CA2555083A1 - Genes associated with canine osteoarthritis and related methods and compositions - Google Patents

Abstract

Described herein is a combination containing polynucleotide molecules that are differentially expressed in osteoarthritis. Also described are methods that may be used for diagnosis and prognosis of osteoarthritis, as well as methods that may be used to screen test substances for effectiveness in treatment modalities for osteoarthritis. Also described are devices and kits that may be used with the described methods.

Description

GENES ASSOCIATED WITH CANINE OSTEOARTHRITIS AND RELATED
METHODS AND COMPOSITIONS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of U.S. Application No. 601541,346, filed February 2, 2004, the disclosure of which is hereby incorporated by reference in its entirety.
i FIELD OF THE INVENTION

[0002] This invention relates to the field of degenerative joint diseases, such as osteoarthritis. More particularly, the invention relates to novel compositions, devices and methods based on unique profiles of gene expression associated with osteoarthritis.
BACKGROUND OF THE INVENTION

[0003] Osteoarthritis (OA), also commonly referred to as degenerative joint disease, is recognized in humans and all veterinary species (Richardson et al., (1997) Vet. Clin. North Am.
27:883-911). OA is a prevalent and debilitating disease in canines and is often associated with hip dysplasia (Martinez, S. (1997) Osteoarthritis, Vet. Clinics of N. Am.:
Small Animal Practice 27 (4):735-758.). There is a high degree of similarity between canine and human osteoarthritis, thus making it an excellent animal model for the study of human osteoarthritis. While causative factors remain largely unknown, the disease is characterized by the imbalance of cartilage matrix degradation outweighing cartilage matrix synthesis. Chondrocyte apoptosis and inflammation may also be associated with the disease (Pelletier, J., et al. (2001) Arthritis ,& Rheumatisf~z 44 (6):1237-1247; Lotz, M. (1999) Osteoarthritis afid Cartilage 7: 389-391).

[0004] The disease is typically slow in progression and characterized by degeneration of articular cartilage with a loss of both proteoglycan and collagen and by proliferation of new bone. In addition, an inflammatory response can occur within the synovial membrane. Canine osteoarthritis can arise as a secondary condition resulting, in particular, from hip displasia or from osteochondritis dissecans (Martinez, supra). Acquired conditions involving traumatic events can also lead to osteoarthritis in the dog (Martinez et al., Vet. Clin.
Nor~tl2 Am. 27:759-775, 1997). Treatment modalities for osteoarthritis can include the administration of anti-inflammatory drugs as well as the manipulation of dietary fatty acids (Richardson et al., supra).
[0005] Diagnosis of canine osteoarthritis is typically based upon symptomatology.
Dogs having osteoarthritis show a lameness which may have a gradual onset but can flare up acutely after exercise. The lameness is exacerbated by rest but decreases after a few minutes of activity. Cold damp conditions, obesity and prolonged exercise often worsen signs of lameness (Pederson et al, in Textbook of Veterinary Internal Medicine, Sth Ed., Ettinger et al., ed., W.B.
Saunders and Co., Philadelphia, 2000, pp. 1862-1886).

[0006] With the emergence of the genomic sciences, it has become apparent that not only is the regulation of gene expression intimately involved in normal homeostasis, alterations in the differential expression of genes is one aspect in the development of diseases. As a result, the evaluation of gene expression patterns in disease has become increasingly recognized as being crucial to the understanding of disease processes at the molecular level. (Going et al., Europeaf2 T. Cafzcer 35:1895-1904, 1999; Wang et al., Cardiovasc. Res. 35:414-421). A number of approaches have emerged for studying comparative gene expression and the current emphasis has been on high throughput analysis methods. (for review see Carulli et al, J. Cell. Biocl2enZ.
Suppl. 30/32:286-296, 1998; Kozian et al., Trefzds Biotechnol 17:73-78, 1999).
Recent methods developed for high throughput analysis of differential gene expression include, for example, EST
sequencing (Adams et al., Science 252:1651-1656, 1991; Adams et al., Nature 377:3-16, 1995), microarray hybridization (Schena et al., Science 270:467-470, 1995), and differential display (Liang et al., Science 257:967-970, 1992; Welsh et al., Nucleic Acids Res.
20:4965-4970, 1992).

[0007] Gene expression in osteoarthritis, and particularly in canine osteoarthritis, has not been comprehensively studied. Accordingly, a need exists to identify nucleic acid sequences and their encoded proteins which are differentially expressed in osteoarthritis. This information would be useful to diagnose the osteoarthritic disease state, or pre-disposition to the disease, in a subject, as well as to identify substances useful in the treatment or prevention of osteoarthritis.
SUMMARY OF THE INVENTION

[0008] In accordance with an aspect of the present invention, a number of polynucleotides comprising at Least a fragment of a gene have been identified as being differentially expressed in osteoarthritic or pre-osteoarthritic subjects, compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic.

[0009] In accordance with an aspect of the present invention, differentially expressed genes, gene fragments, and encoded gene products, as well as the expression patterns associated with the group of genes, are used to advantage in a number of methods for the detection of _2_ changes in gene expression associated with osteoarthritis, particularly canine osteoarthritis.
Additional aspects of the invention relate to methods for the identification of agents useful in treating and/or preventing osteoarthritis.

[0010] In accordance with additional aspects of the present invention, compositions, devices and test kits are provided to facilitate the practice of methods provided according to certain embodiments of the invention.

[0011] Other features and advantages of the present invention will be understood by reference to the detailed description and the examples that follow.
BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 shows representative gels used in differential display analysis of canine osteoarthritis. A. Differential display of osteoarthritic vs. normal 'transcripts loaded in duplicate prior to band excision (D=osteoaxthritic (Diseased), N=Normal). B.
The same gel after band excision.

[0013] Figure 2 shows quantitative PCR analysis (qPCR) for selected OA-associated transcripts in canine cartilage. RNA expression is shown in arbitrary units.
(OA AVG = average expression for osteoarthritic cartilage; C AVG = average expression in normal control).
TABLE 1: Correlation of Gene ID Numbers with Sequence ID Numbers.
Gene SEQ Gene SEQ Gene SEQ Gene SEQ
ID ID ID ID ID ID ID ID

1028c 1 768a 2 141c 3 1548c 4 1357a 5 168c 6 383d 7 2127c 8 530b 9 1405c 10 1765a 11 166a 12 1797a 13 I729a 14 1857c 15 523a 16 2172c 17 58a 18 244a 19 70d 20 1472a 21 452a 22 1481c 23 1940e 24 1930a 25 739a 26 1612a 27 14a 28 1727a 29 1220b 30 33a 31 1146a 32 1738b 33 810a 34 1993b 35 2147a 36 1678a 37 56a 38 1814c 39 129b 40 1924a 41 557b 42 1254a 43 1292c 44 2221c 45 490c 46 907a 47 469d 48 713a 49 1372a 50 482a S1 1098a 52 ' 1785a 53 1624b 54 1441d 55 553b 56 2179a 57 1257b 58 1506d 59 1939c 60 2007a 61 13a 62 1288a 63 1949a 64 142.2c 65 1054a 66 1404c 67 8a 68 46a 69 1985a 70 326e 71 85.1c 72 1675a 73 574a 74 2159b 75 2108b 76 45.1b 77 2173a 78 1676a 79 581a 80 1695a 81 1414b 82 151b 83 112d 84 461a 85 1615b 86 310h 87 297a 88 1801b 89 23a 90 1739a 91 170a 92 1955a 93 2088a 94 2243b 95 1440a 96 2351c 97 1415b 98 2074b ( 99 2250a 10~

1'740a 101 81a 102 1248b 103 82b 104 .

1147a 105 12a 106 2201a 107 2266b 108 795a 109 206a 110 327f 111 212a 112 2083e 113 555b 114 1296a 115 272d 116 1709a 117 1945a 118 1631d 119 24a 120 1284a 121 184a 122 936b 123 la 124 1677b 125 747a 126 737a 127 2166a 128 479c 129 2040d 130 1502a 131 72a 132 1917f 133 1650a 134 1620a 135 1951a 136 2355c 137 1394b 138 2071a 139 340a 140 368b 141 736a 142 17a 143 1475a 144 143.2c 145 1540a 146 1521b 147 2156c 148 2035d 149 1919a 150 1648a 151 1241a 152 1713a 153 144.2a 154 2255a _155__ 690a 156 2163a _15_7 979a 158 1747a 159 507a 160 890a 161 395a 162 1309b 163 1462a 164 1086c 165 1313a 166 1439b 167 153b 168 1790a 169 961a 170 493a 171 1463a 172 172a 173 1454d 174 1143d 175 766b 176 1412b 177 1423b 178 850a 179 148a 180 1696a 181 1396b 182 2141a _ 1503c 184 _ 639a _ 1682a 186 2153a _ 2241a 188 _ l87 _ _ 1438a 190 2059b 191 1646a 192 2263b _ 465b 193 990a l94 1488b _ 1452a 196 ~ 195 1270a 197 2142a 198 945a _ 1367a 200 2198b 201 1139a 202 1138a 203 1008a 204 552a 205 2374a 206 1532a 207 2118a 208 1366a 209 1262b 210 144.1c 211 21a 212 1246a 213 1253a 214 2224a 215 1015d 216 2252b 217 154a 218 718a 219 llb 220 363a 221 370a 222 1551a 223 376a 224 84.2c 225 380a 226 372a 227 2148a 228 1800a 229 1090d 230 60a 231 96e 232 2015e 233 128a 234 621b 235 1174d 236 947a 237 1964a 238 619b 239 2222b 240 1468c 241 1629a 242 174a 243 2085c 244 1461a 245 764b 246 731a 247 1051a 248 613a 249 S3la 250 1471a 251 1381a 252 ' 44c 253 1892a 254 76b 255 366a 256 994b 257 1954e 258 409a 259 2120a 260 638b 261 329d 262 1853a 263 2247a 264 1746a 265 1081a 266 2002c 267 785b 268 ' 1092b 269 1784a 270 1511b 271 1812b 272 1885c 273 1619a 274 2344a 275 1477a 276 360a 277 568a 278 1109a 279 1282b 280 1276a 281 1728a 282 1923b 283 2020b 284 556b 285 1711a 286 49a 287 1271a 288 1497c 289 967b 290 1329a 291 464b 292 1490a 293 188b 294 178a 295 631b 296 1244b 297 758b 298 1807a 299 276a 300 204a 301 543a 302 1764a 303 711a 304 35c 305 1401c 306 3c 307 494a 308 1616a 309 1070b 310 1928a 311 597c 312 1505c 313 1941e 314 742a 315 1299c 316 1960a 317 1191a 318 562a 319 2223a 320 2099a 321 342a 322 1347b 323 738b 324 1744a 325 1918a 326 1060a 327 1224b 328 861c 329 2033a 330 1349b 331 715a 332 1621a 333 379a 334 570b 335 1504d 336 441a 337 1943a 338 1033c 339 1758a 340 _ ~~

1772a 341 1707c 342 1474a 343 1920a 344 34a 345 2205a 346 1712a _347 lOlOa 348 1382d 349 269b _350 1972a 351 1298a 352 567b 353 949c 354 1545b 355 472a 356 1557a 357 489c 358 1495a _359 1302a 360 18a 361 182a 362 991b 363 1513b 364 992a 365 1032d 366 1373a 367 1400a 368 226a 369 13S4a 370 1953a 371 794a 372 1604a 373 1245b 374 192a 375 1398a 376 1651a 377 64.2a 378 2161c 379 1618b 380 1516a' 381 1803a 382 1593b 383 2109a 384 392a 385 1533a 386 1317a 387 1137b 388 51a 389 1708a 390 862c 391 1371a 392 2117b 393 1818a 394 851d 395 2113a 396 99b 397 92c 398 91f 399 90c 400 86.2d 401 86.1d 402 83d 403 80.1b 404 7a 405 78e 406 74c 407 73b 408 6b 409 68a 410 67a 411 66a 412 65.2a 413 63a 414 62c 415 59a 416 57a 417 SSa 418 52a 419 50.1c 420 4a 421 43a 422 38a 423 37c 424 35b 425 2b 426 29a 427 27a 428 26a 429 25a 430 22b 431 20a 432 19c 433 16b 434 15b 435 lOc 436 102a 437 I03a 438 104a _ I06a 440 llla 441 120a 442 121b 443 122c 444 123c 445 124a 446 126a 447 130b 448 _ _ _ 131a 449 132a 450 134b 451 135a _ i36b 453 142.Ic 454 145b 455 146b 456 147b 457 150a 458 152b 4 157b 460 158a 461 159a 462 161b _ _ _ 463 162b 464 164c 465 l6Sa 466 173a 467 175a 468 I76a 469 177b 470 179b 471 180a 472 183a 473 185a 474 186a _475 187b 476 189a 477 190b 478 I9la 479 195a 480 196a 481 197b 482 127b 483 105e 484 107.1a 485 107.2a 486 108a 487 109a 488 117.1d 489 117.2b 490 137b 491 140b 492 194a 493 181d 494 198e 495 199d 496 200a 497 201a 498 202a 499 203a 500 205a 501 208c 502 209a 503 210a 504 211b 505 214a 506 215a S07 216a 508 217b 509 218e 510 219 511 220d 512 221b 513 222b 514 223a 515 224a 516 225a 517 227a 518 228a S19 229a 520 230a 521 231a 522 232a 523 233b 524 234a 525 23Sa 526 236a 527 237c 528 238a 529 239a 530 240a 531 241a 532 242a 533 243a 534 245a 535 246a 536 247a 537 248a 538 249a 539 250a 540 251a S41 252a 542 253b 543 254a 544 255a 545 257a 546 258a 547 260c 548 261c 549 262c 550 263b 551 266d 552 267d 553 268b 554 270b 555 273a 556 274b 557 27Sb 558 277a SS9 278a 560 280c 561 282d 562 283a S63 284b 564 285b 565 286a 566 289a 567 291a 568 292b 569 294a 570 295a 571 296a 572 299a 573 301b 574 302a 575 499a 576 498a 577 497a 578 496c 579 495a 580 491a 581 359a 582 351b 583 344a 584 343b 585 338a 586 337c 587 336a 588 335a 589 334a 590 328b 591 325b 592 324a 593 3I2a 594 311c 595 309a 596 308c 597 307b 598 306b 599 303a 600 300b 601 163a 602 573b 603 561b 604 560b 605 559c 606 554c 607 551b 608 549a 609 542a 6I0 540a 611 539a 612 538a 613 537c 614 536a 615 535a 616 534b 617 533b 618 527a 619 526a 620 521b 621 520a 622 519a 623 517c 624 516c 625 515a 626 514a 627 513a 628 512b 629 509b 630 508a 631 505b 632 504a 633 503a 634 502a 635 501b 636 500a 637 345b 638 362b 639 364a 640 367a 641 369a 642 371a 643 374a 644 377b 645 378a 646 381a 647 386b 648 389c 649 390a 650 391a 651 393b 652 397b 653 455c 654 456c 655 457c 656 458b 657 459a 658 462b 659 466b 660 474a 661 478a 662 480a 663 483a 664 484a 665 485f 666 486a 667 487a 668 488a 669 545a 670 548c 671 558a 672 571a 673 572b 674 578c 675 579a 676 582c 677 584b 678 587b 679 590a 6.80 595a 681 684a 682 685a 683 686b 684 687a 685 688a 686 691a 687 692a 688 695a 689 696a 690 697a 691 698a 692 699a' 693 700a 694 701a 695 702a 696 704b 697 706b 698 708a 699 709a 700 710a 701 712a 702 714a 703 716b 704 717b 705 719a 706 720a 707 722b 708 723a 709 724a 710 725a 711 727a 712 728b 713 730b 714 732a 715 733a 716 734a 717 740b 718 741b 719 743a 720 744a 721 745a 722 748a 723 749a 724 752a 725 753b 726 754d 727 757a 728 759b 729 761a 730 762a 731 763d 732 765a 733 770b 734 773a 735 774a 736 775a 737 780a 738 781a 739 783a 740 784a 741 786a 742 787b 743 788a 744 789a 745 791b 746 792a 747 797a 748 798a 749 799a 750 969a 751 968a 752 966a 753 964a 754 963c 755 959a 756 957c 757 956d 758 953a 759 952a 760 946a 761 944d 762 943b 763 942b 764 939a 765 938b 766 935b 767 934b 768 931a 769 930a 770 928a 771 927a 772 926a 773 925a 774 923a 775 921c 776 919b 777 918a 778 916c 779 915a 780 914a 781 913a 782 912b 783 911a 784 910c 785 909a 786 906a 787 905a 788 904a 789 902a 790 900a 791 899a 792 896b 793 894b 794 893a 795 891a 796 885a 797 883c 798 843a 799 841b 800 839a 801 838b 802 837c 803 836a 804 834b 805 833a 806 832a 807 831a 808 828a 809 826b 810 824b 811 823a 812 821a 813 820a 814 817a 815 816a 816 815a 817 813a 818 811a 819 808b 820 1633a 821 1632a 822 1627a 823 1625b 824 1614b 825 1613b 826 1607a 827 1605b 828 1544b 829 1526a 830 I524a _831 1522b 832 1520a 833 1519a 834 1518a 835 1514a 836 1512a 837 1508b 838 1507a 839 1493a 840 1492a 841 1487b 842 1486d 843 1482a 844 1480a 845 1476a 846 1469a 847 1466b 848 1460a 849 1459c 850 1422a 851 1418a 852 1409b 853 1407a 854 1406a 855 1402b 856 1399a _857 1397b 858 1369c 859 1364d 860 1325b 861 1324a 862 1321a 863 1318a 864 1316b 865 1312a 866 1301a 867 1289a 868 1285a 869 1277a 870 1273b 871 1272a 872 1269b 873 1267a 874 1266a 875 1263b 876 1251a 877 1195a 878 1194a 879 1193b 880 1192b 881 1189a 882 1188b 883 1185a 884 1184a 885 1183a 886 1182a 887 1178a 888 ' 1175a 889 1172a 890 1171a 891 1170a 892 1167b 893 1166b 894 1132a 895 1126b 896 1117a 897 1111b 898 1104b 899 1103a 900 1101a 901 1048c 902 1023c 903 1014d 904 1009c 905 1239b 906 1240a 907 1243a 908 I368a 909 I370a 910 1383a 911 408a 912 415b 913 421a 914 443b 915 863c 916 864c 917 867d 918 870e 919 874e 920 881c 921 940a 922 941a 923 958a 924 975a 925 980b 926 98Ia 927 987a 928 993b 929 996a 930 1012a 931 1013a 932 1018a 933 1019a 934 I020a 935 1022a 936 1026b 937 1029a 938 1031a 939 1034a 940 1036a 94.1 1057b 942 1177c 943 1252a 944 1255a 945 1264c 946 1274c 947 1275c 948 1279c 949 1281c 950 1286d 951 1287c 952 1290d 953 1310a 954 1424a 955 1426a 956 1427a 957 1428a 958 1430a 959 1431a 960 1432a 961 1435a 962 1436b 963 1437c 964 1444b 965 1445b 966 1446a 967 1447a 968 1448a 969 1451a 970 1455c 971 1542c 972 1549a 973 1611a 974 1639a 975 1641b 976 ~1152d 977 1158c 978 1159b 979 1163d 980 1420c 981 1771b 982 1859a 983 1861a 984 1886a 985 1889a 986 1900b 987 1905a 988 2110a 989 2129a 990 2137b 991 2143a 992 2225b 993 2234a 994 2237b 995 2238a 996 2239b 997 2248a 998 2267a 999 436c 1000 446f 1001 524a 1002 525f 1003 529b 1004 541b 1005 547c 1006 563a 1007 564a 1008 565a 1009 566a 1010 575b 1011 589a 1012 591a 1013 609a 1014 610a 1015 611a 1016 612b 1017 614a 1018 617a 1019 620a 1020 622a 1021 623a 1022 624b 1023 625a 1024 626a 1025 629a 1026 630a 1027 632a 1028 633a 1029 634a 1030 637c 1031 640b 1032 641a 1033 642a 1034 825d 1035 846a 1036 847a 1037 852a 1038 948a 1039 1242a 1040 1634a 1041 2138a 1042 2233a 1043 615a 1044 618b 1045 628a 1046 636a 1047 835c 1048 2122a 1049 1050a _1050 1110b 1051 1228a 1052 1655a 1053 1659a 1054 1673b 1055 1694b 1056 1703b 1057 1704b 1058 I714a 1059 1717a 1060 1718a 1061 1719a 1062 1720a 1063 1721a 1064 1722a 1065 1724a 1066 1726a 1067 1730a 1068 1731a 1069 1748b 1070 1749a 1071 1750a 1072 1751a 1073 1816a 1074 1880a 1075 1884a 1076 1887a 1077 1895b 1078 1903a 1079 1912a 1080 1914b 1081 1921a 1082 1967a 1083 1968a 1084 1977a 1085 1979a 1086 1981a 1087 1982a 1088 1986b 1089 1987a 1090 1988a 1091 1990a 1092 1992b 1093 1994a 1094 2073b 1095 2075a 1096 2076c 1097 2078a 1098 2086a 1099 2092c 1100 2093a 1101 2094a 1102 2097a 1103 2100b 1104 2104a 1105 2105a 1106 2106a 1107 2111b 1108 2119a 1109 2126b 1110 2128a 1111 2132a 1112 2135d 1113 2136b 1114 2145c 1115 2149d 1116 2150a 1117 2154a 1118 2158c 1119 2160a 1120 ~

