca acatagtaag accctatctc 2340 taccccccta ataaattaat ttaaaaagcc ccccaatctg tggtatttta ttatggcagc 2400 cctagcaagc taatacagtg gtttgagagg ctgggagggt tgaggggaag ataaactttt 2460 aaaaagctct tatctttcat ttcaatcagt taaaaatact tgctcagtgt aacaattttg 2520 cttctcagct tccactctaa tattgttgtg ccattaagca atttagctaa tcctgacatt 2580 tcttagattc ataatgttag gagcatttaa tctgtatttt acaagttagg aagcagagga 2640 tcagagatgg gaaaggacta gcccaaggcc aacattaaca agccctctaa caaaaacttt 2700 acaatacatt tatgttgaat ggaactccaa gatctcacct ctccatccag gaatggagtc 2760 catg 2764 <210> 24 tttataccaa aaattgtatt tcatggcatt agggcagtct actg WO 00/71710 PCTlFR0010142G

<211> 3228 <212> DNA
<213> Homo sapiens <400> 24 gctcgccgcc gccgctgtcg ccgccacctc ctctgatcta cgaaagtcat gttacccaac 60 -accgggaggc tggcaggatg tacagttttt atcacaggtg caagccgtgg cattggcaaa 120 gctattgcat tgaaagcagc aaaggatgga gcaaatattg ttattgctgc aaagaccgcc 180 cagccacatc caaaacttct aggcacaatc tatactgctg ctgaagaaat tgaagcagtt 240 ggaggaaagg ccttgccatg tattgttgat gtgagagatg aacagcagat cagtgctgca 300 gtggagaaag ccatcaagaa atttggagga attgatattc tggtaaataa tgccagtgcc 360 attagtttga ccaatacatt ggacacacct accaagagat tggatctgat gatgaacgtg 420 aacaccagag gcacctacct tgcatctaaa gcatgtattc cttatttgaa aaagagcaaa 480 gttgctcata tcctcaatat cagtccacca ctgaacctaa atccagtttg gttcaaacag 540 cactgtgctt ataccattgc taagtatggt atgtctatgt atgtgcttgg aatggcagaa 600 gaatttaaag gtgaaattgc agtcaatgca ttatggccta aaacagccat acacactgct 660 gctatggata tgctgggagg acctggtatc gaaagccagt gtagaaaagt tgatatcatt 720 gcagatgcag catattccat tttccaaaag ccaaaaagtt ttactggcaa ctttgtcatt 780 gatgaaaata tcttaaaaga agaaggaata gaaaattttg acgtttatgc aattaaacca 840 ggtcatcctt tgcaaccaga tttcttctta gatgaatacc cagaagcagt tagcaagaaa 900 gtggaatcaa ctggtgctgt tccagaattc aaagaagaga aactgcagct gcaaccaaaa 960 ccacgttctg gagctgtgga agaaacattt agaattgtta aggactctct cagtgatgat 1020 gttgttaaag ccactcaagc aatctatctg tttgaactct ccggtgaaga tggtggcacg 1080 tggtttcttg atctgaaaag caagggtggg aatgtcggat atggagagcc ttctgatcag 1140 gcagatgtgg tgatgagtat gactactgat gactttgtaa aaatgttttc agggaaacta 1200 aaaccaacaa tggcattcat gtcagggaaa ttgaagatta aaggtaacat ggccctagca 1260 atcaaattgg agaagctaat gaatcagatg aatgccagac tgtgaaggaa aatataaaaa 1320 aaaagtcgac tgctatgctc aaaaagtaaa aaaagctcaa cagttaaaat ctaatgtttg 1380 ttttctttcc tgttatatta taaggatatg cacgtttgtt ctggaaaaga tagaatttgt 1440 ctctaaaaga cttgaaattg taattaaaat ggcaagctaa tcaaacataa gcttcattaa 1500 gtgggattct aagacagtct gtgtttttat atttcaaggg tttaaccctt tgagccttac 1560 atctcattca ctgtctttct ccaagaaaag tattttgggc ggacagtcag atcaag.cagt 1620 aaaattagct ctttcaaatc ttcttgtcat gtaaaatgaa gctagtctgt tttaaaattt 1680 ttagttttgg attgtatact aatgaaaatc ttaatgatgt ttttgatttt tatatactta 1740 ttttaaagaa aatcttatat agtacatttt acaaaaatta taaaaaatga attagtactg 1800 gcgaggacta aatgaaacaa taatttttca ttttgataac tagctttcca ggtggactta 1860 gccataggaa aatattacta atgtaattta acaaattgct gcatgtattc catttaaaaa 1920 tatgtttaaa ttgtcctaaa acaaaataat tttctcccta ggagtatgca tttggctaca 1980 gtgttttgaa acagaaacct tagaataggt cattggtatg ggctgaactg tgtatccccc 2040 aattcatttg ttgaggtcct aactcccatt tcttttgaat gtgactgttc ggagatgagg 2100 cctttaaaga ggtgacttaa gttcaaagga ggctgttagt ctaatccaac atggtgtcct 2160 ttggacataa gagataccag caatgtgtgc acagaacaaa gaccaggaga ggacacagtg 2220 agaaggcagt tatctgcaag caaagagaga ggcttcagaa gaaacaaaat caccagcacc 2280 ttgatctttg acttctaatc tccagaatag tgagaaataa atttctgttg ttaagccgtc 2340 cactgtggga ggccgacgca ggaggattgc ttgaggccag gagttcaagg ccagcctgga 2400 caacatagta agaccctatc tctacccccc taataaatta atttaaaaag ccccccaatc 2460 tgtggtattt tattatggca gccctagcaa gctaatacag tggtttgaga ggctgggagg 2520 gttgagggga agataaactt ttaaaaagct cttatctttc atttcaatca gttaaaaata 2580 WO 00/71710 ~~ PCTlFR0010142G
cttgctcagt gtaacaattt tgcttctcag cttccactct aatattgttg tgccattaag 2640 caatttagct aatcctgaca tttcttagat tcataatgtt aggagcattt aatctgtatt 2700 ttacaagtta ggaagcagag gatcagagat gggaaaggac tagcccaagg ccaacattaa 2760 caagccctct aacaaaaact ttacaataca tttatgttga atggaactcc aagatctcac 2820 ctctccatcc aggaatggag tccatgtaat caaagtgaac ttaaaaatag gacagtttca 2880 acaagtcagg agattcacag caactgatca aagggagtcc agtcaacgtg agcaagcgtg 2940 attatgatga ggaagccccc tctgctttaa tccacacaag gaacgtaacc tgaagtaacc 3000 tgatgttaac caatctgctg tgtctactat gctgtttcct tgttcctgct agtgctgctt 3060 tacaaatgca gaccattcta tcatacctgg cggggcttct gttttatttt gtaggctgga 3120 tgctacccag ttcatgaatc gctaataaaa gccaattaga tctttaaaaa aaaaaaaaaa 3180 aaaaaaaaaa aaaaaaaaaa anaanaagan naannaaaan anagaaga 3228 <210> 25 <211> 3106 <212> DNA
<213> Homo sapiens <400> 25 accgaagtga gcgtggacct gccgaaacat gccaaaggcc aggatttgtt tgatcagatt 60 gtgtaccact tggaccttgt ggaaacagat tactttggcc tccagttcct cgactctgcc 120 caggttgcgc actggctgga tcatgccaaa cccataaaaa agcagatgaa aattggacct 180 gcttatgctt tacactttcg agttaaatac tattcttcag aaccaaacaa ccttcgtgag 240 gagtttacaa ggtacctgtt tgttttacaa ctcaggcatg acattctttc tggaaaattg 300 aaatgccctt atgaaacagc tgtggaatta gctgctctct gtctacaagc ggagcttggg 360 gagtgcgagc ttccagaaca cacaccagag cttgtgtctg agtttcggtt cattccaaat 420 cagacagaag caatggaatt tgatatcttc cagagatgga aagagtgcag gggaaagagc 480 cctgcccagg cggaactctc ctatctgaat aaagcgaagt ggctggaaat gtatggggta 540 gacatgcacg ttgtcagggg aagagatggc tgtgaatatt ctcttggact gaccccgaca 600 ggcatattaa tctttgaagg agctaacaaa ataggcttat tcttttggcc taaaattacc 660 aaaatggatt ttaaaaagag caaattgaca ctcgtggtgg tcgaggatga tgatcaggga 720 cgtgagcaag agcacacgtt tgtgttccgg ttagacagtg ccaggacctg caaacacctt 780 tggaagtgtg cagttgagca ccacgcattc ttccgactgc ggacgccagg aaacagcaaa 840 tccaatagat ccgactttat caggctgggc tctcgcttca gattcagtgg gcggacagaa 900 tatcaagcta cacatggctc caggttacga agaaccagca cctttgagag gaagcctagt 960 aaacgttatc catcccggag acattcaacg ttcaaagcaa gcaacccagt gatagcagcc 1020 cagctctgct ctaaaacaaa tccagaagtc cataattacc agcctcaata tcatcctaat 1080 atccatccca gccagccccg gtggcatcct cactctccaa atgtcaggcc atcctttcag 1140 gatgacaggt cgcattggaa agcatcggcc agtggagatg acagccattt tgattatgtc 1200 cacgaccaga accagaagaa cttaggaggg atgcaaagta tgatgtatcg agataaactc 1260 atgactgcac tttgagagac tgaagcatct ctcttccatt caccttcata gtttcattgc 1320 attccatgaa aagtgtcttg gcctcagatg gatggatgtg tttggacgag tgtctttaag 1380 gagtagtcct gaaaggtgtt tttggtgtcc atgtaaatat ttgaagataa aaccactata 1440 gcttgtcata atttactgtt gactgcattc tcattaaaat gaaggtaaag gctcaggaat 1500 catattgatg ttctgatttt aaaattggag tcaaagtcta tgtttatcat tttactatgt 1560 tcctgatgtt ctttgttatt taattaatgg gagcaaataa aaccagaaga gcttgggaag 1620 attgctcagc atatattcct gtcgtagaag ttgagattgc tagggtccag tttccctagt 1680 gtggcctgga cgagtcattt ccccttcatt gacctcattt tccccatctg aaaagagagg 1740 WO 00/71710 PCTlFR0010142G

gttggactaa gtgatctcca aggtcctttc caactctaaa attctgcaat ttgttaacat 1800 ttcattttgt ttaggttgag gacatacatt caaactaatt ttatcacaag gaaaactgca 1860 atacccactt ccttgacaga gttactcctt tcagaagcta aataaagtat ataacttatt 1920 agatgttata tagatacagg gggactttga atttcacatc ttaaagcagt tgagctactt 1980 tgaatttaag cagtcgtact aatcttaaat tgcatagcat ttgttttgat cgaatttgct 2040 gctcaagtat gggaataatt tttaatgtct taatgattgg tgctgctaac ttgcgtgatt 2100 tcagaagaca taattgtgaa tacacactgt cagaattggg ggattggttt ttaccctaga 2160 cttcactctt aaaaagcaac gtgcaatcaa gatcatttat ggctcaaatg aaagcatata 2220 aggttttctt gaagttgtgc caaagcattc tgtagagtag gatgagatgg ttgttgccct 2280 agtctgttgg tagaaccaga aatcaatatg ttgtctttta ggttaaagct tgtaccaaaa 2340 tatttatttc ccccatttca agccctgagt caaacatttt tttctcttaa taatagacct 2400 gaaatgtttt attagtattt ctgtgaaatc agttgattct tgtgccattt ttgtatatgt 2460 aattgtaatt ttgcccatgt taggccctct aaaaaatgtt tgacatcctt tgagatattt 2520 tattactaaa atctgatctt ttttggctac tgcaaaaatc tattcagcaa gaaggtatca 2580 gctgcatacc ttgcacagtg gagctgacta cctataaact ctccctaagg catttgttta 2640 caggtgtatt ccattttagc agacgttctg atgctcagtg tatgtgctgc atacaaataa 2700 atgtgttctg aatcttttca tcttattgat agcattttta caaatgtgtt tccaaggaat 2760 aaagattatt cttgcttttt ttttgactcc atcttcattt tttttaaatt gattcttgtt 2820 gctatgcaga agtctcattt gtgaatgacc ttggtaacag aacagttggc ttttggaagt 2880 ctgaaggtga gcattcagtt aggtgggtgg agcaagatca tcctagaatg aggctgctct 2940 tggcaagagt ggatcttata ggcacagcag ctgatgcctt tcttcatctg gggcaactct 3000 ggtgaaggtt gtcctgcctg tcacaggtgc tgagtagaga gaagtggtgg cagtgggatt 3060 tcctcagtaa tagtcctgta aaggtacgtg tttgtcctgg ctactt 3106 <210> 26 <211> 3313 <212> DNA
<213> Homo sapiens <400> 26 gcgggcccct gctcaccggc ggcgcggccg tgcacatctc cgccgccggc gccgccaagg 60 ccaccctcta ctgccgcgtc ttcctgctcg acgggaccga agtgagcgtg gacctgccga 120 aacatgccaa aggccaggat ttgtttgatc agattgtgta ccacttggac cttgtggaaa 180 cagattactt tggcctccag ttcctcgact ctgcccaggt tgcgcactgg ctggatcatg 240 ccaaacccat aaaaaagcag atgaaaattg gacctgctta tgctttacac tttcgagtta 300 aatactattc ttcagaacca aacaaccttc gtgaggagtt tacaaggtac ctgtttgttt 360 tacaactcag gcatgacatt ctttctggaa aattgaaatg cccttatgaa acagctgtgg 420 aattagctgc tctctgtcta caagcggagc ttggggagtg cgagcttcca gaacacacac 480 cagagcttgt gtctgagttt cggttcattc caaatcagac agaagcaatg gaatttgata 540 tcttccagag atggaaagag tgcaggggaa agagccctgc ccaggcggaa ctctcctatc 600 tgaataaagc gaagtggctg gaaatgtatg gggtagacat gcacgttgtc aggggaagag 660 atggctgtga atattctctt ggactgaccc cgacaggcat attaatcttt gaaggagcta 720 acaaaatagg cttattcttt tggcctaaaa ttaccaaaat ggattttaaa aagagcaaat 780 tgacactcgt ggtggtcgag gatgatgatc agggacgtga gcaagagcac acgtttgtgt 840 tccggttaga cagtgccagg acctgcaaac acctttggaa gtgtgcagtt gagcaccacg 900 cattcttccg actgcggacg ccaggaaaca gcaaatccaa tagatccgac tttatcaggc 960 tgggctctcg cttcagattc agtgggcgga cagaatatca agctacacat ggctccaggt 1020 WO 00/71710 ~~ PCTlFR0010142G
tacgaagaac cagcaccttt gagaggaagc ctagtaaacg ttatccatcc cggagacatt 1080 caacgttcaa agcaagcaac ccagtgatag cagcccagct ctgctctaaa acaaatccag 1140 aagtccataa ttaccagcct caatatcatc ctaatatcca tcccagccag ccccggtggc 1200 atcctcactc tccaaatgtc aggccatcct ttcaggatga caggtcgcat tggaaagcat 1260 cggccagtgg agatgacagc cattttgatt atgtccacga ccagaaccag aagaacttag 1320 gagggatgca aagtàtgatg tatcgagata aactcatgac tgcactttga gagactgaag 1380 catctctctt ccattcacct tcatagtttc attgcattcc atgaaaagtg tcttggcctc 1440 agatggatgg atgtgtttgg acgagtgtct ttaaggagta gtcctgaaag gtgtttttgg 1500 tgtccatgta aatatttgaa gataaaacca ctatagcttg tcataattta ctgttgactg 1560 cattctcatt aaaatgaagg taaaggctca ggaatcatat tgatgttctg attttaaaat 1620 tggagtcaaa gtctatgttt atcattttac tatgttcctg atgttctttg ttatttaatt 1680 aatgggagca aataaaacca gaagagcttg ggaagattgc tcagcatata ttcctgtcgt 1740 agaagttgag attgctaggg tccagtttcc ctagtgtggc ctggacgagt catttcccct 1800 tcattgacct cattttcccc atctgaaaag agagggttgg actaagtgat ctccaaggtc 1860 ctttccaact ctaaaattct gcaatttgtt aacatttcat tttgtttagg ttgaggacat 1920 acattcaaac taattttatc acaaggaaaa ctgcaatacc cacttccttg acagagttac 1980 tcctttcaga agctaaataa agtatataac ttattagatg ttatatagat acagggggac 2040 tttgaatttc acatcttaaa gcagttgagc tactttgaat ttaagcagtc gtactaatct 2100 taaattgcat agcatttgtt ttgatcgaat ttgctgctca agtatgggaa taatttttaa 2160 tgtcttaatg attggtgctg ctaacttgcg tgatttcaga agacataatt gtgaatacac 2220 actgtcagaa ttgggggatt ggtttttacc ctagacttca ctcttaaaaa gcaacgtgca 2280 atcaagatca tttatggctc aaatgaaagc atataaggtt ttcttgaagt tgtgccaaag 2340 cattctgtag agtaggatga gatggttgtt gccctagtct gttggtagaa ccagaaatca 2400 atatgttgtc ttttaggtta aagcttgtac caaaatattt atttccccca tttcaagccc 2460 tgagtcaaac atttttttct cttaataata gacctgaaat gttttattag tatttctgtg 2520 aaatcagttg attcttgtgc catttttgta tatgtaattg taattttgcc catgttaggc 2580 cctctaaaaa atgtttgaca tcctttgaga tattttatta ctaaaatctg atcttttttg 2640 gctactgcaa aaatctattc agcaagaagg tatcagctgc ataccttgca cagtggagct 2700 gactacctat aaactctccc taaggcattt gtttacaggt gtattccatt ttagcagacg 2760 ttctgatgct cagtgtatgt gctgcataca aataaatgtg ttctgaatct tttcatctta 2820 ttgatagcat ttttacaaat gtgtttccaa ggaataaaga ttattcttgc tttttntttt 2880 gactccatct tcattttttt taaattgatt cttgttgcta tgcagaagtc tcatttgtga 2940 atgaccttgg taacagaaca gttggctttt ggaagtctga aggtgagcat tcagttaggt 3000 gggtggagca agatcatcct agaatgaggc tgctcttggc aagagtggat cttataggca 3060 cagcagctga tgcctttctt catctggggc aactctggtg aaggttgtcc tgcctgtcac 3120 aggtgctgag tagagagaag tggtggcagt gggatttcct cagtaatagt cctgtaaagg 3180 tacgtgtttg tcctggctac ttgtgctctt cctggcagga aggcatccaa acccttatct 3240 gtgggctcct ggaaattgtg tatgccatat aataccctct aataaatacc tctctgctta 3300 aaaaaaaaaa aaa 3313 <210> 27 <211> 1539 <212> DNA
<213> Homo sapiens <400> 27 ctgaggatga ttatggtgat gacccttcga ccaactcgtt tgagaaagag aagcaggact 60 WO 00/71710 PCTlFR0010142G
~ s atgtctattg cctggagtca tccctgcaga cctacaaccc agactacgtc ctgatggtag 120 aagacgatgc tgtaccagaa gagcagatct tcccagtctt ggagcacctt ctgcgggctc 180 gcttctctga gccacatctc agagatgccc tttatctcaa gctgtatcac cccgagaggc 240 tccagcacta catcaatcca gagcccatgc ggatcctgga atgggttggt gtaggcatgt 300 tgctggggcc cttactaacc tggatataca tgaggtttgc cagccgccca gggtttagct 360 ggcctgtaat gctcttcttc tccctgtata gcatgggtct ggtggagctg gtgggtcggc 420 actatttcct ggaactgcgg cggctgagtc cttccctgta cagtgtggtt cctgcctctc 480 agtgttgcac cccagccatg ctcttcccgg cacctgcggc ccgccggacc ctcacctacc 540 tgtcccaagt gtactgccac aagggctttg gcaaggacat ggcactgtac tcgctgttga 600 gggccaaggg agagagggcc tatgtagtgg agccgaacct cgtgaaacac atcgggctct 660 tctccagtct ccggtacaac tttcatccca gtctcctcta gggtgccaag agatgccttt 720 ctgaagttgg ccacttcttg aagattcaaa tatttatctc tttatttaga catggttgcc 78D
tgcaggtatt tcactgttta ctgttgttag agatataggc actggggcag ctgaggaacc 840 tcaatatgtt aagagccttg gctttggtag cctcctggca ggagcagcag tttgccacag 900 gtccggacct ctccctccac acagccacac tgcctcatgc agtctgaccc acccagtgag 960 ggtgcatttg aacactgatt atattctcca tttgttttta agctctgctt tgtgttagag 1020 cttgtgactg ccaaaaattt tgtgcacagt gatatgactg ttttaggatc ttaagggtag 1080 aattttgtga aaggtgagat cctttggaat tgagttcttt ctcattgggt atgaaaatgg 1140 atgtatgttt agaatatatg cccaacgagg caggaccatg tggatagatt ccatttgttt 1200 ccttgacctg atgtaataaa aactgataaa agccgtgcag tgcccggcat cttggaggca 1260 ggtgatctgg cttttctgtt acctgggatt ttcttttcct atatatctgt agtgcactga 1320 taattgatat tgttagtgag aactttaagg cacgacaaga tctggaagag cttgtgaacc 1380 atcaaagtca gattgcttat gttgagtagt gatttaacat tgaacatttc tgtactactc 1440 tgactctttg aaaattggac atttcagaat gatacaatat aggggagctc tttacaagta 1500 gcatatcatt tttcctgact ttcctggctg actgcttac 1539 <210> 28 <211> 3404 <212> DNA
<213> Homo sapiens <400> 28 ctcttcctgt gcaacgtgga gcgtagtgtg agccattttg atgccaagtt gctctccaag 60 tatgtccctg tggccaatcg ctatgagggc actgaggatg attatggtga tgacccttcg 120 accaactcgt ttgagaaaga gaagcaggac tatgtctatt gcctggagtc atccctgcag 180 acctacaacc cagactacgt cctgatggta gaagacgatg ctgtaccaga agagcagatc 240 ttcccagtct tggagcacct tctgcgggct cgcttctctg agccacatct cagagatgcc 300 ctttatctca agctgtatca ccccgagagg ctccagcact acatcaatcc agagcccatg 360 cggatcctgg aatgggttgg tgtaggcatg ttgctggggc ccttactaac ctggatatac 420 atgaggtttg ccagccgccc agggtttagc tggcctgtaa tgctcttctt ctccctgtat 48D
agcatgggtc tggtggagct ggtgggtcgg cactatttcc tggaactgcg gcggctgagt 540 ccttccctgt acagtgtggt tcctgcctct cagtgttgca ccccagccat gctcttcccg 600 gcacctgcgg cccgccggac cctcacctac ctgtcccaag tgtactgcca caagggcttt 660 ggcaaggaca tggcactgta ctcgctgttg agggccaagg gagagagggc ctatgtagtg 72D
gagccgaacc tcgtgaaaca catcgggctc ttctccagtc tccggtacaa ctttcatccc 780 agtctcctct agggtgccaa gagatgcctt tctgaagttg gccacttctt gaagattcaa 840 atatttatct ctttatttag acatggttgc ctgcaggtat ttcactgttt actgttgtta 900 WO 00/71710 PCTlFR0010142G
? 9 gagatatagg cactggggca gctgaggaac ctcaatatgt taagagcctt ggctttggta 960 gcctcctggc aggagcagca gtttgccaca ggtccggacc tctccctcca cacagccaca 1020 ctgcctcatg cagtctgacc cacccagtga gggtgcattt gaacactgat tatattctcc 1080 atttgttttt aagctctgct ttgtgttaga gcttgtgact gccaaaaatt ttgtgcacag 1140 tgatatgact gttttaggat cttaagggta gaattttgtg aaaggtgaga tcctttggaa 1200 ttgagttctt tctcattggg tatgaaaatg gatgtatgtt tagaatatat gcccaacgag 1260 gcaggaccat gtggatagat tccatttgtt tccttgacct gatgtaataa aaactgataa 1320 aagccgtgca gtgcccggca tcttggaggc aggtgatctg gcttttctgt tacctgggat 1380 tttcttttcc tatatatctg tagtgcactg ataattgata ttgttagtga gaactttaag 1440 gcacgacaag atctggaaga gcttgtgaac catcaaagtc agattgctta tgttgagtag 1500 tgatttaaca ttgaacattt ctgtactact ctgactcttt gaaaattgga catttcagaa 1560 tgatacaata taggggagct ctttacaagt agcatatcat ttttcctgac tttcctggct 1620 gactgcttac gaaaaaaaaa aaaaaaaagc atggactgaa gtcagaagac ctgacctttt 1680 atttcagatc tctgccatgg cctaacgacg tgaccacctt gggcaggnca tatantcact 1740 ctgggnntca atttcttçga accngtaaaa tgaggacagt aatacttaca tgttaaagtt 1800 gccttgagga ttaaatngca gaatatatgt aaaacaccta gcaagngctt agtccatagn 1860 agacacttgg caaacttttc tctcctataa taaacatata caactcaagc ttnnngcgga 1920 aaaagatatt ggtgatgttg tttaaagtat gagatagggc atggagctgc cacctatgta 1980 ccagctattc cagatgacca agccctgcta gaataaagac tgacttttca ttgtgacctc 2040 tgaaggatgt gcagctcagc tttcacctat ccccacgttc acccaagcca aaaagaagaa 2100 ttgttcattc aaactggaaa tgatctccag cttggaaatg agacttctca tgagcttatt 2160 ctaagatcag agtctgaaaa ttattttctc aaaagttaca aataaatgtc ttttaacagt 2220 actgtcagac tagtgaccaa caagttactt tatgaggatg gatgatgata ttagagttca 2280 agcaattgtc cagtttgttt cgatgccaca gtttgctttt aaattcccat agtgagcttc 2340 catcttgaga cccactcaac acagaaggat tacataaagg ttgatcaccc acgctctaca 2400 gatgaacaaa ttgagaccca gagatgctaa actgctctgc aggtcacaaa cctgaacagc 2460 agcatagcca aaatgggaac ggagctcttc tgacttcaag cccctgcact tttttcttaa 2520 ccacattaat tttatgaata tctatgtggt caaagtctct tttgtaaaat ctgagtataa 2580 gctgaactag atcatgtctc tgtaagctaa gatggcagaa acacattgtc atgttagttt 2640 ggaggagcaa acagatataa gtatgtgttg taatgttata gtgagctgtt atgtatcccc 2700 cagcaatgtc caaagtgatc agagctacta gatgacttat tacaatgttc agatcccact 2760 ccttcattcc tcctctctca gtgacctgtc tacccccaag ctttagaact gagctctctc 2820 caacttagaa ctcattagag tttgttgcat tagtgattgg atctcctcat gaaagttttt 2880 tgaccaatga cagtagagcc cctttaagct agccaggccc aagataggga agcactgctg 2940 gtttacattt ctgctctttc taattcagtt gtctattgca tgcagacatc ccctgcccga 3000 cttctccatt atggaaggct aaggccatcc ttccttgtcc agtttctcta cctacacact 3060 aacatgcctt ttccccatgg agtgaactct gccagttgtc tttggacatt ttctgcagat 3120 gcaggctcag ttctgctctt ttgttcccac ccacttctag atcttcctcc atttaatccc 3180 ttattcttat aaggagtcta atttttgtgt attgtccttg attagggcag ctgacagctt 3240 tacaccaaag ctgaagtctc tcacttaatc ctaagcaagg ggctagggag aactaagata 3300 tccttcccat atcaagggat ataggttact agaagggtgg aggtctctta acaggctcac 3360 tcacctttca gagtttaaat tatggtcagg cttaagaagc tctc 3404 <210> 29 <211> 792 <212> DNA
<213> Homo sapiens WO 00/71710 PCTlFR0010142G
<400> 29 ttgtacagca agttagctct tcagggagtt agctctgtct atcctgcccc tgtctgccta 60 gccactcctt ttctaggtag agtggacctt gctgttcacg tcatagatgg ccattccgtg 120 tacctagact cctttttatt cctttgccaa caagtaattg gaatgtttgg atttaagaac 180 atgtctgtgc tttgcaattt catgtgacca tggtgaaatt atgcacacat tctatcattg 240 tgattcaaca agtatttttt gaatgctgct gtgcatgagg catggtgtta gatggcagat 300 tgacagaaat gactaataca ggtatctggc ctcaaggagt ttacagtttc ataggagaaa 360 gaaaaacaaa actagcaatt ctggtaagca gtatgtgttt tggagagcac ttaacttcat 420 cagagagcat ggttgaaggt gtatctgtgt gtatgagaag gtgttggtga taattagaag 480 gcttccctaa agaggtcact cctggggttg agccataaag atcaagtaga tacaagtggg 540 catgaagcta gtattttgct gccagtcatt tctgtagtta ggttgcctat gtggttggag 600 catgtatgta ttgttacagg tgtagtctgc ttggcttccc taagagaatg ccccagtcct 660 ggccagaata tacatgtctt ttttagggtt tgcaccaagg ggaatagaga gtgtctggct 720 cagtacaaat ctgtttccgt tactccatta tccagaaagc cactgaaatg gcattagcct 780 acacttaatg gg 792 <210> 30 <211> 2733 <212> DNA
<213> Homo sapiens <400> 30 ccacttgcca tgaacatgcc acatgccagc aaagagaagg gaagaagatc tgtatttgca 60 actatggatt tgtagggaac gggaggactc agtgtgttga taaaaatgag tgccagtttg 120 gagccactct tgtctgtggg aaccacacat cttgccacaa cacccccggg ggcttctatt 180 gcatttgcct ggaaggatat cgagccacaa acaacaacaa gacattcatt cccaacgatg 240 gcaccttttg tacagacata gatgagtgtg aagtttctgg cctgtgcagg catggagggc 300 gatgcgtgaa cactcatggg agctttgaat gctactgtat ggatggatac ttgccaagga 360 atggacctga acctttccac ccgaccaccg atgccacatc atgcacagaa atagactgtg 420 gtacccctcc tgaggttcca gatggctata tcataggaaa ttatacgtct agtctgggca 480 gccaggttcg ttatgcttgc agagaaggat tcttcagtgt tccagaagat acagtttcaa 540 gctgcacagg cctgggcaca tgggagtccc caaaattaca ttgccaagag atcaactgtg 600 gcaaccctcc agaaatgcgg cacgccatct tggtaggaaa tcacagctcc aggctgggcg 660 gtgtggctcg ctatgtctgt caagagggct ttgagagccc tggaggaaag atcacttctg 720 tttgcacaga gaaaggcacc tggagagaaa gtactttaac atgcacagaa attctgacaa 780 agattaatga tgtatcactg tttaatgata cctgtgtgag atggcaaata aactcaagaa 840 gaataaaccc caagatctca tatgtgatat ccataaaagg acaacggttg gaccctatgg 900 aatcagttcg tgaggagaca gtcaacttga ccacagacag caggacccca gaagtgtgcc 960 tagccctgta cccaggcacc aactacaccg tgaacatctc cacagcacct cccaggcgct 1020 cgatgccagc cgtcatcggt ttccagacag ctggtagcag aaactcccac gggagaaata 1080 cacatataaa agaagttgat ctcttagaag atgatggaag tttcaatatt tcaatattta 1140 atgaaacttg tttgaaattg aacaggcgtt ctaggaaagt tggatcagaa cacatgtacc 1200 aatttaccgt tctgggtcag aggtggtatc tggctaactt ttctcatgca acatcgttta 1260 acttcacaac gagggaacaa gtgcctgtag tgtgtttgga tctgtaccct acgactgatt 1320 atacggtgaa tgtgaccctg ctgagatctc ctaagcggca ctcagtgcaa ataacaatag 1380 caactccccc agcagtaaaa cagaccatca gtaacatttc aggatttaat gaaacctgct 1440 WO 00/71710 PCTlFR0010142G