2162b 1121 2167a 1122 2170a 1123 2171c 1124 2174a 1125 2178c 1126 2182b 1127 388a 1128 445e 1129 856c 1130 1216a 1131 1705a 1132 1725a 1133 1734b 1134 1781a 1135 1782b 1136 1789a 1137 1791b 1138 1792a 1139 1794a 1140 1795a 1141 1796a 1142 1817a 1143 1897b 1144 1971b 1145 2095a 1146 2I44a II47 2146a 1148 , 384c 1149 600e 1150 878c 1151 lOlla 1152 1021a 1153 1025a 1154 1037c 1155 1039c 1156 1040b 1157 1058a 1158 1059a 1159 1061a 1160 IO62a 1161 1063b 1162 I064a 1163 1068a 1164 1069a 1165 1071b 1166 1072a 1167 1073a 1168 1121a 1169 1122b 1170 1130a 1171 1134a 1172 1135a 1173 1136b 1174 1176a 1175 1180a 1176 1190b 1177 1204a 1178 1208a 1179 1215b 1180 1217a 1181 1227b 1182 1236a 1183 1249a 1184 1297a 1185 1308c 1186 1314a 1187 1355a 1188 1361a 1189 1363b 1190 1386a 1191 1388a 1192 1390a 1193 1391a 1194 1417a 1195 1510a 1196 1536b 1197 1537c 1198 1546b 1199 1547c 1200 1552a 1201 1554c 1202 1556a 1203 1558c 1204 1591a 1205 1592a 1206 1594a 1207 1595b 1208 1596b 1209 I597a 1210 1598a 1211 1599a 1212 1600a 1213 1601a 1214 1602a 1215 1603a 1216 1609c 1217 1617a 1218 1626c 1219 1628a 1220 ~

1637c 1221 1642a 1222 1657a 1223 1661a 1224 1662a 1225 1663a 1226 1665a 1227 1671b 1228 1672a 1229 1688c 1230'. 1691b 1231 1715a 1232 1735a 1233 1810a 1234 1856c 1235 1860a 1236 1874b 1237 1881b 1238 1901c 1239 1913a 1240 2204b 1241 2230a 1242 1035a 1243 1124a 1244 1294b 1245 1319a 1246 1411a 1247 1421a 1248 1588b 1249 1645a 1250 1667a 1251 1798a 1252 450a 1253 1076c 1254 1077a 1255 1085c 1256 1087c 1257 1093b 1258 1094b 1259 1102a 1260 1106a 1261 1108a 1262 1112a 1263 1116a 1264 1335b 1265 1336c 1266 1338a 1267 1339b 1268 1341a 1269 1449a 1270 1457b 1271 1458a 1272 1479a 1273 1485b 1274 1489a 1275 1499a 1276 1501a 1277 1509a 1278 1525a 1279 1531c 1280 _g_ 1534b 1281 1535a 1282 1828b 1283 1834b 1284 1927a 1285 1929c 1286 1937c 1287 1942b 1288 1944a 1289 1946b 1290 1947a 1291 1948b 1292 1950a 1293 1952a 1294 1956a 1295 1958b 1296 2003a 1297 2021a 1298 2022a 1299 2023b 1300 2024a 1301 2029a 1302 2032b 1303 2053a 1304 2056d 1305 2065a 1306 2070a 1307 1334a 1308 1453a 1309 2066b 1310 1737b 1311 1741a 1312 1779b 1313 1891a 1314 1911b 1315 1922a 1316 1067a 1317 109Ib 1318 1095a 1319 1105a 1320 1131b 1321 1169b 1322 1196b 1323 1213d 1324 1222a 1325 1229c 1326 1327a 1327 1346b 1328 1358b 1329 1384a 1330 1484b 1331 1500b 1332 1693b 1333 I752a 1334 I802a 1335 1871a 1336 85.2b 1337 2331c 1338 1687a 1339 1660d 1340 1654c 1341 1808a 1342 1425a 1343 1410b 1344 1378b 1345 1376a 1346 995a 1347 989a 1348 2258a 1349 2084c 1350 1250a 1351 I002b 1352 583e 1353 2229a 1354 1001a 1355 1002b 1356 1003a 1357 1004a 1358 1005a 1359 1006b 1360 1007a 1361 1042a 1362 1044c 1363 1045a 1364 1099c 1365 1120a 1366 1125a 1367 1212b 1368 1225b 1369 1226d 1370 1304a _ 1322c 1372 1515c 1373 1527a 1374 1528b 1375 1539c 1376 1541a 1377 1561a 1378 1690a 1379 1692a 1380 1736b 1381 1763b 1382 1766a 1383 1777a 1384 1883b 1385 1888c 1386 1898a 1387 2043b 1388 2045d 1389 2130b 1390 2139a 1391 213a 1392 ~

2140b 1393 2165a 1394 2199a 1395 2210a 1396 2254a 1397 2264b 1398 2268a 1399 265a 1400 365b 1401 492a 1402 550a 1403 635a 1404 726b 1405 750b 1406 772b 1407 776a 1408 777a 1409 793a 1410 800b 1411 801b 1412 803b 1413 804a 1414 806b 1415 827b 1416 855c 1417 877e 1418 880e 1419 932b 1420 933b 1421 984a 1422 986a 1423 988b 1424 989a 1425 997a 1426 1016b 1427 1027a 1428 1030a 1429 1038b 1430 1052b 1431 1053a 1432 1088c 1433 1089d 1434 1097c 1435 1145a 1436 1165d 1437 1260c 1438 1315c 1439 1348b 1440 I352b 1441 1360b 1442 1387b 1443 1403a 1444 1413b 1445 1416a 1446 1419a 1447 1442d-r 1448 1443a 1449 1450a 1450 1483a 1451 1562a 1452 1564a 1453 1565c 1454 1567a 1455 1568a 1456 1569b 1457 1570a 1458 1572a 1459 1573a 1460 1574b 1461 1575a 1462 1576a 1463 1577a 1464 1578a 1465 1579a 1466 1580b 1467 1581a 1468 1583a 1469 1584a 1470 1585b 1471 1586a 1472 1628d 1473 1630b 1474 1666d 1475 1669d 1476 1670d 1477 1755a 1478 1759b 1479 1760c 1480 1775a 1481 1778c 1482 1780a 1483 1809a 1484 1846d 1485 1849d 1486 1852a 1487 1863c 1488 1864b 1489 1865e 1490 1879a 1491 1894a 1492 1906a 1493 1961e '1494 1966a 1495 1989b 1496 1991d 1497 2008a 1498 2013a 1499 2014f 1500 2034a 1501 2036b 1502 2041d 1503 2042h 1504 2043b 1505 2044a 1506 2045d 1507 2046a 1508 2048a 1509 2101c 1510 2107b 1511 2124a-r 1512 2235a 1513 ~ 2240a 1514 2251d 1515 2271a 1516 ( ~

2341b 1517 2356a 1518 2358b 1519 2371a 1520 2373a 1521 322a 1522 805a 1523 924a 1524 965a 1525 898a 1526 879c 1527 865e 1528 627b 1529 406a-r 1530 321a 1531 320a 1532 319b 1533 317a 1534 315a 1535 314a 1536 313a 1537 2249a 1538 2189b 1539 2134b 1540 2125a 1541 1811b 1542 1553b 1543 1393b 1544 1389b 1545 1377b 1546 1356a 1547 1353a 1548 1041a 1549 1635a 1550 1385b 1551 1365a 1552 50.2b 1553 48b 1554 440a 1555 413a 1556 2123a 1557 1323br 1558 DETAILED DESCRIPTION OF ILLUSTRATIVE EMEODIMENTS
Definitions:

[0014] The following definitions are provided to facilitate an understanding of the present invention:

[0015] "Nucleic acid" or a "nucleic acid molecule" as used herein refers to any DNA or RNA molecule, either single or double stranded and, if single stranded, the molecule of its complementary sequence in either linear or circular form. In discussing nucleic acid molecules, a sequence or structure of a particular nucleic acid molecule may be described herein according to the normal convention of providing the sequence in the 5' to 3' direction.
With reference to nucleic acids according to aspects of the invention, the term "isolated nucleic acid" is sometimes used. This term, when applied to DNA, refers to a DNA molecule that is separated from sequences with which it is immediately contiguous in the naturally occurring genome of the organism in which it originated. For example, an "isolated nucleic acid" may comprise a DNA
molecule inserted into a vector, such as a plasmid or virus vector, or integrated into the genomic DNA of a prokaryotic or eukaryotic cell or host organism.

[0016] When applied to RNA, the term "isolated nucleic acid" refers primarily to an RNA molecule encoded by an isolated DNA molecule as defined above.
Alternatively, the term may refer to an RNA molecule that has been sufficiently separated from other nucleic acids with which it would be associated in its natural state (i.e., in cells or tissues).
An isolated nucleic acid (either DNA or RNA) may further represent a molecule produced directly by biological or synthetic means and separated from other components present,during its production.

[0017] The terms "percent similarity", "percent identity" and "percent homology" when referring to a particular sequence are used as set forth in the University of Wisconsin GCG
software program.

[0018] A "polynucleotide," "polynucleotide molecule" or "polynucleotide sequence"
refers to a chain of nucleotides. It may refer to a DNA or RNA molecule, either single or double stranded and, if single stranded, the molecule of its complementary sequence in either linear or circular form. Preferably, the chain has from about 50 to 10,000 nucleotides, more preferably from about 150 to 3,500 nucleotides. In some instances, the sequences will be fully complementary (no mismatches) when aligned. In other instances, there may be up to about a 30% mismatch in the sequences.

[0019] The term "oligonucleotide," as used herein refers to sequences, primers and probes of the present invention, and is defined as a nucleic acid molecule comprised of two or more ribo or deoxyribonucleotides, preferably more than three. The exact size of the oligonucleotide will depend on various factors and on the particular application and use of the oligonucleotide.

[0020] A "fragment" refers to a nucleic acid sequence that is preferably at least about nucleic acids in length, more preferably about 40 nucleic acids, and most preferably about 100 nucleic acids in length and encompasses, for example, fragments consisting of nucleic acids 1-100, 300-400, 500-600, 800-900 of SEQ ID NOs:l-1558 or fragments of similar length at the 3' end of SEQ ID NOs:1-1558. A "fragment" can also mean a stretch of at least about 100 consecutive nucleotides that contains one or more deletions, insertions or substitutions. A
"fragment" can also mean the whole coding sequence of a gene and may include 5' and 3' untranslated regions. A "fragment" can also refer to polypeptide sequences which are preferably at least about 5 to about 1S amino acids in length, most preferably at least about 10 amino acids long, and which retain some biological activity or immunological activity of a sequence.

[0021] The term "gene" or "genes" refers to the partial or complete coding sequence of a gene. The term also refers to 5' or 3' untranslated regions of a transcript.
The phrase "gene differentially expressed in osteoarthritis" refers to a gene whose amount of mRNA expressed from that gene or the amount of gene product translated from the mRNA is detectably different, i.e. either greater or lesser, in cells from subjects having osteoarthritis or in pre-osteoarthritic subjects compared to the amount of mRNA or translated gene product in cells from normal subjects which are neither osteoarthritic nor pre-osteoarthritic. As used herein, "pre-osteoarthritis" or "pre-osteoarthritic" is intended to mean that a subject is predisposed to developing osteoarthritis at a later date, but may not have any overt signs or symptoms of osteoarthritis. Preferably, the abundance of transcription or translation products of a differentially expressed gene derived from an osteoarthritic or pre-osteoarthritic sample differs by least about 1.15 fold, more preferably at least about 1.2 fold, more preferably at least about 1.3 fold, more preferably at least about 1.4 fold, more preferably at least about 1.5 fold, , more preferably at least about 1.6 fold, more preferably at least about 1.75 fold, more preferably at least about 2 fold, more preferably at least about 3 fold, more preferably at least about 10 fold, more preferably at least about 20 fold than that in a normal sample. The phrase "gene differentially expressed in osteoarthritis" also refers to genes that are not detectable in the normal transcript profile but are preferably at levels of at least about 2 copies per cell, more preferably at least about 3 copies per cell, in the osteoarthritic or pre-osteoarthritic tissue transcript profile.

[0022] The terms "osteoarthritis (OA)-related" and "osteoarthriti's (OA)-associated genes" refer to genes that are differentially expressed in osteoarthritis as defined herein.

[0023] As used herein, the terms "reporter," "reporter system," "reporter gene," or "reporter gene product" refer to an operative genetic system in which a nucleic acid comprises a gene that encodes a product that when expressed produces a reporter signal that is a readily measurable, e.g., by biological assay, immunoassay, radioimmunoassay, or by colorimetric, v fluorogenic, chexniluminescent or other methods. The nucleic acid may be either RNA or DNA, linear or circular, single or double stranded, antisense or sense polarity, and is operatively linked to the necessary control elements for the expression of the reporter gene product. The required control elements will vary according to the nature of the reporter system and whether the reporter gene is in the form of DNA or RNA, but may include, but not be limited to, such elements as promoters, enhancers, translational control sequences, poly A
addition signals, transcriptional termination signals and the like.

[0024] The terms "transform," "transfect," "transduce," refer to any method or means by which a nucleic acid is introduced into a cell or host organism and may be used interchangeably to convey the same meaning. Such methods include, but are not limited to, transfection, electroporation, microinjection, PEG-fusion and the like.

[0025] The term "functional" as used herein implies that the nucleic or amino acid sequence is functional for the recited assay or purpose.

[0026] The phrase "consisting essentially of" when referring to a particular nucleotide or amino acid means a sequence having the properties of a given SEQ ID NO. For example, when used in reference to an amino acid sequence, the phrase includes the sequence per se and molecular modifications that would not affect the basic and novel characteristics of the sequence.

[0027] A "vector" is a replicon, such as a plasmid, cosmid, bacmid, phage, artificial chromosome (BAC, YAC) or virus, into which another genetic sequence or element (either DNA
or RNA) may be inserted so as to bring about the replication of the attached sequence or element.
A "replicon" is any genetic element, for example, a plasmid, cosmid, bacmid, phage, artificial chromosome (BAC, YAC) or virus, that is capable of replication largely under its own control. A
replicon may be either RNA or DNA and may be single or double stranded.

[0028] The term "probe" as used herein refers to either a probe for a nucleic acid or a probe for a protein. When used in connection with nucleic acids, a "probe"
refers to an oligonucleotide, polynucleotide or nucleic acid, either RNA or DNA, whether occurring naturally as in a purified restriction enzyme digest or produced synthetically, which is capable of annealing with or specifically hybridizing to a nucleic acid with sequences complementary to the probe. A probe may be either single stranded or double stranded. The exact length of the probe will depend upon many factors, including temperature, source of probe and method of use. For example, for diagnostic applications, depending on the complexity of the target sequence, an oligonucleotide probe typically contains about 10-100, preferably about 15-50, more preferably about 15-25 nucleotides. In certain diagnostic applications, a polynucleotide probe preferably contains about 90-1150 nucleotides, more preferably about 300-600 nucleotides, more preferably about 300 nucleotides. The probes herein are selected to be "substantially"
complementary to different strands of a particular target nucleic acid sequence. This means that the probes must be sufficiently complementary so as to be able to "specifically hybridize" or anneal with their respective target strands under a set of pre-determined conditions. Therefore, the probe sequence need not reflect the exact complementary sequence of the target. For example, a non complementary nucleotide fragment may be attached to the 5' or 3' end of the probe, with the remainder of the probe sequence being complementary to the target strand.
Alternatively, non complementary bases or longer sequences can be interspersed into the probe, provided that the probe sequence has sufficient complementarity with the sequence of the target nucleic acid to anneal therewith specifically. When used in connection with a protein, a "probe" is a protein binding substance capable of specifically binding a particular protein or protein fragment to the substantial exclusion of other proteins or protein fragments. Such binding substances may be any molecule to which the protein or peptide specifically binds, including DNA
(for DNA
binding proteins), antibodies (as described in greater detail herein), cell membrane receptors, peptides, cofactors, lectins, sugars, polysaccharides, cells, cell membranes, organelles and organellar membranes.

[0029] "Array" refers to an ordered arrangement of at least two probes on a substrate.
At least one of the probes represents a control or standard, and the other, a probe of diagnostic interest. The arrangement of from about two to about 40,000 probes on a substrate assures that the size and signal intensity of each labeled complex formed between a probe and a sample nucleic acid or protein binding substance is individually distinguishable.

[0030] A "hybridization complex" is formed between nucleic acid molecules of a sample when the purines of one molecule hydrogen bond with the pyrimidines of the complementary molecule, e.g., 5'-A-G-T-C-3' base pairs with 3'-T-C-A-G-5'. The degree of complementarity and the use of nucleotide analogs affect the efficiency and stringency of hybridization reactions.

[0031] The term "specifically hybridize" refers to the association between two single stranded nucleic acid molecules of sufficiently complementary sequence to permit such hybridization under pre determined conditions generally used in the art (sometimes termed "substantially complementary"). For example, the term may refer toAhybridization of a nucleic acid probe with a substantially complementary sequence contained within a single stranded DNA
or RNA molecule according to an aspect of the invention, to the substantial exclusion of hybridization of the nucleic acid probe with single stranded nucleic acids of non-complementary sequence.

[0032] "Sample" is used in its broadest sense as containing nucleic acids, proteins, antibodies, and the like. A sample may comprise, for example, a bodily fluid;
the soluble fraction of a cell preparation, or an aliquot of media in Which cells were grown; a chromosome, an organelle, or membrane isolated or extracted from a cell; genomic DNA, RNA, or cDNA in solution or bound to a substrate; a cell; a tissue or a tissue biopsy; a tissue print; a fingerprint, buccal cells, skin, or hair; and the like.

[0033] A "standard" refers to a control sample that comprises material from a source in a normal (as opposed to OA-related) biological state. An OA-related biological state may include, for example, one in which the source has OA, is predisposed to develop OA, or exhibits certain biological characteristics of OA. For example, a standard sample may comprise nucleic acids or proteins from a normal subject that is not osteoarthritic or pre-osteoarthritic. Standard samples may also include samples from normal cells or tissue that have not been treated to elicit an immune response that may model certain aspects of OA.

[0034] "Specific binding" refers to a special and precise interaction between two molecules which is dependent upon their structure, particularly their molecular side groups. For example, the intercalation of a regulatory protein into the major groove of a DNA molecule, the hydrogen bonding along the backbone between two single stranded nucleic acids, or the binding between an epitope of a protein and an agonist, antagonist, or antibody.

[0035] The term "primer" as used herein refers to a nucleic acid molecule, either RNA
or DNA, either single stranded or double stranded, either derived from a biological system, generated by restriction enzyme digestion, or produced synthetically which, when placed in the proper environment, is able to functionally act as an initiator of template-dependent nucleic acid synthesis. When presented with an appropriate nucleic acid template, suitable nucleoside tnpnospnate precursors of nucleic acids, a polymerase enzyme, suitable cofactors and conditions such as appropriate temperature and pH, the primer may be extended at its 3' terminus by the addition of nucleotides by the action of a polymerase or similar activity to yield an primer extension product. The primer may vary in length depending on the particular conditions and requirement of the application. For example, in diagnostic applications according to particular embodiments of the invention, a primer may be an oligonucleotide primer, preferably about 15 -25 or more nucleotides in length. The primer must be of sufficient complementarity to the desired template to prime the synthesis of the desired extension product, that is, to be able anneal with the desired template strand in a manner sufficient to provide the 3' hydroxyl moiety of the primer in appropriate juxtaposition for use in the initiation of synthesis by a polymerase or similar enzyme. It is not required that the primer sequence represent an exact complement of the desired template. For example, a non complementary nucleotide sequence may be attached to the 5' end of an otherwise complementary primer. Alternatively, non complementary bases may be interspersed within the oligonucleotide primer sequence, provided that the primer sequence has sufficient complementarity with the sequence of the desired template strand to functionally provide a template primer complex for the synthesis of the extension product.

[0036] Amino acid residues described herein are preferred to be in the "L"
isomeric form. However, residues in the "h" isomeric form may be substituted for any L
amino acid residue, provided the desired properties of the polypeptide are retained. All amino acid residue sequences represented herein conform to the conventional left-to-right amino terminus to carboxy terminus orientation.

[0037] A "fragment" or "portion" of a polypeptide means a stretch of amino acid residues of at least about five to seven contiguous amino acids, often at least about seven to nine contiguous amino acids, typically at least about nine to thirteen contiguous amino acids and, most preferably, at least about twenty to thirty or more contiguous amino acids. Fragments of the polypeptide sequence, antigenic determinants, or epitopes are useful for eliciting immune responses to a portion of the protein amino acid sequence.

[0038] Different "variants" of the differentially expressed polypeptides exist in nature.
These variants may be alleles characterized by differences in the nucleotide sequences of the gene coding for the protein, or may involve different RNA processing or post translational modifications. The skilled person can produce variants having single or multiple amino acid substitutions, deletions, additions or replacements. These variants may include, ifater olio: (a) variants in which one or more amino acids residues are substituted with conservative or non conservative amino acids, (b) variants in which one or more amino acids are added to the polypeptide, (c) variants in which one or more amino acids include a substituent group, and (d) variants in which the polypeptide is fused with another peptide or polypeptide such as a fusion partner, a protein tag or other chemical moiety, that may confer useful properties to the polypeptide, such as, for example, an epitope for an antibody, a polyhistidine sequence, a biotin moiety and the like. Other polypeptides of the invention may include variants in which amino acid residues from one species are substituted for the corresponding residue in another species, either at the conserved or non conserved positions. In another embodiment, amino acid residues at non conserved positions are substituted with conservative or non conservative residues. The techniques for obtaining these variants, including genetic (suppressions, deletions, mutations, etc.), chemical, and enzymatic techniques are known to the person having ordinary skill in the art. To the extent such allelic variations, analogues, fragments, derivatives, mutants, and modifications, including alternative nucleic acid processing forms and alternative post translational modification forms result in derivatives of the differentially expressed polypeptide that retain any of the biological properties of the differentially expressed polypeptide, they are included within the scope of this invention.

[0039] The term "isolated protein" or "isolated and purified protein" refers primarily to a protein produced by expression of an isolated nucleic acid molecule according to an aspect the invention. Alternatively, this term may refer to a protein that has been sufficiently separated from other proteins with which it would naturally be associated, so as to exist in "substantially pure" form. "Isolated" is not meant to exclude artificial or synthetic mixtures with other compounds or materials, or the presence of impurities that do not interfere with he fundamental activity, and that may be present, for example, due to incomplete purification, addition of stabilizers, or compounding into, for example, immunogenic preparations or pharmaceutically acceptable preparations.

[0040] The term "substantially pure" refers to a preparation comprising at least about 50-60% by weight of a given material (e.g., nucleic acid, protein, etc.). More preferably, the preparation comprises at least about 75% by weight, and most preferably about 90-95% by weight of the given compound. Purity is measured by methods appropriate for the given material (e.g. chromatographic methods, agarose or polyacrylamide gel electrophoresis, HPLC analysis, and the like).

[0041] The term "tag," "tag sequence" or "protein tag" refers to a chemical moiety, either a nucleotide, oligonucleotide, polynucleotide or an amino acid, peptide or protein or other chemical, that when added to another sequence, provides additional utility or confers useful properties, particularly in the detection or isolation, of that sequence.
Thus, for example, a homopolymer nucleic acid sequence or a nucleic acid sequence complementary to a capture oligonucleotide may be added to a primer or probe sequence to facilitate the subsequent isolation of an extension product or hybridized product. In the case of protein tags, histidine residues (e.g., 4 to 8 consecutive histidine residues) may be added to either the amino or carboxy terminus of a protein to facilitate protein isolation by chelating metal chromatography.
Alternatively, amino acid sequences, peptides, proteins or fusion partners representing epitopes or binding determinants reactive with specific antibody molecules or other molecules (e.g., flag epitope, c myc epitope, transmembrane epitope of the influenza A virus hemagglutinin protein, protein A, cellulose binding domain, calmodulin binding protein, maltose binding protein, chitin binding domain, glutathione S transferase, and the like) may be added to proteins to facilitate protein isolation by procedures such as affinity or immunoaffinity chromatography. Chemical tag moieties include such molecules as biotin, which may be added to either nucleic acids or proteins and facilitates isolation or detection by interaction with avidin reagents, and the like.
Numerous other tag moieties are known to, and can be envisioned by, the trained artisan, and are contemplated to be within the scope of this definition.

[0042] An "antibody" or "antibody molecule" is any immunoglobulin, including antibodies and fragments thereof, that binds to a specific antigen. The term includes polyclonal, monoclonal, chimeric, and bispecific antibodies. As used herein, antibody or antibody molecule contemplates both an intact immunoglobulin molecule and an.immunologically active portion of an immunoglobulin molecule such as those portions known in the art as Fab, Fab', F(ab')2 and F(v). ' [0043] As used herein, the term "subject" or "patient" refers to both humans and animals, unless specified that the "subject" or "patient" is an animal or a human. Animal subjects are preferably vertebrates, and more preferably, mammals.

[0044] "Therapeutic modality" refers to any means of treating and/or preventing a disease, condition or disorder.

[0045] In one aspect of the present invention, a number of genes have been identified that are differentially expressed in osteoarthritic subjects as compared to non-osteoarthritic subjects. These genes and gene fragments, as well as their encoded proteins and fragments, may be used, for example, in a variety of diagnostic and prognostic assays, as well as assays useful in screening test substances for effectiveness in treatment modalities for osteoarthritis.

[0046] In certain embodiments of the invention, expression of at least one differentially expressed gene may be measured. In preferred embodiments, expression of two or more differentially expressed genes may be measured, providing a gene expression pattern or gene expression profile. More preferably, measurement of a multiplicity of differentially expressed genes may be performed, providing additional information for a gene expression pattern or profile.

[0047] In various embodiments of the present invention, changes in gene expression may be measured in one or both of two ways: (1) measuring transcription through detection of mRNA produced by a particular gene; and (2) measuring translation through detection of protein produced by a particular transcript.

[0048] Decreased or increased expression can be measured at the RNA level using any of the methods well known in the art for the quantitation of polynucleotides, such as, for example, PCR (including, without limitation, RT-PCR and qPCR),~RNase protection, Northern blotting and other hybridization methods. The genes that are assayed or interrogated according to the present invention are typically in the form of mRNA or reverse transcribed mRNA. The genes may be cloned and/or amplified. The cloning itself does not appear to bias the representation of genes within a population. However, it may be preferable to use polyA+ RNA
as a source, as it can be used with fewer processing steps.

[0049] In accordance with aspects of the present invention, 1558 genes have been identified whose functions are closely associated with osteoarthritis (OA).
The association is deternnined by comparing expression of the genes in normal tissue and tissue from subjects diagnosed with OA. The genes so identified fall into two broad categories. The first category comprises known genes, many of whose association with OA had heretofore been unappreciated.
These genes are listed in Table 6, along with their corresponding gene ID
numbers and SEQ ID
NOs.

[0050] According to another aspect of the invention, a second category comprises nucleic acid segments that do not demonstrate homology to previously identified sequences.
Thus, this category is believed to include one or more novel genes. One preferred embodiment of the, invention relates to an isolated nucleic acid molecule comprising a novel OA-associated gene, mRNA or cDNA produced from the OA-associated gene.

[0051] One aspect of the present invention relates to a combination of 1558 polynucleotide molecules that are differentially expressed in an osteoarthritic subject or in a pre-osteoarthritic subject compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic. In one embodiment of the invention described herein, segments of 1558 OA-related genes from canine cartilage were obtained by employing differential display. The nucleotide sequences of these polynucleotides are set forth herein asSEQ ID
NOs:l-1558 (Table 1 shows the correlation between SEQ ID NO. and Gene ID Number). BLAST analysis of these sequences identified homologies with of a number of nucleic acid sequences previously identified (Table 2) These include a number of previously identified nucleic acid sequences with no identified homologies to known genes. BLAST analysis also identified sequences showing homology to previously-identified genes; information including names of genes as well as database accession numbers for respective homologs of these is provided in Tables 2A and 2B.
Table 2A
CaMax Ensemble GeneEnsemble Description Chrom Chrom ID

Gene Transcri t No. Loc.
ID ID

CaMax:

1002b CaMax:

1002b CaMax: ENSG00000138709ENST00000264584 4 q28.2 1005a ENST00000326703 CaMax: ENSG00000152518ENST00000282388BUTYRATE RESPONSE 2 p21 1006b FACTOR 2 (TIS11D

PROTEIN) (EGF-RESPONSE

FACTOR 2) (ERF-2).

[Source:SWISSPROT;Acc:P47 974]

CaMax: ENSG00000152518ENST00000282388BUTYRATE RESPONSE 2 p21 1007a FACTOR 2 (TIS11D

PROTEIN) (EGF-RESPONSE

FACTOR 2) (ERF-2).

[Source:SWISSPROT;Acc:P47 ' 974]

CaMax:

1008a CaMax:

1008a CaMax: ENSG00000122912ENST00000265870GRAVE'S DISEASE 10 q21.3 1009c CARRIER PROTEIN (GDC) (GRAVE'S DISEASE

AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE

CARRIER PROTEIN

HOMOLOG).

[Source:SWISSPROT;Acc:Pl6 260]

CaMax:

lOlla CaMax:

lOlla CaMax:

1013a CaMax: ENSG00000109775ENST00000264689 4 q35.1 1015d CaMax:

1016b CaMax: ENSGOOOOOI60961ENST00000292530ZINC FINGER PROTEIN 19 p13.12 333.

1019a [Source:SWISSPROT;Acc:Q96 JL9]

CaMax: ENSG00000064989ENST00000264152CALCITONIN GENE- 2 q32.1 1020a RELATED PEPTIDE TYPE

RECEPTOR PRECURSOR

(CGRP TYPE 1 RECEPTOR).

[Source:SWISSPROT;Acc:Ql6 602]

CaMax:

1026b CaMax:

1026b CaMax:

1028c CaMax:

1028c CaMax: ENSG00000171567ENST00000304782TIGGER TRANSPOSABLE 2 q37.1 1029a ELEMENT DERIVED 1;

JERKY (MOUSE) HOMOLOG-LIKE.

[Source:RefSeq;Acc:NM_1457 02]

CaMax:

103a CaMax: ENSG00000041880ENST00000045065POLY [ADP-RIBOSE] 3 p21.2 1044c POLYMERASE-3 (EC

2.4.2.30) (PARP-3) (NAD(+) ADP-RIBOSYLTRANSFERASE-3) (POLY[ADP-RIBOSE]

SYNTHETASE-3) (PADPRT-3) (HPARP-3) (IRTl).

[Source:SWISSPROT;Acc:Q9 Y6F1]

CaMax: ENSG00000169045ENST00000326748HETEROGENEOUS 5 q35.3 I04a ENST00000329433NUCLEAR

RIBONUCLEOPROTEIN
H

(IINRNP H).

[Source:SWISSPROT;Acc:P31 943]

CaMax:

1050a CaMax:

1054a CaMax:

1057b CaMax:

1060a CaMax: ENSG00000138336ENST00000260906LEUKEMIA-ASSOCIATED 10 q21.3 1061a PROTEIN WITH A CXXC

DOMAIN.

[Source:SPTREMBL;Acc:QBN

FU7]

CaMax:

1063b CaMax: ENSG00000167996ENST00000301775FERRITIN HEAVY CHAIN11 q12.3 I06a (FERRITIN H SUBUNIT).

[Source:SWISSPROT;Acc:P02 794]

CaMax:

1070b CaMax:

1072a CaMax:

1072a CaMax:

1089d CaMax:

lOBa CaMax:

1090d CaMax:

1094b CaMax:

1094b CaMax: ENSMUSG0000003ENSMUST0000003 7 B2 1095a 0693 2941 CaMax: ENSMUSG0000003ENSMUST0000003 7 B2 1096a 0693 2941 CaIVIax:ENSG00000135426ENST00000316577 12 q13.2 1098a ENST00000257883 CaMax: ENSG00000138688ENST00000264501 4 q27 109a ENST00000306802 CaMax: ENSG00000119396ENST00000238339RAS-RELATED PROTEIN 9 q33.2 1105a RAB-14.

[Source:SWISSPROT;Acc:P35 287]

CaMax: ENSG00000155755ENST00000286196 2 q33.1 1106a CaMax: ENSG00000133121ENST00000255486STAR-RELATED LIPID 13 q13.1 1108a TRANSFER PROTEIN

(STARD13) (START

DOMAIN- CONTAINING

PROTEIN 13) (46H23.2).

[Source:SWISSPROT;Acc:Q9 Y3M8]

CaMax:

1110b CaMax:

1110b CaMax: ENSG00000080546ENST00000302071SESTRIN 1 (P53- 6 q21 l l ENST00000237504REGULATED PROTEIN
l 1b PA26).