tgagatggag aagcatcaag acagctgata tggaggagat gtatttattc cacatttggg 1500 gccagagatg gtatcagaag gaatttgccc aggaaatgac ctttaatatc agtagcagca 1560 gccgagatcc cgaggtgtgc ttggacctac gtccgggtac caactacaat gtcagtctcc 1620 gggctctgtc ttcggaactt cctgtggtca tctccctgac aacccagata acagagcctc 1680 ccctcccgga agtagaattt tttacggtgc acagaggacc tctaccacgc ctcagactga 1740 ggaaagccaa ggagaaaaat ggaccaatca gttcatatca ggtgttagtg cttcccctgg 1800 ccctccaaag cacattttct tgtgattctg aaggcgcttc ctccttcttt agcaacgcct 1860 ctgatgctga tggatacgtg gctgcagaac tactggccaa agatgttcca gatgatgcca 1920 tggagatacc tataggagac aggctgtact atggggaata ttataatgca cccttgaaaa 1980 gagggagtga ttactgcatt atattacgaa tcacaagtga atggaataag gtgagaagac 2040 actcctgtgc agtttgggct caggtgaaag attcgtcact catgctgctg cagatggcgg 2100 gtgttggact gggttccctg gctgttgtga tcattctcac attcctctcc ttctcagcgg 2.160 tgtgatggca gatggacact gagtggggag gatgcactgc tgctgggcag gtgttctggc 2220 agcttctcag gtgcccgcac agaggctccg tgtgacttcc gtccagggag catgtgggcc 2280 tgcaactttc tccattccca gctgggcccc attcctggat ttaagatggt ggctatccct 2340 gaggagtcac cataaggaga aaactcagga attctgagtc ttccctgcta caggaccagt 2400 tctgtgcaat gaacttgaga ctcctgatgt acactgtgat attgaccgaa ggctacatac 2460 agatctgtga atcttggctg ggacttcctc tgagtgatgc ctgagggtca gctcctctag 2520 acattgactg caagagaatc tctgcaacct cctatataaa agcatttctg ttaattcatt 2580 cagaatccat tctttacaat atgcagtgag atgggcttaa gtttgggcta gagtttgact 2640 ttatgaagga ggtcattgaa aaagagaaca gtgacgtagg caaatgtttc aagcacttta 2700 gaaacagtac ttttcctata attagttgat ata 2733 <210> 31 <211> 2694 <212> DNA
<213> Homo sapiens <400> 31 ccacttgcca tgaacatgcc acatgccagc aaagagaagg gaagaagatc tgtatttgca 60 actatggatt tgtagggaac gggaggactc agtgtgttga taaaaatgag tgccagtttg 120 gagccactct tgtctgtggg aaccacacat cttgccacaa cacccccggg ggcttctatt 180 gcatttgcct ggaaggatat cgagccacaa acaacaacaa gacattcatt cccaacgatg 240 gcaccttttg tacagacata gatgagtgtg aagtttctgg cctgtgcagg catggagggc 300 gatgcgtgaa cactcatggg agctttgaat gctactgtat ggatggatac ttgccaagga 360 atggacctga acctttccac ccgaccaccg atgccacatc atgcacagaa atagactgtg 420 gtacccctcc tgaggttcca gatggctata tcataggaaa ttatacgtct agtctgggca 480 gccaggttcg ttatgcttgc agagaaggat tcttcagtgt tccagaagat acagtttcaa 540 gctgcacagg cctgggcaca tgggagtccc caaaattaca ttgccaagag atcaactgtg 600 gcaaccctcc agaaatgcgg cacgccatct tggtaggaaa tcacagctcc aggctgggcg 660 gtgtggctcg ctatgtctgt caagagggct ttgagagccc tggaggaaag atcacttctg 720 tttgcacaga gaaaggcacc tggagagaaa gtactttaac atgcacagaa attctgacaa 780 agattaatga tgtatcactg tttaatgata cctgtgtgag atggcaaata aactcaagaa 840 gaataaaccc caagatctca tatgtgatat ccataaaagg acaacggttg gaccctatgg 900 aatcagttcg tgaggagaca gtcaacttga ccacagacag caggacccca gaagtgtgcc 960 tagccctgta cccaggcacc aactacaccg tgaacatctc cacagcacct cccaggcgct 1020 cgatgccagc cgtcatcggt ttccagacag ctgaagttga tctcttagaa gatgatggaa 1080 WO 00/71710 PCTlFR0010142G

gtttcaatat ttcaatattt aatgaaactt gtttgaaatt gaacaggcgt tctaggaaag 1140 ttggatcaga acacatgtac caatttaccg ttctgggtca gaggtggtat ctggctaact 1200 tttctcatgc aacatcgttt aacttcacaa cgagggaaca agtgcctgta gtgtgtttgg 1260 atctgtaccc tacgactgat tatacggtga atgtgaccct gctgagatct cctaagcggc 1320 actcagtgca aataacaata gcaactcccc cagcagtaaa acagaccatc agtaacattt 1380 caggatttaa tgaaacctgc ttgagatgga gaagcatcaa gacagctgat atggaggaga 1440 tgtatttatt ccacatttgg ggccagagat ggtatcagaa ggaatttgcc caggaaatga 1500 cctttaatat cagtagcagc agccgagatc ccgaggtgtg cttggaccta cgtccgggta 1560 ccaactacaa tgtcagtctc cgggctctgt cttcggaact tcctgtggtc atctccctga 1620 caacccagat aacagagcct cccctcccgg aagtagaatt ttttacggtg cacagaggac 1680 ctctaccacg cctcagactg aggaaagcca aggagaaaaa tggaccaatc agttcatatc 1740 aggtgttagt gcttcccctg gccctccaaa gcacattttc ttgtgattct gaaggcgctt 1800 cctccttctt tagcaacgcc tctgatgctg atggatacgt ggctgcagaa ctactggcca 1860 aagatgttcc agatgatgcc atggagatac ctataggaga caggctgtac tatggggaat 1920 attataatgc acccttgaaa agagggagtg attactgcat tatattacga atcacaagtg 1980 aatggaataa ggtgagaaga cactcctgtg cagtttgggc tcaggtgaaa gattcgtcac 2040 tcatgctgct gcagatggcg ggtgttggac tgggttccct ggctgttgtg atcattctca 2100 cattcctctc cttctcagcg gtgtgatggc agatggacac tgagtgggga ggatgcactg 2160 ctgctgggca ggtgttctgg cagcttctca ggtgcccgca cagaggctcc gtgtgacttc 2220 cgtccaggga gcatgtgggc ctgcaacttt ctccattccc agctgggccc cattcctgga 2280 tttaagatgg tggctatccc tgaggagtca ccataaggag aaaactcagg aattctgagt 2340 cttccctgct acaggaccag ttctgtgcaa tgaacttgag actcctgatg .tacactgtga 2400 tattgaccga aggctacata cagatctgtg aatcttggct gggacttcct ctgagtgatg 2460 cctgagggtc agctcctcta gacattgact gcaagagaat ctctgcaacc tcctatataa 2520 aagcatttct gttaattcat tcagaatcca ttctttacaa tatgcagtga gatgggctta 2580 agtttgggct agagtttgac tttatgaagg aggtcattga aaaagagaac agtgacgtag 2640 gcaaatgttt caagcacttt agaaacagta cttttcctat aattagttga tata 2694 <210> 32 <211> 2765 <212> DNA
<213> Homo sapiens <400> 32 cacagcagca cattcactat tcagggtgag ccacaggagg aaagaagaga aatagagttt 60 agacgtctgt gccacttgcc atgaacatgc cacatgccag caaagagaag ggaagaagat 120 ctgtatttgc aactatggat ttgtagggaa cgggaggact cagtgtgttg ataaaaatga 180 gtgccagttt ggagccactc ttgtctgtgg gaaccacaca tcttgccaca acacccccgg 240 gggcttctat tgcatttgcc tggaaggata tcgagccaca aacaacaaca agacattcat 300 tcccaacgat ggcacctttt gtacagacat agatgagtgt gaagtttctg gcctgtgcag 360 gcatggaggg cgatgcgtga acactcatgg gagctttgaa tgctactgta tggatggata 420 cttgccaagg aatggacctg aacctttcca cccgaccacc gatgcc ~ cat catgcacaga 480 aatagactgt ggtacccctc ctgaggttcc agatggctat atcataggaa attatacgtc 540 tagtctgggc agccaggttc gttatgcttg cagagaagga ttcttcagtg ttccagaaga 600 tacagtttca agctgcacag gcctgggcac atgggagtcc ccaaaattac attgccaaga 660 gatcaactgt ggcaaccctc cagaaatgcg gcacgccatc ttggtaggaa atcacagctc 720 caggctgggc ggtgtggctc gctatgtctg tcaagagggc tttgagagcc ctggaggaaa 780 WO 00/71710 ~~ PCTlFR0010142G
gatcacttct gtttgcacag agaaaggcac ctggagagaa agtactttaa catgcacaga 840 aattctgaca a.agattaatg atgtatcact gtttaatgat acctgtgtga gatggcaaat 900 aaactcaaga agaataaacc ccaagatctc atatgtgata tccataaaag gacaacggtt 960 ggaccctatg gaatcagttc gtgaggagac agtcaacttg accacagaca gcaggacccc 1020 agaagtgtgc ctagccctgt acccaggcac caactacacc gtgaacatct ccacagcacc 108D
tcccaggcgc tcgatgccag ccgtcatcgg tttccagaca gctgaagttg atctcttaga 1140 agatgatgga agtttcaata tttcaatatt taatgaaact tgtttgaaat tgaacaggcg 1200 ttctaggaaa gttggatcag aacacatgta ccaatttacc gttctgggtc agaggtggta 1260 tctggctaac ttttctcatg caacatcgtt taacttcaca acgagggaac aagtgcctgt 1320 agtgtgtttg gatctgtacc ctacgactga ttatacggtg aatgtgaccc tgctgagatc 1380 tcctaagcgg cactcagtgc aaataacaat agcaactccc ccagcagtaa aacagaccat 1440 cagtaacatt tcaggattta atgaaacctg cttgagatgg agaagcatca agacagctga 1500 tatggaggag atgtatttat tccacatttg gggccagaga tggtatcaga aggaatttgc 1560 ccaggaaatg acctttaata tcagtagcag cagccgagat cccgaggtgt gcttggacct 1620 acgtccgggt accaactaca atgtcagtct ccgggctctg tcttcggaac ttcctgtggt 1680 catctccctg acaacccaga taacagagcc tcccctcccg gaagtagaat tttttacggt 1740 gcacagagga cctctaccac gcctcagact gaggaaagcc aaggagaaaa atggaccaat 1800 cagttcatat caggtgttag tgcttcccct ggccctccaa agcacatttt cttgtgattc 1860 tgaaggcgct tcctccttct ttagcaacgc ctctgatgct gatggatacg tggctgcaga 1920 actactggcc aaagatgttc cagatgatgc catggagata cctataggag acaggctgta 1980 ctatggggaa tattataatg cacccttgaa aagagggagt gattactgca ttatattacg 2040 aatcacaagt gaatggaata aggtgagaag acactcctgt gcagtttggg ctcaggtgaa 2100 agattcgtca ctcatgctgc tgcagatggc gggtgttgga ctgggttccc tggctgttgt 2160 gatcattctc acattcctct ccttctcagc ggtgtgatgg cagatggaca ctgagtgggg 2220 aggatgcact gctgctgggc aggtgttctg gcagcttctc aggtgcccgc acagaggctc 2280 cgtgtgactt ccgtccaggg agcatgtggg cctgcaactt tctccattcc cagctgggcc 2340 ccattcctgg atttaagatg gtggctatcc ctgaggagtc accataagga gaaaactcag 2400 gaattctgag tcttccctgc tacaggacca gttctgtgca atgaacttga gactcctgat 246D
gtacactgtg atattgaccg aaggctacat acagatctgt gaatcttggc tgggacttcc 2520 tctgagtgat gcctgagggt cagctcctct agacattgac tgcaagagaa tctctgcaac 2580 ctcctatata aaagcatttc tgttaattca ttcagaatcc attctttaca atatgcagtg 2640 agatgggctt aagtttgggc tagagtttga ctttatgaag gaggtcattg aaaaagagaa 2700 cagtgacgta ggcaaatgtt tcaagcactt tagaaacagt acttttccta taattagttg 2760 atata 2765 <210> 33 <211> 4745 <212> DNA
<213> Homo sapiens <400> 33 gaccagatcc atgactgttg gtggagcatt tcatactact gaagctgaag ctagttctca 60 gagtttgact cagatatatg ccttacctga aattcctcaa gatcaaaatg ctgcagaatc 120 gtgggaaacc t ~ tagaagcgg acttaattga acttagccaa ctggtcactg acttctctct 180 cctagtgaat tctcagcagg agaagattga cagcattgca gaccatgtca acagtgctgc 240 tgtgaatgtt gaagagggaa ccaaaaactt agggaaggct gcaaaataca agctggcagc 300 tctgcctgtg gcaggtgcac tcatcggggg aatggtaggg ggtcctattg gcctccttgc 360 WO 00/71710 PCTlFR0010142G

aggcttcaaa gtggcaggaa ttgcagctgc acttggtggt ggggtgttgg gcttcacagg 420 tggaaaattg atacaaagaa agaaacagaa aatgatggag aagctcactt ccagctgtcc 480 agatcttccc agccaaactg acaagaaatg cagttaaaaa ccaaatttca gtattattgg 540 tgccaacatg tctatcctga ggacctttgc tgctgttgga cactccgtca ccttttggaa 600 cacaagtata tcaagatagt ggctactgat gttcaagtgg gattgaagtg tgataaatgg 660 atatattttg ttgtttgctg gggtgttcat ggagatgtta agagattgag gccctgggct 720 gagggtatat aatgtatgtc aggtaaagtt tgaagactgc caaggagcag attttctccc 780 tggaaatgtg aaaactgaac ctataactct gataaggact tgagatgtgt agaaacgttg 840 ggttatggaa gactagtttc ttccataacc ctgaattgga gaccttaatg ctaagtgtag 900 attattgagg tttgttagtg aggaaaagaa taagagttca gaagcctttg ttatcagata 960 gcgaaatcag ggcctagtga ggagcacagg tcgactacat aatggagtcc attggcgaac 1020 cctattgcaa tttggtccaa ctatatcttc tggtgaagga aattaatgat gtaagaaaat 1080 gcaagaggct caacttctct tccaaaaatc ttctggcttc tgaactçttc ctctgcctct 1140 ctttaaataa ataacacaga atttcaagtg gtaggagact tattaagcca gtcaccaagc 1200 ttggtctgtc agcctgtctt ctaacacctc aaagatcttg tgccctgtgc tgtccctccc 1260 ttgtaattat gaaaagttct ttggtttctg gggtgaattc tacccatgta taatgaggaa 1320 ttctctcata accttttttg tcttgtctgt catctctgtt catcccttcc tataacctct 1380 aggtaaaaag aaaagaaaaa aagaaatttc gagatatttt caacattgtt agagtttggg 1440 ctaaaatgag caaggagaaa aaaaccacca agaacatttc ctggggcatg ttccagtttt 1500 gaggggtgat atatctgcca gatagggggt atctgaccca gtcttctttt cagctggtct 1560 ctggggggag ctgagaactc gcttgctacc tcacatcctt ttccccagac tttttatctc 1620 ctatgcatcc ctttgctttc tatagctggt gtttcttccc caaaatggcg ttcccatgct 1680 tacctttctc acattctaga caatgatgga caaagacgca tgcaagactc agacccgggg 1740 aatggtgtgg tgctaatctc aacacctgac attcacagca agcatggccc agcccaaccg 1800 catgtctatc tcaaaccgca gaaaggcttt aatactggaa aaaaagaatt caagactaca 1860 ggcagctccc ctctgtaccc caactcattt aaaataggag gaatcacttt ttgccttact 1920 taacgctttt ttctgagcac agggatgggc acctgcaccc cagaaggtgt gagctgtctc 1980 tctgccagga gctaaggttc attaggggat tggatggttt atcacttctt tctttctgag 2040 tttactttta gtaactttta ttgatggcta cctttcatgt ccctgtctaa agagactttc 2100 tctttcatac gtcttaaatc tcatcaatga aatccagtga aacagcacca tttcttagta 2160 tcattaaata actagaaagt atcaagtatt gctctctgct gctttatatc attaacatat 2220 taataatacc aagaaggaaa tactttgaat aagtgtcaga ttctgatcca gtattggaca 2280 cctgtgatat tggacacctg tgaggctggg ataattactt ttgaattaca cctcttctct 2340 agtttctgga ccttgctctg tcactttaac acagggtgat caaacctgaa tgaggatcag 2400 aactcaccca ggcacatact aaagcaagat tcctaaacct cagttccagg ggtaattctg 2460 acatcacccg tccagcatag tcagctgaaa ttataaatct aagaaacagt tacatcaaga 2520 ttctgctgtg tcatttaatt ctgaaactcc cagtattcta cccttcttca tcactgcata 2580 ttaccccact cttccatccc aaattggcta tcctttcagc ccaccaactt agcggcagca 2640 ctagggattc attataaggt aaatctggtt tacataaaga cctgaaggag gcctgtattt 2700 gaagctcaca cttggtattg gtatctctca tttttactga gccagtgtgg aataccactg 2760 tatgtactca tataagccct tgacttttac tgctcatcag gattggaata ttactctagc 2820 agtcttcaca cataggcaag ttacagtcct tttaaaaagn atctcatttc cctataatgg 2880 aacctaatag ccaacttttt catagaaatt gctagaagag tttgatcaac tataaatgat 2940 aaagtgttta taagcatagt cagtgtgaca cagaaaccaa tcttaaaatt gaatttaatg 3000 ttttatcata tcagattaaa tattttctcc atgtcttatt tttactgcaa caagttagaa 3060 agtgggaaca ctttgattaa tgtcttaaaa tttgtgggcc ctcatttgga taaaggcagc 3120 aatcctaagg actttttttt tttttaacat aatctgagaa tttctctgta gagcagagac 3180 tttcaaacct tttggctgta acccacagta aaaaacgcat ttatatcaaa ccttagaata 3240 WO 00/71710 ~~ PCTlFR0010142G
tgtttaatga acaatactta ccattctgat gctttttatt gtttcagttt ttaaaatatg 3300 ccagttgcaa çccactaaat tgatatctac caatgggttg caacccttag cttgaaaaaa 3360 acaccctcac agaggaactg gtatttcttg aataccttct gtttgccagg cacttcacca 3420 ggcattttac aagtaaggaa actgggcttc agagaaaata atttgcagag gtttactcaa 3480 ctacaaaggg gtgaagccag gaatgttaac taggtctgtt gagctacaaa aacttttatg 3540 tctctcagac tatacagcct ctatacaaaa ttgagatggg ggttgggggc aggggctcat 3600 gcctgcaatc ccagcactta gggaggcaga ggccagagga tcacttgagc ccaggagttt 3660 gagaccagcc tgggcaacat agtgagactc tgtctgtatg aaaaaaatta agaattagct 3720 gggtgtggca tagcacacac ctgtggtccc agctacatgg gaagctgaag tgggaggatc 3780 acttgaactc aggagcagcc ttggtgacag aacaagaccc tctctcaaaa aaatatttaa 3840 aaaaaggtgg gtcatccatt ctcctttacc aaacaggctt tgaaatgaca cattccattc 3900 atttgcatct ttttaaaaaa cttctgattc cttactgagt gtccagcagc ctcaaagttt 3960 ttaatggtag ctgatgcaga cataaacagt gctcaatttg gcccttaaac tataaaatca 4020 agaaagtgta tttcaatccc atccacctgc ctgcaagatt tcttaatgtt cactagttat 4080 aaccattgtt taaacagtgc tttttgtgta atttaaaaat aaactttaat gctttttaaa 4140 acaaatttat cataattcat agatcaaatg attatccttt aaaatgatac ccttgggaaa 4200 tcatgtactt actgtagtga tgctagtatt aatattactt agaccaattt tgaagctgct 4260 ctttcagaat tgcctccaaa gacattttgc agatcatccc agaaaagggg gtatgatggt 4320 gctgtgtaga actgaccaga gttcctggag gattttgagg ttatactgaa actgagtgct 4380 gtacagggag aattgcatga gtccagaaac ttccttctgt gggctgcctg ccttcctgcc 4440 ctcccttaag tgctctaaga tttttgtaca ggagtaagaa tcaaatactg gtaacatcaa 4500 tcacaagaag ttgaggaaac ctgtaatata gctagataat atacaacgtt tgtcttccat 4560 cagagtgcag aaaccaaacc atgctttgtg ttaaccttaa atatgaaagg tgtttctcag 4620 ggtccccttt gtccttcgtt gctgccatat gaaatcttac aaggaaggat gaggaaaagc 4680 ctggggggag gttctcctcg gaaatgaggt ggtttttttt gttattaagt agaaccgtgg 4740 ctgtg 4745 <210> 34 <211> 5241 <212> DNA
c213> Homo sapiens <400> 34 tgcgccgtgc ccaccgcccg gcctcgagcg ccccggcggg aggtttttct atatgagtgg 60 agaagacagc tgttaccagg gaggtcatac aacatttttt taggatgtct gaagatgaag 120 aaaaagtgaa attacgccgt cttgaaccag ctatccagaa attcattaag atagtaatcc 1B0 caacagacct ggaaaggtta agaaagcacc agataaatat tgagaagtat caaaggtgca 240 gaatctggga caagttgcat gaagagcata tcaatgcagg acgtacagtt cagcaactcc 300 gatccaatat ccgagaaatt gagaaacttt gtttgaaagt ccgaaaggat gacctagtac 360 ttctgaagag aatgatagat cctgttaaag aagaagcatc agcagcaaca gcagaatttc 420 tccaactcca tttggaatct gtagaagaac ttaagaagca atttaatgat gaagaaactt 480 tgctacagcc tcctttgacc agatccatga ctgttggtgg agcatttcat actactgaag 540 ctgaagctag ttctcagagt ttgactcaga tatatgcctt acctgaaatt cctcaagatc 600 aaaatgctgc agaatcgtgg gaaaccttag aagcggactt aattgaactt agccaactgg 660 tcactgactt ctctctccta gtgaattctc agcaggagaa gattgacagc attgcagacc 720 atgtcaacag tgctgctgtg aatgttgaag agggaaccaa aaacttaggg aaggctgcaa 780 aatacaagct ggcagctctg cctgtggcag gtgcactcat cgggggaatg gtagggggtc 840 WO 00/71710 PCTlFR0010142G