[Source:SWISSPROT;Acc:Q9 Y6P5]

CaMax: ENSG00000113391ENST00000265139 5 q15 1112a CaMax:

111a CaMax: ENSG00000113384ENST00000265070GOLGI PHOSPHOPROTEIN5 p13.3 1120a 3; GOLGI PROTEIN;
GOLGI

PERIPHERAL MEMBRANE

PROTEIN 1, 34 I~DA;
GOLGI-ASSOCIATED PROTEIN;

COAT-PROTEIN.

[Source:RefSeq;Acc:NM_0221 30]

CaMax: ENSG00000185511ENST00000332847 2 p16.3 1121a CaMax:

1131b CaMax:

1132a ~aMax: ENSG00000081189ENST00000325423MYOCYTE-SPECIFIC 5 q14.3 1134a ENHANCER FACTOR 2C.

[Source:SWISSPROT;Acc:Q06 413]

CaMax: ENSG00000128573ENST00000324462FORKHEAD BOX PROTEIN7 q31.1 1135a ENST00000265436P2 (CAG REPEAT PROTEIN

ENST0000032454444) (TRINUCLEOTIDE

REPEAT- CONTAINING

GENE 10 PROTEIN).

[Source:SWISSPROT;Acc:0I5 409]

CaMax:

1137b CaMax:

1138a CaMax:

1139a CaMax: ENSG00000106817ENST00000311316COLLAGEN ALPHA 1(XV)9 q22.33 1145a CHAIN PRECURSOR.

[Source:SWISSPROT;Acc:P39 059]

CaMax:

1145a CaMax:

1146a CaMax:

1159b CaMax: ENSG00000169045ENST00000326748HETEROGENEOUS 5 q35.3 104a ENST00000329433NUCLEAR

RIBONUCLEOPROTEIN
H

(HNRNP H).

[Source:SWISSPROT;Acc:P31 943]

CaMax: ENSG00000140416ENST00000267996TROPOMYOSIN 1 ALPHA 15 q22.2 1169b ' ENST00000334895CHAIN (ALPHA-ENST00000288398TROPOMYOSIN).

ENST00000317516[Source:SWISSPROT;Acc:P09 493]

CaMax: ENSG00000100839ENST00000262237DYNEIN HEAVY CHAIN, 14 q32.32 1177c CYTOSOLIC (DYHC) (CYTOPLASMIC DYNEIN

HEAVY CHAIN 1) (DHC1) j (FRAGMENT).

[Source:SWISSPROT;Acc:Ql4 204]

CaMax: ENSG00000156299ENST00000286827T-LYMPHOMA INVASION 21 q22.11 1184a AND METASTASIS

INDUCING PROTEIN

(TIAM1 PROTEIN).

[Source:SWISSPROT;Acc:Q

009]

CaMax:

1184a CaMax: ENSMUSG0000003ENSMUST0000004 17 C

1190b 8954 3985 CaMax: ENSMUSG0000003ENSMUST0000004 17 C

1192b 8954 3985 CaMax:

llb CaMax:

120a CaMax:

120a CaMax:

1212b CaMax: ENSG00000134215ENST00000280840VAV-3 PROTEIN. 1 p13.3 1213d [Source:SWISSPROT;Acc:Q9 UKW4]

CaMax:

1217a CaMax:

1220b CaMax:

1226d CaMax:

1226d CaMax:

123c CaMax:

123c CaMax: ENSG00000065183ENST00000183319WD-REPEAT PROTEIN 1 p12 3.

1243a ENST00000309112[Source:SWISSPROT;Acc:Q9 UNX4]

CaMax:

1245b CaMax: ENSG00000109775ENST00000264689 4 q35.1 1246a CaMax:

1248b CaMax: ENSG00000109775ENST00000264689 4 q35.1 1253a CaMax:

1257b CaMa~c:

1257b CaMax:

1260c CaMax: ENSMUSG0000004ENSMUST0000005 4 D3 1263b 5004 1907 CaMax: ENSG00000175198ENST00000310787PROPIONYL-COA 13 q32.3 1267a CARBOXYLASE ALPHA

CHAIN, MITOCHONDRIAL

PRECURSOR (EC 6.4.1.3) (PCCASE ALPHA SUBUNIT) (PROPANOYL-COA:CARBON DIOXIDE

LIGASE ALPHA SUBUNIT).

[Source:SWISSPROT;Acc:P05 165]

CaMax: ENSG00000175198ENST00000310787PROPIONYL-COA 13 q32.3 1267a CARBOXYLASE ALPHA

CHAIN, MITOCHONDRIAL

~ PRECURSOR (EC 6.4.1.3) (PCCASE ALPHA SUBUNIT) (PROPANOYL-COA:CARBON DIOXIDE

LIGASE ALPHA SUBUNIT).

[Source:SWISSPROT;Acc:P05 165]

CaMax: ENSG00000144331ENST00000272761 2 q31.2 1270a CaMax: ENSG00000113615ENST00000265341PROTEIN TRANSPORT 5 q31.1 1272a ENST00000322887PROTEIN SEC24A (SEC24-RELATED PROTEIN A) (FRAGMENT).

[Source:SWISSPROT;Acc:095 486]

CaMax:

1273b CaMax:

1276a CaMax:

127b CaMax:

127b CaMax:

1282b CaMax:

1284b CaMax: ENSG00000164190ENST00000296607IDN3 PROTEIN ISOFORM5 p13.2 A.

1287c ENST00000282516[Source:RefSeq;Acc:NM_1334 33]

CaMax: ENSG00000164190ENST00000296607IDN3 PROTEIN ISOFORM5 p13.2 A.

1288a ENST00000282516[Source:RefSeq;Acc:NM_1334 33]

CaMax: ENSMUSG0000002ENSMUST0000002HEAT SHOCK PROTEIN 17 C
HSP

128a 3944 4739 90-BETA (HSP 84) (TUMOR

SPECIFIC

KDA ANTIGEN) (TSTA).

[Source:SWISSPROT;Acc:Pl l 499]

CaMax: ENSG00000079246ENST00000328063ATP-DEPENDENT DNA 2 q35 1292c HELICASE II, 80 KDA

SUBUNIT (LUPUS KU

AUTOANTIGEN PROTEIN

P86) (KU86) (KU80) (86 KDA

SUBUNIT OF KU ANTIGEN) (THYROID- LUPUS

AUTOANTIGEN) (TLAA) (CTC BOX BINDING

FACTOR 85 KDA SUBUNIT) (CTCBF) (CTC85) (NUCLEAR FACTOR IV) (DNA-REPAIR PROTEIN

XRCCS).

[Source: SWISSPROT;Acc:P ' 010]

CaMax: ENSG00000136628ENST00000259146BIFUNCTIONAL 1 q41 1294b ENST00000335149AMINOACYL-TRNA

SYNTHETASE [INCLUDES:

GLUTAMYL-TRNA

SYNTHETASE (EC 6.1.1.17) (GLUTAMATE--TRNA

LIGASE); PROLYL-TRNA

SYNTHETASE (EC 6.1.1.15) (PROLINE--TRNA LIGASE)].

jSource:SWISSPROT;Acc:P07 814]

CaMax: ENSG00000163625ENST00000295888WD REPEAT AND FYVE 4 q21.23 1299c ENST00000322366DOMAIN CONTAINING

ISOFORM 1.

[Source:RefSeq;Acc:NM_0149 91]

CaMax:

129b CaMax:

129b CaMax:

12a CaMax: ENSMUSG0000004ENSMUST0000005 16 B2 1301a 9076 8033 CaMax: ENSG00000168952ENST00000323944AMISYN; SYNTAXIN 14 qI2 1304a BINDING PROTEIN 6.

[Source:RefSeq;Acc:NM

78]

CaMax:

1308c CaMax:

1308c CaMax:

130b CaMax;

1316b CaMax:

1318a CaMax;

CaMax: ENSRNOG0000000 UDP-N- 21 q31 1322c 3359 ACETYLGLUCOSAMINE--PEPTIDE N-ACETYLGLUCOSAMINYLT

SUBUNIT (EC 2.4.1.-) (O-GLCNAC TRANSFERASE

P110 SUBUNIT).

[Source:SWISSPROT;Acc:P56 558]

CaMax:

1323br CaMax:

1323br CaMax: ' 1324a CaMax;

1324a CaMax:

1335b CaMax:

1335b CaMax: ENSG00000166923ENST00000300177CYSTEINE KNOT 15 q13.3 1341a ENST00000322805SUPERFAMILY 1, BMP

ANTAGONIST 1; GREMLIN.

[Source:RefSeq;Acc:NM_0133 72]

CaMax: ' 1352b CaMax: ENSG00000171567ENST00000304782TIGGER TRANSPOSABLE 2 q37.1 1354a ELEMENT DERIVED 1;

JERKY (MOUSE) ' HOMOLOG-LIKE.

[Source:RefSeq;Acc:NM_1457 02]

CaMax:

1355a CaMax:

1355a CaMax: ENSG00000033170ENST00000315759ALPHA-(1,6)- 14 q23.3 1361a ENST00000261677FUCOSYLTRANSFERASE

(EC 2.4.1.68) (GLYCOPROTEIN 6-ALPHA-L-FUCOSYLTRANSFERASE) (GDP-FUCOSE--FUCOSYLTRANSFERASE) (GDP-L-FUC:N-ACETYL-BETA-D-GLUCOSAMINIDE

ALPHA1,6-FUCOSYLTRANSFERASE) (ALPHA1-6FUCT) (FUCOSYLTRANSFERASE

8).

[Source:SWISSPROT;Acc:Q9 BYCS]

CaMax:

1364d CaMax:

1364d CaMax: ENSG00000064205ENST000001909,83CONNECTIVE TISSUE 20 q13.12 1366a GROWTH FACTOR-LIKE

PROTEIN PRECURSOR

(CTGF-L) (WNT1 INDUCIBLE SIGNALING

PATHWAY PROTEIN 2) (WISP-2) (CONNECTIVE

TISSUE GROWTH FACTOR-RELATED PROTEIN 58).

[Source:SWISSPROT;Acc:076 076]

CaMax: ENSMUSG0000003ENSMUST0000003 7 F3 1368a 0871 3159 CaMax: ENSG00000119326ENST00000325551CATENIN (CADHERIN- 9 q31.3 1371a ENST00000325580ASSOCIATED PROTEIN),i ALPHA-LIKE 1; ALPHA-CATULIN.

[Source:RefSeq;Acc:NM_0037 98]

CaMax: ENSG00000083771ENST00000218546M-PHASE 13 q12.11 137b , PHOSPHOPROTEIN 8 (FRAGMENT).

[Source:SWISSPROT;Acc:Q99 549]

CaMax:

1381a CaMax:

1381a CaMax: ENSG00000067208ENST00000263785ECOTROPIC VIRAL 1 p22.1 1383a INTEGRATION SITE
5;

NEUROBLASTOMA STAGE

4S GENE.

' [Source:RefSeq;Acc:NM_0056 65]

CaMax:ENSG00000099194ENST00000266053ACYL-COA DESATURASE 10 q24.31 1384a (EC 1.14.19.1) (STEAROYL-COA DESATURASE) (FATTY ACID

DESATURASE) (DELTA(9)-DESATURASE).

[Source:SWISSPROT;Acc:O00 767]

CaMax:

1391a CaMax:

1394b CaMax:ENSG00000111912ENST00000229634NUCLEAR RECEPTOR 6 q22.32 1397b ENST00000318575COACTIVATOR 7;

ESTROGEN RECEPTOR

ASSOCIATED PROTEIN

KDA.

[Source:RefSeq;Acc:NM_1817 82]

CaMax:

1399a CaMax:

13a CaMax:

1400a CaMax:ENSG00000109756ENST00000264431PDZ DOMAIN CONTAINING4 q32.1 1401c GUANINE NUCLEOTIDE

EXCHANGE FACTOR (GEF) 1; RA(RAS/RAPIA-ASSOCIATING)-GEF;
PDZ

DOMAIN CONTAINING

GUANINE NUCLEOTIDE

EXCHANGE

FACTOR(GEF) 1;

RA(RAS/RAP 1 A-ASSOCIATING)-GEF;
PDZ

DOMAIN CONTAINING

GUANINE NUCLEOTIDE

EXCHANGE

FACTOR(GEF) 1.

[Source:RefSeq;Acc:~

47]

CaMax:

1403a CaMax:

I406a CaMax:ENSG00000166170ENST00000299204BAG-FAMILY MOLECULAR14 q32.32 1409b CHAPERONE REGULATOR-5 (BAG-5).

[Source:SWISSPROT;Acc:Q9 UL15]

CaMax:ENSG00000058272ENST00000261207PROTEIN PHOSPHATASE 12 q21.2 1, 1411a ENST00000312727REGULATORY (INHIBITOR) SUBUNIT I2A; MYOSIN

PHOSPHATASE,TARGET

SUBUNIT 1.

[Source:RefSeq;Acc:NM_0024 80]

CaMax:ENSMUSG0000003ENSMUST0000005 4 C7 1'415b 4794 4209 CaMax:

1416a CaMax:

1419a CaMax:

141c CaMax:

141c CaMax:

142.1c CaMax:

142.1c CaMax: ENSG00000128845ENST00000267809CELL CYCLE 15 q21.3 1420c ENST00000310958PROGRESSION 8 PROTEIN.

[Source:RefSeq;Acc:NM

39]

CaMax: ENSG00000172175ENST00000313958MUCOSA ASSOCIATED 18 q21.31 1421a ENST00000303708LYMPHOID TISSUE

LYMPHOMA

TRANSLOCATION PROTEIN

1 (EC 3.4.22.-) (MALT-LYMPHOMA ASSOCIATED

TRANSLOCATION) (PARACASPASE).

[Source:SWISSPROT;Acc:Q9 UDYB]

CaMax:

I423b CaMax: ENSG00000152583ENST00000282470SPARC-LIKE PROTEIN 4 q22.1 143.2c PRECURSOR (HIGH

' ENDOTHELIAL VENULE

PROTEIN) (HEVIN) (MAST

9). ' [Source: SWISSPROT;Acc:Q

515]

CaMax: ENSG00000152583ENST00000282470SPARC-LIKE PROTEIN 4 q22.1 143.2c PRECURSOR (HIGH

ENDOTHELIAL VENULE

PROTEIN) (HEVIN) (MAST

9).

[Source: SWISSPROT;Acc:

515]

CaMax:

1431a CaMax:

144.2a CaMax:

144.2a CaMax: ENSG00000154430ENST00000284618TESTICAN-3 PRECURSOR.4 q32.3 1448a [Source:SWISSPROT;Acc:Q9 BQ16]

CaMax: ENSG00000170631ENST00000276816ZINC FINGER PROTEIN 8 q24.3 1449a ENST00000317284CLONE 647.

ENST00000332620[Source:SWISSPROT;Acc:Pl5 ENST00000317099622]

CaMax: ENSG00000170891ENST00000307746CYTOKINE-LIKE PROTEIN4 p16.2 1450a C17 PRECURSOR.

[Source:SWISSPROT;Acc:Q9 NRR1]

CaMax:

1452a CaMax:

1457b CaMax: ENSG00000113387ENST00000265073ACTIVATED RNA 5 p13.3 1459c POLYMERASE II

TRANSCRIPTIONAL

COACTIVATOR P15 (PC4) (P14).

[Source:SWISSPROT;Acc:P53 999]

CaMax:

1459c CaMax: ENSG00000147403ENST0000027637160S RIBOSOMAL PROTEIN24 q28 145b L10 (QM PROTEIN) (TUMOR

SUPPRESSOR QM) (LAMININ RECEPTOR

HOMOLOG).

[Source:SWISSPROT;Acc:P27 635]

CaMax:

1460a CaMax:

1460a CaMax:

1461a CaMax:

1461a CaMax:

1466b CaMax:

1466b I

CaMax: ENSMUSG0000004ENSMUST0000006UPREGULATED DURING 20 A2 1469a 6599 0592 SKELETAL MUSCLE

GROWTH 5.

[Source:RefSeq;Acc:NM_0232 11]

CaMax: ENSGOOOOOI12365ENST00000230122 6 q21 146b CaMax: ENSMUSG0000004ENSMUST0000006UPREGULATED DURING 20 A2 ' 1469a 6599 0592 SKELETAL MUSCLE

GROWTH 5.

[Source:RefSeq;Acc:NM_0232 11]

CaMax:

1472a CaMax:

1475a CaMax: ENSG00000172201ENST00000326913DNA-BINDING PROTEIN 6 p22.3 , 1476a INHIBITOR ID-4.

[Source:SWISSPROT;Acc:P47 928]

CaMax: ENSG00000159388ENST00000290551BTG2 PROTEIN (NGF- 1 q32.1 1477a INDUCIBLE ANTI-PROLIFERATIVE PROTEIN

' PC3).

[Source:SWISSPROT;Acc:P78 543]

CaMax:

147b CaMax: ENSG00000105997ENST00000317201HOMEOBOX PROTEIN 7 p15.2 1481c HOX-A3 (HOX-lE).

[Source:SWISSPROT;Acc:043 365]

CaMax: ENSG00000115998ENST00000264434 2 _ p13.3 1482a CaMax:

1484b CaMax: ENSG00000I22566ENST00000265398HETEROGENEOUS 7 pI5.2 1488b ENST00000312091NUCLEAR

RIB ONUCLEOPROTEINS

A2lB 1 (HNRNP A2 / HNRNP

Bl).

[Source:SWISSPROT;Acc:P22 626]

CaMax:

148a CaMax:

1497c CaMax:

1497c CaMax:

1500b CaMax:

1504d CaMax:

1506d CaMax:

1506d CaMax: ENSG00000106853ENST00000333580NADP-DEPENDENT 9 q31.3 150a ENST00000309195,LEUKOTRIENE B4 12-HYDROXYDEHYDROGENA

SE (EC 1.1.1.-).

[Source:SWISSPROT;Acc:Ql4 914]

CaMax: ENSG00000115998ENST00000264434 2 p13.3 1516a CaMax:

1519a -CaMax:

1519a CaMax:

151b CaMax:

1520a CaMax:

1520a CaMax: ENSG00000165421ENST00000333218PROTEIN PHOSPHATASE 11 q13.4 1521b ENST00000327431METHYLESTERASE-1.

ENST00000328257[Source:RefSeq;Acc:NM_0161 47]

CaMax:

1522b CaMax:

2531c CaMax:

1532a CaMax:

1532a CaMax: ENSG00000133637ENST00000309041 12 q2,1.32 1534b ENST00000322687 CaMax:

1534b CaMax:

1535a CaMax:

1541a CaMax: ENSG00000151012ENST00000280612CYSTINE/GLUTAMATE 4 q28.3 1546b TRANSPORTER (AMINO

ACID TRANSPORT SYSTEM

XC-) (XCT) (CALCIUM

CHANNEL BLOCKER

RESISTANCE PROTEIN

CCBRl).

[Source:SWISSPROT;Acc:Q9 UPYS]

CaMax:

1548c CaMax:

1549a CaMax: ENSG00000179454ENST00000324772BTB (POZ) DOMAIN 1.4 q21.2 1551a CONTAINING 5.

[Source:RefSeq;Acc:NM_0176 58]

CaMax:

1554c CaMax: ENSG00000178074ENST00000319974 2 q33.1 1573a CaMax:

1574b CaMax:

1574b CaMax: ENSG00000144785ENST00000273308TRANSMEMBRANE 12 q13.3 1577a PROTEIN 4.

[Source:RefSeq;Acc:NM_0142 55]

CaMax:

1578a CaMax:

157b CaMax:

157b CaMax:

1591a CaMax:

1591a CaMax:

1594a CaMax:

1596b CaMax:

1596b CaMax:

1598a CaMax:

159a CaMax:

159a CaMax: ENSG00000174132ENST00000312637 5 q21.1 15b CaMax: ENSG00000113838ENST00000265025 3 q27.3 1602a CaMax;

1604a ' CaMax: ENSG00000183456ENST00000330170 2 q33.1 1626c CaMax:

I628d CaMax: , 1629a CaMax;

I629a CaMax:

1630b CaMax:

1630b CaMax: ENSG00000083290ENST00000261504UNC-51-LIKE KINASE 17 p11.2 2.

1631d [Source:RefSeq;Acc:NM_0146' 83]

CaMax: ENSG00000083290ENST00000261504UNC-51-LIKE KINASE 17 p11.2 2.

1635a [Source:RefSeq;Acc:NM_0146 83]

CaMax: ENSG00000083290ENST00000261504UNC-51-LIKE KINASE 17 p11.2 2.

1635a [Source:RefSeq;Acc:NM_0146 83]

CaMax;

1639a CaMax:

1639a CaMax: ENSG00000006015ENST00000326666 19 p13.11 163a ENST00000326636 CaMax: ENSG00000120254ENST00000265365 6 q25.1 1646a CaMax: ENSMUSG0000003ENSMUST0000003 19 C1 1648a 3207 6069 CaMax: ENSG00000163734ENST00000296026MACROPHAGE 4 q13.3 164c INFLAMMATORY

PRECURSOR (MIP2-BETA) (CXCL3) (GROWTH

REGULATED PROTEIN

GAMMA) (GRO-GAMMA).

[Source:SWISSPROT;Acc:Pl9 876]

CaMax:

1659a CaMax:

1659a CaMax: ENSG00000162384ENST00000294360 1 p32.3 166a CaMax:

1671b CaMax:

1671b CaMax:

1675a CaMax:

1676a CaMax:

1676a CaMax:

1678a CaMax:

1682a CaMax:

168c CaMax: ENSRNOG0000001 CYTOCHROME C OXIDASE19 q12 1690a 7817 SUBUNIT IV ISOFORM
1, MITOCHONDRIAL

PRECURSOR (EC 1.9.3.1) (COX IV-1) (CYTOCHROME

C OXIDASE POLYPEPTIDE

IV).

[Source:SWISSPROT;Acc:PlO

888]

CaMax: ENSG00000081177ENST00000193422 14 q24.1 1691b CaMax: ENSRNOG0000001 CYTOCHROME C OXIDASE19 q12 1692a 7817 SUBUNIT IV ISOFORM
1, MITOCHONDRIAL

PRECURSOR (EC 1.9.3.1) (COX IV-1) (CYTOCHROME

C OXIDASE POLYPEPTIDE

IV).

[Source:SWISSPROT;Acc:PIO

888]

CaMax: ENSG00000066468ENST00000263455FIBROBLAST GROWTH 10 q26.13 1693b ENST00000310977FACTOR RECEPTOR 2 ENST00000263451PRECURSOR (EC 2.7.1.112) ENST00000263454(FGFR-2) (KERATINOCYTE

ENST00000310973RECEPTOR 2).

ENST00000263453[Source:SWISSPROT;Acc:P21 ENST00000332961802]

CaMax:

1696a CaMax:

1696a CaMax:

16b CaMax: ENSG00000132357ENST00000254691CASPASE RECRUITMENT 5 p13.1 1705a DOMAIN PROTEIN 6.

[Source:SWISSPROT;Acc:Q9 BX69]

CaMax:

1709a CaMax: ENSG00000033178ENST00000322244 4 q13.2 1714a CaMax:

2715a CaMax: ENSG00000179010ENST00000320912T-CELL ACTIVATION 4 p16.1 1717a PROTEIN.

[Source:RefSeq;Acc:NM_0332 96]

CaMax: ENSG00000021355ENST00000229479LEUKOCYTE ELASTASE 6 25.2 1721a INHIBITOR (LEI) (MONOCYTE/NEUTROPHIL

ELASTASE INHIBITOR) (M/NEI) (EI).

[Source:SWISSPROT;Acc:P30 740]

CaMax: ENSG00000144674ENST00000273176GOLGI AUTOANTIGEN, 3 p22.3 1722a GOLGIN SUBFAMILY
A

MEMBER 4 (TRANS-GOLGI

P230) (256 KDA GOLGII~

(GOLGIN-245) (72.1 PROTEIN).

[Source:SWISSPROT;Acc:Ql3 439]

CaMax: ENSG00000143147ENST00000271357G-PROTEIN COUPLED 1 q24.2 1724a RECEPTOR.

[Source:RefSeq;Acc:NM_1538 32]

CaMax:

1725a CaMax:

1726a CaMax:

1726a CaMax: ENSG00000131355ENST00000253673EGF-LIKE MODULE- 19 p13.12 1727a CONTAINING MUCIN-LIKE

A.

[Source:RefSeq;Acc:NM_0325 71]

CaMax:

1730a CaMax:

1738b CaMax:

1741a CaMax: ENSG00000109883ENST00000227288LEUCINE-RICH REPEAT-11 p14.1 1744a CONTAINING G PROTEIN-COUPLED RECEPTOR

PRECURSOR (G PROTEIN-COUPLED RECEPTOR
48).

[Source:SWISSPROT;Acc:Q9 BXB 1]

CaMax:

1744a CaMax: ENSG00000139688ENST00000267164TRANSCRIPTION 13 q14.12 174a INITIATION FACTOR
IIF, BETA SUBUNIT (TFIIF-BETA) (TRANSCRIPTION

INITIATION FACTOR

RAP30).

[Source:SWISSPROT;Acc:Pl3 984]

CaMax:

174a CaMax:

1750a CaMax:

1751a CaMax:

1755a CaMax:

1~755a CaMax: ENSG00000104852ENST00000221448U1 SMALL NUCLEAR 19 q13.33 1758a RIBONUCLEOPROTEIN

KDA (U1 SNRNP 70 KDA) (SNRNP70) (U1-70K).

[Source:SWISSPROT;Acc:P08 621]

CaMax: ENSG00000179454ENST00000324772BTB (POZ) DOMAIN 14 q21.2 ~

1759b CONTAINING 5.

[Source:RefSeq;Acc:NM_0176 58]

CaMax:

1760c CaMax:

1760c CaMax:

1772a CaMax: ENSG00000179562ENST00000321407GOLGI COILED COIL 7 q32.1 1775a PROTEIN 1.

[Source:SWISSPROT;Acc:Q96 CN9]

CaMax: ENSG00000179562ENST00000321407GOLGI COILED COIL 7 q32.1 1775a PROTEIN 1.

[Source:SWISSPROT;Acc:Q96 CN9]

CaMax:

1778c CaMax: ENSG00000184880ENST00000332933OK/SW-CL.87. 11 q23.3 1782b [Source:SPTREMBL;Acc:QBN

I68] ' CaMax: ENSG00000135457ENST00000257915TRANSCRIPTION FACTOR12 q13.12 178a ENST00000307660CP2; TRANSCRIPTION

FACTOR CP2, ALPHA

GLOBIN.

[Source:RefSeq;Acc:NM_0056 53]

CaMax:

1794a CaMax:

1794a CaMax:

17a CaMax:

1800a CaMax: ENSG00000166855ENST00000300107ATP-DEPENDENT CLP 15 q22.31 1801b PROTEASE ATP-BINDING

SUBUNIT CLPX-LIKE, MITOCHONDRIAL

PRECURSOR.

[Source:SWISSPROT;Acc:076 031]

CaMax: ENSG00000171567ENST00000304782TIGGER TRANSPOSABLE 2 q37.1 180a ELEMENT DERIVED 1;

JERKY (MOUSE) HOMOLOG-LIKE.

[Source:RefSeq;Acc:NM_I457 02]

CaMax: ENSG00000102901ENST00000219172 16 q22.1 1810a CaMax:

1811b CaMax: ENSG00000105492ENST00000270604SIALIC ACID BINDING 19 q13.41 IG-1812b LIKE LECTIN 6 PRECURSOR (SIGLEC-6) (OBESITY- BINDING

PROTEIN 1) (OB-BP1) (CD33 ANTIGEN-LIKE 1).

[Source:SWISSPROT;Acc:043 699]

CaMax: ENSG00000145730ENST00000304400PEPTIDYL-GLYCINE 5 q21.1 1814c ENST00000304406ALPHA-AMIDATING

ENST00000325306PRECURSOR (EC 1.14.17.3) ENST00000274392(PAM).

[Source:SWISSPROT;Acc:Pl9 021 ]

CaMax:

1814c CaMax:

1818a CaMax: ENSMUSG0000002ENSMUST0000005PROTEOGLYCAN LINK 13 C3 1828b 1613 3227 PROTEIN PRECURSOR

" ENSMUST0000002(CARTILAGE LINK

2108 PROTEIN) (LP).

[Source:SWISSPROT;Acc:Q9 QUPS]

CaMax:

1834b CaMax:

1849d CalVIax:

1852a CaMax: ENSRNOG0000001 SPLICEOSOMAL PROTEIN9 q31 1853a 3516 SAPf55 (FRAGMENT).

[Source:SPTREMBL;Acc:Q9E

T34]

CaMax: ENSRNOG0000001 CYTOCI3ROME B5. 18 q12.3 1857c 5205 [Source:SWISSPROT;Acc:P00 173]

CaMax: ENSG00000055609ENST00000312661MYELOID/LYMPHOID 7 q36.1 OR

1859a ENST00000262189MIXED-LINEAGE

LEUKEMIA 3; ALR-LIKE

PROTEIN.

[Source:RefSeq;Acc:NM_0212 30]

CaMax:

1863c CaMax:

1863c CaMax: ENSMUSG0000003ENSMUST0000004 8 D3 1864b 3732 2012 CaMax: ENSG00000173210ENST00000309868 5 q33.1 186a ENST00000326685 CaMax:

1874b CaMax:

1874b CaMax:

1879a -CaMax I

1$79a CaMax:

1881b CaMax: ENSG00000151806ENST00000281543 4 p13 1894a CaMax:

18a CaMax:

1912a CaMax:

1912a CaMax:

1913a CaMax:

1913a CaMax: ENSG00000146414ENSTOb000275233SNF2 HISTONE LINKER 6 q24.3 1917f ENST00000334592PHD RING HELICASE.

[Source:RefSeq;Acc:NM_1730 82]

CaMax: ENSG00000057019ENST00000326857ENDOTHELIAL AND 3 q12.1 1919a ENST00000326840SMOOTH MUSCLE CELL-DERIVED NEUROPILIN-LIKE PROTEIN;

COAGULATION FACTOR

V/VIII-HOMOLOGY

DOMAINS PROTEIN 1.

[Source:RefSeq;Acc:NM_0809 27]

CaMax: ENSMUSG0000002ENSMUST0000005 16 B5 1920a 2649 2314 CaMax:

1928a CaMax: ENSG00000142207ENST0000027020I 21 q22.11 1929c CaMax: ENSG00000117868ENST00000251527 7 q36.3 1930a CaMax: ENSGOOOOOllb957ENST00000264180BETA-TUBULIN 1 q42.3 1940e COFACTOR E.

[Source:RefSeq;Acc:NM_0031 93]

CaMax: ENSG00000070214ENST00000185520CDW92 ANTIGEN; 9 q31.1 1941e CHOLINE TRANSPORTER-LIKE PROTEIN.

[Source:RefSeq;Acc:NM_0805 46]

CaMax: ENSG00000154553ENST00000284770ALPHA-ACTININ-2- 4 q35.1 1943a ENST00000284771ASSOCIATED LIM

ENST00000284767PROTEIN; ENIGMA

HOMOLOG.

[Source:RefSeq;Acc:NM_0144 76]

CaMax:

1944a CaMax:

1944a CaMax:

1945a CaMax:

1945a CaMax:

1948b CaMax:

1948b CaMax:
~

1949a CaMax:

1949a CaMax: ENSG00000134215ENST00000280840VAV-3 PROTEIN. 1 p13.3 1950a [Source:SWISSPROT;Acc:Q9 UKW4]

CaMax: ENSG00000138386ENST00000321041NGFI-A BINDING PROTEIN2 q32.2 1953a 1 (EGR-1 BINDING
PROTEIN

I) (TRANSCRIPTIONAL

REGULATORY PROTEIN

P54). .

[Source:SWISSPROT;Acc:Ql3 506]

CaMax:

1954e CaMax: ENSG00000157077ENST00000287722MOTHERS AGAINST 1 p32.3 1961e ENST00000287727DECAPENTAPLEGIC

HOMOLOG INTERACTING

PROTEIN (MADH-INTERACTING PROTEIN) ' (SMAD ANCHOR FOR

RECEPTOR ACTIVATION) (RECEPTOR ACTIVATION

ANCHOR) (HSARA) (NOVEL

SERINE PROTEASE) (NSP).

[Source:SWISSPROT;Acc:095 405]

CaMax: ENSG00000080469ENST00000328494ANTIGEN PEPTIDE 6 p21.32 1967a ENST00000190846TRANSPORTER 2 (APT2) (PEPTIDE TRANSPORTER

TAP2) (PEPTIDE

TRANSPORTER PSF2) (PEPTIDE SUPPLY FACTOR

2) (PSF-2) (PEPTIDE

TRANSPORTERINVOLVED

IN ANTIGEN PROCESSING

2).

[Source:SWISSPROT;Acc:Q03 519]

CaMax: ENSG00000138063ENST00000260632PELLINO PROTEIN. 2 p14 1968a [Source:RefSeq;Acc:NM_0206 51]

CaMax: ENSG00000060718ENST00000305302COLLAGEN ALPHA 1(XI)1 p2I.1 1982a ENST00000193186CHAIN PRECURSOR.

ENST00000314022[Source:SWISSPROT;Acc:Pl2 ENST00000305262107]

CaMax:

1989b CaMax: ENSG00000166974ENST00000300249MICROTUBULE- 18 q12.1 1990a ASSOCIATED PROTEIN, RP/EB FAMILY, MEMBER
2;

T-CELL ACTIVATION

PROTEIN, EB 1 FAMILY;

APC-BINDING PROTEIN

EB 1.

[Source:RefSe ;Acc:NM

68]

CaMax: -1991d CaMax:

la CaMax:

2002c CaMax: ENSG00000081019ENST00000261441 1 p13.2 2003a CaMax: ENSMUSG0000002ENSMUST0000002PINS. 3 F3 2008a 7883 9482 [Source:RefSeq;Acc:NM_0295 22]

CaMax: ENSG00000180530ENST00000318948NUCLEAR FACTOR RIP14021 q1 1.2 2013a ~ (NUCLEAR RECEPTOR

INTERACTING PROTEIN
1).

[Source:SWISSPROT;Acc:P48 552]

CaMax:

2014f CaMax: ENSG00000174444ENST0000030796160S RIBOSOMAL PROTEIN15 q22.31 2015e L4 (L1).

[Source:SWISSPROT;Acc:P36 57s]

CaMax: ENSG00000011566ENST00000263881MITOGEN-ACTIVATED 2 p22.1 2020b PROTEIN KINASE KINASE

KINASE KINASE 3 (EC

2.7.1.37) (MAPK/ERK

KINASE KINASE KINASE
3) (MEK KINASE KINASE
3) (MEKKK 3) (GERMINAL

CENTER KINASE RELATED

PROTEIN KINASE) (GLK).

[Source:SWISSPROT;Acc:QBI

VH8]

CaMax:

2020b CaMax: ENSG00000020577ENST00000305831 14 q22.2 2022a ENST00000251091 CaMax:

2023b CaMax:

2023b CaMax:

2024a CaMax: ENSG00000172155ENST00000326233LATE ENVELOPE PROTEIN1 q21.3 2034a 4.

[Source:RefSeq;Acc:NM_1783 52]

CaMax: ENSG00000161980ENST00000293860DNA-DIRECTED RNA 16 p13.3 2035d POLYMERASES III 12.5 KDA

POLYPEPTIDE (EC 2.7.7.6) (RNA POLYMERASE III

SUBUNIT) (HSC11P) (HRPC11) (MY010 PROTEIN).

[Source:SWISSPROT;Acc:Q9 Y2Y 1]

CaMax:

204a CaMax: ENSG00000141331ENST00000269073POTENTIAL HELICASE 17 24.2 2b56d WITH ZINC-FINGER

DOMAIN.

[Source:SWISSPROT;Acc:P42 694]

CaMax:

2059b CaMax:

205a CaMax: ENSG00000129116ENST00000261509PALLADIN; CGI-151 4 q32.3 2070a ENST00000335213PROTEIN.

ENST00000333488[Source:RefSeq;Acc:NM_0160 81]

CaMax:

2073b CaMax:

2073b CaMax: ENSG00000124406ENST00000264449POTENTIAL 4 p13 2074b PHOSPHOLIPID-TRANSPORTING ATPASE

IA (EC 3.6.3.1) (CHROMAFFIN GRANULE

ATPASE II) (ATPASE
CLASS

1).