ctattggcct ccttgcaggc ttcaaagtgg caggaattgc agctgcactt ggtggtgggg 900 tgttgggctt cacaggtgga aaattgatac aaagaaagaa acagaaaatg atggagaagc 960 tcacttccag ctgtccagat cttcccagcc aaactgacaa gaaatgcagt taaaaaccaa 1020 atttcagtat tattggtgcc aacatgtcta tcctgaggac ctttgctgct gttggacact 1080 ccgtcacctt ttggaacaca agtatatcaa gatagtggct actgatgttc aagtgggatt 1140 gaagtgtgat aaatggatat attttgttgt ttgctggggt gttcatggag atgttaagag 1200 attgaggccc tgggctgagg gtatataatg tatgtcaggt aaagtttgaa gactgccaag 1260 gagcagattt tctccctgga aatgtgaaaa ctgaacctat aactctgata aggacttgag 1320 atgtgtagaa acgttgggtt atggaagact agtttcttcc ataaccctga attggagacc 1380 ttaatgctaa gtgtagatta ttgaggtttg ttagtgagga aaagaataag agttcagaag 1440 cctttgttat cagatagcga aatcagggcc tagtgaggag cacaggtcga ctacataatg 1500 gagtccattg gcgaacccta ttgcaatttg gtccaactat atcttctggt gaaggaaatt 1560 aatgatgtaa gaaaatgcaa gaggctcaac ttctcttcca aaaatcttct ggcttctgaa 1620 ctcttcctct gcctctcttt aaataaataa cacagaattt caagtggtag gagacttatt 1680 aagccagtca ccaagcttgg tctgtcagcc tgtcttctaa cacctcaaag atcttgtgcc 1740 ctgtgctgtc cctcccttgt aattatgaaa agttctttgg tttctggggt gaattctacc 1800 catgtataat gaggaattct ctcataacct tttttgtctt gtctgtcatc tctgttcatc 1860 ccttcctata acctctaggt aaaaagaaaa gaaaaaaaga aatttcgaga tattttcaac 1920 attgttagag tttgggctaa aatgagcaag gagaaaaaaa ccaccaagaa catttcctgg 1980 ggcatgttcc agttttgagg ggtgatatat ctgccagata gggggtatct gacccagtct 2040 tcttttcagc tggtctctgg ggggagctga gaactcgctt gctacctcac atccttttcc 2100 ccagactttt tatctcctat gcatcccttt gctttctata gctggtgttt cttccccaaa 2160 atggcgttcc catgcttacc tttctcacat tctagacaat gatggacaaa gacgcatgca 222D
agactcagac ccggggaatg gtgtggtgct aatctcaaca cctgacattc acagcaagca 228D
tggcccagcc caaccgcatg tctatctcaa accgcagaaa ggctttaata ctggaaaaaa 2340 agaattcaag actacaggca gctcccctct gtaccccaac tcatttaaaa taggaggaat 2400 cactttttgc cttacttaac gcttttttct gagcacaggg atgggcacct gcaccccaga 2460 aggtgtgagc tgtctctctg ccaggagcta aggttcatta ggggattgga tggtttatca 2520 cttctttctt tctgagttta cttttagtaa cttttattga tggctacctt tcatgtccct 2580 gtctaaagag actttctctt tcatacgtct taaatctcat caatgaaatc cagtgaaaca 2640 gcaccatttc ttagtatcat taaataacta gaaagtatca agtattgctc tctgctgctt 2700 tatatcatta acatattaat aataccaaga aggaaatact ttgaataagt gtcagattct 2760 gatccagtat tggacacctg tgatattgga cacctgtgag gctgggataa ttacttttga 2820 attacacctc ttctctagtt tctggacctt gctctgtcac tttaacacag ggtgatcaaa 2880 cctgaatgag gatcagaact cacccaggca catactaaag caagattcct aaacctcagt 2940 tccaggggta attctgacat cacccgtcca gcatagtcag ctgaaattat aaatctaaga 3000 aacagttaca tcaagattct gctgtgtcat ttaattctga aactcccagt attctaccct 3060 tcttcatcac tgcatattac cccactcttc catcccaaat tggctatcct ttcagcccac 3120 caacttagcg gcagcactag ggattcatta taaggtaaat ctggtttaca taaagacctg 3180 aaggaggcct gtatttgaag ctcacacttg gtattggtat ctctcatttt tactgagcca 3240 gtgtggaata ccactgtatg tactcatata agcccttgac ttttactgct catcaggatt 3300 ggaatattac tctagcagtc ttcacacata ggcaagttac agtcctttta aaaagnatct 3360 catttcccta taatggaacc taatagccaa ctttttcata gaaattgcta gaagagtttg 3420 atcaactata aatgataaag tgtttataag catagtcagt gtgacacaga aaccaatctt 3480 aaaattgaat ttaatgtttt atcatatcag attaaatatt ttctccatgt cttattttta 3540 ctgcaacaag ttagaaagtg ggaacacttt gattaatgtc ttaaaatttg tgggccctca 3600 tttggataaa ggcagcaatc ctaaggactt tttttttttt taacataatc tgagaatttc 3660 tctgtagagc agagactttc aaaccttttg gctgtaaccc acagtaaaaa acgcatttat 3720 WO 00/71710 ~ 7 PCTlFR0010142G
atcaaacctt agaatatgtt taatgaacaa tacttaccat tctgatgctt tttattgttt 3780 cagtttttaa aatatgccag ttgcaaccca ctaaattgat atctaccaat gggttgcaac 3840 ccttagcttg aaaaaaacac cctcacagag gaactggtat ttcttgaata ccttctgttt 3900 gccaggcact tcaccaggca ttttacaagt aaggaaactg ggcttcagag aaaataattt 3960 gcagaggttt actcaactac aaaggggtga agccaggaat gttaactagg tctgttgagc 4020 tacaaaaact tttaCgtctc tcagactata cagcctctat acaaaattga gatgggggtt 4080 gggggcaggg gctcatgcct gcaatcccag cacttaggga ggcagaggcc agaggatcac 4140 ttgagcccag gagtttgaga ccagcctggg caacatagtg agactctgtc tgtatgaaaa 4200 aaattaagaa ttagctgggt gtggcatagc acacacctgt ggtcccagct acatgggaag 4260 ctgaagtggg aggatcactt gaactcagga gcagccttgg tgacagaaca agaccctctc 4320 tcaaaaaaat atttaaaaaa aggtgggtca tccattctcc tttaccâaac aggctttgaa 4380 atgacacatt ccattcattt gcatcttttt aaaaaacttc tgattcctta ctgagtgtcc 4440 agcagcctca aagtttttaa tggtagctga tgcagacata aacagtgctc aatttggccc 4500 ttaaactata aaatcaagaa agtgtatttc aatcccatcc acctgcctgc aagatttctt 4560 aatgttcact agttataacc attgtttaaa cagtgctttt tgtgtaattt aaaaataaac 4620 tttaatgctt tttaaaacaa atttatcata attcatagat caaatgatta tcctttaaaa 4680 tgataccctt gggaaatcat gtacttactg tagtgatgct agtattaata ttacttagac 4740 caattttgaa gctgctcttt cagaattgcc tccaaagaca ttttgcagat catcccagaa 4800 aagggggtat gatggtgctg tgtagaactg accagagttc ctggaggatt ttgaggttat 4860 actgaaactg agtgctgtac agggagaatt gcatgagtcc agaaacttcc ttctgtgggc 4920 tgcctgcctt cctgccctcc cttaagtgct ctaagatttt tgtacaggag taagaatcaa 4980 atactggtaa catcaatcac aagaagttga ggaaacctgt aatatagcta gataatatac 5040 aacgtttgtc ttccatcaga gtgcagaaac caaaccatgc tttgtgttaa ccttaaatat 5100 gaaaggtgtt tctcagggtc ccctttgtcc ttcgttgctg ccatatgaaa tcttacaagg 5160 aaggatgagg aaaagcctgg ggggaggttc tcctcggaaa tgaggtggtt ttttttgtta 5220 ttaagtagaa ccgtggctgt g 5241 <210> 35 <211> 3014 <212> DNA
<213> Homo sapiens <400> 35 cccactctcg ctgttctcct ccactctctc tccccatgaa ggaagagacc actggagttt 60 gcatgtaccc tccaatcaaa acgaggctga taaaaacatt cccggttgat acaatgaccc 120 cgtttcctga tactttcacc acagggccac agtttactgc agacttcaga gacagtaaat 180 tacaatgctg tcctggcccg acttccccgc tgatcccagc agcgaccctg aggcctttga 240 cagagaccgt ctccacagtg cagaccattt acaccacccg gaaacctgtt tctctggcag 300 ccagtgcaga gacactccgg caggaactgg agagagagaa gatgatgaaa agactgttga 360 tgaccgaact gtgaaattct ccccttgtca cctggaagat ggcatggtgc cttctgtccg 420 tcttctttct tcgggctttg tgtgctcact ctagcacagc atacaagtgt gtgctttgtt 480 cgcccaggtc tccatggtta gttgaagcca atttctggct tgacttttgt gggaaaagtt 540 attttatgtc tcctaagcat tagagttttt ctattactct atgtagttga gacaggattt 600 gataagtcta ggaaaagaaa gatgggaaaa cgggattcct tttcagaagt acctgtgtgt 660 atctgttaat aaccacaggg gttaatatga, tgtaggatct tttactatca atttcaacca 720 tttgattttg tatgattgaa acttgcaccg agctttgact gtttgttaaa gagtcatttt 780 taatgaaaga ataattcttt attgctggtt tttcatttac actgataaat acacagatct 840 WO 00/71710 3s PCTlFR0010142G
tataaagtct ttaacattca tttgtattca gatgtgagta gaagaactaa aaaaagaaag 900 ttacatatca ctatgactga aggtacttca gcttaatctg aaatataatt taacttgtga 960 actccttgga tatgatatta tttggaataa acagaattta tcattgaacc caaagtagga 1020 aatgatagct tacattgtct aaaaatcctt acaaggttaa gatgattcaa tatcaagaat 1080 attcagaaaa ttatttctaa agttgatcga ttcatgtcgt attgatagaa tcttgaccag 1140 aagaaatttt gctcttttta tatagtttca agaaatgtgt ttttaaattt ttattaatgc 1200 acttgaacaa ctttgcagga ataaagcaac cccctaacca caaaatatcc ctctaaatta 1260 gttccctagc tttctcaatg aatacacaca tatttttaca tagctatgat cgttgtgtac 1320 attctccttt gttttacttc tcggcctaac acttgtctcc tcttgtcaac acagattcta 1380 ctctcaccaa tttaaatgtc tttatatcca tgtaacatgg gtaacctcac ttcaccccat 1440 tattagatat ttgagttata tctaattttt cactcttata aatagtgctg ctatgaatgt 1500 ctgtaaaaaa aaaaaaactg ctccttcttt tggattattc ccttaggaat atctccaaag 1560 agggattaca aggtcaaaga gcatgaagta ttttatagct cttgttttat attgccagat 1620 tgctttctag aaagatccaa tctttgggtt ggaaggacct taaaggtcat ctagtttagc 1680 ctccccaccc cctctgaatg cttgaatccc ctcgacaatt tatgatgcca ccagcaatgt 1740 ataagcattt ctgtttacca atagctctgc cagtattggg ttttgccatt tttatttatt 1800 tttgctagtt taataggtat gtatagttgt tcttgaagag ttgttttatt tcattaattg 1860 ctagcaaggc tgagcacttt tccatgtgat gatttactag ttgtatttcc ttgtgtgtaa 1920 aatgttcatt catttcttat gaccacttgt taagaggaac tgatctcata tatttgtatc 1980 agaactgtat ttttatgtta tattgtatag tttgctctcc tgcccctctc cttaaaactg 2040 aatggtgcca ataatttgat actaatgact acaaaaaaag gtaatgcctc atttactagt 2100 attgttgtaa aatgaggaat gtatgtgaat attcagataa ccgaggatta.accctttaag 2160 tgctgaatct ttaaaatttt aatatatttt tttttgaggg aaatctttct aaaatgtatt 2220 acgcacttcc ctgccttagt aaacagagta tactggagag tatttaacct tttcttgatg 2280 agtcatggtc atgattataa acatcagccc cttttatacc ttggtacggt gcagtgatat 2340 cattaagagc tatcaatatg tgtagggctt ggcttggcct tttataggat attatgctgt 2400 tctcactgat ggttttttac tgctctctgc tctgtcagtg gagctatccg gggcaattgt 2460 agcgtttggg tccttttacc cctatgtccc ccggctatac ttttaaaaca gctttagctg 2520 ttctttatct tgtgcacatg atacaaaata tgttcccgta caatatgggg ctgtcacttc 2580 ttgccaaccc agcaccctct tcctcttcta acctgctttc tgaggcttct gctcttcacc 2640 tcctgctcgc tgatggaaac ctccagggca aagctgaagg tttcttgggg aagccaggaa 2700 agccagtatt tcctatgtgt cagatctgct tggcttccaa gaagggatgc atgggctttt 2760 tggccagtgt ttccaggagg ctctgggctt cctgcttctt ccccgcttcc cccagagttc 2820 acagatgttg aagtttctga aggttgacgt cactggaagt ctgaccacaa acaagttggc 2880 tgttactgta tttgaaaccc agtacctttg gcagctcacc tctaaccagt aaaataagag 2940 gattccatgg tttcagcagt tgtcctggtt atttgcctat ttaagtgaat gatgggtgct 3000 tggcattgtg actg 3014 <210> 36 <211> 1575 <212> DNA
<213> Homo sapiens <400> 36 tccaggggag atccagaatg catgtgtctc ttcccacgca tttatgtcat gttggtagct 60 ttagatcagc catggtgaga aaagaacaaa agcttttagt tgtttttgtt ttgttttgga 120 gaatttgttt accagtaaat acatcactgc ctgtacccca aatgttacca gctccctgag 180 WO 00/71710 39 PCTlFR0010142G
gtgtcccaca tactattgtg agttctcaga gcatgaactg tcctcagaag agcagggcta 240 ggacttgtcc cagcatctgt gcctccatac caatcctctt tctcacagag aaccacttcc 300 catataagat gcttaaggct ctcaaaacag cagaacaatg aaacatàctc tccctacact 360 tgcttagcca agagatacca ctcaggtaac ttttttcagg acatggaaga tctgtttcaa 420 ggagatttac tgctatttta tttggaagaa gctggcaact ggtcttgacc aaaatagaaa 480 aaaaaaaaaa agtccacaaa tttaatcact tgtagggaac ccatctatca aggtacccta 540 ccatatactt ttgtatttaa tagattactt agaaaccaca aaaataggaa tccttacccc 600 ttcaattcct gttcaaccct aaaaactgtg ataaacgctc ccaaccctgt ggtgatcagg 660 gttatgtaat gttcaaagat tcagacacac ctgggtttgg attcagttgc aactgggttg 720 ttatcacact cacttctttt tagctgtgtg agcatgaata atttacttag cctctctgtg 780 tctttccacc taattaaaga ggatcyaccc cagggttatt ttgaggattc aaaaaggcat 840 gcaacacacc tggagcacaa ttccactttc attcaactaa ttcccttccc ttcccccttc 900 ttccccttct acaagatcaa tatgtaaagg agacatgagg cttactggtt gcttttgaac 960 acttacttag ttcttagcta cacccactct aaaattaact ggacattagt gtacagccca 1020 tgtccaagcc cagagagaaa acaatgggaa caatttcaag gtcctcacca ctccttcatt 1080 tgcagagggg acaacagact ttctgacctg agaactggag aatttttaaa acaaaatctc 1140 tcattccagc ccaacctatt taactttttg tggaggaatt ttacatggag gaagtgagca 1200 catgtcatgc tagccaagag gacattattg tcattaaaga gaggcattat ttatacaccc 1260 tgcaatgtgc acattaaaat atggaaattt taaaattatg accaagggct tgaaacatat 1320 tggattacat gctcacattt aacaaagaga ggaaatgtgt ttcagtttct ggagtggctg 1380 gaatttacaa gctaattgtt caataaatct actcaagata gttacctaag gctttgtggc 1440 aatgaccttg aactgagagc ctgtatctgg atttagcact tgaaagatct aactggatat 1500 ttgggttaaa agaatcacat ttattcccaa atcggaatgc tttgtttttc ctgtcagtta 1560 attgccagtt gccaa 1575 <210> 37 <211> 1607 <212> DNA
<213> Homo sapiens <400> 37 gcgaatcacg acgggcggtg gccgttgggt cccggcggga ggcggggttt ccgctccctg 60 gggcgcacgt cagtcaggag gcggaagcgc agcgggggcg ggaaggttgt agtgccgcga 120 gttgagctcc tcttgcctaa gtggtcgcgc cccctttaag agcagcgatt gtaaggagag 180 gcggtcccgg tgtcctcggg tcccaggtga ttgtgaagtg ctgaccaatt gccactggac 240 atacttgaaa caaaatagga aaatggcagc aaactcttca ggacaaggtt ttcaaaacaa 300 aaatagagtt gcaatcttgg cagaactgga caaagagaaa agaaaactac ttatgcagaa 360 ccagtcttca acaaatcatc ctggagctag cattgcactc tcgagaccct ctcttaataa 420 ggacttccgg gatcacgctg agcagcagca tattgcagcc caacagaagg cagntttnca 480 gcatgctcat gcacattcat ctggatactt catcactcaa gactctgcat ttgggaacct 540 tattcttcct gttttacctc gccttgaccc agaatgaaga aaacatttgc gatggaaaag 600 tgactttgta atatcaaatg ccaaagctac tatcattcag tgctacatga actgtgactt 660 taagaatttt ggtgaacttt gatatttttt gtttgtctga aagaaaggaa tgtgtaagtg 720 aaagctgaaa gaagaataac caggatgatg agagctgtgg aagctgtatc gtccaaggaa 780 ttgattatgt accgtgactg taactttttt gtaatgctgt ttaactctca atcagactgt 840 gaactggatg gtcacgaagt cattccccaa ctcctagcaa gtttgactga atatatcatg 900 tccacagtag attttcaaga atcatttata gtacttaact ttaaagaaac aaggctgctt 960 WO 00/71710 40 PCTlFR0010142G
ttaaaaaatg aactaatagg cttaaatcaa ttgcatccat atttgctgtt tataggattg 1020 ctatcagtat accttttgcg tttatagtca acatgtatca tcctgaaata ttctttctgg 1080 acttataact acttccccct ttttcacttt aaaacaaacc tcaagaataa attactaacc 1140 agtcttaacc atcttttata aacatatgct cttataaatg ttgtgactag atgcaattaa 1200 aaataatagg gaatgtggta ggtttttaat ttgtacatcc tcttatttag tgttaccaca 1260 taaatgatga gtttgtgtgg ttctgttttc catttttgtt ctaactgaaa actttttggc 1320 tgggcacggt gcctcatgcc tgtaatccca gcactttggg aggccaaggc gggcagatca 1380 cttgagatca ggagtttgag accagcctgg ccaacatggt gaaaccçtgt ctctactaaa 1440 agtataaaaa attagccatg tgtggtggca cacgcctgta ntcccagcta ctcnggaggc 1500 tgaggcagga gaatcgcttg aacctgggag gcaggggttg cagtgagctg agacggtgtc 1560 actgcactcc agcctgggtg acagtgagtc tttgtctcaa agaaaaa 1607 <210> 38 <211> 1161 <212> DNA
<213> Homo sapiens <400> 38 agctcctctt gcctaagtgg tcgcgccccc tttaagagca gcgattgtaa ggagaggcgg 60 tcccggtgtc ctcgggtccc aggtgattgt gaagtgctga ccaattgcca ctggacatac 120 ttgaaacaaa ataggaaaat ggcagcaaac tcttcaggac aaggttttca.aaacaaaaat 180 agagttgcaa tcttggcaga actggacaaa gagaaaagaa aactacttat gcagaaccag 240 tcttcaacaa atcatcctgg agctagcatt gcactctcga gaccctctct taataaggac 300 ttccgggatc acgctgagca gcagcatatt gcagcccaac agaaggcagc tttgcagcat 360 gctcatgcac attcatctgg atacttcatc actcaagact ctgcatttgg gaaccttatt.420 cttcctgttt tacctcgcct tgacccagaa tgaagaaaac atttgcgatg gaaaagtgac 480 tttgtaatat caaatgccaa agctactatc attcagtgct acatgaactg tgactttaag 540 aattttggtg aactttgata ttttttgttt gtctgaaaga aaggaatgtg taagtgaaag 600 ctgaaagaag aataaccagg atgatgagag ctgtggaagc tgtatcgtcc aaggaattga 660 ttatgtaccg tgactgtaac ttttttgtaa tgctgtttaa ctctcaatca gactgtgaac 720 tggatggtca cgaagtcatt ccccaactcc tagcaagttt gactgaatat atcatgtcca 780 cagtagattt tcaagaatca tttatagtac ttaactttaa agaaacaagg ctgcttttaa 840 aaaatgaact aataggctta aatcaattgc atccatattt gctgtttata ggattgctat 900 cagtatacct tttgcgttta tagtcaacat gtatcatcct gaaatattct ttctggactt 960 ataactactt cccccttttt cactttaaaa caaacctcaa gaataaatta ctaaccagtc 1020 ttaaccatct tttataaaca tatgctctta taaatgttgt gactagatgc aattaaaaat 1080 aatagggaat gtggtaggtt tttaatttgt acatcctctt atttagtgtt accacataaa 1140 atgatgagtt tgtgtggttc t 1161 <210> 39 <211> 1332 <212> DNA
<213> Homo sapiens <400> 39 gattaccggt gtganccacc angcccggcc aagaactgat tttaaaataa attccatctc 60 WO 00/71710 4 ~ PCTlFR0010142G
agcaataaca atgaaaaata aatgnatana caaatanatt tggtctcaag cattnagaaa 120 gaggtaattg taatgccctt gggtcganga atgtgnantc tatgtnaata gnttaattgg 180 cctttttgtt tggaatcttt cgcagcatag ctcatgcaca ttcatctgga tacttcatca 240 ctcaagactc tgcatttggg aaccttattc ttcctgtttt acctcgcctt gacccagaat 300 gaagaaaaca tttgcgatgg aaaagtgact ttgtaatatc aaatgccaaa gctactatca 360 ttcagtgcta catgaâctgt gactttaaga attttggtga actttgatat tttttgtttg 420 ' tctga.aagaa aggaatgtgt aagtgaaagc tgaaagaaga ataaccagga tgatgagagc 480 tgtggaagct gtatcgtcca aggaattgat tatgtaccgt gactgtaact tttttgtaat 540 gctgtttaac tctcaatcag actgtgaact ggatggtcac gaagtcattc cccaactcct 600 agcaagtttg actgaatata tcatgtccac agtagatttt caagaatcat ttatagtact 660 taactttaaa gaaacaaggc tgcttttaaa aaatgaacta ataggcttaa atcaattgca 720 tccatatttg ctgtttatag gattgctatc agtatacctt ttgcgtttat agtcaacatg 780 tatcatcctg aaatattctt tctggactta taactacttc cccctttttc actttaaaac 840 aaacctcaag aataaattac taaccagtct taaccatctt ttataaacat atgctcttat 900 aaatgttgtg actagatgca attaaaaata atagggaatg tggtaggttt ttaatttgta 960 catcctctta tttagtgtta ccacataaat gatgagtttg tgtggttctg ttttccattt 1020 ttgttctaac tgaaaacttt ttggctgggc acggtgcctc atgcctgtaa tcccagcact 1080 ttgggaggcc aaggcgggca gatcacttga gatcaggagt ttgagaccag cctggccaac 114D
atggtgaaac cctgtctcta ctaaaagtat aaaaaattag ccatgtgtgg tggcacacgc 1200 ctgtantccc agctactcng gaggctgagg caggagaatc gcttgaacct gggaggcagg 1260 ggttgcagtg agctgagacg gtgtcactgc actccagcct gggtgacagt gagtctttgt 1320 ctcaaagaaa aa 1332 <210> 40 <211> 10419 <212> DNA
<213> Homo sapiens <400> 40 accgcntccg ggctccttcg gccncgccat gggctgctgc agctccgcct cctccgccgc 60 gcagagctcc aaacgagaat ggaagccgct ggaggaccgt agctgcacag acataccatg 120 gctgctgctc ttcatcctct tctgcattgg gatgggattt atttgtggct tttcaatagc 180 aacaggtgca gcagcaagac tagtgtcagg atacgacagc tatggaaata tctgtgggca 240 gaaaaataca aagttggaag caataccaaa cagtggcatg gaccacaccc agcggaagta 300 tgtattcttt ttggatccat gcaacctgga cttgataaac cggaagatta agtctgtagc 360 actgtgtgta gcagcgtgtc caaggcaaga actgaaaact ctgagtgatg ttcagaagtt 420 tgcagagata aatggttcag ccctatgtag ctacanccta aagccttctg aatacactac 480 atctccaaaa tcttctgttc tctgccccaa actaccagtt ccagcgagtg cacctattcc 540 attcttccat cgctgtgctc ctgtgaacât ttcctgctat gccaagtttg cagaggccct 600 gatcaccttt gtcagtgaca atagtgtctt acacaggctg attagtggag taatgaccag 660 caaagaaatt atattgggac tttgcttgtt atcactagtt ctatccatga ttttgatggt 720 gataatcagg tatatatcaa gagtacttgt gtggatctta acgattctgg tcatactcgg 780 ttcacttgga ggcacaggtg tactatggtg gctgtatgca aagcaaagaa ggtctcccaa 840 agaaactgtt actcctgagc agcttcagat agctgaagac aatcttcggg ccctcctcat 900 ttatgccatt tcagctacag tgttcacagt gatcttattc ctgataatgt tggttatgcg 960 caaacgtgtt gctcttacca tcgccttgtt ccacgtagct ggcaaggtct tcattcactt 1020 gccactgcta gtcttccaac ccttctggac tttctttgct cttgtcttgt tttgggtgta 1080 WO 00/71710 PCTlFR0010142G

ctggatcatg acacttcttt ttcttggcac taccggcagt cctgttcaga atgagcaagg 1140 ctttgtggag ttcaaaattt ctgggcctct gcagtacatg tggtggtacc atgtggtggg 1200 cctgatttgg atcagtgaat ttattctagc atgtcagcag atgacagtgg caggagctgt 1260 ggtaacatac tattttacta gggataaaag gaatttgcca tttacaccta ttttggcatc 1320 agtaaatcgc cttattcgtt accacctagg tacggtggca aaaggatctt tcattatcac 1380 attagtcaaa attccgcgaa tgatccttat gtatattcac agtcagctca aaggaaagga 1440 aaatgcttgt gcacgatgtg tgctgaaatc ttgcatttgt tgcctttggt gtcttgaaaa 1500 gtgcctaaat tatttaaatc agaatgcata cacagccaca gctatcaaca gcaccaactt 1560 ctgcacctca gcaaaggatg cctttgtcat tctggtggag aatgctttgc gagtggctac 1620 catcaacaca gtaggagatt ttatgttatt ccttggcaag gtgctgatag tctgcagcac 1680 aggtttagct gggattatgc tgctcaacta ccagcaggac tacacagtat gggtgctgcc 1740 tctgatcatc gtctgcctct ttgctttcct agtcgctcat tgcttcctgt ctatttatga 1800 aatggtagtg gatgtattat tcttgtgttt tgccattgat acaaaataca atgatgggag 1860 ccctggcaga gaattctata tggataaagt gctgatggag tttgtggaaa acagtaggaa 1920 agcaatgaaa gaagctggta agggaggccg tcgctgattc cagagagcta aagccgatgg 1980 cttcgggagc aagttctgct tgaacctagc cgacggttat ggaaacccat tgacattcca 2040 aaacaatata tacacataac tatgtatttg tgtgtgtggg tgtgtgtata tatgtatatg 2100 tatgtgtgta tatatgtata tgtatataca cacacacaca taaatcagcc aaaatcagag 2160 aaaaggaaca gggatttaat acctttttta tgcttatttt tgtcaaacat gtactccttt 2220 catacgggtg gcttttacaa ggcaacttcc gtcatttaat gttttcaact gtaattgtct 2280 taatggaaat gttaaaattc atatctgatt aacattttta ataacttaga ggagatttta 2340 actttattta aaaataggta aaattattgt acctaattat gtctaaagtt tattcagggg 2400 taatttccct gatgtctgta taaaatcaag atcttatttt actgatgcat aagtcctagt 2460 gggtcaagac taggcatatg ctttcagata aataaggaat tactccaatc agttttcccc 2520 aatcaaagaa gccatgtcat tttactttta gaaacataca attgggccca atatgggaat 2580 tttcataata gttcatacat ttgtcagcca acattaaaag gtaaccaact cctcaggtat 2640 ttgtagttta ccctaacgct tctttaaaag aaagtaggta aaaaaagaaa agggtagata 2700 atctttcgta tgcaaacttt tcccttatat tttgtctttc tttccttttt gactttagta 2760 gcatcctcca cacatttgtg tgcctgattt gaaaggaagc tggggcaccc agcgagttta 2820 gcctttaagt ttctgtgtat tgatttgcag attaagtaat gctgggagga ataaagaagg 2880 gacagaaaca tggaacataa agcattgaaa attccggtgc ttgggcttcg gcttcagagt 2940 aacgtcagtg gcttagggtt aaacggccat tttattcaaa tgcttgctat acaatctgaa 3000 aacacactgg caggtgctcc tctccttggc aattcattga gtatccagag ttctacgatg 3060 tttaactgaa gaattggcta atgttttgat cctccagtgt gactgttgtt tttgtttggg 3120 ggtgggttgg ggttttttgc tttttattcc tgaagcttac cagatatgaa tggctaatac 3180 tcçattgttc tgcttgttgt aatggtgaat gctttaagaa aaaaaagtgt aatttgctaa 3240 gaataattca tgatctgttt atgcgataac tcctttttgt tacaattttt ttaaaaaaag 3300 ctatttttgt taatgtaaag taaatatttc agagcaaatt ttttaaactt attgcactaa 3360 atacaggctc tgtacaaaaa aaaaaaaaaa aaaaaaaagc ctcagcattt tatcattcca 3420 tggaaggaga atcttttgaa agaaagcatt gcctcctacc agaactagac agtgaattag 3480 atcggtatta tggaaatgca tacaagtaat gtcactaggg cttaataagc agccgtttgc 3540 taatgtgctt cctttcaaag ggttggacct ttaaattgct gcaaaaggta aattgtattt 3600 ttttttaagt attggtgttc tttactctag ctaggctaaa atttgctaaa tgccttggtt 3660 tcttttaaaa gttcatgtaa tatttctgat ttttcagaat atttgcaata agagtctgga 3720 ttttaaaaaa cacatgcata cacacaatta agagctcatg tcttagcaag atctgggaaa 3780 ccaacattgc gagagtagct attttgaaag aataattctc cagaagttaa catctaatat 3840 ctagtatcac caaacagtat cgctgttctc ttttattcat ttgaaatgaa tataattata 3900 taactaacaa ttgtccaaat agatgagaga gcaaatcatg tgagaaaatt cagaatacca 3960 WO 00/71710 PCTlFR0010142G