[Source:SWISSPROT;Acc:Q9 Y2Q0]

CaMax: ENSG00000138709ENST00000264584 4 q28.2 2075a ENST00000326703 CaMax:

2076c CaMax: ENSG00000122545ENST00000322406SEPTIN 7 (CDC10 PROTEIN7 p14.2 2078a HOMOLOG).

[Source:SWISSPROT;Acc:Ql6 181]

CaMax: ENSG00000085449ENST00000233055WD REPEAT AND FYVE 2 q36.1 2083e ENST00000272881DOMAIN CONTAINING

ISOFORM 1;

PHOSPHOINOSITIDE-BINDING PROTEIN SR1;

CONTAINING 1.

[Source:RefSeq;Acc:NM_0208 30]

CaMax: ENSG00000152487ENST00000302150 10 p12.31 2088a CaMax:

2092c CaMax:

2095a CaMax:

2099a CaMax:

2099a CaMax:

20a CaMax:

20a CaMax: ENSG00000166147ENST00000316623FIBRILLIN 1 PRECURSOR.15 q21.1 2100b [Source:SWISSPROT;Acc:P35 555]

CaMax:

2105a CaMax:

2108b CaMax:

2109a CaMax: ENSG00000180837ENST00000318177ZINC FINGER PROTEIN 19 q13.12 2110a (ZINC FINGER PROTEIN

HZF10).

[Source:SWISSPROT;Acc:Ql4 585]

CaMax:

2113a CaMax: ENSG00000103222ENST00000263013MULTIDRUG RESISTANCE-16 p13.11 211b ENST00000263018ASSOCIATED PROTEIN
1.

ENST00000263015[Source:SWISSPROT;Acc:P33 ENST00000263019527]

CalVIax:

2122a CaMax: ENSG00000139370ENST00000266771PEPTIDE-HISTIDINE 12 q24.32 2123a TRANSPORTER 4.

[Source:RefSeq;Acc:NM_1456 4s]

CaMax: ENSG00000143415ENST00000271682SMALL PROTEIN 1 q21.3 2129a EFFECTOR 1 OF CDC42.

[Source:RefSeq;Acc:NM_0202 39]

CaMax:

2132a CaMax:

2135d CaMax:

2136b CaMax:

2141a CaMax:

2142a CaMax:

2160a CaMax: ENSG00000138709ENST00000264584 4 q28.2 2161c ENST00000326703 CaMax:

2165a CaMax:

2167a CaMax:

2189b CaMax:

2198b CaMax:

2201a CaMax:

2201a CaMax:

2205a CaMax:

2210a CaMax:'ENSG00000117868ENST00000251527 7 q36.3 ' 2222b CaMax:

2223a CaMax: ENSG00000116690ENST00000251819PROTEOGLYCAN 4; 1 q31.1 2224a MEGAKARYOCYTE

STIMULATING FACTOR;

PROTEOGLYCAN 4, (MEGAKARYOCYTE

STIMULATING FACTOR, ARTICULAR SUPERFICIAL

ZONE PROTEIN); JACOBS

CAMPTODACTYLY-' ARTHROPATHY-PERICARDITIS

SYNDROME;

CAMPTODACTYLY, ARTHROPATHY,COXA

VARA, PERICARDITIS

SYNDROME.

[Source:RefSeq;Acc:NM_0058 07]

CaMax: ENSG00000151544ENST00000281234 10 q25.3 2225b CaMax: ENSMUSG0000003ENSMUST0000003THYROTROPIN- ' ~ 15 D1 2234a 8760 8856 RELEASING HORMONE

RECEPTOR (TRH-R) (THYROLIBERIN

RECEPTOR).

[Source:SWISSPROT;Acc:P21 761]

CaMax:

2235a CaMax:

2235a CaMax: ENSG00000172572ENST00000325802CGMP-INHIBITED 3',5'-12 p12.2 2238a CYCLIC

PHOSPHODIESTERASE
A

(EC 3.1.4.17) (CYCLIC
GMP

INHIBITED

PHOSPHODIESTERASE
A) (CGI-PDE A).

[Source:SWISSPROT;Acc:Ql4 432]

CaMax: ENSG00000172572ENST00000325802CGMP-INHIBITED 3',5'-12 p12.2 a PHOSPHODIESTERASE
A

(EC 3.1.4.17) (CYCLIC
GMP

INHIBITED

PHOSPHODIESTERASE
A) (CGI-PDE A).

[Source:SWISSPROT;Acc:Ql4 432]

CaMax: ENSG00000172572ENST00000325802CGMP-INHIBITED 3',5'-12 p12.2 2238a CYCLIC

PHOSPHODIESTERASE
A

(EC 3.1.4.17) (CYCLIC
GMP

INHIBITED

PHOSPHODIESTERASE
A) (CGI-PDE A).

[Source:SWISSPROT;Acc:Ql4 =42-432]

CaMax:

224a CaMax:

2251d CaMax:ENSG00000109775ENST00000264689 4 q35.1 2252b CaMax:

2258a CaMax:

2258a CaMax:

2258a CaMax:

225a CaMax:

2264b CaMax:

2264b CaMax:

2266b CaIVIax:ENSG00000137801ENST00000260356THROMBOSPONDIN 1 15 q14 2267a PRECURSOR.

[Source:SWISSPROT;Acc:P07 996]

CaMax:

231a CaMax:

2331c CaMax:ENSG00000119397ENST00000238341. 9 q33.2 2341b CaMax:

2351c CaMax:

2351c CaMax:ENSG00000172572ENST00000325802CGMP-INHIBITED 3',5'-12 p12.2 a PHOSPHODIESTERASE
A

(EC 3.1.4.17) (CYCLIC
GMP

INHIBITED

PHOSPHODIESTERASE
A) (CGI-PDE A).

[Source: SWISSPROT;Acc:

432]

CaMax:

235a CaMax:ENSG00000137801ENST00000260356THROMBOSPONDIN 1 15 q14 2374a PRECURSOR.

[Source:SWISSPROT;Acc:P07 996]

CaMax:

238a CaMax:ENSG00000119363ENST00000238302SPECTRIN ALPHA CHAIN,9 q34.11 239a BRAIN (SPECTRIN, NON-ERYTHROID ALPHA

CHAIN) (ALPHA-II

SPECTRIN) (FODRIN

ALPHA CHAIN).

[Source:SWISSPROT;Acc:Ql3 813]

CaMax: ENSG00000162419ENST00000294409GLUCOCORTICOID 1 p35.3 23a MODULATORY ELEMENT

(GMEB-1) (PARVOVIRUS

INITIATION FACTOR
P96) (PIF P96) (DNA BINDING

PROTEIN P96PIF).

[Source:SWISSPROT;Acc:Q9 Y692]

CaMax: ENSG00000154I44ENST00000284290 11 q24.2 240a CaMax:

243a CaMax: ENSGOOOOOI66800ENST00000280706 11 plS.I

245a CaMax: ENSG00000162437ENST00000294428 1 p31.3 248a CaMax:

24a CaMax:

258a CaMax:

261c CaMax:

261c CaMax: ENSG00000041982ENST00000265131TENASCIN PRECURSOR 9 q33.1 267d (TN) (HEXABRACHION) (CYTOTACTIN) (NEURONECTIN) (GMEM).

(Jn (MIOTENDINOUS

ANTIGEN) (GLIOMA-ASSOCIATED-EXTRACELLULAR MATRIX

ANTIGEN) (GP 150-225) (TENASCIN-C) (TN-C).

[Source:SWISSPROT;Acc:P24 821 ]

CaMax: ENSG00000141642ENST00000269466ELAC HOMOLOG 1. 18 q21.1 272d [Source:RefSeq;Acc:NM_0186 96]

CaMax:

27a CaMax:

28s CaMax: ENSG00000141378ENST00000311824PROTEIN CGI-147. 17 q23.2 307b [Source:SWISSPROT;Acc:Q9 Y3E5]

CaMax: ENSG00000116745ENST00000262340RETINAL PIGMENT 1 p31.2 308c EPITHELIUM-SPECIFIC

PROTEIN 65KDA; RETINAL

PIGMENT EPITHELIUM-SPECIFIC PROTEIN
(65KD);

RETINITIS PIGMENTOSA

(AUTOSOMAL RECESSIVE).

[Source:RefSeq;Acc:NM_0003 29]

CaMax:

310h CaMax:

311c CaMax 313a CaMax:

314a CaMax:

319b CaMax: ENSG00000090989ENST00000317642EXOCYST COMPLEX 4 q12 320a ENST00000333951COMPONENT SEC3 (BM-012).

[Source:SWISSPROT;Acc:Q9 NV70]

CaMax:

320a CaMax:

322a CaMax: ENSG00000135913ENST00000258399 2 q35 324a CaMax: ENSMUSG0000002ENSMUST0000002MICROSOMAL SIGNAL 7 D2 326e 5724 6818 PEPTIDASE 18 KDA

SUBUNIT (EC 3.4.-.-) (SPASE

18 KDA SUBUNIT) (SPC18) (ENDOPEPTIDASE SP18).

jSource:SWISSPROT;Acc:Q9 ROP6]

CaMax:

327f CaMax:

327f CaMax: ENSG00000129116ENST00000261509PALLADIN; CGI-151 4 q32.3 328b ENST00000335213PROTEIN.

ENST00000333488[Source:RefSeq;Acc:NM_0160 81]

CaMax: ENSG00000173320ENST00000308497 4 q35.1 336a CaMax:

33a CaMax:

33a CaMax:

340a CaMax:

340a CaMax:

343b CaMax:

343b CaMax:

34a CaMax:

34a CaMax: ENSG00000167996ENST00000301775FERRITIN HEAVY CHAIN11 q12.3 106a (FERRITIN H SUBUNIT).

[Source:SWISSPROT;Acc:P02 794]

CaMax: ENSG00000167996ENST00000301775FERRITIN HEAVY CHAIN11 q12.3 106a (FERRITIN H SUBUNIT).

[Source:S WISSPROT;Acc:P02 794]

CaMax:

360a CaMax:

360a CaMax:ENSG00000182944ENST00000331029RNA-BINDING PROTEIN22 q12.2 364a ENST00000329871EWS (EWS ONCOGENE) (EWING SARCOMA

BREAKPOINT REGION

PROTEIN).

[Source:SWISSPROT;Acc:Q01 844]

CaMax:

370a CaMax:ENSG00000136938ENST00000277182ACIDIC L;EUCINE-RICH9 q22.33 374a NUCLEAR

FAMILY MEMBER B

(PHAPI2 PROTEIN) (SILVER-STAINABLE

PROTEIN SSP29) (ACIDIC

PROTEIN RICH IN

LEUCINES).

[Source:SWISSPROT;Acc:Q92 688]

CaMax:

375d CaMax:

379a CaMax:ENSG00000145216ENST00000306932FIPl-LIKE 1; REARRANGED4 q12 38a ENST00000273816IN HYPEREOSINOPHILIA.

[Source:RefSeq;Acc:NM_0309 17]

CaMax:

391a CaMax:

392a CaMax:

392a CaMax:

395a CaMax:

395a CaMax:

397b CaMax:ENSRNOG0000000 8 q24 3c 6864 CaMax:

406a-r CaMax:

406a-r CaMax:

408a CaMax:

409a CaMax:ENSG00000134001ENST00000256383EUKARYOTIC 14 q23.3 415b TRANSLATION INITIATION

(EUKARYOTIC

TRANSLATION INITIATION

SUBUNIT) (EIF-2-ALPHA) (EIF- 2ALPHA) (EIF-2A).

[Source:SWISSPROT;Acc:P05 198]

CaMax:

421a CaMax: ENSG00000174132ENST00000312637 5 q21.1 43a CaMax:

446f CaMax:

44c CaMax:

44c CaMax:

45.1b CaMax:

45.1b CaMax:

450a CaMax:

450a CaMax:

452a CaMax:

455c CaMax:

455c ' CaMax:

457c CaMax: ENSG00000102908ENST00000317142NUCLEAR FACTOR OF 16 q22.1 459a ACTIVATED T CELLS
5 (T

CELL TRANSCRIPTION

FACTOR NFATS) (NF-AT5) (TONICITY-RESPONSIVE

ENHANCER-BINDING

PROTEIN) (TONE- BINDING

PROTEIN) (TONEBP).

[Source:SWISSPROT;Acc:O94 916]

CaMax:

461a CaMax:

461a CaMax: ENSG00000035687ENST00000263828ADENYLOSUCCINATE 1 q44 464b SYNTHETASE (EC 6.3.4.4) (IMP--ASPARTATE LIGASE) (ADSS) (AMPSASE).

[Source:SWISSPROT;Acc:P30 520]

CaMax: ENSG00000064309ENST00000263577SURFACE GLYCOPROTEIN,11 q24.2 465b IG SUPERFAMILY

MEMBER.

[Source:RefSeq;Acc:NM_0169 52]

CaMax:

46a CaMax:

472a CaMax:

472a ' CaMax: ENSG00000165169ENST00000297871T-COMPLEX ASSOCIATED-24 p11.4 478a TESTIS-EXPRESSED

(PROTEIN 91/23).

[Source:SWISSPROT;Acc:P51 808]

CaMax: ENSG00000165169ENST00000297871T-COMPLEX ASSOCIATED-24 p11.4 479c TESTIS-EXPRESSED

(PROTEIN 91/23).

[Source:SWISSPROT;Acc:P51 808]

CaMax:

482a CaMax: ENSG00000116584ENST00000313695RHO GUANINE 1 q22 487a ENST00000313667NUCLEOTIDE EXCHANGE

FACTOR 2 (GEF-H1 PROTEIN) (PROLIFERATING CELL

NUCLEOLAR ANTIGEN

P40).

[Source:SWISSPROT;Acc:Q92 974]

CaMax: ENSG00000159399ENST00000290573HEXOKINASE, TYPE 2 p12 II (EC

488a 2.7.1.1) (HK II) (MUSCLE

FORM HEXOKINASE).

[Source:SWISSPROT;Acc:P52 i 789]

CaIVIax:

48b CaMax:

48b CaMax:

490c CaMax:

490c CaMax:

494a CaMax:

494a CaMax:

498a CaMax:

50.1c ' I

CaMax:

50.1c CaMax:

501b CaMax:

504a CaMax:

505b CaMax:

507a CaMax:

516c CaMax:

517c CaMax:

51a CaMax:

51a CaMax: ENSG00000179454ENST00000324772BTB (POZ) DOMAIN 14 q21.2 520a CONTAINING 5.

[Source:RefSeq;Acc:NM_0176 58]

CaMax:ENSG00000081189ENST00000325423MYOCYTE-SPECIFIC 5 q14.3 521b ENHANCER FACTOR
2C.

[Source:SWISSPROT;Acc:Q06 413]

CaMax:

523a CaMax:

52a CaMax:ENSG00000100567ENST00000216455PROTEASOME SUBUNIT 14 q23.1 530b ALPHA TYPE 3 (EC
3.4.25.1) (PROTEASOME

COMPONENT C8) (MACROPAIN SUBUNIT
C8) (MULTICATALYTIC

ENDOPEPTIDASE

COMPLEX SUBUNIT
C8).

[Source:SWISSPROT;Acc:P25 788]

CaMax:

538a CaMax:ENSG00000133059ENST00000255422HDCMD38P. 1 q32.1 539a ENST00000335353[Source:SPTREMBL;Acc:Q9P

1S5]

CaMax:

540a CaMax:

543a CaMax:ENSG00000144785ENST00000273308TRANSMEMBRANE 12 q13.3 545a PROTEIN 4.

[Source:RefSeq;Acc:NM_0142 55]

CaMax:ENSG00000174560ENST00000310012 6 q12 547c CaMax:ENSG00000174560ENST00000310012 6 q12 548c ' CaMax:ENSG00000133226ENST00000334537SER/ARG-RELATED 1 p36.11 550a ENST00000323848NUCLEAR MATRIX

PROTEIN (PLENTY
OF

PROLINES 101-L;
SER/ARG-RELATED NUCLEAR

MATRIX PROTEIN (PLENTY

OF PROLINES 101-LIKE).

[Source:RefSeq;Acc:NM_0058 39]

CaMax:

552a CaMax:ENSG00000180185ENST00000326061 16 p13.3 553b CaMax:ENSG00000005812ENST00000281993F-BOX AND LEUCINE-RICH13 q22.3 555b REPEAT PROTEIN 3A;
F-BOX PROTEIN FBL3A.

[Source:RefSeq;Acc:NM_012I

58]

CaMax:

556b CaMax:

557b CaMax:

558a CaMax:

558a CaMax:

560b CaMax:

561b CaMax:

568a CaMax:

568a CaMax:

56a CaMax:

56a CaMax: ENSG00000143924ENST00000318522ECHINODERM 2 p21 571a MICROTUBULE-ASSOCIATED PROTEIN-LIKE 4 (EMAP-4) (RESTRICTEDLY

OVEREXPRESSED

PROLIFERATION-ASSOCIATED PROTEIN) (ROPP 120).

[Source:SWISSPROT;Acc:Q9 HC35]

CaMax:

574a CaMax: ENSG00000124193ENST00000244020SPLICING FACTOR, 20 q13.11 579a ARGININEISERINE-RICH

(PRE-MRNA SPLICING

FACTOR SRP55).

[Source:SWISSPROT;Acc:Q

247]

CaMax: ENSG00000091409ENST00000264107INTEGRIN ALPHA-6 2 q31.1 57a ENST00000264106PRECURSOR (VLA-6) (CD49F).

[Source:SWISSPROT;Acc:P23 229]

CaMax: ENSG00000115112ENST00000263707LBP-9. 2 q14.2 581a [Source:RefSeq;Acc:NM_0145 53]

CaMax: ENSMUSG0000002ENSMUST0000005 1 C3 583e 6193 5226 CaMax:

58a CaMax: ENSG00000171634ENST00000306378FETAL ALZHEIMER 17 q24.2 597c ENST00000335221ANTIGEN (FETAL ALZ-50-ENST00000321866REACTIVE CLONE 1).

ENST00000321892[Source:SWISSPROT;Acc:Ql2 830]

CaMax:

59a CaMax:

59a CaMax:

609a CaMax:

611a CaMax:

622a CaMax:

622a CaMax: ENSG00000140575ENST00000268182RAS GTPASE-ACTIVATING-15 q26.1 623a LIKE PROTEIN IQGAP1 (P195). , [Source:SWISSPROT;Acc:P46 940]

CaMax:

624b CaMax:

626a CaMax:

626a CaMax: ENSG00000183762ENST00000327813KREMEN PROTEIN 1 22 q12.1 628a PRECURSOR (KRINGLE-CONTAINING PROTEIN

MARKING THE EYE
AND

THE NOSE) (DICKKOPF

RECEPTOR).

[Source:SWISSPROT;Acc:Q96 MU8]

CaMax: ENSG00000133226ENST00000334537SER/ARG-RELATED 1 p36.11 635a ENST00000323848NUCLEAR MATRIX

PROTEIN (PLENTY
OF

PROLINES 101-L;
SER/ARG-RELATED NUCLEAR

MATRIX PROTEIN (PLENTY

OF PROLINES 101-LIKE).

[Source:RefSeq;Acc:NM_0058 39]

CaMax: ENSG00000165169ENST00000297871T-COMPLEX ASSOCIATED-24 p11.4 638b TESTIS-EXPRESSED

(PROTEIN 91/23).

[Source:SWISSPROT;Acc:P51 808]

CaMax:

639a CaMax:

63a CaMax:

63a CaMax: ENSG00000144560ENST00000273038 3 p25.3 64.2a CaMax: ENSG00000125149ENST00000219139UPF0183 PROTEIN. 16 q22.1 685a [Source:SWISSPROT;Acc:Q9 BSU1]

CaMax:

690a CaMax:

690a CaMax: ENSG00000171567ENST00000304782TIGGER TRANSPOSABLE2 q37.1 692a ELEMENT DERIVED
1;

JERKY (MOUSE) HOMOLOG-LIKE.

[Source:RefSeq;Acc:NM_1457 02]

CaMax: ENSRNOG0000000 8 q23 697a 7325 CaMax:

6b CaMax: ENSMUSG0000003ENSMUST0000003 9 B

701a 2077 6099 CaMax: ENSG00000119509ENST00000262457INVERSIN. 9 q22.33 704b ENST00000262456[Source:RefSeq;Acc:NM_0144 25]
~

CaMax: ENSG00000119509ENST00000262457INVERSIN. 9 q22.33 704b ENST00000262456[Source:RefSeq;Acc:NM_0144 25]

CaMax:

70d CaMax: ENSG00000123500ENST00000243222COLLAGEN ALPHA 1(X) 6 q22.1 710a CHAIN PRECURSOR.

[Source:SWISSPROT;Acc:Q03 692j CaMax:

711a CaMax:

711a CaMax:

713a CaMax:

713a CaMax:

714a CaMax:

718a CaMaxJ

720a CaMax: ENSG00000133454ENST00000335473 22 q12.1 725a ENST00000335460 CaMax: ENSG00000122912ENST00000265870GRAVE'S DISEASE 10 q21.3 726b CARRIER PROTEIN (GDC) (GRAVE'S DISEASE

AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE

CARRIER PROTEIN

HOMOLOG).

[Source:SWISSPROT;Acc:Pl6 260]

CaMax:

72a CaMax:

72a CaMax:

731a CaMax:

731a CaMax: ENSG00000130066ENST00000252349DIAMINE 24 p22.11 736a ACETYLTRANSFERASE
(EC

2.3.1.57) (SPERMIDINE/SPERMINE

N( 1 )-ACETYLTRANSFERASE) (SSAT) (PUTRESCINE

ACETYLTRANSFERASE).

[Source:SWISSPROT;Acc:P21 673]

CaMax: ENSG00000166938ENST00000319194 15 q22.31 739a ENST00000319212 CaMax: ENSG00000112473ENST00000230235HISTIDINE-RICH 6 p21.32 73b ENST00000325843MEMBRANE PROTEIN
KE4.

[Source:SWISSPROT;Acc:Q92 504]

CaMax:

745a CaMax: ENSG00000164190ENST00000296607IDN3 PROTEIN ISOFORM5t p13.2 A.

747a ENST00000282516[Source:RefSeq;Acc:NM_1334 33]

CaMax:

749a CaMax:

74c CaMax: ENSMUSG0000003ENSMUST0000003 4 C1 753b 9203 6300 CaMax:

759b CaMax:

759b CaMax:

764b CaMax:

764b CaMax: ENSG00000102763ENST00000251030 13 q14.11 765a ENST00000281496 CaMax:

768a CaMax:

76b CaMax: ENSG00000171867ENST00000305832MAJOR PRION PROTEIN 20 p13 785b PRECURSOR (PRP) (PRP27-30) (PRP33-35C) (ASCR) (CD230 ANTIGEN).

[Source:SWISSPROT;Acc:P04 I56]

CaMax:

788a CaMax: ENSG00000102471ENST00000218652 13 q31.1 789a CaMax: ENSG00000123096ENST00000242729SARCOSPAN (K-RAS 12 p12.1 794a ONCOGENE-ASSOCIATED

PROTEIN) (KIRSTEN-RAS-ASSOCIATED PROTEIN).

[Source:SWISSPROT;Acc:

714]

CaMax: ENSG00000106554ENST00000262570 7 q32.3 795a CaMax: ENSG00000131388ENST00000253706 3 p25.1 810a CaMax:

813a CaMax:

815a CaMax:

81a CaMax:

820a CaMax:

820a CaMax:

827b CaMax:

827b CaMax:

828a CaMax:

82b CaMax:

831a CaMax:

831a CaMax: ENSMUSG0000002ENSMUST0000005 1 C3 832a 6193 5226 CaMax: ENSG00000090581ENST00000204679 16 p13.3 833a CaMax:

835c CaMax: ENSG00000068885ENST00000326448 3 q25.33 839a CaMax:

841b CaMax:

841b CaMax:

847a CaMax: ENSG00000136003ENST00000311893NITROGEN FIXATION 12 q23.3 85.1c ENST00000228459CLUSTER-LIKE.

[Source:RefSeq;Acc:NM_0143 O1]

CaMax: ENSG00000149218ENST00000278505 11 q21 85.2b CaMax:

850a CaMax:

851a CaMax: ENSG00000060982ENST00000261192BRANCHED-CHAIN AMINO12 p12.1 856c ENST00000334327ACID

AMINOTRANSFERASE, CYTOSOLIC (EC 2.6.1.42) (BCAT(C)) (ECA39 PROTEIN).

[Source:SWISSPROT;Acc:P54 687]

CaMax: ENSMUSG0000002ENSMUST0000002ZINC FINGER PROTEIN 16 B 1 863c 2676 3356 SLUG (NEURAL CREST

TRANSCRIPTION FACTOR

SLUG) (SNAIL HOMOLOG

2).

[Source:SWISSPROT;Acc:P97 469]

CaMax: ENSG00000175582ENST00000310653RAS-RELATED PROTEIN 11 q13.4 890a ENST00000334372RAB-6A (RAB-6).

[Source:SWISSPROT;Acc:P20 340]

CaMax:

8a CaMax:

905a CaMax:

906a CaMax:

907a CaMax: ENSG00000145730ENST00000304400PEPTIDYL-GLYCINE 5 q21.1 909a ENST00000304406ALPHA-AMIDATING

ENST00000325306PRECURSOR (EC 1.14.17.3) ENST00000274392(PAM).

[Source:SWISSPROT;Acc:Pl9 021 ]

CaMax: ENSMUSG0000002ENSMUST0000002HEAT SHOCK PROTEIN 17 C
HSP

90c 3944 4739 90-BETA (HSP 84) (TUMOR

SPECIFIC

KDA ANTIGEN) (TSTA).

[Source:SWISSPROT;Acc:Pl 499]

CaMax:

911a CaMax:

911a CaMax:

912b CaMax:

914a CaMax:

914a CaMax:

915a CaMax:

915a CaMax: ENSG00000104177ENST00000267836MYELIN GENE 15 q21.1 919b ENST00000324324EXPRESSION FACTOR
2.

[Source:RefSeq;Acc:NM_0161 32]

CaMax:

91f CaMax:

91f CaMax: ENSG00000104177ENST00000267836MYELIN GENE 15 q21.1 919b ENST00000324324EXPRESSION FACTOR
2.

[Source:RefSeq;Acc:NM

32]

CaMax: ENSG00000084676ENST00000288599NUCLEAR RECEPTOR 2 p23.3 92c ENST00000326011COACTIVATOR 1 ISOFORM

1.

[Source:RefSeq;Acc:NM_0037 43]

CaMax: ENSG00000125953ENST00000246165CHURCHILL PROTEIN 14 q23.3 935b (MY015 PROTEIN).

[Source:SWISSPROT;Acc:Q8 WUHI]

CaMax:

936b CaMax:

936b CaMax: ENSRNOG0000001 4 q24 945a 1175 CaMax:

947a CaMax:

947a CaMax: ENSG00000144592ENST00000316654 3 p25.1 949c ENST00000273079 CaMax; ENSMUSG0000002ENSMUST00000026.8 KDA MITOCHONDRIAL12 F2 953a 1290 1719 PROTEOLIPID.

[Source:SWISSPROT;Acc:P56 379]

CaMax: ENSG00000134644ENST00000257075PUMILIO HOMOLOG 1. 1 p35.2 963c [Source:RefSeq;Acc:NM_0146 76]

CaMax:

96e CaMax:

981a CaMax:

984a CaMax:

984a CaMax: ENSG00000118971ENST00000261254G1/S-SPECIFIC CYCLIN12 p13.32 D2.

986a [Source:SWISSPROT;Acc:P30 279]

CaMax: ENSG00000125398ENST00000245479TRANSCRIPTION FACTOR17 q24.3 990a SOX-9.

[Source:SWISSPROT;Acc:P48 436]

CaMax:

992a CaMax: ENSG00000005700ENST00000306270INHIBITOR OF BRUTON'S6 q14.1 994b TYRSOINE I~INASE;
BTK-BINDING PROTEIN.

[Source:RefSeq;Acc:NM_0155 25]

CaMax; ENSG00000008988ENST0000000958940S RIBOSOMAL PROTEIN8 qI2.I

996a S20.

[Soarce:SWISSPROT;Acc:P

075]

Table 2B
CaMax SwissprotOMIM RefSeq Pfam InterProSig.TMHMM HUGO

Gene Ensemble Pep.

ID

CaMax:ENST000 1002b 00244769 CaMax:ENST000 1002b 00244769 CaMax: NM_178043PF05383 IPR001199 1005a NM_032239 NM_018078 CaMax:TISD_HU NM 006887PF04553 IPR000571 ZFP36L2 1006b MAN PF00642 IPR007635 CaMax:TISD_HU NM_006887PF04S53 IPR000571 ZFP36L2 1007a MAN PF00642 IPR007635 CaMax:ENST000 1008a 00245479 CaMax:ENST000 1008a 00245479 CaMax:GDC_IitT139080NM_152707PF00153IPR001993 SLC25A16 1009c MAN IPR002167 CaMax:trembl~AB

lOlla 012223 CaMax:Transcript 1011 :ENSRNO
a CaMax:ENST000 1013a 00326567 CaMax: NM_018359 , 1015d CaMax:Transcript 1016b :ENST000 CaMax:Z333_HU NM_032433.PF01352IPR007087 2019a MAN PF00096IPR007086 CaMax:CGRR 114190NM 005795PF02793IPR000832Sigp Tmhmm CALCRL
H

1020a UMAN PF00002IPR003287 CaMax:trembl~AB

1026b 012223 CaMax:Transcript 1026b :ENSRNO

CaMax:trembl~HS

1028c RBP1_1 CaMax:ENST000 1028c 00260780 CaMax: NM_145702PF04218IPR004875 TIGD1 1029a PF03184IPR006695 CaMax:ENST000 103a 00287239 CaMax:PP03_HU 607726NM_005485PF05406IPR001290 ADPRTL3 1044c MAN PF02877IPR004102 CaMax:ROH1 601035NM_005520PF00076IPR000504 HNRPHl H

104a UMAN

CaMax:ENST000 1050a 00322598 CaMax:ENST000 1054a 00261710 CaMax:trembl~AB

1057b 012223_1 CaMax:pironly~S7 1060a 2489 CaMax: PF02008IPR002857 1061a CaMax:ENST000 1063b 00277359 CaMax:FRIH_HU 134770NM_002032PF00210IPR001519 FTH1 106a MAN

CaMax:Transcript 1070b :ENST000 CaMax:trembl~HS

1072a 09953_1 CaMax:ENST000 1072a 00295955 CaMax:gpnew~37 1089d 790758 CaMax:ENST000 ' 108a 00297846 CaMax:swiss~ATP

1090d 6 CANF

A

CaMax:gpnew~37 1094b 790758 CaMax:ENSMUS

1094b T0000000 CaMax: NM_019974PF00089IPR001254Sigp Prss20-1095a NM_133712 IPR001314 pending 3Rik CaMax: NM 019974PF00089IPR001254Sigp Prss20-1096a NM_133712 IPR001314 pending 3Rik CaMax: NM_014796 1098a CaMax: NM_032202 IPR001969 109a CaMax:RB 14_HU NM_016322PF00071IPR001687 RAB 14 1105a MAN IPR001806 CaMax: NM_152388 Tmhmm ALS2CR4 1106a CaMax:SR13_HU NM_052851PF00620I1'R001687 STARD13 1108a MAN PF01852IPR000198 CaMax:gpnew~37 1110b 790758 CaMax:gpnew~37 1110b 790758 CaMax:SES1 606'103NM_014454PF04636IPR006730 SESN1 HU

llllb MAN

CaMax: NM_032042 IPR000886Sigp 1112a IPR001472 CaMax:Transcript llla :ENST000 CaMax: NM_022130PF05719 GOLPH3 1120a CaMax: IPR000566 1121a CaMax:gpnew~37 1131b 790758 CaMax:trembl~PM

1132a 43360 CaMax:MEFC_H 600662NM_002397PF00319IPR002100 MEF2C

1134a UMAN

CaMax:FXP2 605317NM_148898PF00904IPR007087 FOXP2 HU

1135a MAN 602081NM_148899PF00250IPR001766 NM_148900 IPR000354 NM_01449I

_~8_ CaMax:ENST000 1137b 00256429 CaMax:ENST000 1138a 00261765 CaMax:ENST000 1139a 00245479 CaMax:CAlE_H 120325NM_001855PF02210IPR008160Sigp COL15A1 1145a UMAN PF01391IPR003129 CaMax:CAlE_H

1145a UMAN

CaMax:ENST000 1146a 00308148 CaMax:ENST000 1159b 00296084 CaMax:ROH1 601035NM_005520PF00076IPR000504 HNRPH1 H

104a UMAN

CaMax:TPMI 191010NM_000366PF00261IPR000533 TPM1 II

1169b UMAN

CaMax:DYHC_H 600112NM_001376PF03028IPR001687 DNCHl 1177c UMAN IPR000169 CaMax:TIAM 600687NM_003253PF00169IPR001331 TIAM1 H

1184a UMAN PF02196IPR001849 PF,00621IPR000219 CaMax:TIAM
H

1184a UMAN

CaMax: PF02269IPR003195 1190b CaMax: PF02269IPR003195 1192b CaMax:ENST000 llb 00307407 CaMax:swiss~UB
l 120a 5 HUMA

N

CaMax:ENST000 120a 00280377 CaMax:ENST000 1212b 00235420 CaMax:VAV3_H 605541NM 006113PF00307IPR002086 VAV3 1213d UMAN PF00621IPR002219 CaMax:ENST000 1217a 00305327 CaMax:Transcript 1220b :ENST000 CaMax:ENST000 1226d 00244769 CaMax:ENST000 1226d 00244769 CaMax:trembl~AY

123c 027883_1 CaMax:ENST000 123c 00313779 CaMax:WDR3 604737NM_006784PF00400 IPR001680 WDR3 H

1243a UMAN PF04003 IPR007148 CaMax:ENST000 1245b 00319046 CaMax: NM_018359 1246a CaMax;ENST000 1248b 00263196 CaMax: NM_018359 1253a CaMax;trembl~BC

1257b 043468_1 CaMax;Genscan;

1257b AC07365 5.26.1.188 105.67776 .86719 CaMax;ENST000 1260c 00325918 CaMax: PF00036 IPR002048 1263b IPR000694 CaMax;PCCA_H 232000NM_000282PF00289 IPR001882 PCCA

1267a LTMAN 606054 PF02786 IPR005479 CaMax:PCCA_H 232000NM_000282PF00289 IPR001882 PCCA

1267a LTMAN 606054 PF02786 IPR005479 CaMax: NM_152520PF00096 IPR007087 1270a CaMax:S24A_HU 607183 PF04810 IPR007123 SEC24A

1272a MAN PF04811 IPR006895 CaMax:trembl~AB

1273b 012223_1 CaMax:trembl~AB

1276a 012223_1 CaMax:trembl~AY

127b 027883_1 CaMax:ENST000 127b 00313779 CaMax:Genscan:

1282b CAAA012 09745.1.1.