tctgtttcat agccgcacag attttggact ttcacaaaca ttgggaacta aatttagaat 4020 tggcaaaagt ctagaagatg ggtatcaaaa cagaagacat tccaggagct agcaatttta 4080 agaggtgtcc ctccaaagtg acctgatgga agtcctgaac ttggaaatta ggttctactc 4140 acttggacat ccctgcatca tggactgttg ctgctccctg ttccatatgc tcgcaatctc 4200 agctatttgg aagctaccag gaatgctttc taattatcat ttgcaactag aactgtaatc 4260 agaaagaaat tttgtatttt tgtataactt gattgtgtgc cattttâtat aacaggtcct 4320 gttttacaaa taaattttgt tttactaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaggg 4380 tggggggaaa agagttgcaa attaattgcc aggctgtttt ccttaagtaa attcatgtgc 4440 cgtgtagaaa tatgcagata tgcattacac aggcacacac agagagatat ttaatatgtg 4500 gaatatcact ctttcatgag ctttattcct tgattaattt gataaagcct cacagaggat 4560 tttaagcaat atttaaatgt gttgaggtta tgtttggata ttcctgctgc ctcttttcat 4620 tcatttcaag tcattcttca gctagctatg ggctgcctta ttgctattcg ctcactgctt 4680 ccatcttctg cccaagtgag aagaatagat gaagaacaga aatttctctg tgaaatgtgg 4740 atacccgaat aatttcataa atcattgatt ctatgtggtg gtttttgtct tcttctgtgg 4800 tgaatcttca aaactgtatt caggactcat atttctagag ttttaattgg ggtcctctat 4860 tgtcaattgt agtagtgacc agagtatcgt ggtttttgcc atcagataat taaggctctg 4920 gtgcataatt tagactttct aagctcctgc ctgaagaata aggtcttcca taatatggaa 4980 gagaaaagtt atatttcagt gtaaatccaa gagacccatc ttctatgaga ggcttaccag 5040 tgcattagta ataaaacatt agcaatttag ctagagcact gagattgtat aatccttgca 5100 tggatgagca gagctcaaag ccagttgttc ctttaaagca tttaatgcaa tggctaatgt 5160 ttaggattaa agtttttatt ttatcctata agataattaa gtcctaagtc actacaactt 5220 aagtagctta actgtatgtt ggtacccaaa ctttttctat aatggttaag gaggaggcac 5280 ttactgagtt tattttaaag ttatgctaga aatgtttttc ttttgtagag atgctctctc 5340 tctctctctc tttttttttt tttttttttt ttccgtgagg gcattaggct gctgattgta 5400 agttatttcc aataccactg atcttggtat ctgccaaggg cttccttgcc ttccctgggc 5460 agttttagga tttcacccta gtagggggta tgaggcactg acccctttat tctggaccca 5520 aactgcttta gagcagagtt aatacctctc cctccctctt caaaacagct acaggaactg 5580 caggcaccac atatgtgtga ggccacatca ctgcccctga ggcttcaact atttccacca 5640 tgcactatta ctagctacta acagccattt taagagatct cctagcctgc aaggtagaat 5700 tctgggatca gttccaaaac cagaactgcc agtaatggtg acttgaatat tttatttgat 5760 ttttggtcag taaccttgtc atttaaattg gactttccaa tagccttaac atggcctctg 5820 agaagtttcc tccagaaagg tctttaagct ttcgcttttc aataagtaag ttctttactg 5880 cttttctact gctactttaa aaaaaaacac acacacaacc accaataaaa ctctcagagt 5940 ctggaggctt atcagtgcac ctgccacagt taatttctgt attcttttca tacattccat 6000 ctgacacata agagtgcact ataatggctt gcctagaact ggtaagaagt ggtctgtgaa 6060 tgtatattga aaaaatgtgg gttcataagt aaaagcgtaa cgcagatatt tgtgtattct 6120 gtattcacag cgtaggctgc cttttgcttt aaatgcatat tcatgtatct ttgtgtgcta 6180 agaatgcatg ttagcccttt tgaaaagtag gcactattca tacacagtag cttcttggaa 6240 ttaactcatc tttgttaact tagtggcaca tagtccaaat ttttaaaaag caagaccctt 6300 gaatatgcca agagaaaatc taaagctagc aaacttaaaa aacaaaataa aaattacacg 6360 tcgtgtacag ttatgaattt agaatagcac actttttcca ttcagatttc atacatttga 6420 gccaaattct tatactccat gttttaattt taaaaggata attttaatcc aagatttaaa 6480 tctttgaaaa tatctttctt atagaaaact ttaatgcagt ttttaaactt actgatttct 6540 gtggaaaacc tttcttttct atagaaatac tgtagtgccc tttcttccca tcttgatttt 6600 gtacatgtaa agacaaatga tgattcagtt tcaatattgc atgaacaatt gccactttgt 6660 aaattatatg gacagaatgt ~ gttctaagga aattcgttag taaatttgtg aaaaacatgt 6720 gagattgttc gagacctatt aggctattct tcagttttga tgctcagttt tacaacttaa 6780 atgattttct ccaggacacg gagctcagaa taataaagct tttattaatg gtctagtgaa 6840 WO 00/71710 4 ~ PCTlFR0010142G
gatctagttg aacatggaaa cattgtaatt tacaaatgtc tcagaaattt ctcactttta 6900 tttgctaaga cctgaattta atatttgata ttcaaaaaca agttattttg aagagacaat 6960 gggtctcttt gagcttaaga aagctatgga ctatctttcc ttcaaatgca catcacatgt 7020 ctgtgaacac tcaaaatgct catagaattt cagggccctc agacggccag cttccacccc 7080 tgtaccccct caggggctaa tgaacccaag tcaaaaggct gctctaaagt tgttctgata 7140 atgtgttttg aaatgaggaa gtgattaggc ctccactaga gatacttttg agatgatgct 7200 taccaccttc tgacctggaa tcatttttat aacttaaaga ctttatgtaa tttagtagca 7260 ggttagggaa tagaaaccac actaatctga aggaataaca agatgatcaa cactgaatct 7320 tcatgacagt aagattttct ttccttggag gtatgagggt gtgtgtgtgt gtgtgtgtgt 7380 gtgtgtgtgt ttgtgtgtgt gtgtgtgtgt gtcctggcgg ttatttgggg gcaaggtacc 7440 agattatttg cagtgagcca aaaaaaaaaaa atatccaaga agaaataaat agggaatcct 7500 tgtaattaat ccatctacca aaacacttga ttctttttat tgtagctcag ctatgacatt 7560 atgacattat gtggcttagt gttatcagta tactactgtc ttaaaatata tttgtcaaca 7620 tgtccagttc caacaacagt tgaagatgat gataaattag caaactcaag ggtagtccat 7680 agttggcaaa aaataaattt ggtagaaagt tggaggagca gatgctgaag gtagaaatgc 7740 aaaagatgtt ttttcttcct gcataaatca cggaggtgtg ttctgtttta gtgttttcca 7800 gtcacccact agagcagctt cagattcctc tgccaataga actccacccc cagtccctta 7860 cctactctat cttctttagg gaagcatgtg gatttcttca catctgcacc ttactattag 7920 gtaagggtgc tgcatctaca tggaaggctc cctgggccct tgaaaaagca ggcagaaact 7980 catcaagggg tttgaagttc ttgtgaaatt tgatcccagt ggctcatgac ttatagtcag 8040 gcatcaaacc atttcctact ttttcaggct gaagaaagtg gaaatataac tggctggtga 8100 agaaaggaga aaagtcagcc ccctaccccg ccccacactc ctagaaaagt.ttgggggttt 8160 tttttgtttg tttttggtgt ttttttgaga cggagtctcg ctctatcgcc agcttagagt 8220 gcagtggctc aatcttagct cactgcaacc tccacctccc aggttcaagt gattctcctg 8280 catcagcctc ctgagtagct gggaccacag gcatgtgcca ccacacccag ctaatttttg 8340 tatttttagt agagacgggg tttcaccacg ttggccaggc caatctcgaa ctcctgacct 8400 caggtgatcc acccgcctca gcctcccaaa gtgctgggat tacaggcatg agccaccgcg 8460 cccggcctag aagagtttta atgaaccttc cacagtagta aatgcagaga ccactggtgg 8520 aaattcccat gttggataga aaagggcgta agtccagtct aagtatctaa atgtgatatg 8580 cccttttgtc acagaagtgt aagacttaaa gggaatattc tgaccttcgt gtatgaatct 8640 gatccaccca tcctgtcagc taggattata atttgaactg tcgtttcagg agcatgtgtt 8700 aaatcatatg agtaaaaaaa aagtagacat tgaaaagaag acttgggaat aattgggcag 8760 atagaatggg ttccatggat cattctagtt gccactagaa aatgtgagct ccttcttcat 8820 ttaccatgtt gataatccgg tggtgacttt tttttttttt ttgtaaattg tattagatac 8880 cccacaggaa tgtgacaata ataggatagc tttgggggct ggtgatttga aacagggact 8940 attaagtaga ttttccccca tcctctaggt tcctgtagtc tgtgctcaga acttggtttt 9000 tggcccctat tgtttttgcc tattttgatt ttcagagatg atcacatggg gacagttaac 9060 ttttcttctg ctgtgttgcc ttaatgctac tagattgtgt tgtgttgttg gagttttctg 9120 acttcttccc tataaaaaga tactgagagc tccataatga aagaagttgt tatactttct 9180 cagaatattc tggaccactg aatgcacttc taatagagct ttaatctaaa gaagttagtt 9240 cagtggttat taactgattt tattacagga gaaaaaaact ttaacaaaaa ggcagggaga 9300 aaagtgtgaa gggcatcaag caaaatgaca ggggcttcaa aaaacaacca aagacaaaac 9360 cctatcttct gaagaccaaa ggtccaactt tacttactgg ctggcacagc ctttctgaac 9420 tccttgagtt tagaatagag ctcctagaat aataaggcgg ccaaatttta aagatcagtc 9480 aatacagtag ggacctgcta ttgatctctc aggcactgag ttcttcacat ccagtgtcaa 9540 gcccagccca gcatatgggg tgatatgagc agaaaacaca catcggtgtg tcttgatttc 9600 tcgcagctgt gtaatgtggc atgagaagta tgttttggtg ccacatattt ctcaatctga 9660 tgcctttttg tctttttttt tttttgccat ttgcatccta tttcatagtg ccaaaatgaa 9720 WO 00/71710 45 PCTlFR0010142G
tttttgtatc ttgtcttgtc tttgtccatt ataaactgga ggatcacagt taagccttcc 9780 atgaattcat agtttggaat catttacctt accattattt tggatttttt tcttattaca 9840 gtgtcactac actgtattca tgtgggggaa caaacatgta ggtgcttgaa catgccccac 9900 agacacagtt gtagccctag tatttgtgac ggtcattatt gacacagtgc agactttnca 9960 gatggagcat tatgctctca gaggacttta aaaatatgta tattaagcaa ttaactttct 10020 ggagttggag ttatcaaatc ttgctgggaa attaacttcc aagagctctg aattggatgg 10080 aattccatct ggcttcagag aacaatcagc ctatatgaaa cggagctttg aaatgttttt 10140 cttgtgcaga aatacgaact agaaagaaaa gtgctgatct aatgctaagt tttctctgtg 10200 tactgactca gttgccagaa ttataatgaa aactgtattt tagtctaaca aatgtataga 10260 attttttatg taataaataa aattttatag gaaagadaaa aaaaaaaaac tgtgttgtaa 10320 cacttcccat gcccagggtg gtgacgataa aatcatgggc aacatcttcg tttcaaatta 10380 ggtcagtatg ctgcaagggt gccccagaat tcccagctg 10419 <210> 41 <211> 1813 <212> DNA
<213> Homo sapiens <400> 41 tgtgtgtagc agcgtgtcca aggcaagaac tgaaaactct gagtgatgtt cagaagtttg 60 cagagataaa tggttcagcc ctatgtagct acaacctaaa gccttctgaa .tacactacat 120 ctccaaaatc ttctgttctc tgccccaaac taccagttcc agcgagtgca cctattccat 180 tcttccatcg ctgtgctcct gtgaacattt cctgctatgc caagtttgca gaggccctga 240 tcacctttgt cagtgacaat agtgtcttac acaggctgat tagtggagta atgaccagca 300 aagaaattat attgggactt tgcttgttat cactagttct atccatgatt ttgatggtga 360 taatcaggta tatatcaaga gtacttgtgt ggatcttaac gattctggtc atactcggtt 420 cacttggagg cacaggtgta ctatggtggc tgtatgcaaa gcaaagaagg tctcccaaag 480 aaactgttac tcctgagcag cttcagatag ctgaagacaa tcttcgggcc ctcctcattt 540 atgccatttc agctacagtg ttcacagtga tcttattcct gataatgttg gttatgcgca 600 aacgtgttgc tcttaccatc gccttgttcc acgtagctgg caaggtcttc attcacttgc 660 cactgctagt cttccaaccc ttctggactt tctttgctct tgtcttgttt tgggtgtact 720 ggatcatgac acttcttttt cttggcacta ccggcagtcc tgttcagaat gagcaaggct 780 ttgtggagtt caaaatttct gggcctctgc agtacatgtg gtggtaccat gtggtgggcc 840 tgatttggat cagtgaattt attctagcat gtcagcagat gacagtggca ggagctgtgg 900 taacatacta ttttactagg gataaaagga atttgccatt tacacctatt ttggcatcag 960 taaatcgcct tattcgttac cacctaggta cggtggcaaa aggatctttc attatcacat 1020 tagtcaaaat tccgcgaatg atccttatgt atattcacag tcagctcaaa ggaaaggaaa 1080 atgcttgtgc acgatgtgtg ctgaaatctt gcatttgttg cctttggtgt cttgaaaagt 1140 gcctaaatta tttaaatcag aatgcataca cagccacagc tatcaacagc accaacttct 1200 gcacctcagc aaaggatgcc tttgtcattc tggtggagaa tgctttgcga gtggctacca 1260 tcaacacagt aggagatttt atgttattcc ttggcaaggt gctgatagtc tgcagcacag 1320 gtttagctgg gattatgctg ctcaactacc agcaggacta cacagtatgg gtgctgcctc 1380 tgatcatcgt ctgcctcttt gctttcctag tcgctcattg cttcctgtct atttatgaaa 1440 tggtagtgga tgtattattc ttgtgttttg ccattgatac aaaatacaat gatgggagcc 1500 ctggcagaga attctatatg gataaagtgc tgatggagtt tgtggaaaac agtaggaaag 1560 caatgaaaga agctggtaag ggaggcgtcg ctgattccag agagctaaag ccgatgctga 1620 agaaaaggtg actggtctca tgagccctga agaatgaact cagaggaggt tgtttacatg 1680 WO 00/71710 a6 PCTlFR0010142G
aggttctccc actcaccagc tgttgagagt ctgcgattat gaagagcagg atcttattac 1740 ttcaatgaaa gcàtgtaaca agtttctcaa accaccaaca gccaagtgga tttggtacag 1800 tgcggctgtc taa 1813 <210> 42 <211> 1377 <212> DNA
<213> Homo sapiens <400> 42 ggggcccccc ccncccncca taataggntt tttgggannc ctggtcccta aacctcnaaa 60 gntngcccng gggnatattt ttgaggcaan aaagnccgac attgatggaa ggtcccaata 120 tgttactccc tncacccctc ccttaccatt tgggaagcag tgnctaaacc ctgggaaaat 180 acaaagnagt ctcctgccta cacattcatc aaactttctg tatggtacca tggtttcata 240 cacctgtaac ccaggatatg aacttctggg gaaccctgtg ctgatctccc aggaagatgg 300 aacttggaat ggcagtgcac catcctgcat ttcaattgaa tgtgacttgc ctactgctcc 360 tgaaaatggc tttttgcgtt ttacagagac tagcatggga agtgctgtgc agtatagctg 420 taaacctgga cacattctag cgggctctga cttaaggctt tgtctagaga atagaaagtg 480 gagtggtgcc tccccacgct gtgaagccat ttcatgcaaa aagccaaatc cagtcatgaa 540 tggatccatc aaaggaagca actacacata cctgagcacg ttgtactatg agtgtgaccc 600 cggatatgtg ctgaatggca ctgagaggag aacatgccag gatgacaaaa.actgggatga 660 ggatgagccc atttgcattc ctgtggactg cagttcaccc ccagtctcag ccaatggcca 720 ggtgagagga gacgagtaca cattccaaaa agagattgaa tacacttgca atgaagggtt 780 cttgcttgag ggagccagga gtcgggtttg tcttgccaat ggaagttgga gtggagccac 840 tcccgactgt gtgcctgtca gatgtgccac cccgccacaa ctggccaatg gggtgacgga 900 aggcctggac tatggcttca tgaaggaagt aacattccac tgtcangagg gctacatctt 960 gcacggtgct ccaaaactca cctgtcagtc agatggcaac tgggatgcag agattcctct 1020 ctgtaaacca gtcaactgtg gacctcctga agatcttgcc catggtttcc ctaatggttt 1080 ttcctttatt catgggggcc atatacagta tcagtgcttt cctggttata agctccatgg 1140 aaattcatca agaaggtgcc tctccaatgg ctcctggagt ggcagctcac cttcctgcct 1200 gccttgcaga tgttccacac cagtaattga atatggaact gtcaatggga cagattttga 1260 ctgtggaaag gcagcccgga ttcagtgctt caaaggcttc aagctcctag gactttctga 1320 aatcacctgt gaagcngatg gcnngtnnag ntntgggttc ccccactgtg aacacac 1377 <210> 43 <211> 452 <212> DNA
<213> Homo sapiens <400> 43 acaatcttga gcttcaagtc agtggaaaga aatgtacaat ctaattgaac acaaaaaaat 60 ttatatttca aaacattcaa agtgtcagat tggttgcata aattaaaaga gattagagaa 120 gaggaaaatc agtggacttg gagtgatcag caaaggcttc aataagtagg tagaacttaa 180 tctgggactt aaatgtgaaa attgaccagc ttgggaaggg aaaaagggag gtggtaccac 240 attaaggatg tggaagtcaa gcaggaacag caggaaatgg gataatgcta acggtatttt 300 gaaggcccag cagtggctgc ttgcagggaa gttggagtcc aatcnttttc cntacgtgcc 360 WO 00/71710 PCTlFR0010142G

ntttttgggg tatccttccn gatttgctta agtttttntt ttnattaatt gctngggttt 420 tttttttccc gcngttttgc ccgtntcccc cg 452 <210> 44 <211> 562 <212> DNA
<213> Homo sapiens <400> 44 gtgcacatct tcagaaaact gatcctaagc aaatatcata atgaaaaacc atagattgtt 60 aatggactaa gagaccttta ggttcattag ctccaaaccc ctcattttac agaagagaga 120 attgtaagat agatagaaaa ctagtggcag aatcaagagt aaaactcagg tctgatgctt 180 ctcagatctt tccataagtt agcacttgtt tcccatgcct cttagttatc tcaaagaatg 240 acccccatcc gtataaacat cacagataat gcccaggtat ctgggacttt caatcctgtt 300 ttcatcaact cctaaagaga tgttagctct tcagttcaat tttttctttt gaatctattt 360 ggttgctttt tttttttttt ccagggaaaa ggaggactgg gttttaacca ctgcacgacc 420 atctgggctc tcccaaaagg cagggatcca tctctcctcg gtagtggcct ggggcatcct 480 ggggaactta tggcaaagga aagtcccaac atgggtgctg gggtcttgtt tagtnaaact 540 tgttnacttg ggggttactt tt 562 <210> 45 <211> 1766 <212> DNA
<213> Homo sapiens <400> 45 anggaaaggg ttaattcccc nnttgggaat tnccnggatt ttcccagant tncaatttcc 60 accnttggtc aanaaaaann ttggggnncc nctnnnttcn ccngtcânaa agannnnncn 120 cccttgaaag gnnccntnag agaatctcct gcagtccnaa aaaatgtcct ctcccggaaa 18D
acataacaca tatacttgtt catggggacg atttcagtgt gaataggcaa gtttctgtgt 240 catgtgcaga agggtatacc tttgagggag ttaacatatc agtatgtcag cttgatggaa 300 cctgggagcc accattctcc gatgaatctt gcagtccagt ttcttgtggg aaacctgaaa 360 gtccagaaca tggatttgtg gttggcagta aatacacctt tgaaagcaca attatttatc 420 agtgtgagcc tggctatgaa ctagagggga acagggaacg tgtctgccag gagaacagac 480 agtggagtgg aggggtggca atatgcaaag agaccaggtg tgaaactcca cttgaatttc 540 tcaatgggaa agctgacatt gaaaacagga cgactggacc caacgtggta tattcctgca 600 acagaggcta cagtcttgaa gggccatctg aggcacactg cacagaaaat ggaacctgga 660 gccacccagt ccctctctgc aaaccaaatc catgccctgt tccttttgtg attcccgaga 720 atgctctgct gtctgaaaag gagttttatg ttgatcagaa tgtgtccatc aaatgtaggg 780 aaggttttct gctgcagggc cacggcatca ttacctgcaa ccccgacgag acgtggacac 840 agacaagcgc caaatgtgaa aaaatctcat gtggtccacc agctcacgta gaaaatgcaa 900 ttgctcgagg cgtacattat caatatggag acatgatcac ctactcatgt tacagtggat 960 acatgttgga gggtttcctg aggagtgttt gtttagaaaa tggaacatgg acatcacctc 1020 ctatttgcag agctgtctgt cgatttccat gtcagaatgg gggcatctgc caacgcccaa 1080 atgcttgttc ctgtccagag ggctggatgg ggcgcctctg tgaagaacca atctgcattc 1140 ttccctgtct gaacggaggt cgctgtgtgg ccccttacca gtgtgactgc ccgccttggc 1200 WO 00/71710 PCTlFR0010142G

tggacggggt ctcgctgtca tacagctgtt tgccagtctc cctgcttaaa tggtggaaaa 1260 tgtgtaagac caaaccgatg tcactgtctt tcttcttgga cgggacataa ctgttccagg 1320 aaaaggagga ctgggtttta accactgcac gaccatctgg ctctcccaaa agcaggatca 1380 tctctcctcg gtagtgcctg ggcatcctgg aacttatgca aagaaagtcc aacatggtgc 1440 tgggtcttgt ttagtaaact tgttacttgg ggttactttt tttattttgt gatatatttt 1500 gttattcctt gtgacatact ttcttacatg tttccatttt taaatatgcc tgtattttct 156 atataaaaat tatattaaat agatgctgct ctaccctcac aaaatgtaca tattctgctg 1620 tctattggga aagttcctgg tacacatttt tattcagtta cttaaaatga tttttccatt 1680 aaagtatatt ttgctactaa ataatattnn gctggatagn accattttat gaggngccaa 1740 gggatcatag agaggctcat ganttc 1766 <210> 46 <211> 601 <212> DNA
<213> Homo sapiens <400> 46 cagtggaaag aaatgtacaa tctaattgaa cacaaaaaaa tttatagttc aaaacattca 60 aagtgtcaga ttggttgcat aaattaaaag agattagaga agaggaaaat cagtggactt 120 ggagtgatca gcaaaggctt caataagtag gtagaactta atctgggact taaatgtgaa 180 aattgaccag cttggaagga aaaagggagg tggtaccaca taaggatgtg aagtcaagca 240 gaacagcaga aatggataat gctaacggta tatgaagacc agcagtggct gctgcaggaa 300 gtagagtcaa atcttatcct acgtgccttt atggatatca tcagaattgc taagtattaa 360 ttaaataaat gcatgggttt tttattccag ctgtttgcca gtctccctgc ttaaatggtg 420 gaaaatgtgt aagaccaaac cgatgtcact gtctttcttc ttggacggga cataactgtt 480 ccaggaaaag gaggactggg ttttaaccac tgcacgacca tctggctctc ccaaaagcag 540 gatcatctct cctcggtagt gcctgggcat cctggaactt atgcaaagaa agtccaacat 600 <210> 47 <211> 3706 <212> DNA
<213> Homo sapiens <400> 47 gaatggcaaa ttctcttaca cggacctaca ctatggacag accgttacct actcttgcaa 60 ccgaggcttt cggcncgaag gtcccagtgc cttgacctgt ttagagacag gtgattggga 120 tgtagatgcc ccatcttgca atgccatcca ctgtgattcc ccacaaccca ttgaaaatgg 180 ttttgtagaa ggtgcagatt acagctatgg tgccataatc atctacagtt gcttccctgg 240 gtttcaggtg gctggtcatg ccatgcagâc ctgtgaagag tcaggatggt caagttccat 300 cccaacatgt atgccaatag actgtggcct ccctcctcat atagattttg gagactgtac 360 taaactcaaa gatgaccagg gatattttga gcaagaagac gacatgatgg aagttccata 420 tgtgactcct caccctcctt atcatttggg agcagtggct aaaacctggg aaaatacaaa 480 ggagtctcct gctacacatt catcaaactt tctgtatggt accatggttt catacacctg 540 taanccagga tatgaacttc tggggaaccc tgtgctgatc tnccaggaag atggaacttg 600 gaatggcagt gcaccatcct gcatttcaat tgaatgtgac ttgcctactg ctcctgaaaa 660 WO 00/71710 PCTlFR0010142G
~ 19 tggctttttg cgttttacag agactagcat gggaagtgct gtgcagtata gctgtaaacc 720 tggacacatt ctagcgggct ctgacttaag gctttgtcta gagaatagaa agtggagtgg 780 tgcctcccca cgctgtgaag ccatttcatg caaaaagcca aatccagtca tgaatggatc 840 catcaaagga agcaactaca catacctgag cacgttgtac tatgagtgtg accccggata 900 tgtgctgaat ggcactgaga ggagaacatg ccaggatgac aaaaactggg atgaggatga 960 gcccatttgc attcctgtgg actgcagttc acccccagtc tcagccaatg gccaggtgag 1020 aggagacgag tacacattcc aaaaagagat tgaatacact tgcaatgaag ggttcttgct 1080 tgagggagcc aggagtcggg tttgtcttgc caatggaagt tggagtggag ccactcccga 114D
ctgtgtgcct gtcagatgtg ccaccccgcc acaactggcc aatggggtga cggaaggcct 1200 ggactatggc ttcatgaagg aagtaacatt ccactgtcat gagggctaca tcttgcacgg 1260 tgctccaaaa ctcacctgtc agtcagatgg caactgggat gcagagattc ctctctgtaa 1320 accagtcaac tgtggacctc ctgaagatct tgcccatggt ttccctaatg gtttttcctt 1380 tattcatggg ggccatatac agtatcagtg ctttcctggt tataagctcc atggaaattc 1440 atcaagaagg tgcctctcca atggctcctg gagtggcagc tcaccttcct gcctgccttg 1500 cagatgttcc acaccagtaa ttgaatatgg aactgtcaat gggacagatt ttgactgtgg 1560 aaaggcagcc cggattcagt gcttcaaagg cttcaagctc ctaggacttt ctgaaatcac 1620 ctgtgaagcc gatggccagt ggagctctgg gttcccccac tgtgaacaca cttcttgtgg 1680 ttctcttcca atgataccaa atgcgttcat cagtgagacc agctcttgga aggaaaatgt 1740 gataacttac agctgcaggt ctggatatgt catacaaggc agttcagatc tgatttgtac 1800 agagaaaggg gtatggagcc agccttatcc agtctgtgag cccttgtcct gtgggtcccc 1860 accgtctgtc gccaatgcag tggcaactgg agaggcacac acctatgaaa gtgaagtgaa 1920 actcagatgt ctggaaggtt atacgatgga tacagataca gatacattca cctgtcagaa 1980 agatggtcgc tggttccctg agagaatctc ctgcagtcct aaaaaatgtc ctctcccgga 2040 aaacataâca catatacttg tncatgggga cgatttcagt gtgaataggc aagtttctgt 210D
gtcatgtgca gaagggtata cctttgaggg agttaacata tcagtatgtc agcttgatgg 2160 aacctgggag ccaccattct ccgatgaatc ttgcagtcca gtttcttgtg ggaaacctga 2220 aagtccagaa catggatttg tggttggcag taaatacacc tttgaaagca caattattta 2280 tcagtgtgag cctggctatg aactagaggg gaacagggaa cgtgtctgcc aggagaacag 2340 acagtggagt ggaggggtgg caatatgcaa agagaccagg tgtgaaactc cacttgaatt 2400 tctcaatggg aaagctgaca ttgaaaacag gacgactgga cccaacgtgg tatattcctg 2460 caacagaggc tacagtcttg aagggccatc tgaggcacac tgcacagaaa atggaacctg 2520 gagccaccca gtccctctct gcaaaccaaa tccatgccct gttccttttg tgattcccga 2580 gaatgctctg ctgtctgaaa aggagtttta tgttgatcag aatgtgtcca tcaaatgtag 2640 ggaaggtttt ctgctgcagg gccacggcat cattacctgc aaccccgacg agacgtggac 2700 acagacaagc gccaaatgtg aaaaaatctc atgtggtcca ccagctcacg tagaaaatgc 2760 aattgctcga ggcgtacatt atcaatatgg agacatgatc acctactcat gttacagtgg 2820 atacatgttg gagggtttcc tgaggagtgt ttgtttagaa aatggaacat ggacatcacc 2880 tcctatttgc agagctgtct gtcgatttcc atgtcagaat gggggcatct gccaacgccc 2940 aaatgcttgt tcctgtccag agggctggat ggggcgcctc tgtgaagaac caatctgcat 3000 tcttccctgt ctgaacggag gtcgctgtgt ggccccttac cagtgtgact gcccgcctgg 3060 ctggacgggg tctcgctgtc atacagctgt ttgccagtct ccctgcttaa atggtggaaa 3120 atgtgtaaga ccaaaccgat gtcactgtct ttcttcttgg acgggacata actgttccag 3180 gaaaaggagg actgggtttt aaccactgca cgaccatctg gctctcccaa aagcaggatc 3240 atctctcctc ggtagtgcct gggcatcctg gaacttatgc aaagaaagtc caacatggtg 3300 ctgggtcttg tttagtaaac ttgttacttg gggttacttt ttttattttg tgatatattt 3360 tgttattcct tgtgacatac tttcttacat gtttccattt ttaaatatgc ctgtattttc 3420 tatataaaaa ttatattaaa tagatgctgc tctaccctca caaaatgtac atattctgct 3480 gtctattggg aaagttcctg gtacacattt ttattcagtt acttaaaatg atttttccat 3540 WO 00/71710 PCTlFR0010142G
SO
taaagtatat tttgctacta aataanannn tgctggatag taccatttta tgaggtggcc 3600 aagggattca tagagaggac tcatgatctt tcatctgtgc cactggcacc acataggaga 3660 ccccttacaa taaaggagac ccctttgttc tggttccatc ttctat 3706 <210> 48 <211> 373 <212> DNA
<213> Homo sapiens <400> 48 tgagacattt ccactctggc attctagagt tctctggctt gcccttgttg ctttaaagct 60 ggttccaact tcgtgggctt tatgattgag caacactggt gattgtgatt tctaatacca 120 ccctccagat tcatgtcaca ggtgaaagtc tgcctgtggg gagagctttc acattctcct 180 ggagttgaac caaaataagg aaaacatcaa caaacacagt taccaaaagc ttccaaggag 240 ggatggagga gaaattctgt tcattgcaga tggggagaaa ttaaatgaca tcaagtgcat 300 aatggaactg ggtaggattc aaactcaagt cccctggttc aagtccttga ctccactctg 360 ggcatggctt aag 373 <210> 49 <211> 459 <212> DNA
<213> Homo sapiens <400> 49 agtcaaaagg tgaatatata aacatgattt cagatagaat gcagaagctg tatttaatta 60 agttggcttt tgtcattaaa gaaatcagaa agtttggaca actcaggaat ggatttccat 120 cctagatggt atttactact atttctggaa ttaagtttac tgtctatatt caggattttg 180 tgcataagag acgtgaccac tgaggttgtg tgtcattctt atctctactc caggggtcag 240 caaactttct ctgttaaggg tcagatagta gttttttggc ttttcagtct ctgtttggct 300 ctgctataaa caatacataa atgaatgagc atggctatgt tccaataaaa cttaattgac 360 actgaacttt gaatttcatg tacttttcaa atgtcacaaa tgttttcctt ttgatttttt 420 tcagaaagcc attaaaaaaa tccaaagacc attcttagc 45g <210> 50 <211> 2575 <212> DNA
<213> Homo sapiens <400> 50 tctggcattc tagagttctc tggcttgccc ttgttgcttt aaagctggtt ccaacttcgt 60 gggctttatg attgagcaac actggtgatt gtgatttcta ataccaccct ccagattcat 120 gtcacaggtg aaagtctgcc tgtggggaga gctttcacat tctcctggag ttgaaccaaa 180 ataaggaaaa catcaacaaa cacagttacc aaaagcttcc aaggagggat ggaggagaaa 240 ttctgttcat tgcagatggg gagaaattaa atgacatcaa gtgcataatg gaactgggta 300 ggattcaaac tcaagtcccc tggttcaagt ccttgactcc actctgggca tggctaagtc 360 WO 00/71710 PCTlFR0010142G

tggcctgtgt ctcatcttct cagctctagt ggctgtttag tagtgaagat actgatatgc 420 aggcagccat gttgtaaata agaagcaaat atttttatat ttctctctct tatgtgtata 480 atatttgagc tacaaacagg ttaaaacaaa agagagactt cagcttagta gcaggcaggg 540 aaggaagaag tgaatgcagc ttccttccgc ttacatttct aatcaagcta attatttcac 600 tagtgatttc tcatttgatt accgattttg cttatttatg cttagaactt tcaatgactt 660 ctcagtgcca ttaaggtaaa atgcaagcca tttctgtgac ctgcaatatc atcttttgcc 720 actcctcctc acttgctatg tcttagcaag actgagaggc tctcagttct tcagacctgc 780 tctatctcac ctctcatttt gttcatattc tccacctctt gtgcttgatg aactcctatt 840 cacctatcag gtcacaactt aaatattttt tcctccaaat ctctggacta cataggtcca 900 ggcccccatc aaatgctccc atagcacatt gggcttcctc atcaacatgc tcgttatact 960 tttctagaat tgctggcttg tcctccttgt tatctcccta atgcagagac cattactcat 102b cattgtagca gatatttatc catatcaggt actcagcaaa catttgtgga atgaatctat 1080 atgtgaaact atacttctat ggcaagtttg tttggttcag aaggcttgca tttcatgtat 1140 attgggagac tggccaacat ttttatattc ttcctcctat gctcaaacca taaataatta 1200 tgttagcaaa cactgaactt tgtcntttga aacataaata gaaacatcct tagtaacagt 1260 actaacagta atcatttttc agaaataaga attcacacca gtgatacaga atggcctttg 1320 accattatct cagagaacta gcagtcgata gacatgctga agtgataatt ccaaaaactt 1380 cagtttcatt catccctact taaatataag agaatcaact tctattttat gtctgtattc 1440 ccattttcta atatactact tgtcacagag gagatgccca accagtgttt ttcgtaaagt 1500 acctgaatag attaataata atgctagtga aatatattta gtgctgttct aagcacttta 1560 catgaattaa ctcatttaat cctcaccgca accataggaa gtagattcta ttatttatcc 1620 aattttacag atgaaaaaac tgaggctggt cacttgacat aaattaccag tgctggccag 1680 gactttagag accatttaat ccaatgctct tattttacag gggtgcagct gaagcctaag 1740 gaggtgatat gatttcctac acattcatgc accttcgtgc acatccatta aaacttttat 1800 taaatggaac ccactatcca tactccaatt agctaggtgc cttttttccc ccatttagta 1860 atttacaatt aattggagga ctttttatag ttatatttag aggaaaggag catgttttac 1920 tctatatcaa ctttcttttc tgcttaaaag cattttgatt ctttatttta ccagtcattt 1980 tagttctttt aataggttta atacacagat caaacaagac ttaaatacat ttttaacaat 2040 gtaacaattt aaaagaaatt gcctaaancc taggtcttct aacttggagc ccagtgcttt 2100 ttttattgct ccgctgagtc aaaaggtgaa tatataaaca tgatttcaga tagaatgcag 2160 aagctgtatt taattaagtt ggcttttgtc attaaagaaa tcagaaagtt tggacaactc 2220 aggaatggat ttccatccta gatggtattt actactattt ctggaattaa gtttactgtc 2280 tatattcagg attttgtgca taagagacgt gaccactgag gttgtgtgtc attcttatct 2340 ctactccagg ggtcagcaaa ctttctctgg taagggtcag atagtagttt tttggctttt 2400 cagtctctgt ttggctctgc tataaacaat acataaatga atgagcatgg ctatgttcca 2460 ataaaactta attgacactg aactttgaat ttcatgtact tttcaaatgt cacaaatgtt 2520 ttccttttga tttttttcag aaagccatta aaaaaatcca aagaccattc ttagc 2575 <210> 51 <211> 231 c212> DNA
<213> Homo sapiens <400> 51 tgattatttt cttttcccta tgtttagtta ctgtagtaga aggctatatg aacctttggg 60 aaaagttaga aggaaaatta acagtgtcag gcctcagtaa catatattaa gtttgtttct 120 caaggagatc tgtcctcgct ttccttaaac atgttctgga tctgtaaaat aggggattct 180 WO 00/71710 PCTlFR0010142G

tccatgaagg caaaagggtt gatttagaga gaaaagttta agcgtgggaa t 231 <210> 52 <211> 344 <212> DNA
<213> Homo sapiens <400> 52 aatcccagaa ggaccttata ggtgagatac aaagtgttac ctgtgaggaa gtgtattcca 60 ctcccccacc aaaaaaaatc tttggaatat atacaagcag aaatcgggcg aatatgtgtg 120 ggaatgccta ttaagggtat aggataatgg tggaaggaac ataaagattg aacaggccaa 180 attattgata tattggccca ctaaacagga attatttttt attgttgctg ctcatggagt 240 tagaaaggtc tctagcagta tggttagttt gctgaaacat acatcaaaat ggtccaccat 300 gagtgaattg gagatgttga acctctcttg gtttcatgca gagg 344 <210> 53 <211> 402 <212> DNA
<213> Homo sapiens <400> 53 ttgttgattc tccccccacc agcccctttg tttccagacc tataagtaga caagaatccc 60 agaaggacct tataggtgag atacaaagtg ttacctgtga ggaagtgtat tccactcccc 120 caccaaaaaa aatctttgga atatatacaa gcagaaatcg ggcgaatatg tgtgggaatg 180 cctattaagg gtataggata atggtggaag gaacataaag attgaacagg ccaaattatt 240 gatatattgg cccactaaac aggaattatt ttttattgtt gctgctcatg gagttagaaa 300 ggtctctagc agtatggtta gtttgctgaa acatacatca aaatggtcca ccatgagtga 360 attggagatg ttgaacctct cttggtttca tgcagaggaa gg 402 <210> 54 <211> 228 <212> DNA
<213> Homo sapiens <400> 54 attttcttcc ctagtccatt tctttttgtc cagtattcct tttgttcata ggcagttcca 60 ctgtgagtcc tgtactcttt ctcattcatt catggctcac tgtgtgtcat gttctattct 120 aggtgttggg gatatagcag tgaacgaaac agaagacccc tgacactgag gagctcatgt 180 tctatgggga aggtgaagtg gaaaaaaact caaaagaata aataaggg 228 <210> 55 <211> 270 <212> DNA
<213> Homo sapiens WO 00/71710 PCTlFR0010142G
i3 <400> 55 tgccnttaca atttcancgt tttttacccc caaatggtta atgtaggtgt tttttttttt 60 ttttggaatc attttattct ttcgtatttc tgtgtcagtc gctaggagaa agaccaggaa 120 aatctgttaa actctaaacc aaaaattccc attcactgca gagtgatgat tcgcaacact 180 gctgcaattc aggtagtggg gtgtcctgaa gtgacaacac atcaccactg cagtcctaat 240 aaattaagtc tttttgtttt gaaaaaaaaa 270 <210> 56 <211> 1130 <212> DNA
<213> Homo sapiens <400> 56 accaattctc agtccctaga ccccattctt tgttcctctt cttcctgatt ttcttcccta 60 gtccatttct ttttgtccag tattcctttt gttcataggc agttccactg tgagtcctgt 120 actctttctc attcattcat ggctcactgt gtgtcatgtt ctattctagg tgttggggat 180 atagcagtga acgaaacaga agacccctga cactgaggag ctcatgttct atggggaagg 240 tgaagtggaa aaaaactcaa aagaataaat aagggaattt caagaggttt gaaggaaatc 300 taactaggta atgtgattgc gggacctagg gatagggaag ggcatagact gctttagata 360 ggatgggaaa tctcttaggg gagattaaaa ttgaactaag acctgaatta .catggaaaaa 420 tttagtcaaa ggaaaagcat tccagagaga gagcatggca gtgcaaagcc ttgcagaaag 480 aaccagtgta gaaagtccaa ggatgaaaga aagccagtgt agctagagcc tgaagaatga 540 ggatgggagt ggaagatgtg aaggtaagtt tgcaggggcc agatcatatc aggcctggaa 600 gatgatatag ctgtttaaag tttattctaa atgcaatgag a.agccagctc ctagcaagat 660 aataaattgc ttttccagaa cgttaactgt ccattattta gttcctttgc attctccata 720 ggctggtctt ataaaggttc tgtgacagta gggaatccat taaagatcta ttacataagg 780 gaatgtggga catgcaaaag cagaagacaa atgtagaaac cctctgcttc acttggcatt 840 tctgtccttc atctttctga tattttaaag ctactgtgtt cctacataca tatgctatct 900 gttccttcat tctttttgat aaattcatca tttgccttta catttttgtc gttttttacc 960 cccaaatggt taatgtaggt gttttttttt tttttggaat cattttattc tttcgtattt 1020 ctgtgtcagt cgctaggaga aagaccagga aaatctgtta aactctaaac caaaaattcc 1080 cattcactgc agagtgatga ttcgcaacac tgctgcaatt caggtagtgg 1130 <210> 57 <211> 463 <212> DNA
<213> Homo sapiens <400> 57 cctaatgagt ggctctgtat tcccatttcc tcatgtggac taatgcggtg tgtggtgttt 60 ttcttttcct tttcagaagc agtggacagg ggagaatccg ctccaacgtt gtccacctcc 120 ccttcaccct cctccccttc acccacttcc ccttcaccta ctctgggcag acgaaggcct 180 gnaaatagga acgtttctta gaaagaagaa aactagtgac atctactttg tgtctctagt 240 ttgggccatt gtcgtcatgc agatctggtt gaacctgtgg attgtgcagt ttgctgccag 300 tgccgattgc aggtcgttat ctggttnaag tacgatctcg tcttgtcttt ggaagattga 360 WO 00/71710 PCTlFR0010142G

tttttttttt tttttttttt tnggatttta atntttgagn gacattttac cgtntttgca 420 aagtaaaaca ttttgatggt ttggnatttt aaatagttna ctt 463 <210> 58 <211> 289 <212> DNA
<213> Homo sapiens <400> 58 gactacagtg gagagcagct tccaaaaatc agattacgtt ttaatciata gtgaaaaacc 60 ttgacatagg aaatgaggag taatcaaatg tagaaggtac tcagaaggca aaatccacag 120 cagccactaa ggacttaata aatttgggca caaaatatgg gctgccataa ggaagagagc 180 ccaaataatc aggaaâatat tagggtaaaa gatgtttcta caatgcacct gtcaggggaa 240 aactctccct tgctctttct agtcttaggg nggaaggaca gttttaggg 289 <210> 59 <211> 1542 <212> DNA
<213> Homo sapiens <400> 59 tgggccattg tcgtcatgca gatctggttg aacctgtgga ttgtgcagtt gctgccagtg 6D
ccgattgcag gtcgttatct ggttaagtac gatctcgtct tgtctttgaa gattgatttt 120 tttctttttt tacttttgga ttttaatatt tgagatacat ttaccgtctt gcaaagtaaa 180 acaatcttat gtttgcattt aaatagtaaa caaacaccat ttggttaatt tattactttg 240 atacatcttt aatatttcac tttttttttt ttttttgaga cggagtcttg cccaggctgg 300 aagtgcagtg gcaccatttc agctcactgc aagctccacc tcccaggttc atgccatttt 360 cctgcctcag cctcccgagt agctgggact ataggtgccc accaccacac ccggctaatt 420 ttttttttat ttttagtaga gacagcgttt caccatgtta gccaggatag tctcgatctc 480 ctgacctcgt gatctgccca tctcggcctc ccaaagtgct gggattatag gtgtgagcca 540 ccgcgcccgg ccagtatttc acttttaagc tcaaaaaatg tgtttagctt cttacaattt 600 catgtagtat ttgagattaa tagctccata gagagatttg attgtttagc catccatgat 660 tctgtgaagg agaatgttaa caatatctgt gttttggaat ttgaagatcg aatgattttt 720 tgtttttttt tgagacggag tctcgctctg tcacccaggc tggattgcag tggcgcgatc 780 tcagctcact gcagcctttg ccccctgggt tcaagcaatt ctcccacctc agcctcctga 840 gttgctggga ctacaggcat gcgccaccac ccctggctaa ttttttgtat ttttagtaga 900 gacggagttt caccatgttg gccaggctgg tctcgaatcc ttaccttaag tcatccgctc 960 acctccgcct cccaaagtgc tggcattaca ggagtgagcc actgcgccta gctgagattg 1020 aatgattttt gagcgctact cttagggaag cacgttttac cttgcctttt taattcaaag 1080 gaaatgtagg ctttgagaaa tacatgtatg caaagtcttg tgatttggca gaaaaattaa 1140 attacatgta tatctatatt atatgtatta catcaaaatg gaatcatagt tttccataat 1200 ccattaaatc aggtctttgt atcttaatgc tgtggtaatt taaggcccac ctctattgtt 1260 ttgattctct ctaaaactgt ctttctccta agactagaaa gagcaaggga gagttttctc 1320 tgacaggtgc attgtagaaa catcttttac ctaatatttt cctgattatt tgggctctct 1380 tcttatggca gccatatttt gtgccaaatt tattaagtcc ttagtggctg ctgtggattt 1440 tgccttctga gtaccttcta catttgatta ctcctcattt cctatgtcaa ggtttttcac 1500 WO 00/71710 PCTlFR0010142G
tattgattaa aacgtaatct gatttttgga agctgctctc ca 1542 <210> 60 <211> 1417 <212> DNA
c213> Homo sapiens c400> 60 gacacggctg gctgcttttc tcagcgccga agccgcgcca tgctcgtcct cagaagcgcc 60 ctgactcggg cgctggcctc acggacgctg gcgccteaga tgtgctcatc ttttgctacg 120 ggacccagac aatacgatgg aatattctat gaatttcgtt cttattacct taagccctca 180 aagatgaatg agttcctgga aaattttgag aaaaacgctc atcttcggac agctcactct 240 gaattggttg gatactggag tgtagaattt ggaggcagaa tgaatacagt gtttcatatt 300 tggaagtatg ataattttgc tcatcgaact gaagttcgga aagccttggc caaagataag 360 gaatggcaag aacaattcct cattccaaat ttggctctca ttgataaaca agagagtgag 420 attacttatc tggtaccatg gtgcaaatta gaaaaacctc caaaagaagg agtctatgaa 480 ctggccactt ttcagatgaa acctggtggg ccagctctgt ggggtgatgc atttaaaagg 540 gcagttcatg ctcatgtcaa tctaggctac acaaaactag ttggagtgtt ccacacagag 600 tacggagcac tcaacagagt tcatgttctt tggtggaatg agagtgcaga tagtcgtgca 660 gctgggagac ataagtccca tgaggatccc agagttgtgg cagctgttcg ggaaagtgtc 720 aactacctag tatctcagca gaatatgctt ctgattccta catcgttttc accactgaaa 780 tagttttcta ctgaaataca aaacatttca ttaactgcta taggatctgt ctgctaatgg 840 tgcttaaatt ctcccaagag gttctcactt ttatttgaag gaggtggtaa gttaatttgc 900 tatgtttctt gcattatgaa ggctacatct gtgctttgta agtaccactt caaaaaatag 960 ttctgtttac tttctgcatg gtatttcagt gtctgtcata cattaaaaat acttgtcact 1020 gttttaagat cttgactctt catttgtttc agaatagctc ttctactgta ttctgacaac 1080 tctttgcttt atagcatttt gttgtattca aatgataatg gtagcatttc catgcttgtg 1140 acagcatttt taagttatta atatatttta tcaacctttc catcatgtct gttttcctgg 1200 ttttttttgg ttgttttttg accagtaaaa tttattttgt aataccaaat aggatttaag 1260 aaaattaacg tatttcttta ctatggaaaa ccacattgtc atttgtgaca tcatctatat 1320 taaatatggt tttcacatta gttatttgtc acttacttgg aaaatgatgc tgttaggtcc 1380 tggtattaaa aatctagaaa agacttgttg gtttatg 1417 <210> 61 <211> 696 <212> DNA
c213> Homo sapiens <400> 61 ctctaagcga tctgcagttt atctgggcta ttatgcaatg tgagatatta tttatgagag 60 gcaggcagtg gcagcttaaa cagacatacc tcctcagcat tcttttccat gcagagttca 120 aagaggccta agacatctca catttatgtg aaatagttga ggcacaagta tgtggttaac 180 tacacataaa ttaccaataa aattaaaagt taactaaaat actacagaag acatttaata 240 ttttgcttca gactgttata gtaccttagg gttatgaaca tcaattacct ttgagcctta 300 ctatatttaa agggaagggg aagctgacat ttttatcttt tttaatgggt acactctacg 360 ttaccttaaa ggcttccccg gtttaagcaa aaatagaatt atgtggttta aatcatatac 420 WO 00/71710 PCTlFR0010142G
SG
cttattcttc atacttagct ccaagtagat tatgactttt cctaaaactt aacatgacag 480 agatttgcct tccagggggt ctaatttgaa gaggaaagta atttaaatgt ataggtttat 540 ataatagcat tgtatttttc tctattttat tcattctttc attctcttcg atgactccca 600 gcacctgcgc gtccatcttc attcttagcc aatgaccttt ccttttactt aacagagaaa 660 ataacaatca gaagagtctt cataagttcc cacccc 696 <210> 62 <211> 2702 <212> DNA
<213> Homo sapiens <400> 62 ctcagaaagg acacggctgg ctgcttttct cagcgccgaa gccgcgccat gctcgtcctc 60 agaagcgccc tgactcgggc gctggcctca cggacgctgg cgcctcagat gtgctcat-ct 120 tttgctacgg gacccagaca atacgatgga atattctatg aatttcgttc ttattacctt 180 aagccctcaa agatgaatga gttcctggaa aattttgaga aaaacgctca tcttcggaca 240 gctcactctg aattggttgg atactggagt gtagaatttg gaggcagaat gaatacagtg 300 tttcatattt ggaagtatga taattttgct catcgaactg aagttcggaa agccttggcc 360 aaagataagg aatggcaaga acaattcctc attccaaatt tggctctcat tgataaacaa 420 gagagtgaga ttacttatct ggtaccatgg tgcaaattag aaaaacctcc aaaagaagga 480 gtctatgaac tggccacttt tcagatgaaa cctggtgggc cagctctgtg .gggtgatgca 540 tttaaaaggg cagttcatgc tcatgtcaat ctaggctaca caaaactagt tggngttttc 600 cacacagaat atggagaact caacagagtt catgttcttt ggtggaatga gagtgcagat 660 agtcgtgcag ctgggagaca taagtcccat gaggatccca gagttgtggc ggctgttcgg 720 gaaagtgtca actacctagt ttctcagcag aatatgcttc tgattcctgc atcattttca 780 ccattgaaat agttttctac tgaaatacaa aacatttcat taactgctct aagatgtgtc 840 tgctaatggt gcttaaattc tcccaagagg ttctcgcttt tatttgaagg aggtggtaag 900 ttaattagtt atgtttcttg cattatgaag gctacatctg tgctttgtaa gtaccacttc 960 aaaaaatagt tctgtttact ttctgcatgg tatttcagtg tctgtcatac attaaaaata 1020 cttgtcactg ttttaagatc ttgactcttc atttgtttca gaatagctct tctactgtat 1080 tctgacaact ctttgcttta tagcattttg ttgtattcaa atgataatgg tagcatttcc 1140 atgcttgtga cagcattttt aagttattaa tatattttat caacctttcc atcatgtctg 1200 ttttcctggt tttttttggt tgttttttga ccagtaaaat ttattttgta ataccaaata 1260 ggatttaaga aaattaacgt atttctttac tatggaaaac cacattgtca tttgtgacat 1320 catctatatt aaatatggtt ttcacattag ttatttgtca cttacttgga aaatgatgct 1380 gttaggtcct ggtattaaaa atctagaaaa gacttgttgg tttatgtgct gaaatgtntt 1440 tntttataat taattttact aatttctact tagtttggat cactaacaga gatcttggga 1500 catttatttg ttttaaagaa atatttatgg ttatggaaac gcttgcccta ataaaaatcc 1560 tgcatattca ttgttttttt aaattcacat tttatactta tatgatctct aaagctcttg 1620 ctatgttgct ataagacagt aatatagtga taatttacca actttattga aaatgttgtt 1680 acatcaataa aatagcatgc tgggaacctg agaaggaagg tttctttagt actgccacag 1740 atgtcctgga gttttccttg aaacatcttt catttccatt ttacttgatg cctctaccta 1800 ctaaaactag atttggtact tccgatagtg tatatttaca gctatattat atttacattt 1860 ttacagacta tcttctgata atctgtattt acagctatgt tattttatat ttttaaaatc 1920 ttacagctat aaaatagtaa attgtgaatt agctgtccaa gggcaatttg gaaaacaaac 1980 tgtacagttt cctctcattt atcaggctct aagcgatctg cagtttatct gggctattat 2040 gcaatgtgag atattattta tgagaggcag gcagtggcag cttaaacaga catacctcct 2100 WO 00/71710 ~~ PCTlFR0010142G
cagcattctt ttccatgcag agttcaaaga ggcctaagac atctcacatt tatgtgaaat 2160 agttgaggca caagtatgtg gttaactaca cataaattac caataaaatt aaaagttaac 2220 taaaatacta cagaagacat ttaatatttt gcttcagact gttatagtac cttagggtta 2280 tgaacatcaa ttacctttga gccttactat atttaaaggg aaggggaagc tgacattttt 2340 atctttttta atgggtacac tctacgttac cttaaaggct tccccggttt aagcaaaaat 2400 agaattatgt ggtttaaatc atatacctta ttcttcatac ttagctccaa gtagattatg 2460 acttttccta aaacttaaca tgacagagat ttgccttcca gggggtctaa tttgaagagg 2520 aaagtaattt aaatgtatag gtttatataa tagcattgta tttttctcta ttttattcat 2580 tctttcattc tcttcgatga ctcccagcac ctgcgcgtcc atcttcattc ttagccaatg 2640 acctttcctt ttacttaaca gagaaaataa caatcagaag agtcttcata agttcccacc 2700 cc 2702 <210> 63 <211> 335 <212> DNA
<213> Homo sapiens <400> 63 taccttacca ttgtgcctgt tatgttcaaa aatacatttt gaaaagttct taaaataatt 60 gctctaaatt gaaatgtcaa aacctgaata ttctacatgt gtcttgggtg atgtccttta 120 agctaatcct atantacact aaggtacatt taattgtgga aatgtcattt cacaaggcta 1B0 tgtaaggcat ccctcgaggc ctgcatttta atgtctagtt ttcaatttta tggcacctaa 240 aatatcccna tggtggagga tattagggat ggggntatta tcccngggat ntctcacngg 300 cccggttggg gccccgggga tcttagggtt ttcca 335 <210> 64 <211> 447 <212> DNA
<213> Homo sapiens <400> 64 tccttactgg attgagcctt ggttacttgc cacccagagg gtgattgagt tgcagtattc 60 tgttgcacct ttgatgtcaa cttatttttg gcttaaattt tttaaataac ataaggttaa 120 agaaaggatc acatctctat cttttcctca ttgacctccc tagttctaga caaattctat 180 acttttttcc tttctttttc tctgtggtcg attatgtcat tattccctcc ccctcaaaac 240 ctaccttctc ccttggtctc cgggaatact gcactctagt gattttcctc ctactacgga 300 aaatgatttc attacctctc tgggctgggt atttccttgg tctttagggc cctttatgga 360 aaacacaacc tttggcctan tttctctnca atttgccctt tttaagaatg gtcctggtac 420 tccttttata attaatctgg gtgnggc 447 <210> 65 <211> 2324 <212> DNA
<213> Homo sapiens WO 00/71710 ~ S PCTlFR0010142G
<400> 65 actacaagcc agtgaagtgg gtgataagcc tgactccact atctcagcca ggtccttctt 60 ctaatattat tggccagtct gtggaagaag ctatcagagg ggtgtttgat gcttccctca 120 aaatggctgg cttctatgga ttgtatacct ggctgactca tactatgttt ggcatcaata 180 ttgtcttcat accatcagca ttagcagcaa tccttggagc agtgccattc ctggggacat 240 actgggcagc agtacctgca gttcttgacc tgtggctgac acaagggtta ggatgcaagg 300 ccattttact gttgattttt catctcttgc caacatactt tgtagatact gcaatctact 360 ctgacatatc aggaggtggc catccttacc tgacaggctt ggcagtggcc ggtggagcat 420 actacctagg cctggaagga gcaatcatcg gtcctattct tctctgcata cttgtggttg 480 cttccaatat ctatagtgcc atgctagtga gtcccacgaa ttcagttccc acgccaaacc 540 agaccccatg gcctgctcag cctcagcgga ctttccgtga catttctgaa gatctgaaat 600 cttcagtagg ttgatgtggt ttcctctgca gtgatttttc taggaagttc aaatttgaca 660 gcgagttcag ctcagctgtg gccctctgcc cttccagctg tgcctagcaa gcaaaaccca 720 ggaaagaagc agaagcctcc tggccttaca tacagaatgc ctggacaaga gagaacttgc? 80 tgcgggctgc tttgtatttt aaaacacagc ttgagagttc agagttggtg gtttgctcac 840 ttaactgttg ttaagatggc ttgaaaagtt tcattttata cactggtacc ctggcttgaa 900 atttttccac tttggttatc tatgttacta tattatatat ttataaagtt attttaagaa 960 ctctaaacta cctgctgtta aaagaataga tggtgtaatt ttttcctggt ttaagaaatg 1020 tattgttaaa cttttctaag acagtcactt ttcaaggaag agggctttca cttttgagtg 1080 tgtagttgag tgagcaggaa aaatgaatct tctacccttc tcccacaatg tattatacgc 1140 tctttaagaa ataataaatc ataagtataa gggtggggtg gcttatttga tgttcagttt 1200 tatattataa ccctgggaga tacaaagact gaagctcttc ctcctcttcc ttttctcttc 1260 acgcttcttt acactattgc caaattataa aacttggctg accacgttga agtgaaatac 1320 ttattaagct gctatgaatg gtaacagtat gataaaattc atgctgttat taggttttct 1380 ccttccaggt ggttgaagtg aaaaatctca ggtgtagcaa tactctgatt tgttaaatgt 1440 atccgtttca ttatttggaa ctctgccaat aagttagttt tcagcagaat tttgtattta 1500 tgtagtattt tcccatctct tagcacagtg ccttgcacat gactctaaat gaatgcttgt 1560 tgaattgaat tgcaacttta aaaatatctc agatatcaca ataaccagca tagtgcttta 1620 cattttacaa agtccttttg cacatactat ttcacaagta catcacatca gctttcatat 1680 agctttatat tattttacat cagttttaca ctgatggaga agctaaggtt cagaaaagtg 1740 accaactcaa agtcgtaaag tgtagtagga tttggcctca gatctttgac tccgttgtgt 1800 gcagattctg ctgtattagt gttccttcta aatattgtat gcagttttcc cagtgttacg 1860 agattggtgt tgctatccat ttgttgtgaa tgaagacttg tcctatagta catgacaggg 1920 ctgagagtgg actgtagttc ttagctgaac cctttctact gtttaaaaca atcatcaggc 1980 ctatcctctg ctcccagggg aatgtgggag agaaaagggt tcttggccag gctgtaggtg 2040 gtggctcaca tctgtaatcc cagcactttg gaaggctgag gtgggtggat tgcttgagcc 2100 cagggatttg agatcagcct aggcaacatg gcaaaacccc atctctacaa aaaaaaaaaa 2160 aaaaaaaaaa aaattagctg ngnacggtgg tgtggctata gtctgagcta ctcaggaggc 2220 tgatgtatga ggatcacctg agtccaggag gtcgaggctg cagtgagcca agatggcgcc 2280 actgcactcc agcctgggtg agagagtgag acactgtccc aagg 2324 <210> 66 <211> 447 <212> DNA
<213> Homo sapiens <400> 66 WO 00/71710 ~~ PCTlFR0010142G
tgttggacct ggtactctcc accacataat tatgtcctgg tacttagggt agcctggcta 60 attcttttca caacatttga aaagccgtac gtttaacttc atggatgtgg agaaacagca 120 taatgacctt ggttcacaat gaaagtgcta gccttctttc tcgtggctgg aataagaaat 180 gcaagaactg gaagattaac agagagctga tacccggact ggtaatccca caactcacta 240 ttttgggagg aaggggaaga cagggaaaga gaaggaaaaa gggcaaatgg ggaaacattt 300 ccccagagct gtgntcctgg gtcttcacct gcaaaaaaga tttgcagcca cctaaggaga 360 ' aagntgagct tgcccntcag ttcctcantg ttcacctacc ttttttcaca acatttgtta 420 cccaggttga ggttttttcc agatttt <210> 67 <211> 564 <212> DNA
<213> Homo sapiens <400> 67 attgggcctc gggnccaaaa aacgggcacg angcggactg ggtaanccca naactcacta 60 ntttgggagg gaaggggaag acaggggaaa gaganggaaa aaggcaaang ggaaacatnc 120 cccagagctg tgcncctggt ctcacctgca aaaaagaatt gcagcccacc ctaagagaaa 180 gctgagctgc ccccctcagt cctcactgtc accctacctc tatcacaaca attgtaccca 240 agatgaagac ttctcccaga cttcagaaaa taaagtcaaa ccctagattt tgttttaaaa 300 taggaaactc agaatcaact tgcctccatc ctctgggaaa actgctccca cacaggcctt 360 ggagtgtgtt gtagcactgt ggaggaatgc agaaaggatg aaagagatct tgattctcct 420 agtggttctc ttcactaccg taggcatccc tcagccattg actcctcctt ctttctcttg 480 acattcactt tcttggccag tcttacatgc ttatgagtct actttccaat aaatttactc 540 atagtccnat taacttccna aant 564 <210> 68 <211> 604 <212> DNA
<213> Homo sapiens <400> 68 cacataatta tgtcctggta cttagggtag cctggctaat tcntttcaca acatttgaaa 60 agccgtaggc attaacttca tggatgtgga gaaacagcat aatgaccttg gttcacaatg 120 aaagtgctag ccttctttct cgtggctgga ataagaaatg caagaactgg aagattaaca 180 aagagctgat acccggactg gtaatcccac aactcactat tttgggagga aggggaagac 240 agggaaagag aaggaaaaag gcaaatggga aacattcccc agagctgtgc tcctggtctc 300 acctgcaaaa aagaattgca gccacctaag agaaagctga gctgcccctc agtcctcact 360 gtcacctacc tctatcacaa caattgtacc aagatgaagc cttccccaga cttcagaaaa 420 taaagtcaaa ccctagattt tgttttaaaa taggaaactc agaatcaact tgcctccatc 480 ctctgggaaa actgctccca cacaggcctt ggagtgtgtt gtagcactgt ggaggaatgc 540 agaaaggatg aaagagatct tgattctcct agtggttctc ttcactaccg taggcatccc 600 tcag 604 <210> 69 WO 00/71710 ~ 0 PCTlFR0010142G
<211> 482 <212> DNA
<213> Homo sapiens <400> 69 aaaaagctct gccâgctgag cgnacttaaa ttgaggaaga gttcccttct ctattaactc 60 attttgggca gtaacaacat accctgcctg atattttcct tctgagactt tggcatagga 120 ' cccacgaaca aaaagtatca actcaggatt atccaatgga gcatctcata aatcaacaca 180 aggggctact agtttggata ctacacctac acaattgtga tctttaccac agtcagtcag 240 aggtaatgga gtagcagggt taagtaggtt ttaggatggg agtaggcatt ttaggatggg 300 aggtcagaag ggaggncagg gaggaaaatt tncattaagg ttcataaggt gttagttttc 360 tttggctgga aaantgctgg agcttgggtt gggattttag gtaggacttt tccacagcct 420 gtgggaattt tggcaantta agtttcnttc ccttaaaacc cgttccggtg gaaanttgtt 480 gg 482 <210> 70 <211> 402 <212> DNA
<213> Homo sapiens <400> 70 ttccagntat ggatatgtta cagacatgac tgaattggtg gccttagctg aacattttga 60 gaggactctg gagcaagaaa aaacccaaaa gactaccaag cttatgtctc accaattaca 120 acagttacag gggctgagac caaaggaacc ttctttttta ttttaaatca caaccaagag 180 atagatccta ggaacaagaa attcttttcc ccgaggatgt ctgccttcct tggcaaataa 240 ggcagggaca ctgggaaaag agttgtctgc ttctctgtta ggtctaccaa taaggcctcc 300 tcccattagg gccacactgt ttcaccacta aagggaaggc ctaaggacag atcctgtgtc 360 tttaaaaaaa aaaaaaattg gaggcggcgg caggccacca ng 402 <210> 71 <211> 758 <212> DNA
<213> Homo sapiens <400> 71 agtaacaaca taccctgcct gatattttcc ttctgagact ttggcatagg acccacgaac 60 aaaaagtatc aactcaggat tatccaatgg agcatctcat aaatcaacac aaggggctac 120 tagtttggat actacaccta cacaattgtg atctttacca cagtcagtca gaggtaatgg 180 agtagcaggg ttaagtaggt tttagatgga gtagcatttt agatggaggt cagaaggagg 240 caggagaaaa tttcataaga tcataagatg ttagttttct tgctgaaaaa tgctgagctt 300 ggttggaatt tagtagactt tccacagcat gtggaatttg caaattaagt tcattcccta 360 aaaccagctc agatgaaact tgtagcaact tggtggctgc tgctgcttct attttttttt 420 ttttttttaa gacacaggat ctgtcttagg cttcctttag tggtgaaaca gtgtggccta 480 atgggaggag gcttattggt agactaacag agaagcagac aactcttttc cagtgtcctg 540 cttatttgca aggaaggcag acatctcggg gaaaagaatt tcttgttcta ggatctatct 600 cttggttgtg atttaaaata aaaaagaagg ttcctttggt ctcagcccct gtaactgttg 660 WO 00/71710 ~ ~ PCTlFR0010142G
taattggtga gacataagct tggtagtctt ttgggttttt tcttgctcca gagtcctctc 720 aaaatgttca gctaaggcca ccaattcagt catgtctg 75g <210> 72 <211> 673 <212> DNA
<213> Homo sapiens <400> 72 caggttgagc ccttgaaaaa cacaaaaagg acaagttcct gtgttgaaac acccccatcc 60 cctcacgttc tcacccccag gcccagaagt aggttgcaac tgcctttgga agattttgcc 120 ccttagccat ccccacccac ttgtaccagc taagaatgct ggagactctg ccaccatgct 180 ctgcgtgccc ctgaacctct gtgcagcccg gaaggctgat gtacaggtgt acctcaatcc 240 acattacagc catgctccta atgtacatgg acatttttgt aactcagctc atattctgac 300 tgtatttgag aagctggctg tttaagggaa cccagaagtg aattcttttg taaagtaaag 360 cacccttttg taatgcaatt aattatccct taatgtatct gttttgtaag tctgcatttt 420 tgtatatcgg atttacctta agcttctcta gtgaggcatt ctgagcagtg gtgatcacat 480 gccagatccg gccctgccna tccacaaaag tagatganca atgcacgctc ctcaaacatc 540 tttggaggaa ctacctgggc canancactg gccagggtgg cagcaagcag cagcaggggc 600 tgacagcagg gtttactgnc attcaacatt gcttganatt gcctctaatg ttctgnatta 660 aangaaaaac cat 673 <210> 73 <211> 554 <212> DNA
<213> Homo sapiens <400> 73 aaagggggaa aggaaactac tttaagagcc ccctttttcn tcccnaactc caaatttttg 60 aaaggggaaa aaacnggaaa accccacccc agttccttcc agaaaaatgc cttttcctag 120 gncattaaat acctaccttt acctatccta anactgntta agntaaatcc ctttccttta 180 ccccacccta aactanccca ttctaanccc ggantccctc actctttttt tttagttact 240 aatcatttta tgaaaataat gtatttataa gtattttcct taaggtttgt gaagagtatt 300 tgcantgtgt ccttcatttt natgtgtttg cnannnctcc gctccaggaa gaacggaaat 360 gctgtcttgt gagcatgaag tgaacgggct gttttgctcc agccactttt cttgtacaac 420 cacatggatg gattagatgt cctcaggtct tttccatctt cagtttctat gactgtggaa 480 taaatgttca gatagaaact tcaaaaaaaa aaaaaaaaaa aaaaaaaaaa gtacctcggc 540 cgcgaccacg ctaa 554 <210> 74 <211> 1794 <212> DNA
<213> Homo sapiens <400> 74 WO 00/71710 G ~ PCTlFR0010142G
gttctcaccc caggcccaga agtaggttgc aactgccttt ggaagatttt gccccttagc 60 catccccacc cacttgtacc agctaagaat gctggagact ctgccaccat gctctgcgtg 120 cccctgaacc tctgtgcagc ccggaaggct gatgtacagg tgtacctcaa tccacattac 180 agccatgctc ctaatgtaca tggacatttt tgtaactcag ctcatattct gactgtattt 240 gagaagctgg ctgtttaagg gaacccagaa gtgaattctt ttgtaaagta aagcaccctt 300 ttgtaatgca attaâttatc ccttaatgta tctgttttgt aagtctgcat ttttgtatat 360 cgggtttacc ttaagcttct ctagtgaggc attctgagca gtggtgatca catgccagat 420 cgccctgcct atccacaaag tagatgacca atgcacgctc ctcaaacatc tttggaggaa 480 ctacctggcc aaaacactgg ccaggatgca gcaagcagca gcaggggctg acagcaggct 540 tactgccatc aacattgctt gaaatgcctc tatgttctga ataaagaaaa accataattg 600 cttgtggtga aacgaagcag tcttcatgtt aagtagcaat ggttattttt attggtagta 660 actgaacagt gttttgcaat ttgtgaaaca gtgtattgtg ttttgtaaaa tgatgtcatg 720 aaatggtggg tccttggaaa cctcctttcc gttcagctct gcctctgttc tttcaactcc 780 tttgaggctc aaaaaaaaca caaagatcag aagccttcag atagagggtg gtattctggt 840 aaagaagaaa gagataaggg acgctacctt gcttttctgg cacaggaagc acatgataaa 900 gcatgctcag atgagctgga acagatatag ctacctggtt cgtgtaaata agaataatca 960 aggccccaga gtgtgtatgc ttccaggtgg aggagaaagg ggaatctccc aaaatttaaa 1020 aacaaattgg aagaataacc aggacagcca agtgaagcag ccacagggac ccaagcagtc 1080 gaggtcttta atgtgcctgg agatgactct ctgctattca tgaatcttgc tattgcacaa 1140 accctatcaa gagctgctgc ttcccttcca gccagaaaag tggtaagcgg agcaagtgcc 1200 aagcagaaca gaccttatca tctgggtaac agacttctca gtgttggtgc tgtgtctgtt 1260 agagccttag agcaagttaa gcacttcctt ggtgtgggta aagaataaag.gggaaagaaa 1320 ctactttaga gcctcttttt ctcccaactc atatttttga taggaaaaac agaaaaccca 1380 tccagttctt cagaaattgc tttctaggca ttaatactac tttactatct atactgttta 1440 gttattcctt tctttaccca cctaaactat ccatctaatc caggattccc tcactctttt 1500 tttttagtta ctaatcattt tatgaaaata atgtatttat aagtattttc ttaaggtttg 1560 tgaagagtat ttgcattgtg tcttcatttt aatgtgtttg caatcgctcc gctccaggaa 1620 gaacggaaat gctgtcttgt gagcatgaag tgaacgggct gttttgcaat ccagccactt 1680 ttcttgtaca accacatgga tggattagat gtcctcaggt cttttccatc ttcagtttct 1740 atgactgtgg aataaatgtt cagatagaaa cttcaaaaaa aaaaaaaaaa aaaa 1794 <210> 7s <211> 507 <212> DNA
<213> Homo sapiens <400> 75 aagaaatgat tgaaatgttt caaggggaca tggagctgaa aggtggaatg agagacttcc 60 gtttgggcta taagcttgtg gttttatttg accttttaaa ctcagcactt acactacttt 120 atttctaaat gttctatgaa ggaataagag tttgtagaac aaaagagaag ggctaaaaga 180 gagaccagtt agaaagaggt ggagagtcag aactggagtg caaaagcaca aagattccag 240 ggcatacaag gatgataaat cacttccaca aatgagcgca aagggatatt gtgtacaatg 300 cttccatgaa ggaaagaggg gcactggatt aggtacccac ctgggtttga attgaacaac 360 tactgttttt cccaagcttt tgtgtttgac agtttttaac cctttggcat gttccatttt 420 cccgggggng ttgaggaccn tttaggagct tgggatgcct taagtcccgt taacnttaag 480 ttttctttcc ccccaaaggn gggttna 507 WO 00/71710 ~~ PCTlFR0010142G
<210> 76 <211> 415 <212> DNA

<213> Homo sapiens <400> 76 ttttttttaa tatttcgatg acatgttgaa tgcatataag aggttagagt gaacaaggaa 60 gttaagggct ttcttttttc aaaatcatat ttgcatttaa cttgaaattc tttccagtca 120 tacgattttt gcataaatat ttatgggatc ttgatggcta attagattat aagtctttta 180 tccaggaatt tgtctaattt tatgctctcc atcaaacctg agctctgtgc tgatcttcag 240 tccatgttaa acaaaattat tttaacaccc tttaaggctg catttcaaat tctctcattt 300 gttactcata ctatgtcatg ggaatatata gtctttattt ttgggatgaa agtttgaaga 360 cccaaatccc ccaaaaattg gatttcccnt gtggaaagct ctcattttgg atcca 415 <210> 77 <211> 1318 <212> DNA
<213> Homo sapiens <400> 77 ggagctgaaa ggtggaatga gagacttccg tttgggctat aagccttgtg gttttatttg 60 accttttaaa ctcagcactt acactacttt atttctaaat gttctatgaa ggaataagag 120 tttgtagaac aaaagagaag ggctaaaaga gagaccagtt agaaagaggt ggagagtcag 180 aactggagtg caaaagcaca aagattccag gcatacaagg atgataaatc acttccacaa 240 atgagcgcaa agggatattg tgtacaatgc ttccatgaag aaagagggca ctgataggta 300 cccacctggt tgaaatgaac aactactgta ttccaagctt tgtgttgaca gttttaacct 360 ttgcatgtca ttttccaggg agtgagacct ttagagctgg atgcttaagt ctgtaactta 420 agtttcttcc acaaagagga tttattttgc tttttgtgac atgatggtgc tagaacaaaa 480 tgtactaaga aaaatttgat ggcagtgata gcattatctt gagggataaa gaagtggagt 540 gagaatgcta agtgtagatg aaaaggcctc ttcaaaaccc atttggattt gtaaagtgca 600 tgcctggaga cagcttgagc ctctagaaat gagaagaaca atgggagaat ggttttattc 660 ccatctgaat aattgcaagt tgaccttcct ccaactagaa aagtggggtt gtgtctgagg 720 acttggttgg agaataattt ttccttagtt gcttcatgat actgaacagg tcacttagcc 780 tttctcctcc ttactttctt tcacagtaaa atgagatggt aatctccact tctaagggtt 840 gttgtggaga ccacatgaag acattgatgt aactctgcct ggcagatgat gtaaagtgcc 900 catttgtgcc ttttgctttc tttgcttttg aggcatttgg cacttttatt attctttgat 960 caaaatgaga gctttcacat gggaaatcaa tttttggggg atttgggtct tcaaactttc 1020 atccaaaaat aaagactata tattccgtga catagtatga gtaacaaatg agagaatttg 1080 aaatgcagcc ttaaagggtg ttaaaataat tttgtttaac atggactgaa gatcagcaca 1140 gagctcaggt ttgatggaga gcataaaatt agacaaattc ctggataaaa gacttataat 1200 ctaattagcc atcaagatcc cataaatatt tatgcaaaaa tcgtatgact ggaaagaatt 1260 tcaagttaaa tgcaaatatg attttgaaaa aagaaagccc ttaacttcct tgttcact 1318 <210> 78 <211> 530 WO 00/71710 6 ~ PCTlFR0010142G
<212> DNA
<213> Homo sapiens <400> 78 tagtctctac aatattgtca gactgatctc tgcaaaactc aaaagtcaaa ttactcttct 60 actttaaact tccagtagct cccggattca tttaagggta gaatctaaat cctttggcat 120 agcacttaag accatttcca agggagtggc tctaccatgg agccctagag actctacatg 180 tgtctacatg ggatgcacag gcaaagcttg gactgccata tgacctaaat ctgggtggaa 240 tgccctgtga tcctcctagg aacatgggca agggaggaaa tcttcagaga aggcttcgcg 300 aggttgtttt ctcatctgcc tctatcttgt ggggatgctg ccatgaggcg gttttctgga 360 tattaactcc caggtttcca gaggaacatg gaggatttcc aacttaaccc natggtttcc 420 gtagggtcag gaactgcagn tctattaggc ctttagrngg cagtctggga tttgacntgg 480 ccagcattag gggtgtattc acaantttgc tgnaggcctt ttgaccctat 530 <210> 79 <211> 495 <212> DNA
<213> Homo sapiens <400> 79 ctgtatttgt atagagcaga aaatggatag tcagataaag aagcagactt, tcacaatatc 60 atatgttaat tttgtaatga gatagttgtt tagactagta aatagatcag ggttaaaggc 120 tttgattgaa tcagattatg aaaggtgcca aacacaaagg accgtccaag tctaacactt 180 acagattcag ctggtaaaga aataatgaac taattttaga ttcagccaga ttattactta 240 tatacatagg tgaaggaaaa gagaagctaa aggtgtcagc cctatgagtc cttatcccac 300 acaccaaaag ggtgggcact ggaaacaaan ggggtcagnt gggcttcagc nangngttgt 360 ggatacaccc tnttgctggc cngtcnattc cagactggca gctaantggc tatagagctg 420 cagttctgcc ctacgggngc ctaggggtta agttgggagt ctcntgttcc cctgggccng 480 gggtttatat cngtt 495 <210> 80 <211> 594 <212> DNA
<213> Homo sapiens <400> 80 catttaaggg tagaatctaa atcctttggc atagcactta agaccatttc caagggagtg 60 gctctaccat ggagccctag agactctaca tgtgtctaca tgggatgcac aggcaaagct 120 tggactgcca tatgacctaa atctgggtgg aatgccctgt gatcctccta ggaacatggc 180 aagggaggaa atcttcagag aaggcttcgc gaggttgttt tctcatctgc ctctatcttg 240 tgggatgctg ccatgaggcg gttttctgat ataactccca ggttccagag gaacatgaga 300 cttccaactt aacccctatg cttccgtagg gcagaactgc agctctatag ccatttagct 360 gcagtctgga attgactggc cagcaatagg gtgtatcaca actcttgctg aagccatctg 420 accccttttg tttcagtgcc atccttttgg tgtgtgggat aaggactcat agggctgaca 480 tctttagctt ctcttttctt cactatgtat ataagtaata atctggctga atctaaaatt 540 agttcattat ttctttacca gctgaatctg taagtgttag acttggacgg tcct 594 WO 00/71710 65 PCTlFR0010142G
<210> 81 <211> 582 <212> DNA
<213> Homo sapiens <400> 81 gttttctgga agtagggaga aaatcagagg ctaaagagtt tgaaaatgtg cacagaacag 60 tttgagctca aaatgccact cctaccttat tttgccaggt gattatcaat tcaccacaat 120 tcccacagga aatgagaggc attatctttt gccaaataga acttgatagg ctattaactt 180 gggtaccctg ggcctggagg aggatggaaa taagatagaa gactaaaaac aggatactaa 240 gtggaagtct gaataaaagg ggatgaactc caactcctat cccaccatgt ggcgtgcctc 300 tgcctgctcg ccagtaatgg tagccaggct tatatccccc atgctgacta gaacatcctt 360 ctctggggaa attackaagagc agacctctgg agaaattaca cttctcaaag aaaaattaac 420 aggcactgac atttagggtc ccaaaggcaa aaagtaggtc acactcaaag catctaactc 480 aaagaccctg gacttcagtt gtagaccctg agcagattag actttggatt gtctcccttg 540 ggtaaaatac agtggtctcc ccttattcaa agtttcactt tc 582 <210> 82 <211> 321 <212> DNA
<213> Homo sapiens <400> 82 agtaaggctt ggcagttgac cttgtttgtt ggagagaagg gataagattt taaagctaca 60 tgtctgaaag aatgatgctg ctgattgaaa taaaggaaga aaggatgcat ttcgggctcc 120 aacctgtcct aggaaggcct agacctcaaa caccaacacc tccatgcatt tcctctttgg 180 ctactatgtc ttttccctga cttctgcctc tccagctctc tgggctgctg cttccacctg 240 ttcatctgac ttagaccctc cctgctgggt ccttgttcac ctactcattt ggtgcttcgt 300 ctgccatcag tacctccatt g 321 <210> 83 <211> 545 <212> DNA
<213> Homo sapiens <400> 83 gtcaattaca tcagcacttg gactggacca gggaaaggaa tgattctgct tcctgggaat 60 gtcagaagga cctgatgatt atatttggca aagccaggag gagtggcttt gaatgtcatt 120 gctaagaatt acactttgag tagcatttct ggatgtctga gcttttcaaa tgatacttct 180 tttctgctgt ggctttcctt tctgttggac tggttcccag agggtcctct tgtttgtcct 240 tgccctcgct tttatatcag ttcatgtttt ctcttctgtc atcttccttc ccagcgctgt 300 ttctccaccc cctcctgctg cactcacaac agcttcccct ctcctgttta gaggtggaag 360 catgtaagaa tgcgtttgag ggggatgctt gccaaaggac agcatattca acatctggta 420 tcaacaaggt aatgtttaac cttagactag ccaaactagt gatgacçtgc ttccatgctg 480 WO 00/71710 ~~ PCTlFR0010142G
catctgctgc tttttgtgtt gatgggactc agaaatcatg agaaaggtct tcagtgatcc 540 atgac 545 <210> 84 <211> 183 <212> DNA
<213> Homo sapiens <400> 84 caccaaagct gaagtctctc acttaatcct aagcaagggg ctagggagaa ctaagatatc 60 cttcccatat caagggatat aggttactag aagggtggag gtctcttaac aggctcactc 120 acctttcaga gtttaaatta tggtcaggct taagaagctc tctcttgtga ctgagtgtat 180 tgc 183 <210> 85 <211> 843 <212> DNA
<213> Homo sapiens <400> 85 ggaatggaca tgaagaggat ttcacagtat gtagagcaga aggcacgtga atgtgtttgc 60 tttggcttgg agcttattaa gttttgacta cggttaaaat aagtcaaata gtaagtggta 120 aaacacattt ttgttagtat tggaactttc tggagaacat aagggctatg agaatgcata 180 tatatatttt ttaacatttc ctatatatct aaggtaccaa agcactgagt ctaatttacc 240 tattaaggga gactctttaa aatcaacttt ataactaatt catactataa gacagataat 300 agctaaagtt ttggaataat ttatattaaa agccgcaagt cttaaaaatc cctggatatg 360 acataaaaag gattttggct tcttttttga agtatttaaa attaatcacc ttagctctac 420 catatactag atctgtgacc gctacacaaa ttgtttatca tctttgggtc tctattgcct 480 tctttataaa ataagtgtaa gttgttcagc ctgcctcaca gggctgttgt gaggaaataa 540 aatgaaatgg agtatgtgaa attgcttcag caacagcaaa gtgctacgta aatgtaaagt 600 gttgttttta gctaataatg gatttaagtg tttggataat tgtagatgca tttactttga 660 taaagcgtgt gcttaaagtg gtatcaccag tgatttctaa catgatttta aaaaaataaa 720 accccaatta aaatgttctt taatattcat ttaatttgtg catgacttgt ggcctttttg 780 tattttctca agcctattac tctagagctg taaaagctct tgcacagcat tgttgtgtca 840 gtg 843 <210> 86 <211> 613 <212> DNA
<213> Homo sapiens <400> 86 aggttatcca cttttgctga agatattttt tattgaatca aagattgagt tacaattata 60 cttttcttac ctaagtggat aaaatgtact tttgatgaat cagggaattt ttttaaagtt 120 ggagtttagt tctaaattga ctttacgtat tactgcagtt aattcctttt ttggctaggg 180 WO 00/71710 ~~ PCTlFR0010142G
atggtttgat aaaccacaat tggctgatat tgaaaatgaa agaaacttaa aaggtgggât 240 ggatcatgat tactgtcgat aactgcagat aaatttgatt agagtaataa ttttgtcatt 300 taaaaacaca gttgtttata ctgcccatcc taggatgctc accttccaag attcaacgtg 360 gctaaaacat cttctggtaa attgtgcgtc catattcatt ttgtcagtag ccaggagaaa 420 tggggatggg ggaaatacga cttagtgagg catagacatc cctggtccat cctttctgtc 480 tccagctgtt tcttggaacc tgctctcctg cttgctggtc cctgacgcag agaccgttgc 540 ' ctcccccaca gccgtttgac tgaaggctgc tctggagacc tagagtaaaa cggctgatgg 600 aagttgtggg acc 613 <210> 87 <211> 705 <212> DNA
<213> Homo sapiens <400> 87 gctaatgttt cttgctgggt aattattagc ataaatatca ggttcttaga ggtctttaag 60 agaatacttt agagctacca aaattagcag cagtgatgta atatcaccct gaaataccag 120 gagcagaggt gccccagagt gcttcacagc tatgatcagg aaacttgacc tgccccattg 180 ctacagcaac ggcataagga ctaggaaggt ccactagctg gggaggtctt ggaaccctcc 240 gagccagaaa gaagcattcc agcatgattc ctcagatgca atgaggaagg tttacagaat 300 tttcacaggg caacagagat caagtggtat gaaaaggtag gagttttaag ctcaagtctc 360 aaagataacc tacctttaca ttctcagtca gaatttgacc cagaaagagg aagtttcttc 420 aggaacagac cgtacgttga tgaagtagaa gtcatttcag taaaaacgga gtacagaact 480 tggtcataat atcttgcatt ttatagattt attaaagatt agtttcaagt tcacattcgc 540 tattcagttg taaaccgaat ggatgggagg ggagaaaata caagctctcc acacaggtat 600 gctcctctct tttctgagag agaaggcatg ggattttcag cataaattcc atgttatgtg 660 agtgctgttt gagttctgaa gttcctatca atatctgttc ctgca 705 <210> 88 <211> 459 <212> DNA
<213> Homo sapiens <400> 88 ctcgttgctc agtttagggc actactctta aaaaaggaaa gttaacaaac tggaatagag 60 tcagagataa ctttgagaaa accgatgtca ttaaactggt gtctctggac ctgaggtttg 120 cactcacatt tccatctggc ggccccataa gcaatctgtc ctacagataa ctcgtcctac 180 acaaaactta gtctcttttc agctcagctc tctcactctc aattatatct ccttacttcc 240 atatggcact gttgtacact catttactca gagccagaaa cgtcagcgtc atcttggatt 300 tttcttatgc tctttctctc tctagtcata tgccagactt taaactctgc ttgaaagctt 360 tctcataagc tctttccttt tccctttcta ctgctttgca tttgctactt aacccttttc 420 ttcaggctgt ttgctttcca gtccatcgtt cgctctgct 459 <210> 89 <211> 775 tgccctcgct tttatatcag ttcatgtttt ctc WO 00/71710 ~ s PCTlFR0010142G
<212> DNA
<213> Homo sapiens <400> 89 tctatccgtc cgcgtcagcg ccttgccacc ctcatctcca atatgcctgg tccgaccccc 60 agtggcacta acgtgggatc ctcagggcgc tctcccagca aagcagtggc cgcccgggcg 120 gcgggatcca ctgtccggca gaggtaagga accctgcagt tcgttcgctt ccagactcgg 180 agataggacc cagaacctcg ctgattctgg ggtggagacc ctagcatgtg aagattgaca 24D
aaggcaaaat gagcttctag tgacgtggcc gtgggagtag ttaaaggcct tttgggagga 300 aggcgacatt ttttttctcg ttgctcagtt tagggcacta ctcttaaaaa aggaaagtta 360 acaaactgga atagagtcag agataacttt gagaaaaccg atgtcattaa actggtgtct 420 ctggacctga ggtttgcact cacatttcca tctggcggcc ccataagcaa tctgtcctac 480 agataactcg tcctacacaa aacttagtct cttttcagct cagctctctc actctcaatt 540 atatctcctt acttccatat ggcactgttg tacactcatt tactcagagc cagaaacgtc 600 agcgtcatct tggatttttc ttatgctctt tctctctcta gtcatatgcc agactttaaa 660 ctctgcttga aagctttctc ataagctctt tccttttccc tttctactgc tttgcatttg 720 ctacttaacc cttttcttca ggctgtttgc tttccagtcc atcgttcgct ctgct 775 c210> 90 <211> 727 <212> DNA
<213> Homo sapiens <400> 90 gaatgctgtt acctgaaccc cttacttcga aggatcataa gattcacagg ggtgtttgca 60 tttggacttt ttgctactga catttttgta aacgccggac aagtggtcac tgggcactta 120 acgccatact tcctgactgt gtgcaagcca aactacacca gtgcagactg ccaagcgcac 180 caccagttta taaacaatgg gaacatttgt actggggacc tggaagtgat agaaaaggct 240 cggagatcct ttccctccaa acacgctgct ctgagcattt actccgcctt atatgccacg 300 atgtatatta caagcacaat caagacgaag agcagtcgac tggccaagcc ggtgctgtgc 360 ctcggaactc tctgcacagc cttcctgaca ggcctcaacc gggtctctga gtatcggaac 420 cactgctcgg acgtgattgc tggtttcatc ctgggcactg cagtggccct gtttctggga 480 atgtgtgtgg ttcataactt taaaggaacg caaggatctc cttccaaacc caagcctgag 540 gatccccgtg gagtacccct aatggctttc ccaaggatag aaagccctct ggaaacctta 600 agtgcacaga atcactctgc gtccatgacc gaagttacct gagacgactg atgtgtcaca 660 agctgttttt taaaatcatc ttccaattct atacttcaaa acacacagtt gctcaatgtc 720 aaactgt 727 <210> 91 <211> 478 <212> DNA
<213> Homo sapiens <400> 91 cagtttttat cacaggtgca agccgtggca ttggcaaagc tattgcattg aaagcagcaa 60 aggatggagc aaatattgtt attgctgcaa agaccgccca gccacatcca aaacttctag 120 WO 00/71710 6 ~ PCTlFR0010142G
gcacaatcta tactgctgct gaagaaattg aagcagttgg aggaaaggcc ttgccatgta 180 ttgttgatgt gagagatgaa cagcagatca gtgctgcagt ggagaaagcc atcaagaaat 240 ttggaggaat tgatattctg gtaaataatg ccagtgccat tagtttgacc aatacattgg 300 acacacctac caagagattg gatctgatga tgaacgtgaa caccagaggc acctaccttg 360 catctaaagc atgtattcct tatttgaaaa agagcaaagt tgctcatatc ctcaatatca 420 gtccaccact gaacctaaat ccagtttggt tcaaacagca ctgtgcttat accattgc 478 <210> 92 <211> 679 <212> DNA
<213> Homo sapiens <400> 92 gccaggaaac agcaaatcca atagatccga ctttatcagg ctgggctctc gcttcagatt 60 cagtgggcgg acagaatatc aagctacaca tggctccagg ttacgaagaa ccagcacctt 120 tgagaggaag cctagtaaac gttatccatc ccggagacat tcaacgttca aagcaagcaa 180 cccagtgata gcagcccagc tctgctctaa aacaaatcca gaagtccata attaccagcc 240 tcaatatcat cctaatatcc atcccagcca gccccggtgg catcctcact ctccaaatgt 300 caggccatcc tttcaggatg acaggtcgca ttggaaagca tcggccagtg gagatgacag 360 ccattttgat tatgtccacg accagaacca gaagaactta ggagggatgc aaagtatgat 420 gtatcgagat aaactcatga ctgcactttg agagactgaa gcatctctct tccattcacc 480 ttcatagttt cattgcattc catgaaaagt gtcttggcct cagatggatg gatgtgtttg 540 gacgagtgtc tttaaggagt agtcctgaaa ggtgtttttg gtgtccatgt aaatatttga 600 agataaaacc actatagctt gtcataattt actgttgact gcattctcat taaaatgaag 660 gtaaaggctc aggaatcat <210> 93 <211> 691 <212> DNA
<213> Homo sapiens <400> 93 ctgaggatga ttatggtgat gacccttcga ccaactcgtt tgagaaagag aagcaggact 60 atgtctattg cctggagtca tccctgcaga cctacaaccc agactacgtc ctgatggtag 120 aagacgatgc tgtaccagaa gagcagatct tcccagtctt ggagcacctt ctgcgggctc 180 gcttctctga gccacatctc agagatgccc tttatctcaa gctgtatcac cccgagaggc 240 tccagcacta catcaatcca gagcccatgc ggatcctgga atgggttggt gtaggcatgt 300 tgctggggcc cttactaacc tggatataca tgaggtttgc cagccgccca gggtttagct 360 ggcctgtaat gctcttcttc tccctgtata gcatgggtct ggtggagctg gtgggtcggc 420 actatttcct ggaactgcgg cggctgagtc cttccctgta cagtgtggtt cctgcctctc 480 agtgttgcac cccagccatg ctcttcccgg cacctgcggc ccgccggacc ctcacctacc 540 tgtcccaagt gtactgccac aagggctttg gcaaggacat ggcactgtac tcgctgttga 600 gggccaaggg agagagggcc tatgtagtgg agccgaacct cgtgaaacac atcgggctct 660 tctccagtct ccggtacaac tttcatccca g 691 WO 00/71710 PCTlFR0010142G
<210> 94 <211> 451 <212> DNA
<213> Homo sapiens <400> 94 caactttctc cattcccagc tgggccccat tcctggattt aagatggtgg ctatccctga 60 ggagtcacca taaggagaaa actcaggaat tctgagtctt ccctgctaca ggaccagttc 120 tgtgcaatga acttgagact cctgatgtac actgtgatat tgaccgaagg ctacatacag 18 ~
atctgtgaat cttggctggg acttcctctg agtgatgcct gagggtcagc tcctctagac 240 attgactgca agagaatctc tgcaacctcc tatataaaag catttctgtt aattcattca 300 gaatccattc tttacaatat gcagtgagat gggcttaagt ttgggctaga gtttgacttt 360 atgaaggagg tcattgaaaa agagaacagt gacgtaggca aatgtttcaa gcactttaga 420 aacagtactt ttcctataat tagttgatat a 451 <210> 95 <211> 662 <212> DNA
<213> Homo sapiens <400> 95 ggacctttgc tgctgttgga cactccgtca ccttttggaa cacaagtata tcaagatagt 60 ggctactgat gttcaagtgg gattgaagtg tgataaatgg atatattttg ttgtttgctg 120 gggtgttcat ggagatgtta agagattgag gccctgggct gagggtatat aatgtatgtc 180 aggtaaagtt tgaagactgc caaggagcag attttctccc tggaaatgtg aaaactgaac 240 ctataactct gataaggact tgagatgtgt agaaacgttg ggttatggaa gactagtttc 300 ttccataacc ctgaattgga gaccttaatg ctaagtgtag attattgagg tttgttagtg 360 aggaaaagaa taagagttca gaagcctttg ttatcagata gcgaaatcag ggcctagtga 420 ggagcacagg tcgactacat aatggagtcc attggcgaac cctattgcaa tttggtccaa 480 ctatatcttc tggtgaagga aattaatgat gtaagaaaat gcaagaggct caacttctct 540 tccaaaaatc ttctggcttc tgaactcttc ctctgcctct ctttaaataa ataacacaga 600 atttcaagtg gtaggagact tattaagcca gtcaccaagc ttggtctgtc agcctgtctt 660 ct 662 <210> 96 <211> 766 <212> DNA
<213> Homo sapiens <400> 96 ctatcctttc agcccaccaa cttagcggca gcactaggga ttcattataa ggtaaatctg 60 gtttacataa agacctgaag gaggcctgta tttgaagctc acacttggta ttggtatctc 120 tcatttttac tgagccagtg tggaatacca ctgtatgtac tcatataagc ccttgacttt 180 tactgctcat caggattgga atattactct agcagtcttc acacataggc aagttacagt 240 ccttttaaaa agnatctcat ttccctataa tggaacctaa tagccaactt tttcatagaa 300 attgctagaa gagtttgatc aactataaat gataaagtgt ttataagcat agtcagtgtg 360 WO 00/71710 PCTlFR0010142G

acacagaaac caatcttaaa attgaattta atgttttatc atatcagatt aaatattttc 420 tccatgtctt atttttactg caacaagtta gaaagtggga acactttgat taatgtctta 480 aaatttgtgg gccctcattt ggataaaggc agcaatccta aggacttttt ttttttttaa 540 cataatctga gaatttctct gtagagcaga gactttcaaa ccttttggct gtaacccaca 600 gtaaaaaacg catttatatc aaaccttaga atatgtttaa tgaacaatac ttaccattct 660 gatgcttttt attgtttcag tttttaaaat atgccagttg caacccacta aattgatatc 720 ' taccaatggg ttgcaaccct tagcttgaaa aaaacaccct cacaga 766 <210> 97 <211> 5B4 <212> DNA
<213> Homo sapiens <400> 97 agttgatcga ttcatgtcgt attgatagaa tcttgaccag aagaaatttt gctcttttta 60 tatagtttca agaaatgtgt ttttaaattt ttattaatgc acttgaacaa ctttgcagga 120 ataaagcaac cccctaacca caaaatatcc ctctaae_tta gttccctagc tttctcaatg 180 aatacacaca tatttttaca tagctatgat cgttgtgtac attctccttt gttttacttc 240 tcggcctaac acttgtctcc tcttgtcaac acagattcta ctctcaccaa tttaaatgtc 300 tttatatcca tgtaacatgg gtaacctcac ttcaccccat tattagatat ttgagttata 360 tctaattttt cactcttata aatagtgctg ctatgaatgt ctgtaaaaaa aaaaaaactg 420 ctccttcttt tggattattc ccttaggaat atctccaaag agggattaca aggtcaaaga 480 gcatgaagta ttttatagct cttgttttat attgccagat tgctttctag aaagatccaa 540 tctttgggtt ggaaggacct taaaggtcat ctagtttagc ctcc 584 <210> 98 <211> 1251 <212> DNA
<213> Homo sapiens <400> 98 gtgtgtagca gcgtgtccaa ggcaagaact gaaaactctg agtgatgttc agaagtttgc 60 agagataaat ggttcagccc tatgtagcta cancctaaag ccttctgaat acactacatc 120 tccaaaatct tctgttctct gccccaaact accagttcca gcgagtgcac ctattccatt 180 cttccatcgc tgtgctcctg tgaacatttc ctgctatgcc aagtttgcag aggccctgat 240 cacctttgtc agtgacaata gtgtcttaca caggctgatt agtggagtaa tgaccagcaa 300 agaaattata ttgggacttt gcttgttatc actagttcta tccatgattt tgatggtgat 360 aatcaggtat atatcaagag tacttgtgtg gatcttaacg attctggtca tactcggttc 420 acttggaggc acaggtgtac tatggtggct gtatgcaaag caaaga ~ ggt ctcccaaaga 480 aactgttact cctgagcagc ttcagatagc tgaagacaat cttcgggccc tcctcattta 540 tgccatttca gctacagtgt tcacagtgat cttattcctg ataatgttgg ttatgcgcaa 600 acgtgttgct cttaccatcg ccttgttcca cgtagctggc aaggtcttca ttcacttgcc 660 actgctagtc ttccaaccct tctggacttt ctttgctctt gtcttgtttt gggtgtactg 720 gatcatgaca cttctttttc ttggcactac cggcagtcct gttcagaatg agcaaggctt 780 tgtggagttc aaaatttctg ggcctctgca gtacatgtgg tggtaccatg tggtgggcct 840 gatttggatc agtgaattta ttctagcatg tcagcagatg acagtggcag gagctgtggt 900 WO 00/71710 PCTlFR0010142G

aacatactat tttactaggg ataaaaggaa tttgccattt acacctattt tggcatcagt 960 aaatcgcctt attcgttacc acctaggtac ggtggcaaaa ggatctttca ttatcacatt 1020 agtcaaaatt ccgcgaatga tccttatgta tattcacagt cagctcaaag gaaaggaaaa 1080 tgcttgtgca cgatgtgtgc tgaaatcttg catttgttgc ctttggtgtc ttgaaaagtg 1140 cctaaattat ttaaatcaga atgcatacac agccacagct atcaacagca ccaacttctg 1200 cacctcagca aaggatgcct ttgtcattct ggtggagaat gctttgçgag t 1251 <210> 99 <211> 710 <212> DNA
<213> Homo sapiens <400> 99 tttgatcctc cagtgtgact gttgtttttg tttgggggtg ggttggggtt ttttgctttt 60 tattcctgaa gcttaccaga tatgaatggc taatactcca ttgttctgct tgttgtaatg 120 gtgaatgctt taagaaaaaa aagtgtaatt tgctaagaat aattcatgat ctgtttatgc 180 gataactcct ttttgttaca atttttttaa aaaaagctat ttttgttaat gtaaagtaaa 240 tatttcagag caaatttttt aaacttattg cactaaatac aggctctgta caaaaaaaaa 300 aaaaaaaaaa aaaagcctca gcattttatc attccatgga aggagaatct tttgaaagaa 360 agcattgcct cctaccagaa ctagacagtg aattagatcg gtattatgga aatgcataca 420 agtaatgtca ctagggctta ataagcagcc gtttgctaat gtgcttcctt.tcaaagggtt 480 ggacctttaa attgctgcaa aaggtaaatt gtattttttt ttaagtattg gtgttcttta 540 ctctagctag gctaaaattt gctaaatgcc ttggtttctt ttaaaagttc atgtaatatt.600 tctgattttt cagaatattt gcaataagag tctggatttt aaaaaacaca tgcatacaca 660 caattaagag ctcatgtctt agcaagatct gggaaaccaa cattgcgaga 710 <210> 100 <211> 580 <212> DNA
<213> Homo sapiens <400> 100 aggttcctgt agtctgtgct cagaacttgg tttttggccc ctattgtttt tgcctatttt 60 gattttcaga gatgatcaca tggggacagt taacttttct tctgctgtgt tgccttaatg 120 ctactagatt gtgttgtgtt gttggagttt tctgacttct tccctataaa aagatactga 180 gagctccata atgaaagaag ttgttatact ttctcagaat attctggacc actgaatgca 240 cttctaatag agctttaatc taaagaagtt agttcagtgg ttattaactg attttattac 300 aggagaaaaa aactttaaca aaaaggcagg gagaaaagtg tgaagggcat caagcaaaat 360 gacaggggct tcaaaaaaca accaaagaca aaaccctatc ttctgaagac caaaggtcca 420 actttactta ctggctggca cagcctttct gaactccttg agtttagaat agagctccta 480 gaataataag gcggccaaat tttaaagatc agtcaataca gtagggacct gctattgatc 540 tctcaggcac tgagttcttc acatccagtg tcaagcccag 580 <210> 101 <211> 223 WO 00/71710 PCTlFR0010142G

<212> DNA
<213> Homo sapiens <400> 101 atgacagaga tttgccttcc agggggtcta atttgaagag gaaagtaatt taaatgtata 60 ggtttatata atagcattgt atttttctct attttattca ttctttcatt ctcttcgatg 120-actcccagca cctgcgcgtc catcttcatt cttagccaat gacctttcct tttacttaac 180 agagaaaata acaatcagaa gagtcttcat aagttcccac ccc 223 <210> 102 <211> 19 <212> DNA
<213> Homo sapiens <400> 102 ctcctttccc accagacac 19 <210> 103 <211> 20 <212> DNA
<213> Homo sapiens <400> 103 cattccaagg ttcccttttt 20 <210> 104 <211> 22 <212> DNA
<213> Homo sapiens <400> 104 agctcctctt gcctaagtgg tc 22 <210> 105 <211> 22 <212> DNA
<213> Homo sapiens <400> 105 gtttgtgtgg ttctgttttc ca 22 <210> 106 <211> 19 WO 00/71710 PCTlFR0010142G

<212> DNA
<213> Homo sapiens <400> 106 aaccctgtgc tgatctccc 19 <210> 107 <211> 18 <212> DNA
<213> Homo sapiens <400> 107 gtgcttcaaa ggcttcaa 18 <210> 108 <211> 17 <212> DNA
<213> Homo sapiens <400> 108 tcagtggaaa gaaatgt 17 <210> 109 <211> 18 <212> DNA
<213> Homo sapiens <400> 109 atggggacga tttcagtg 1g <210> 110 <211> 21 <212> DNA
<213> Homo sapiens <400> 110 ctgctgtcta ttgggaaagt t 21 <210> 111 <211> 20 <212> DNA
<213> Homo sapiens WO 00/71710 PCTlFR0010142G
<4D0> 111 agaagcagtg gacaggggag 20 <210> 112 <211> 22 <212> DNA
<213> Homo sapiens <400> 112 ctggttgaac ctgtggattg tg 22 <210> 113 <211> 22 <212> DNA
<213> Homo sapiens <400> 113 tggagagcag cttccaaaaa tc 22 <210> 114 <211> 1B
<212> DNA
<213> Homo sapiens <400> 114 caatgcacct gtcagggg 18 <210> 115 <211> 22 <212> DNA
<213> Homo sapiens <400> 115 tgttggacct ggtactctcc ac 22 <210> 116 <211> 18 <212> DNA
<213> Homo sapiens <400> 116 gggcaaatgg ggaaacat 1g WO 00/71710 PCTlFR0010142G

<210> 117 <211> 19 <212> DNA
<213> Homo sapiens <400> 117 gggaagacag gggaaagag <210> 118 <211> 22 <212> DNA
<213> Homo sapiens <400> 118 ccattgactc ctccttcttt ct 22 <210> 119 <211> 19 <212> DNA
<213> Homo sapiens <400> 119 agtaacaaca taccctgcc 19 <210> 120 <211> 21 <212> DNA
<213> Homo sapiens <400> 120 cagacatgac tgaattggtg g 21 <210> 121 <211> 20 <212> DNA
<213> Homo sapiens <400> 121 aaacaccccc atcccctcac 20 <210> 122 <211> 19 WO 00/71710 PCTlFR0010142G

<212> DNA
<213> Homo sapiens <400> 122 ggggctgaca gcagggttt <210> 123 <211> 20 <212> DNA
<213> Homo sapiens <400> 123 aaaccccacc ccagttcctt 20 <210> 124 <211> 21 <212> DNA
<213> Homo sapiens <400> 124 gaagtgaacg ggctgttttg c 21 <210> 125 <211> 19 <212> DNA
<213> Homo sapiens <400> 125 ggagctgaaa ggtggaatg 1g <210> 126 <211> 22 <212> DNA
<213> Homo sapiens <400> 126 agtgaacaag gaagttaagg gc 22 <210> 127 <211> 21 <212> DNA
<213> Homo sapiens WO 00/71710 PCTlFR0010142G

<400> 127 cccggattca Gttaagggta g 21 <210> 128 <211> 18 <212> DNA
<213> Homo sapiens <400> 128 cacaaaggac cgtccaag 18 <210> 129 <211> 461 <212> PRT
<213> Homo sapiens <400> 129 Met Asp Ser Gln Lys Tyr Cys Phe Lys Glu Asn Glu Asn Val Thr Val Asp Lys Ala Cys Phe Leu Ile Ser Asn Ile Thr Ile Gly Pro Glu Ser Ile Asn Leu Gln Gln Glu Ala Leu Gln Arg Ile Ile Ser Thr Leu Ala Asn Lys Asn Asp Glu Ile Gln Asn Phe Ile Asp Thr Leu His His Thr Leu Lys Gly Val Gln Glu Asn Ser Ser Asn Ile Leu Ser Glu Leu Asp Glu Glu Phe Asp Ser Leu Tyr Ser Ile Leu Asp Glu Val Lys Glu Ser Met Ile Asn Cys Ile Lys Gln Glu Gln Ala Arg Lys Ser Gln Glu Leu Gln Ser Gln Ile Ser Gln Cys Asn Asn Ala Leu Glu Asn Ser Glu Glu Leu Leu Glu Phe Ala Thr Arg Ser Leu Asp Ile Lys Glu Pro Glu Glu Phe Ser Lys Ala Ala Arg Gln Ile Lys Asp Arg Val Thr Met Ala Ser WO 00/71710 PCTlFR0010142G

Ala Phe Arg.Leu Ser Leu Lys Pro Lys Val Ser Asp Asn Met Thr His Leu Met Val Asp Phe Ser Gln Glu Arg Gln Met Leu Gln Thr Leu Lys Phe Leu Pro Val Pro Lys Ala Pro Glu Ile Asp Pro Val Glu Cys Leu Val Ala Asp Asn Ser Val Thr Val Ala Trp Arg Met Pro Glu Glu Asp Asn Lys Ile Asp His Phe Ile Leu Glu His Arg Lys Thr Asn Phe Asp Gly Leu Pro Arg Val Lys Asp Glu Arg Cys Trp Glu Ile Ile Asp Asn Ile Lys Gly Thr Glu Tyr Thr Leu Ser Gly Leu Lys Phe Asp Ser Lys Tyr Met Asn Phe Arg Val Arg Ala Cys Asn Lys Ala Val Ala Gly Glu Tyr Ser Asp Pro Val Thr Leu Glu Thr Lys Ala Leu Asn Phe Asn Leu 290,295. 300 Asp Asn Ser Ser Ser His Leu Asn Leu Lys Val Glu Asp Thr Cys Val Glu Trp Asp Pro Thr Gly Gly Lys Gly Gln Glu Ser Lys Ile Lys Gly Lys Glu Asn Lys Gly Ser Val His Val Thr Ser Leu Lys Lys His Thr Arg Ser Gly Thr Pro Ser Pro Lys Arg Thr Ser Val Gly Ser Arg Pro Pro Ala Val Arg Gly Ser Arg Asp Arg Phe Thr Gly Glu Ser Tyr Thr Val Leu Gly Asp Thr Ala Ile Glu Ser Gly Gln His Tyr Trp Glu Val Lys Ala Gln Lys Asp Cys Lys Ser Tyr Ser Val Gly Val Ala Tyr Lys 405 410 ~ 415 WO 00/71710 PCTlFR0010142G
Thr Leu Gly Lys Phe Asp Gln Leu Gly Lys Thr Asn Thr Ser Trp Cys Ile His Val Asn Asn Trp Leu Gln Asn Thr Phe Ala Ala Lys His Asn Asn Lys Val Lys Ala Leu Asp Val Thr Val Leu Lys Lys <210> 130 <211> 32 <212> PRT
<213> Homo sapiens <400> 130 Ile Lys Asn Ile Ile Leu Ser Val Ser Leu Trp Ser Lys Met Phe Met Val Glu Thr Gly Asp Leu Ala Ala Ser Leu Thr Thr Phe Ser, Lys Cys <210> 131 c211> 183 <212> PRT
c213> Homo sapiens <400> 131 Asn Ile Ile Gly Gln Ser Val Glu Glu Ala Ile Arg Gly Val Phe Asp Ala Ser Leu Lys Met Ala Gly Phe Tyr Gly Leu Tyr Thr Trp Leu Thr His Thr Met Phe Gly Ile Asn Ile Val Phe Ile Pro Ser Ala Leu Ala Ala Ile Leu Gly Ala Val Pro Phe Leu Gly Thr Tyr Trp Ala Ala Val Pro Ala Val Leu Asp Leu Trp Leu Thr Gln Gly Leu Gly Cys Lys Ala WO 00/71710 PCTlFR0010142G

65 70 75 g0 Ile Leu Leu Leü Ile Phe His Leu Leu Pro Thr Tyr Phe Val Asp Thr Ala Ile Tyr Ser Asp Ile Ser Gly Gly Gly His Pro Tyr Leu Thr Gly Leu Ala Val Ala Gly Gly Ala Tyr Tyr Leu Gly Leu Glu Gly Ala Ile Ile Gly Pro Ile Leu Leu Cys Ile Leu Val Val Ala Ser Asn Ile Tyr Ser Ala Met Leu Val Ser Pro Thr Asn Ser Val Pro Thr Pro Asn Gln Thr Pro Trp Pro Ala Gln Pro Gln Arg Thr Phe Arg Asp Ile Ser Glu Asp Leu Lys Ser Ser Val Gly <210> 132 <211> 291 <212> PRT
<213> Homo sapiens <400> 132 Met Asp Ser Pro Trp Asp Glu Leu Ala Leu Ala Phe Ser Arg Thr Ser Met Phe Pro Phe Phe Asp Ile Ala His Tyr Leu Val Ser Val Met Ala Val Lys Arg Gln Pro Gly Ala Ala Ala Leu Ala Trp Lys Asn Pro Ile Ser Ser Trp Phe Thr Ala Met Leu His Cys Phe Gly Gly Gly Ile Leu Ser Cys Leu Leu Leu Ala Glu Pro Pro Leu Lys Phe Leu Ala Asn His Thr Asn Ile Leu Leu Ala Ser Ser Ile Trp Tyr Ile Thr Phe Phe Cys WO 00/71710 PCTlFR0010142G

Pro His Asp Leu Val Ser Gln Gly Tyr Ser Tyr Leu Pro Val Gln Leu Leu Ala Ser Gly_Met Lys Glu Val Thr Arg Thr Trp Lys Ile Val Gly Gly Val Thr His Ala Asn Ser Tyr Tyr Lys Asn Gly Trp Ile Val Met Ile Ala Ile Gly Trp Ala Arg Gly Ala Gly Gly Thr Ile Ile Thr Asn Phe Glu Arg Leu Val Lys Gly Asp Trp Lys Pro Glu Gly Asp Glu Trp Leu Lys Met Ser Tyr Pro Ala Lys Val Thr Leu Leu Gly Ser Val Ile Phe Thr Phe Gln His Thr Gln His Leu Ala Ile Ser Lys His Asn Leu Met Phe Leu Tyr Thr Ile Phe_ Ile Val Ala Thr Lys Ile Thr Met Met Thr Thr Gln Thr Ser Thr Met Thr Phe Ala Pro Phe Glu Asp Thr Leu Ser Trp Met Leu Phe Gly Trp Gln Gln Pro Phe Ser Ser Cys Glu Lys Lys Ser Glu Ala Lys Ser Pro Ser Asn Gly Val Gly Ser Leu Ala Ser Lys Pro Val Asp Val Ala Ser Asp Asn Val Lys Lys Lys His Thr Lys Lily Asn Glu <210> 133 <211> 48 <212> PRT
<213> Homo sapiens <400> 133 WO 00/71710 PCTlFR0010142G
s3 Ser Ile Arg Pro Arg Gln Arg Leu Ala Thr Leu Ile Ser Asn Met Pro 1 ~ 5 10 15 Gly Pro Thr Pro Ser Gly Thr Asn Val Gly Ser Ser Gly Arg Ser Pro Ser Lys Ala Val Ala Ala Arg Ala Ala Gly Ser Thr Val Arg Gln Arg <21D> 134 <211> 22 <212> PRT
<213> Homo sapiens <400> 134 Asn Lys Thr Gln Arg Pro Cys Ala Gln Gln His Ser Arg Met Pro Pro Ile Pro Arg Phe Pro Phe <210> 135 <211> 95 <212> PRT
<213> Homo sapiens <400> 135 Met Trp Asp Phe Arg Ala Arg Ile Phe Asn Ser Gln Gln Tyr Trp Lys Leu Arg Leu Gln Asn Pro Gly Met Glu Gly Arg Glu Phe Glu Leu Cys Ser Leu His Arg Met Gly Ser Gln Glu Asn Ala Asn Val Lys Leu Ser Tyr Arg Glu Val Ser Ile Asn Leu His Arg Thr Pro Thr Lys Asp Thr Leu Arg Glu Lys Val Cys Ser Pro Lys Tyr Thr Ser Leu Phe Asn Leu WO 00/71710 PCTlFR0010142G
s ~
Leu Pro Lys.Ile Arg Glu Asn Ala Asp Thr Ala Gly Lys Arg Ser <210> 136 <211> 108 <212> PRT
<213> Homo sapiens <400> 136 Leu Lys Thr His Phe Pro Pro Cys Pro Arg His Lys Phe Ile Leu Met Leu Ile Leu Gln Ser Leu Arg Tyr His Ala Ser Tyr Arg Asp Ile Leu Asp Asp Leu Leu His Gln Asp Arg Ile Gly Gln His Met Ser Pro Glu Gly Cys Met Leu Lys Gln Gln Ser Lys Gln Leu Ala His Asn Arg Gln Leu Leu Arg Pro Asn Ser Val His Pro Gln Ala Leu Gln His Gln Pro Glu Asp Ser Arg Gln Glu Ser Gln Asp Gly Asp Thr Asp Pro Pro Gln Leu Val Pro Thr Ile Thr Glu Thr Glu Met Ser Gln <210> 137 <211> 213 <212> PRT
<213> Homo sapiens <400> 137 Glu Cys Cys Tyr Leu Asn Pro Leu Leu Arg Arg Ile Ile Arg Phe Thr Gly Val Phe Ala Phe Gly Leu Phe Ala Thr Asp Ile Phe Val Asn Ala Gly Gln Val Val Thr Gly His Leu Thr Pro Tyr Phe Leu Thr Val Cys WO 00/71710 PCTlFR0010142G
ss Lys Pro Asn Tyr Thr Ser Ala Asp Cys Gln Ala His His Gln Phe Ile Asn Asn Gly Asn Ile Cys Thr Gly Asp Leu Glu Val Ile Glu Lys Ala Arg Arg Ser Phe Pro Ser Lys His Ala Ala Leu Ser Ile Tyr Ser Ala Leu Tyr Ala Thr Met Tyr Ile Thr Ser Thr Ile Lys Thr Lys Ser Ser Arg Leu Ala Lys Pro Val Leu Cys Leu Gly Thr Leu Cys Thr Ala Phe Leu Thr Gly Leu Asn Arg Val Ser Glu Tyr Arg Asn His Cys Ser Asp Val Ile Ala Gly Phe Ile Leu Gly Thr Ala Val Ala Leu Phe Leu Gly Met Cys Val Val His Asn Phe Lys Gly Thr Gln Gly Ser Pro Ser Lys Pro Lys Pro Glu Asp Pro Arg Gly Val Pro Leu Met Ala Phe Pro Arg Ile Glu Ser Pro Leu Glu Thr Leu Ser Ala Gln Asn His Ser Ala Ser Met Thr Glu Val Thr c210> 138 <211> 325 <212> PRT
<213> Homo sapiens c400> 138 Met Ala Val Gly Asn Asn Thr Gln Arg Ser Tyr Ser Ile Ile Pro Cys Phe Ile Phe Val Glu Leu Val Ile Met Ala Gly Thr Val Leu Leu Ala WO 00/71710 PCTlFR0010142G

Tyr Tyr Phe Glu Cys Thr Asp Thr Phe Gln Val His Ile Gln Gly Phe Phe Cys Gln Asp Gly Asp Leu Met Lys Pro Tyr Pro Gly Thr Glu Glu Glu Ser Phe Ile Thr Pro Leu Val Leu Tyr Cys Val Leu Ala Ala Thr Pro Thr Ala Ile Phe Island Gly Glu Island Ser Met Tyr Phe Island Lys Island Ser Thr Arg Glu Ser Leu Ile Ala Gln Glu Lys Thr Ile Leu Thr Gly Glu Cys Cys Tyr Leu Asn Pro Leu Leu Arg Arg Ile Ile Arg Phe Thr Gly Val Phe Ala Phe Gly Leu Phe Ala Thr Asp Ile Phe Val Asn Ala Gly Gln Val Val Thr Gly His Leu Thr Pro Tyr Phe Leu Thr Val Cys Lys Pro Asn Tyr Thr Ser Ala Asp Cys Gln Ala His His Gln Phe Ile 165 170 ~ 175 Asn Asn Gly Asn Ile Cys Thr Gly Asp Leu Glu Val Ile Glu Lys Ala Arg Arg Ser Phe Pro Ser Lys His Ala Ala Leu Ser Ile Tyr Ser Ala Leu Tyr Ala Thr Met Tyr Ile Thr Ser Thr Ile Lys Thr Lys Ser Ser Arg Leu Ala Lys Pro Val Leu Cys Leu Gly Thr Leu Cys Thr Ala Phe Leu Thr Gly Leu Asn Arg Val Ser Glu Tyr Arg Asn His Cys Ser Asp Val Ile Ala Gly Phe Ile Leu Gly Thr Ala Val Ala Leu Phe Leu Gly Met Cys Val Val His Asn Phe Lys Gly Thr Gln Gly Ser Pro Ser Lys WO 00/71710 PCTlFR0010142G

Pro Lys Pro.Glu Asp Pro Arg Gly val Pro Leu Met Ala Phe Pro Arg Ile Glu Ser Pro Leu Glu Thr Leu Ser Ala Gln Asn His Ser Ala Ser Met Thr Glu Val Thr <210> 139 <211> 406 <212> PRT

<213> Homosapiens <400> 139 Val Phe ThrGlyAla SerArgGly IleGlyLys AlaIleAlaLeu Isle Lys Ala LysAspGly AlaAsnIle ValIleAla AlaLys_ThrAla To the Gln Pro ProLysLeu LeuGlyThr IleTyrThr AlaAlaGluGlu His Ile Glu ValGlyGly LysAlaLeu ProCysIle ValAspValArg To the Asp Glu GlnIleSer AlaAlaVal GluLysAla IleLysLysPhe Gln Gly Gly AspIleLeu ValAsnAsn AlaSerAla IleSerLeuThr Isle Asn Thr AspThrPro ThrLysArg LeuAspLeu MetMetAsnVal Leu Asn Thr GlyThrTyr LeuAlaSer LysAlaCys IleProTyrLeu Arg Lys Lys LysValAla HisIleLeu AsnIleSer ProProLeuAsn Ser Leu Asn ValTrpPhe LysGlnHis CysAlaTyr ThrIleAlaLys Pro WO 00/71710 PCTlFR0010142G
ss Tyr Gly Met Ser Met Tyr Val Leu Gly Met Ala Glu Glu Phe Lys Gly Glu Ile Ala Val Asn Ala Leu Trp Pro Lys Thr Ala Ile His Thr Ala Ala Met Asp Met Leu Gly Gly Pro Gly Ile Glu Ser Gln Cys Arg Lys Val Asp Ile Ala Island Asp Ala Ala Tyr Ser Ile Phe Gln Lys Pro Lys Ser Phe Thr Gly Asn Phe Val Ile Asp Glu Asn Ile Leu Lys Glu Glu Gly Ile Glu Asn Phe Asp Val Tyr Ala Ile Lys Pro Gly His Pro Leu Gln Pro Asp Phe Phe Leu Asp Glu Tyr Pro Glu Ala Val Ser Lys Lys Val Glu Ser Thr Gly Ala Val Pro Glu Phe Lys Glu Glu Lys Leu Gln Leu Gln Pro Lys Pro Arg Ser Gly Ala Val Glu Glu Thr Phe Arg Ile Val Lys Asp Ser Leu Ser Asp Asp Val Val Lys Ala Thr Gln Ala Ile Tyr Leu Phe Glu Leu Ser Gly Glu Asp Gly Gly Thr Trp Phe Leu Asp Leu Lys Ser Lys G1 ~ Gly Asn Val Gly Tyr Gly Glu Pro Ser Asp Gln Ala Asp Val Val Met Ser Met Thr Thr Asp Asp Phe Val Lys Met Phe Ser Gly Lys Leu Lys Pro Thr Met Ala Phe Met Ser Gly Lys Leu Lys Ile Lys Gly Asn Met Ala Leu Ala Ile Lys Leu Glu Lys Leu Met Asn Gln Met Asn Ala Arg Leu WO 00/71710 PCTlFR0010142G

<210> 140 <211> 422.
<212> PRT
<213> Homo sapiens <400> 140 Ser Thr Lys Val Met Leu Pro Asn Thr Gly Arg Leu Ala Gly Cys Thr Val Plie Ile Thr Gly Ala Ser Arg Gly Ile Gly Lys A1a Ile Ala Leu Lys Ala Ala Lys Asp Gly Ala Asn Ile Val Ile Ala Ala Lys Thr Ala Gln Pro His Pro Lys Leu Leu Gly Thr Ile Tyr Thr Ala Ala Glu Glu Ile Glu Ala Val Gly Gly Lys Ala Leu Pro Cys Ile Val Asp Val Arg Asp Glu Gln Gln Ile Ser Ala Ala Val Glu Lys Ala Ile Lys Lys Phe Gly Gly Ile Asp Ile Leu Val Asn Asn Ala Ser Ala Ile Ser Leu Thr lOD 105 110 Asn Thr Leu Asp Thr Pro Thr Lys Arg Leu Asp Leu Met Met Asn Val Asn Thr Arg Gly Thr Tyr Leu Ala Ser Lys Ala Cys Ile Pro Tyr Leu Lys Lys Ser Lys Val Ala His Ile Leu Asn Ile Ser Pro Pro Leu Asn Leu Asn Pro Val Trp Phe Lys Gln His Cys Ala Tyr Thr Ile Ala Lys Tyr Gly Met Ser Met Tyr Val Leu Gly Met Ala Glu Glu Phe Lys Gly Glu Ile Ala Val Asn Ala Leu Trp Pro Lys Thr Ala Ilé His Thr Ala Ala Met Asp Met Leu Gly Gly Pro Gly Ile Glu Ser Gln Cys Arg Lys WO 00/71710 ~ p PCTlFR0010142G

Val Asp Ile Ala Island Asp Ala Ala Tyr Ser Ile Phe Gln Lys Pro Lys Ser Phe Thr Gly-Asn Phe Val Ile Asp Glu Asn Tle Leu Lys Glu Glu Gly Ile Glu Asn Phe Asp Val Tyr Ala Ile Lys Pro Gly His Pro Leu Gln Pro Asp Phe Phe Leu Asp Glu Tyr Pro Glu Ala Val 5er Lys Lys Val Glu Ser Thr Gly Ala Val Pro Glu Phe Lys Glu Glu Lys Leu Gln Leu Gln Pro Lys Pro Arg Ser Gly Ala Val Glu Glu Thr Phe Arg Ile Val Lys Asp Ser Leu Ser Asp Asp Val Val Lys Ala Thr Gln Ala Ile Tyr Leu Phe Glu Leu Ser Gly Glu Asp Gly Gly Thr Trp Phe Leu Asp Leu Lys Ser Lys Gly Gly Asn Val Gly Tyr Gly Glu Pro Ser Asp Gln Ala Asp Val Val Met Ser Met Thr Thr Asp Asp Phe Val Lys Met Phe Ser Gly Lys Leu Lys Pro Thr Met Ala Phe Met Ser Gly Lys Leu Lys Ile Lys Gly Asn Met Ala Leu Ala Ile Lys Leu Glu Lys Leu Met Asn Gln Met Asn Ala Arg Leu <210> 141 <211> 424 <212> PRT
<213> Homo sapiens WO 00/71710 ~ ~ PCTlFR0010142G
<400> 141 Thr Glu Val.Ser Val Asp Leu Pro Lys His Ala Lys Gly Gln Asp Leu 1. 5 10 15 Phe Asp Gln Ile Val Tyr His Leu Asp Leu Val Glu Thr Asp Tyr Phe Gly Leu Gln Phe Leu Asp Ser Ala Gln Val Ala His Trp Leu Asp His Ala Lys Pro Ile Lys Lys Gln Met Lys Ile Gly Pro Ala Tyr Ala Leu His Phe Arg Val Lys Tyr Tyr Ser Ser Glu Pro Asn Asn Leu Arg Glu Glu Phe Thr Arg Tyr Leu Phe Val Leu Gln Leu Arg His Asp Ile Leu Ser Gly Lys Leu Lys Cys Pro Tyr Glu Thr Ala.Val Glu Leu Ala Ala Leu Cys Leu Gln Ala Glu Leu Gly Glu Cys Glu Leu Pro Glu His Thr Pro Glu Leu Val Ser Glu Phe Arg Phe Ile Pro Asn Gln Thr Glu Ala Met Glu Phe Asp Ile Phe Gln Arg Trp Lys Glu Cys Arg Gly Lys Ser Pro Ala Gln Ala Glu Leu Ser Tyr Leu Asn Lys Ala Lys Trp Leu Glu Met Tyr Gly Val Asp Met His Val Val Arg Gly Arg Asp Gly Cys Glu Tyr Ser Leu Gly Leu Thr Pro Thr Gly Ile Leu Ile Phe Glu Gly Ala Asn Lys Ile Gly Leu Phe Phe Trp Pro Lys Ile Thr Lys Met Asp Phe Lys Lys Ser Lys Leu Thr Leu Val Val Val Glu Asp Asp Asp Gln Gly Arg Glu Gln Glu His Thr Phe Val Phe Arg Leu Asp Ser Ala Arg Thr WO 00/71710 ~~ PCTlFR0010142G
Cys Lys His.Leu Trp Lys Cys Ala Val Glu His His Ala Phe Phe Arg Leu Arg Thr Pro Gly Asn Ser Lys Ser Asn Arg Ser Asp Phe Ile Arg Leu Gly Ser Arg Phe Arg Phe Sèr Gly Arg Thr Glu Tyr Gln Ala Thr His Gly Ser Arg Leu Arg Arg Thr Ser Thr Phe Glu Arg Lys Pro Ser Lys Arg Tyr Pro Ser Arg Arg His Ser Thr Phe Lys Ala Ser Asn Pro Val Ile Ala Ala Gln Leu Cys Ser Lys Thr Asn Pro Glu Val His Asn Tyr Gln Pro Gln Tyr His Pro Asn Ile His Pro Ser Gln Pro Arg Trp His Pro His Ser Pro Asn Val Arg Pro Ser Phe Gln Asp Asp Arg Ser His Trp Lys Ala Ser Ala Ser Gly Asp Asp Ser His Phe Asp Tyr Val His Asp Gln Asn Gln Lys Asn Leu Gly Gly Met Gln Ser Met Met Tyr Arg Asp Lys Leu Met Thr Ala Leu <210> 142 <211> 455 <212> PRT
<213> Homo sepiens <400> 142 Gly Pro Leu Leu Thr Gly Gly Ala Ala Val His Ile Ser Ala Ala Gly Ala Ala Lys Ala Thr Leu Tyr Cys Arg Val Phe Leu Leu Asp Gly Thr WO 00/71710 9 ~ PCTlFR0010142G
Glu Val Ser Val Asp Leu Pro Lys His Ala Lys Gly Gln Asp Leu Phe 35 ~ 40 45 Asp Gln Ile Val Tyr His Leu Asp Leu Val Glu Thr Asp Tyr Phe Gly 50 55 ~ 60 Leu Gln Phe Leu Asp Ser Ala Gln Val Ala His Trp Leia Asp His Ala Lys Pro Ile Lys Lys Gln Met Lys Ile Gly Pro Ala Tyr Ala Leu His Phe Arg Val Lys Tyr Tyr Ser Ser Glu Pro Asn Asn Leu Arg Glu Glu Phe Thr Arg Tyr Leu Phe Val Leu Gln Leu Arg His Asp Ile Leu Ser Gly Lys Leu Lys Cys Pro Tyr Glu Thr Ala Val Glu Leu Ala Ala Leu Cys Leu Gln Ala Glu Leu Gly Glu Cys Glu Leu Pro Glu His Thr Pro Glu Leu Val Ser Glu Phe Arg Phe Ile Pro Asn Gln Thr Glu Ala Met Glu Phe Asp Ile Phe Gln Arg Trp Lys Glu Cys Arg Gly Lys Ser Pro Ala Gln Ala Glu Leu Ser Tyr Leu Asn Lys Ala Lys Trp Leu Glu Met Tyr Gly Val Asp Met His Val Val Arg Gly Arg Asp Gly Cys Glu Tyr Ser Leu Gly Leu Thr Pro Thr Gly Ile Leu Ile Phe Glu Gly Ala Asn Lys Ile Gly Leu Phe Phe Trp Pro Lys Ile Thr Lys Met Asp Phe Lys Lys Ser Lys Leu Thr Leu Val Val Val Glu Asp Asp Asp Gln Gly Arg Glu Gln Glu His Thr Phe Val Phe Arg Leu Asp Ser Ala Arg Thr Cys WO 00/71710 ~ 4 PCTlFR0010142G
Lys His Leu Trp Lys Cys Ala Val Glu His His Ala Phe Phe Arg Leu Arg Thr Pro Gly Asn Ser Lys Ser Asn Arg Ser Asp Phe Ile Arg Leu Gly Ser Arg Phe Arg Phe Ser Gly Arg Thr Glu Tyr Gln Ala Thr His Gly Ser Arg Leu Arg Arg Thr Ser Thr Phe Glu Arg Lys Pro Ser Lys Arg Tyr Pro Ser Arg Arg His Ser Thr Phe Lys Ala Ser Asn Pro Val Ile Ala Ala Gln Leu Cys Ser Lys Thr Asn Pro Glu Val His Asn Tyr Gln Pro Gln Tyr His Pro Asn Ile His Pro Ser Gln Pro Arg Trp His Pro His Ser Pro Asn Val Arg Pro Ser Phe Gln Asp Asp Arg Ser His Trp Lys Ala Ser Ala Ser Gly Asp Asp Ser His Phe Asp Tyr Val His Asp Gln Asn Gln Lys Asn Leu Gly Gly Met Gln Ser Met Met Tyr Arg Asp Lys Leu Met Thr Ala Leu <210> 143 <211> 232 <212> PRT
<213> Homo sapiens <400> 143 Glu Asp Asp Tyr Gly Asp Asp Pro Ser Thr Asn Ser Phe Glu Lys Glu Lys Gln Asp Tyr Val Tyr Cys Leu Glu Ser Ser Leu Gln Thr Tyr Asn Pro Asp Tyr Val Leu Met Val Glu Asp Asp Ala Val Pro Glu Glu Gln WO 00/71710 ~ 5 PCTlFR0010142G

Ile Phe .Pro Val Leu Glu His Leu Leu Arg Ala Arg Phe Ser Glu Pro His Leu Arg Asp Ala Leu Tyr Leu Lys Leu Tyr His Pro Glu Arg Leu Gln His Tyr Ile Asn Pro Glu Pro Met Arg Ile Leu Glu Trp Val Gly Val Gly Met Leu Leu Gly Pro Leu Leu Thr Trp Ile Tyr Met Arg Phe Ala Ser Arg Pro Gly Phe Ser Trp Pro Val Met Leu Phe Phe Ser Leu Tyr Ser Met Gly Leu Val Glu Leu Val Gly Arg His Tyr Phe Leu Glu Leu Arg Arg Leu Ser Pro Ser Leu Tyr Ser Val Val Pro Ala Ser Gln Cys Cys Thr Pro Ala Met Leu Phe Pro Ala Pro Ala Ala Arg Arg Thr Leu Thr Tyr Leu Ser Gln Val Tyr Cys His Lys Gly Phe Gly Lys Asp Met Ala Leu Tyr Ser Leu Leu Arg Ala Lys Gly Glu Arg Ala Tyr Val Val Glu Pro Asn Leu Val Lys His Ile Gly Leu Phe Ser Ser Leu Arg Tyr Asn Phe His Pro Ser Leu Leu <210> 144 <211> 263 <212> PRT
<213> Homo sapiens <400> 144 Leu Phe Leu Cys Asn Val Glu Arg Ser Val Ser His Phe Asp Ala Lys WO 00/71710 96 PCTlFR0010142G
Leu Leu Ser.Lys Tyr Val Pro Val Ala Asn Arg Tyr Glu Gly Thr Glu Asp Asp Tyr Gly Asp Asp Pro Ser Thr Asn Ser Phe Glu Lys Glu Lys 35 "40 45 Gln Asp Tyr Val Tyr Cys Leu Glu Ser Ser Leu Gln Thr Tyr Asn Pro Asp Tyr Val Leu Met Val Glu Asp Asp Ala Val Pro Glu Glu Gln Ile Phe Pro Val Leu Glu His Leu Leu Arg Ala Arg Phe Ser Glu Pro-His Leu Arg Asp Ala Leu Tyr Leu Lys Leu Tyr His Pro Glu Arg Leu Gln His Tyr Ile Asn Pro Glu Pro Met Arg Ile Leu Glu Trp Val Gly Val Gly Met Leu Leu Gly Pro Leu Leu Thr Trp Ile Tyr Met Arg Phe Ala Ser Arg Pro Gly Phe Ser Trp Pro Val Met Leu Phe Phe Ser Leu Tyr Ser Met Gly Leu Val Glu Leu Val Gly Arg His Tyr Phe Leu Glu Leu Arg Arg Leu Ser Pro Ser Leu Tyr Ser Val Val Pro Ala Ser Gln Cys Cys Thr Pro Ala Met Leu Phe Pro Ala Pro Ala Ala Arg Arg Thr Leu Thr Tyr Leu Ser Gln Val Tyr Cys His Lys Gly Phe Gly Lys Asp Met Ala Leu Tyr Ser Leu Leu Arg Ala Lys Gly Glu Arg Ala Tyr Val Val Glu Pro Asn Leu Val Lys His Ile Gly Leu Phe Ser Ser Leu Arg Tyr Asn Phe His Pro Ser Leu Leu WO 00/71710 ~ 7 PCTlFR0010142G
<210>

<211>

<212> -PRT

<213> sapiens Homo <400>

Leu Tyr Lys Ala Leu GlyVal Ser Tyr Pro Ser Leu Gln Ser Val Ala Pro Val Leu Thr Pro LeuGly Val Leu Ala Cys Ala Phe Arg Asp Val His Val Asp His Ser TyrLeu Ser Leu Phe Ile Gly Val Asp Phe Leu 35. 40 45 Cys Gln Gln Val Ile Gly Met Phe Gly Phe Lys Asn Met Ser Val Leu Cys Asn Phe Met <210> 146 <211> 720 <212> PRT
<213> Homo sapiens <400> 146 Thr Cys His Glu His Ala Thr Cys Gln Gln Arg Glu Gly Lys Lys Ile Cys Ile Cys Asn Tyr Gly Phe Val Gly Asn Gly Arg Thr Gln Cys Val Asp Lys Asn Glu Cys Gln Phe Gly Ala Thr Leu Val Cys Gly Asn His Thr Ser Cys His Asn Thr Pro Gly Gly Phe Tyr Cys Ile Cys Leu Glu Gly Tyr Arg Ala Thr Asn Asn Asn Lys Thr Phe Ile Pro Asn Asp Gly Thr Phe Cys Thr Asp Ile Asp Glu Cys Glu Val Ser Gly Leu Cys Arg WO 00/71710 ~ s PCTlFR0010142G

His Gly Gly Arg Cys Val Asn Thr His Gly Ser Phe Glu Cys Tyr Cys Met Asp Gly Tyr'Leu Pro Arg Asn Gly Pro Glu Pro Phe His Pro Thr Thr Asp Ala Thr Ser Cys Thr Glu Ile Asp Cys Gly Thr Pro Pro Glu Val Pro Asp Gly Tyr Ile Gly Asn Tyr Thr Ser Ser Leu Gly Ser Gln Val Arg Tyr Ala Cys Arg Glu Gly Phe Phe Ser Val Pro Glu Asp Thr Val Ser Ser Cys Thr Gly Leu Gly Thr Trp Glu Ser Pro Lys Leu His Cys Gln Glu Ile Asn Cys Gly Asn Pro Pro Glu Met Arg His Ala Ile Leu Val Gly Asn His Ser Ser Arg Leu Gly Gly Val Ala Arg Tyr Val Cys Gln Glu Gly Phe Glu Ser Pro Gly Gly Lys Ile Thr Ser Val Cys Thr Glu Lys Gly Thr Trp Arg Glu Ser Thr Leu Thr Cys Thr Glu Ile Leu Thr Lys Ile Asn Asp Val Ser Leu Phe Asn Asp Thr Cys Val Arg Trp Gln Ile Asn Ser Arg Arg Ile Asn Pro Lys Ile Ser Tyr Val Ile Ser Ile Lys Gly Gln Arg Leu Asp Pro Met Glu Ser Val Arg Glu Glu Thr Val Asn Leu Thr Thr Asp Ser Arg Thr Pro Glu Val Cys Leu Ala Leu Tyr Pro Gly Thr Asn Tyr Thr Val Asn Ile Ser Thr Ala Pro Pro Arg Arg Ser Met Pro Ala Val Ile Gly Phe Gln Thr Ala Gly Ser WO 00/71710 ~ 9 PCTlFR0010142G

Arg Asn Ser His Gly Arg Asn Thr His Ile Lys Glu Val Asp Leu Leu Glu Asp Asp Gly Ser Phe Asn Ile Ser Ile Phe Asn Glu Thr Cys Leu Lys Leu Asn Arg Arg Ser Arg Lys Val Gly Ser Glu His Met Tyr Gln Phe Thr Val Leu Gly Gln Arg Trp Tyr Leu Ala Asn Phe Ser His Ala Thr Ser Phe Asn Phe Thr Thr Arg Glu Gln Val Pro Val Val Cys Leu Asp Leu Tyr Pro Thr Thr Asp Tyr Thr Val Asn Val Thr Leu Leu Arg Ser Pro Lys Arg His Ser Val Gln Ile Thr Ile Ala Thr Pro Pro Ala Val Lys Gln Thr Ile Ser Asn Ile Ser Gly Phe Asn Glu Thr Cys Leu Arg Trp Arg Ser Ile Lys Thr Ala Asp Met Glu Glu Met Tyr Leu Phe His Ile Trp Gly Gln Arg Trp Tyr Gln Lys Glu Phe Ala Gln Glu Met Thr Phe Asn Ile Ser Ser Ser Ser Arg Asp Pro Glu Val Cys Leu Asp Leu Arg Pro Gly Thr Asn Tyr Asn Val Ser Leu Arg Ala Leu Ser Ser Glu Leu Pro Val Val Ile Ser Leu Thr Thr Gln Ile Thr Glu Pro Pro Leu Pro Glu Val Glu Phe Phe Thr Val His Arg Gly Pro Leu Pro Arg 565,570,575 Leu Arg Leu Arg Lys Ala Lys Glu Lys Asn Gly Pro Ile Ser Ser Tyr Gln Val Leu Val Leu Pro Leu Ala Leu Gln Ser Thr Phe Ser Cys Asp WO 00/71710 ~ 00 PCTlFR0010142G

Ser Glu Gly Ala Ser Ser Phe Phe Ser Asn Ala Ser Asp Ala Asp Gly Tyr Val Ala Ala Glu Leu Leu Ala Lys Asp Val Pro Asp Asp Ala Met 625 630 635 ~ 640 Glu Ile Pro Ile Gly Asp Arg Leu Tyr Tyr Gly Glu Tyr Tyr Asn Ala Pro Leu Lys Arg Gly Ser Asp Tyr Cys Ile Ile Leu Arg Ile Thr Ser Glu Trp Asn Lys Val Arg Arg His Ser Cys Ala Val Trp Ala Gln Val Lys Asp Ser Ser Leu Met Leu Leu Gln Met Ala Gly Val Gly Leu Gly Ser Leu Ala Val Val Ile Ile Leu Thr Phe Leu Ser Phe Ser Ala Val 705,710,715,720 <210> 147 <211> 707 <212> PRT
<213> Homo sapiens <400> 147 Thr Cys His Glu His Ala Thr Cys Gln Gln Arg Glu Gly Lys Lys Ile Cys Ile Cys Asn Tyr Gly Phe Val Gly Asn Gly Arg Thr Gln Cys Val Asp Lys Asn Glu Cys Gln Phe Gly Ala Thr Leu Val Cys Gly Asn His Thr Ser Cys His Asn Thr Pro Gly Gly Phe Tyr Cys Ile Cys Leu Glu Gly Tyr Arg Ala Thr Asn Asn Asn Lys Thr Phe Ile Pro Asn Asp Gly WO 00/71710 ~ 0 ~ PCTlFR0010142G
Thr Phe Cys.Thr Asp Ile Asp Glu Cys Glu Val Ser Gly Leu Cys Arg His Gly Gly Arg Cys Val Asn Thr His Gly Ser Phe Glu Cys Tyr Cys Met Asp Gly Tyr Leu Pro Arg Asn Gly Pro Glu Pro Phe His Pro Thr Thr Asp Ala Thr Ser Cys Thr Glu Ile Asp Cys Gly Thr Pro Pro Glu Val Pro Asp Gly Tyr Ile Gly Asn Tyr Thr Ser Ser Leu Gly Ser Gln Val Arg Tyr Ala Cys Arg Glu Gly Phe Phe Ser Val Pro Glu Asp Thr Val Ser Ser Cys Thr Gly Leu Gly Thr Trp Glu Ser Pro Lys Leu His Cys Gln Glu Ile Asn Cys Gly Asn Pro Pro Glu Met Arg His Ala Ile Leu Val Gly Asn His Ser Ser Arg Leu Gly Gly Val Ala Arg Tyr Val Cys Gln Glu Gly Phe Glu Ser Pro Gly Gly Lys Ile Thr Ser Val Cys Thr Glu Lys Gly Thr Trp Arg Glu Ser Thr Leu Thr Cys Thr Glu Ile Leu Thr Lys Ile Asn Asp Val Ser Leu Phe Asn Asp Thr Cys Val Arg Trp Gln Ile Asn Ser Arg Arg Ile Asn Pro Lys Ile Ser Tyr Val Ile Ser Ile Lys Gly Gln Arg Leu Asp Pro Met Glu Ser Val Arg Glu Glu Thr Val Asn Leu Thr Thr Asp Ser Arg Thr Pro Glu Val Cys Leu Ala Leu Tyr Pro Gly Thr Asn Tyr Thr Val Asn Ile Ser Thr Ala Pro WO 00/71710 PCTlFR0010142G

Pro Arg Arg. Ser Met Pro Ala Val Ile Gly Phe Gln Thr Ala Glu Val Asp Leu Leu Glu Asp Asp Gly Ser Phe Asn Ile Ser Ile Phe Asn Glu Thr Cys Leu Lys Leu Asn Arg Arg Ser Arg Lys Val Gly Ser Glu His Met Tyr Gln Phe Thr Val Leu Gly Gln Arg Trp Tyr Leu Ala Asn Phe Ser His Ala Thr Ser Phe Asn Phe Thr Thr Arg Glu Gln Val Pro Val Val Cys Leu Asp Leu Tyr Pro Thr Thr Asp Tyr Thr Val Asn Val Thr Leu Leu Arg Ser Pro Lys Arg His Ser Val Gln Ile Thr Ile Ala Thr Pro Pro Ala Val Lys Gln Thr Ile Ser Asn Ile Ser Gly Phe Asn Glu Thr Cys Leu Arg Trp Arg Ser Ile Lys Thr Ala Asp Met Glu Glu Met Tyr Leu Phe His Ile Trp Gly Gln Arg Trp Tyr Gln Lys Glu Phe Ala Gln Glu Met Thr Phe Asn Ile Ser Ser Ser Ser Arg Asp Pro Glu Val Cys Leu Asp Leu Arg Pro Gly Thr Asn Tyr Asn Val Ser Leu Arg Ala Leu Ser Ser Glu Leu Pro Val Val Ile Ser Leu Thr Thr Gln Ile Thr Glu Pro Pro Leu Pro Glu Val Glu Phe Phe Thr Val His Arg Gly Pro Leu Pro Arg Leu Arg Leu Arg Lys Ala Lys Glu Lys Asn Gly Pro Ile 565,570,575 Ser Ser Tyr Gln Val Leu Val Leu Pro Leu Ala Leu Gln Ser Thr Phe WO 00/71710 PCTlFR0010142G

Ser Cys Asp. Ser Glu Gly Ala Ser Ser Phe Phe Ser Asn Ala Ser Asp Ala Asp Gly Tyr Val Ala Ala Glu Leu Leu Ala Lys Asp Val Pro Asp Asp Ala Met Glu Ile Pro Ile Gly Asp Arg Leu Tyr Tyr Gly Glu Tyr Tyr Asn Ala Pro Leu Lys Arg Gly Ser Asp Tyr Cys Ile Ile Leu Arg Ile Thr Ser Glu Trp Asn Lys Val Arg Arg His Ser Cys Ala Val Trp Ala Gln Val Lys Asp Ser Ser Leu Met Leu Leu Gln Met Ala Gly Val Gly Leu Gly Ser Leu Ala Val Val Ile Ile Leu Thr Phe Leu Ser Phe Ser Ala Val <210>

<211>

<212>
PRT

<213> sapiens Homo <400>

Ser Leu Val Ala Thr HisGlu His Ala Cys Gln Asp Cys Cys Thr Gln Arg Glu Lys Ile Cys CysAsn Tyr Gly Val Gly Gly Lys Ile Phe Asn Gly Arg Gln Val Asp AsnGlu Cys Gln Gly Ala Thr Cys Lys Phe Thr Leu Val Cys Gly Asn His Thr Ser Cys His Asn Thr Pro Gly Gly Phe Tyr Cys Ile Cys Leu Glu Gly Tyr Arg Ala Thr Asn Asn Asn Lys Thr WO 00/71710 PCTlFR0010142G

Phe Ile Pro Asn Asp Gly Thr Phe Cys Thr Asp Ile Asp Glu Cys Glu Val 5er Gly Leu Cys Arg His Gly Gly Arg Cys Val Asn Thr His Gly Ser Phe Glu Cys Tyr Cys Met Asp Gly Tyr Leu Pro Arg Asn Gly Pro Glu Pro Phe His Pro Thr Thr Asp Ala Thr Ser Cys Thr Glu Ile Asp Cys Gly Thr Pro Pro Glu Val Pro Asp Gly Tyr Ile Ile Gly Asn Tyr Thr Ser Ser Leu Gly Ser Gln Val Arg Tyr Ala Cys Arg Glu Gly Phe Phe Ser Val Pro Glu Asp Thr Val Ser Ser Cys Thr Gly Leu Gly Thr Trp Glu Ser Pro Lys Leu His Cys Gln Glu Ile Asn Cys Gly Asn Pro Pro Glu Met Arg His Ala Ile Leu Val Gly Asn His Ser Ser Arg Leu Gly Gly Val Ala Arg Tyr Val Cys Gln Glu Gly Phe Glu Ser Pro Gly Gly Lys Ile Thr Ser Val Cys Thr Glu Lys Gly Thr Trp Arg Glu Ser Thr Leu Thr Cys Thr Glu Ile Leu Thr Lys Ile Asn Asp Val Ser Leu Phe Asn Asp Thr Cys Val Arg Trp Gln Ile Asn Ser Arg Arg Ile Asn Pro Lys Ile Ser Tyr Val Ile Ser Ile Lys Gly Gln Arg Leu Asp Pro Met Glu Ser Val Arg Glu Glu Thr Val Asn Leu Thr Thr Asp Ser Arg Thr Pro Glu Val Cys Leu Ala Leu Tyr Pro Gly Thr Asn Tyr Thr Val WO 00/71710 PCTlFR0010142G
IOJ
Asn Ile Ser Thr Ala Pro Pro Arg Arg Ser Met Pro Ala Val Ile Gly Phe Gln Thr Ala Glu Val Asp Leu Leu Glu Asp Asp Gly Ser Phe Asn Ile Ser Ile Phe Asn Glu Thr Cys Leu Lys Leu Asn Arg Arg Ser Arg Lys Val Gly Ser Glu His Met Tyr Gln Phe Thr Val Leu Gly Gln Arg Trp Tyr Leu Ala Asn Phe Ser His Ala Thr Ser Phe Asn Phe Thr Thr Arg Glu Gln Val Pro Val Val Cys Leu Asp Leu Tyr Pro Thr Thr Asp Tyr Thr Val Asn Val Thr Leu Leu Arg Ser Pro Lys Arg His Ser Val Gln Ile Thr Ile Ala Thr Pro Pro Ala Val Lys Gln Thr Ile. Ser Asn Ile Ser Gly Phe Asn Glu Thr Cys Leu Arg Trp Arg Ser Ile Lys Thr Ala Asp Met Glu Glu Met Tyr Leu Phe His Ile Trp Gly Gln Arg Trp Tyr Gln Lys Glu Phe Ala Gln Glu Met Thr Phe Asn Ile Ser Ser Ser Ser Arg Asp Pro Glu Val Cys Leu Asp Leu Arg Pro Gly Thr Asn Tyr Asn Val Ser Leu Arg Ala Leu Ser Ser Glu Leu Pro Val Val Ile Ser Leu Thr Thr Gln Ile Thr Glu Pro Pro Leu Pro Glu Val Glu Phe Phe Thr Val His Arg Gly Pro Leu Pro Arg Leu Arg Leu Arg Lys Ala Lys 565,570,575 Glu Lys Asn Gly Pro Ile Ser Ser Tyr Gln Val Leu Val Leu Pro Leu WO 00/71710 PCTlFR0010142G

Ala Leu Gln Ser Thr Phe Ser Cys Asp Ser Glu Gly Ala Ser Ser Phe Phe Ser Asn Ala Ser Asp Ala Asp Gly Tyr Val Ala Ala Glu Leu Leu 610 615 Fi20 Ala Lys Asp Val Pro Asp Asp Ala Met Glu Ile Pro Ile Gly Asp Arg Leu Tyr Tyr Gly Glu Tyr Tyr Asn Ala Pro Leu Lys Arg Gly Ser Asp Tyr Cys Ile Ile Leu Arg Ile Thr Ser Glu Trp Asn Lys Val Arg Arg His Ser Cys Ala Val Trp Ala Gln Val Lys Asp Ser Ser Leu Met Leu Leu Gln Met Ala Gly Val Gly Leu Gly Ser Leu Ala Val Val Ile Ile Leu Thr Phe Leu Ser Phe Ser Ala Val 705,710 <210> 149 <211> 170 <212> PRT
<213> Homo sapiens <400> 149 Arg Ser Met Thr Val Gly Gly Ala Phe His Thr Thr Glu Ala Glu Ala Ser Ser Gln Ser Leu Thr Gln Tyr Island Ala Leu Pro Glu Pro Gln Island Asp Gln Asn Ala Ala Glu Ser Trp Glu Thr Leu Glu Ala Asp Leu Ile Glu Leu Ser Gln Leu Val Thr Asp Phe Ser Leu Leu Val Asn Ser Gln Gln Glu Lys Ile Asp Ser Ile Ala Asp His Va1 Asn Ser Ala Ala Val Asn Val Glu Glu Gly Thr Lys Asn Leu Gly Lys Ala Ala Lys Tyr Lys WO 00/71710 PCTlFR0010142G

Leu Ala Ala Leu Pro Val Ala Gly Ala Leu Ile Gly Gly Met Val Gly Gly Pro Ile Gly Leu Leu Ala Gly Phe Lys Val Ala Gly Ile Ala Ala Ala Leu Gly Gly Gly Val Leu Gly Phe Thr Gly Gly Lys Leu Ile Gln 130 _ 135 140 Arg Lys Lys Gln Lys Met Met Glu Lys Leu Thr Ser Ser Cys Pro Asp Leu Pro Ser Gln Thr Asp Lys Lys Cys Ser <210> 150 <211> 31B
<212> PRT
<213> Homo sapiens <400> 150 Val Glu Lys Thr Ala Val Thr Arg Glu Val Ile Gln His Phe Phe Arg Met Ser Glu Asp Glu Glu Lys Val Lys Leu Arg Arg Leu Glu Pro Ala Ile Gln Lys Phe Ile Lys Ile Val Ile Pro Thr Asp Leu Glu Arg Leu Arg Lys His Gln Ile Asn Ile Glu Lys Tyr Gln Arg Cys Arg Ile Trp Asp Lys Leu His Glu Glu His Ile Asn Ala Gly Arg Thr Val Gln Gln Leu Arg Ser Asn Ile Arg Glu Ile Glu Lys Leu Cys Leu Lys Val Arg Lys Asp Asp Leu Val Leu Leu Lys Arg Met Ile Asp Pro Val Lys Glu Glu Ala Ser Ala Ala Thr Ala Glu Phe Leu Gln Leu His Leu Glu Ser LARGE APPLICATIONS OR PATENTS
THIS PART OF THIS APPLICATION OR THIS PATENT
INCLUDED: ND MORE THAN ONE TOME.

NOTE: For additional volumes, please contact the Canadian Bureau of Patents.
JUMBO APPLICATIONS / PATENTS
TRIS SECTION OF THE APPLICATION / PATENT CONTAINS MORE
THAN ONE VOLUME.

NOTE: For additional valumes please contact the Canadian Patent Office.

Claims (29)

1. Nucleic acid encoding a protein having a sequence in amino acids selected from the group of amino acid sequences SEQ ID No. 129 to SEQ ID No. 160 or a peptide fragment or a varying of the latter, or a nucleic acid of complementary sequence. 2. Nucleic acid comprising at least eight nucleotides sequences of a polynucleotide selected from the group consisting of nucleotide sequences SEQ ID No. 1 to SEQ ID No. 81, or an acid complementary sequence nucleic acid. 3. Nucleic acid according to claim 2 comprising at least twenty consecutive nucleotides of a polynucleotide selected from the group consisting of the nucleotide sequences SEQ ID No. 1 to SEQ ID No. 81, Where a nucleic acid of complementary sequence. 4. Nucleic acid with at least 80% nucleotide identity with a nucleic acid according to any one of claims 1 to 3, or a nucleic acid of complementary sequence. 5. Hybridizing nucleic acid, under hybridization conditions of high stringency, with a nucleic acid according to any one of claims 1 to 4, or a nucleic acid of sequence additoinal. 6. Probe or nucleotide primer comprising at least eight consecutive nucleotides of a nucleic acid according to any one of claims 1 to 5. 7. Probe or nucleotide primer according to claim 6 having a length of 15 to 300 nucleotides. 8. Probe or nucleotide primer according to claim 6 having a length of 20 to 200 nucleotides. 9. Probe or nucleotide primer comprising at least eight consecutive nucleotides of a polynucleotide chosen from the sequences SEQ ID Nos 82 to 101 and 102 to 128. 10. Process for the amplification of a nucleic acid according to one any of claims 1 to 5 contained in a sample, said method comprising the steps of:
a) contacting the sample in which the presence of the target nucleic acid is suspected with a pair of primers nucleotides whose hybridization position is located respectively on the 5' side and on the 3' side of the region of the target nucleic acid whose amplification is sought, in the presence of the reagents necessary for the amplification reaction; and b) detection of amplified nucleic acids. 11. Amplification method according to claim 10, characterized in that the nucleotide primers are chosen from the primers according to any one of claims 6 to 9. 12. Necessary for the amplification of a nucleic acid according to any of claims 1 to 5 comprising:

a) a pair of nucleotide primers whose position of hybridization is located respectively on the 5' side and on the 3' side of the target nucleic acid whose amplification is sought; .
b) where appropriate, the reagents necessary for the reaction of amplification. 13. Necessary for the amplification of a nucleic acid according to claim 12, characterized in that the nucleotide primers are selected from the group consisting of primers according to one of claims 6 to 9. 14. Nucleotide probe according to any one of claims 6 to 9, characterized in that it comprises a compound marker whose presence is detectable. 15. Method for detecting the presence of a nucleic acid according to any one of claims 1 to 5 in a sample, said method comprising the steps of:
a) contacting one or more nucleic acid probes according to one of claims 6 to 9 and 14 with the sample to be tested;
b) detecting the complex possibly formed between the probes and the nucleic acid present in the sample. 16. Detection method according to claim 15, characterized in that the probe or probes are immobilized on a support. 17. Necessary for the detection of the presence of an acid nucleic acid according to any one of claims 1 to 5 in a sample, said kit comprising:

a) one or more nucleotide probes according to any claims 6 to 9 and 14;
b) where appropriate, the reagents necessary for the reaction of hybridization. 18. Detection kit according to claim 17, characterized in that the probe or probes are immobilized on a support. 19. Recombinant vector comprising a nucleic acid according to any one of claims 1 to 5. 20. Recombinant host cell comprising nucleic acid according to any one of claims 1 to 5. 21. Recombinant host cell comprising a vector recombinant according to claim 18. 22. Polypeptide chosen from the group of the following polypeptides:
a) a polypeptide comprising a sequence of at least 15 acids amines chosen from the group consisting of peptides of sequences SEQ
ID No129 to SEQ ID No160, or a peptide fragment or variant of this last ;
b) a polypeptide having at least 80% amino acid identity with a polypeptide as defined in a). 23. Polypeptide comprising amino acid modifications from 1, 2, 3, 4, 5, 10 to 20 substitutions, additions or deletions of an acid amino relative to the amino acid sequence of a polypeptide according to claim 21. 24. Antibody directed against a polypeptide according to one of claims 21 or 22. 25. Antibody according to claim 23, characterized in that it includes a detectable compound. 26. Method for detecting the presence of a polypeptide according to one of claims 21 or 22 in a sample, comprising the stages of:
a) bringing the sample into contact with an antibody according to one claims 23 or 24;
b) detection of the antigen/antibody complex formed. 27. Presence detection diagnostic kit of a polypeptide according to one of Claims 21 or 22 in a sample, said kit comprising:
a) an antibody according to one of claims 23 or 24;
b) a reagent allowing the detection of the complexes antigens/antibodies formed. 28. Method for screening a molecule or a substance candidate interacting with a polypeptide according to one of claims 21 or 22, said method comprising the steps of:

a) bringing into contact a polypeptide according to one of the claims 21 or 22 with the candidate substance or molecule;
b) detecting any complexes formed between said polypeptide and said candidate substance. 29. Necessary for the screening of a molecule or substance candidate interacting with a polypeptide according to one of claims 21 or 22, said kit comprising a) a polypeptide according to one of claims 21 or 22:
b) where applicable, the means necessary to detect the complex formed between said polypeptide and the molecule or substance candidate