24557.315 9.16476 CaMax:ENSRNO

1284b T0000002 CaMax: NM 133433 1287c NM_015384 CaMax: NM_133433 1288a NM_015384 CaMax:HS9B_M NM_008302PF02518IPR001404 Hspcb 128a OUSE PF00183IPR003594 CaMax:KU86_H 194364NM_021141PF03731IPR006164 XRCCS

1292c UMAN PF02735IPR005160 CaMax:SYEP_H'~138295NM_004446PF00749IPR001589~ EPRS

1294b UMAN PF03950IPR001412 IPR002314 , CaMax: NM_014991PF02138IPR001680 WDFY3 1299c NM_178583PF00400IPR000306 CaMax:tremblnew 129b ~AX40003 CaMax:ENST000 129b 00265677 CaMax:ENST000 12a 00288263 CaMax: PF00023IPR002110 1301a CaMax: 607958NM_014178 STXBP6 1304a CaMax:trembl~AB

1308c 012223_1 CaMax:' ENST000 1308c 00297641 CaMax:ENSRNO

130b T0000001 CaMax:ENSRNO

1316b T0000002 CaMax:LIN1_HU

1318a MAN

CaMax:LIN1_HU

CaMax:OGT1 PF00515IPR001440 R

1322c AT

CaMax:trembl~HS

1323br09953_1 CaMax:ENST000 1323br00295955 CaMax:trembl~HS

1324a 09953_1 CaMax:ENST000 1324a 00295955 CaMax:pironly~B3 1335b 4087 CaMax:ENST000 1335b 00321183 CaMax: 603054NM_013372PF03045IPR004133Sigp CKTSF1B

1341a IPR001472 1 CaMax:LINT
NY

1352b CCO

CaMax: NM_145702PF04218 IPR004875 TIGD1 1354a PF03184 IPR006695 CaMax:trembl~AF

1355a 318340_1 CaMax:ENST000 1355a 00324229 CaMax:FUT8_HU 602589NM_178157PF00018 IPR001452SigpTmhmm FUT8 1361a MAN NM_178154 IPR001472 NM_178155 NM_178156 CaMax:trembl~AB

1364d 012223_1 CaMax:ENST000 1364d 00304487 CaMax:CTGL_H 603399NM_003881PF00219 IPR001525Sigp WISP2 1366a UMAN PF00093 IPR000867 CaMax: NM_026140PF00749 IPR001412 3230401I0 1368a IPR000924 lRik CaMax: 604785NM_003798PF01044 IPR001033 CTNNAL1 a CaMax:MPP8_H PF00385 IPR000953 137b UMAN PF00023 IPR002110 CaMax:trembl~S7 1381a 7350_1 CaMax:ENST000 1381a 00228938 CaMax: 602942NM_005665PF00566 IPR001687 EVIS

1383a ~ IPR000515 CaMax:ACOD_H 604031NM_005063PF00487 IPR001522 Tmhmm SCD

1384a UMAN IPR005804 CaMax:ENST000 1391a 00222271 CaMax:ENST000 1394b 00256429 CaMax: NM_181782PF01476 IPR002482 NCOA7 1397b CaMax:ENST000 1399a 00318060 CaMax:ENST000 13a 00295709 CaMax:trembl~AB

1400a 012223 CaMax: NM_014247PF00027 IPR000595 PDZGEF1 1401c PFOOS95 IPR001478 CaMax:ENST000 1403a 00231061 CaMax:Transcript 1406a :ENST000 CaMax:BAGS 603885NM_004873PF02179 IPR003103 BAG5 H

1409b UMAN

CaMax: 602021NM_002480PF00023 IPR002110 PPP1R12A

1411a CaMax: Tmhmm 2900042B

1415b lRik CaMax:Transcript 1416a :ENST000 CaMax:ENST000 1419a 00325584 CaMax:trembl~BC

141c 018999_1 CaMax:Transcript 141c :ENST000 00307901 , CaMax:tremblnew 142.1c~AI~00130 CaMax:ENST000 142.1c00311713 CaMax: NM_004748PF02987 IPR001687 Tmhmm 1420c NM 020739 Il'R004238 CaMax:MLT1 604860NM_006785PF00531 IPR007110 MALTl H

1421a UMAN NM_173844PF00047 IPR000488 CaMax:gpnew~37 1423b 790758 CaMax:SPL1 606041NM_004684PF00050 IPR002048Sigp SPARCL1 HU

143.2cMAN IPR001999 CaMax:SPL1 606041NM_004684PF00050 IPR002048Sigp SPARCL1 HU

143.2cMAN IPR001999 CaMax:Transcript 1431a :ENST000 CaMax:trembl~AY

144.2a157990_1 CaMax:ENST000 144.2a00249297 CaMax:TIC3_HU 607989NM_016950PF00050 IPR000716SigpTmhmm SPOCI~3 1448a MAN PF00086 IPR002350 CaMax:2271 604754NM_006958PF00096 IPR001687 ZNF271 HU

1449a MAN 601262NM 003415PF01352 IPR007087 NF16 Z

ZN16_HLT606024 IPR007086 ZNF268 Z268_HU IPR001909 MAN

ZF64_HU

MAN

CaMax:C17_HU 607930NM_018659 Sigp 1450a MAN

CaMax:ENST000 1452a'00261976 CaMax:gp~345281 1457b 69 CaMax:P15_HU 600503NM_006713F02229 IPR003173 P

1459c MAN IPR001472 CaMax:TCP4_HU

1459c MAN

CaMax:RL10_HU 312173NM_006013PF00826Il'R001197 RPL10 145b MAN

CaMax:trembl~HS

1460a U93567 CaMax:ENST000 1460a 00322543 CaMax:trembl~BC

1461a 049156_1 CaMax:ENSMUS

1461a T0000003 CaMax:trembl~AF

1466b 325902_1 CaMax:ENST000 1466b 00222271 CaMax: NM_023211 Tmhmm Usmg5 1469a CaMax:Y441 NM_014797PF00651IPR007087 ZNF450 HLT

146b MAN PF02178IPR000345 CaMax: NM 023211 Tmhmm UsmgS

1469a CaMax:ENST000 1472a 00296084 CaMax:CN4B_R

1475a AT

CaMax:ID4 HLT 600581NM_001546PF00010IPR001092 ID4 1476a MAN IPR000694 CaMax:BTG2 601597NM_006763PF01211IPR002087 BTG2 H

1477a UMAN

CaMax:ENST000 147b 00317517 CaMax:HXA3_H 142954NM_030661PF00046IF'R001356 HOXA3 1481c UMAN NM_153631' IPR001827 NM_153632 IPR002965 CaMax; NM_017880 IPR000169 1482a CaMax:UTRO_H

1484b UMAN

CaMax;ROA2 600124NM_002137PF00076IPR000504 HNRPA2B
H

1488b UMAN NM 031243 - 1 CaMax:ENST000 148a 00271717 CaMax:swiss~SEC

1497c 3 HUMA

N

CaMax:ENST000 1497c 00317675 CaMax:ENST000 1500b 00322519 CaMax:ENST000 1504d 00278824 CaMax:trembl~AY

1506d 061884_1 CaMax:ENST000 1506d 00229488 CaMax:LB4D_H 601274NM_012212PF00107IPR002085 LTB4DH

150a UMAN

CaMax: NM_017880 IPR000169 1516a CaMax:gpJ375890 ' 1519a 39 CaMax:ENST000 1519a 00311733 CaMax:ENST000 151b 00281131 CaMax:tremblJAY

1520a 267013_1 CaMax:ENST000 1520a 00261435 CaMax: NM_016147 IPR000734 1521b IPR003089 CaMax:tremblJAY

1522b 154463_1 CaMax:tremblJAY

1531c 154463_1 CaMax:trembl~BC

1532a 038422_1 CaMax:ENST000 1532a 00272761 CaMax:Y373 NM_014684PF02524IPR001687 HU

1534b MAN NM 025114 IPR003900 CaMax:Y373_BO

1534b VIN

CalVIax:ENST000 1535a 00277895 CaMax:

1541a CaMax:XCT_HU 607933NM_014331PF00324IPR004841 Tmhmm SLC7Al1 1546b MAN IPR002293 CaMax:ENST000 1548c 00254926 , CaMax:ENST000 1549a 00294618 CaMax: NM_017658PF00651I1'R000210 BTBD5 1551a CaMax:tremblJAB

1554c 012223 CaMax: NM_153689 Sigp 1573a CaMax:tremblJAB

1574b 012223_1 CaMax:ENST000 1574b 00310739 CaMax: 605861NM_014255 IPR000886Sigp TMEM4 1577a Il'R008139 CaMax:gpJ345350 1578a 28 CaMax:tremblJS7 157b 7350_1 CaMax:ENST000 157b 00228938 CaMax:gpJ348496 1591a 66 CaMax:Transcript 1591a :ENSRNO

CaMax:ENSMUS

1594a T0000006 CaMax:trembl~AF

1596b 081111 CaMax:Transcript 1596b :ENST000 CaMax:LINT
NY

1598a CCO

CaMax:trembl~CS

159a AAE_1 CaMax:Transcript 159a :ENST000 CaMax: IPR000694SigpTmhmm 15b CaMax: NM_O18138 1602a CaMax:ENSDAR

1604a T0000002 CaMax: PF00076IPR000504 1626c CaMax:ENST000 1628d 00325761 CaMax:tremblnew 1629a ~BC02153 CaMax:ENST000 1629a 00229238 CaMax:tremblnew 1630b ~BC02153 CaMax:ENST000 1630b 00229238 CaMax: NM_014683PF00069IPR000719 ULK2 1631d IPR002290 CaMax: NM_014683PF00069IPR000719 ULK2 1635a IPR002290 CaMax: NM_014683PF00069IPR000719 ULK2 1635a Il'R002290 CaMax:pironly~B2 1639a 8096 CaMax:Transcript 1639a :ENST000 CaMax: NM_017967 163a CaMax: NM_015440PF00763IPR000559 FTHFSDC

1646a PF02882IPR000672 1 CaMax: PF00629IPR000998Sig 1648a CaMax:MI2B_HU 139111NM_002090PF00048IPR001089 CXCL3 164c MAN IPR002473 CaMax:trembl~SS

1659a 7162_1 CaMax:ENST000 1659a 00316200 CaMax: NM_017887PF05907 166a CaMax:trembl~AB

1671b 012223_1 CaMax:Transcript I671b :ENST000 CaMax:ENST000 1675a 00321491 CaMax:trembl~AF

1676a 081104_2 CaMax:ENST000 1676a 00299933 CaMax:ENST000 1678a 00307746 CaMax:ENSRNO

1682a T0000001 CaMax:RL32_HU

168c MAN

CaMax:CX41_RA NM_017202PF02936IPR004203 Tmhmm 1690a T

CaMax: NM_018199PF01612IPR000345 Cl4orf114 1691b IPR002562 CaMax:CX41_RA NM_017202PF02936IPR004203 Tmhmm 1692a T

CaMax:FGR2 176943NM_022971PF00047IPR000719SigpTmhmm FGFR2 H

1693b LTMAN 101200NM_022974PF00069IPR001245 BFR2_HU 101600NM_022976 IPR007110 MAN 123150NM_022969 123500NM_022972 NM_022973 NM_000141 NM_023028 NM_023029 NM_022975 NM_022970 NM_023031 CaMax:gp~375891 1696a 32 CaMax:ENST000 1696a 00259146 CaMax:ENST000 16b 00303924 CaMax:CAR6_H NM_032587PF00619IPR001687 CARD6 1705a LTMAN IPR001315 CaMax:Genscan:

1709a AC09196 6.3.1.9129 6.20868.4 CaMax: NM_018227PF00899IPR000594 1714a PF02134IPR000127 CaMax:ENST000 1715a 00299230 ' CaMax: NM_033296 1717a CaMax:ILEU_HU 130135NM_030666PF00079IPR000215 SERPINB

a CaMax:GOA4 602509NM_002078PF00904IPR006162 GOLGA4 H

1722a UMAN 270150 PF01465IPR001990 CaMax: NM_153832PF00001IPR000276 Tmhmm 1724a NM 007369 CaMax:ENST000 1725a 00026952 CaMax:trembl~AB

1726a 012223_1 CaMax:ENST000 1726a 00325761 CaMax: 606101NM_032571PF01825IPR000152Sigp Tmhmm 1727a NM_152939PF00002IPR001881 CaMax:ENST000 1730a 00222271 CaMax:ENST000 1738b 00318296 CaMax:ENST000 1741a 00221700 CaMax:LGR4_H 606666NM_018490PF01462I1'R007087Sigp Tmhmm GPR48 1744a UMAN PF00560IPR002131 CaMax:LGR4_H

1744a UMAN

CaMax:T2FB 189969NM_004128PF02270IPR003196 GTF2F2 HU

174a MAN

CaMax:T2FB_HU

174a MAN

CaMax:ENST000 1750a 00282228 'CaMax:ENST000 1751a 00319353 CaMax:trembl~AK

1755a 051102_1 CaMax:Genscan:

1755a AL109926 .9.1.11429 8.7096.11 CaMax:RU17_HU 180740NM 003089PF00076IPR000504 SNRP70 1758a MAN

CaMax: NM_017658PF00651IPR000210 BTBDS

1759b CaMax:trembl~AX

1760c 648027_1 CaMax:ENST000 1760c 00326555 CaMax:ENSMUS

1772a T0000005 CaMax:GCC1_H 607418NM_024523PF01465 IPR000237 GCC1 1775a UMAN

CaMax:GCC1_H 607418NM_024523PF01465 IPR000237 GCC1 1775a UMAN

CaMax;Transcript 1778c :ENST000 CaMax; SigpTmhmm 1782b CaMax: 189889NM_005653PF04516 IPR007604 TFCP2 178a IPR001472 CaMax:gp~345275 1794a 09 CaMax:ENST000 1794a 00310739 CaMax:trembl~AB

17a 012223_1 CaMax:ENST000 1800a 00320480 CaMax:CLPX_H NM_006660PF00004 IPR001687Sigp CLPX

1801b UMAN IPR000345 CaMax; NM_145702PF04218 IPR004875 TIGD1 180a PF03184 IPR006695 CaMax: NM_025082 IPR001472 1810a CaMax:pironly~B3 1811b 4087 CaMax:SIL,6_HU604405NM_001245PF00047 IPR003006SigpTmhmm SIGLEC6 1812b MAN IPR007110 CaMax:AMD HU 170270NM_000919PF01082 IPR002086SigpTmhmm PAM

1814c MAN NM_138766PF03712 IPR000323 NM_138822PF01436 IPR000720 CaMax:AMD_BO

1814c VIN

CaMax:ENST000 1818a 00324450 CaMax:PLK MO NM_013500PF00047 IPR000538Sigp Crtll 1828b USE PF00193 IPR003006 CaMax:trembl~AY

1834b 293286_1 CaMax:gpnew~37 1849d 790758 CaMax:Transcript 1852a :ENST000 CaMax: Sigp 1853a CaMax:CYBS_R NM_022245PF00173 IPR001199 Tmhmm 1857c AT

CaMax: 606833NM_170606PF02178 IPR000194 MLL3 1859a NM_021230PF00904 IPR000345 CaMax:swiss~PEN

1863c 2 HUMA

N

CaMax:ENST000 1863c 00222266 CaMax: NM_133953 IPR003006 1810061H2 1864b 4Rik CaMax: NM_014945PF00412 IPR001781 186a PF02209 IPR003128 CaMax:trembl~AX , 1874b 648027_1 CaMax:ENST000 1874b 00326555 CaMax:trembl~AX

1879a 648027_1 CaMax:ENST000 1879a 00326555 CaMax:ENST000 1881b 00253814 CaMax: NM_021927PF00009 IPR001687 1894a PF03144 IPR000795 PF00679 I1'R001806 Il'R004161 CaMax:trembl~AB

18a 012223_1 CaMax:trembl~BC

1912a 019022_1 CaMax:ENST000 1912a 00318072 CaMax:swiss~CO

1913a Gl_HUM

AN

CaMax:ENST000 1913a 00299886 CaMax: NM_173082PF00176 IPR000345 SHPRH

1917f PF00538 IPR001841 CaMax: NM 080927PF00431 IPR000859 Tmhmm 1919a PF03815 IPR000421 CaMax:

1920a CaMax:ENSMUS

1928a T0000004 CaMax:Y539_HU C21orf108 1929c MAN

CaMax: PF00168 IPR000008 Tmhmm 1930a CaMax: 604934NM_003193PF01302IPR001611 TBCE

1940e PF00560IPR000938 CaMax: 606105NM_022109PF04515IPR007603Sigp Tmhmm 1941e NM 080546 CaMax: 605889NM_014476PF00595IPR001781 1943a PF00412IPR001478 CaMax: trembl~AK

1944a 025270_1 CaMax: ENST000 1944a 00319557 CaMax: gpnew~37 1945a 748505 CaMax: ENST000 1945a 00312037 CaMax: gpnew~37 1948b 748505 CaMax: ENST000 1948b 00312037 CaMax: gp~375906 1949a 86 CaMax: ENST000 1949a 00320480 CaMax: VAV3_H 605541NM_006113PF00307IPR002086 VAV3 1950a UMAN PF00621IPR002219 CaMax: NAB 600800NM_005966PF04904IPR006986 NAB 1 1953a UMAN PF04905IPR006988 CaMax: ENST000 1954e 00321787 CaMax: MADI_H 603755NM_007323PF01363IPR000345 MADHIP

1961e UMAN NM_004799 IPR000306 CaMax: TAP2 170261NM_000544PF00664IPR001687Sigp Tmhmm TAP2 HU

1967a MAN NM_018833PF00005IPR003439 CaMax: NM 020651PF04710IPR006800 PELI1 1968a CaMax: CA1B 120280NM_080629PF02210IPR001687Sigp COL11A1 H

1982a UMAN 604841NM 080630PF01391IPR001230 154780NM_001854PF01410IPR008160 CaMax: trembl~AB

1989b 030650 CaMax: 605789NM_014268PF00307IPR001715 MAPRE2 1990a PF03271IPR004953 CaMax: ENST000 1991d 00244096 CaMax: ENST000 _ la 00322438 CaMax: ENSMUS

2002c T0000003 4996 ' CaMax: NM_018364 IPR001472 a CaMax: NM_029522PF00515IF'R001440 Pins-2008a PF02188IPR003109 endin CaMax:RI14 602490NM 003489 IPR001687 NRIPl HU

2013a MAN

CaMax:ENSMUS

2014f T0000002 CaMax:RL4_HU 180479NM_000968PF00573IPR002086 RPL4 2015e MAN IPR002136 CaMax:M4K3_H 604921NM_003618PF00069IPR000719 MAP4K3 2020b UMAN PF00780IPR001180 CaMax:M4K3_M

2020b OUSE

CaMax: NM_015589PF00536IPR001660Sigp SAMD4 2022a CaMax:trembl~BT

2023b 008100_1 CaMax:ENST000 2023b 00312547 CaMax:ENST000 2024a 00314543 CaMax: NM_178352 IPR003267 2034a CaMax:RPCZ_H 606007NM_016310PF02150IPR001222 POLR3K

2035d UMAN PF01096IPR001529 CaMax:ENST000 204a 00276230 CaMax:HELZ_H 606699NM_014877PF00642IPR001687 HELZ

2056d UMAN IPR000571 CaMax:ENST000 2059b 00282218 CaMax:ENST000 205a 00276230 CaMax: NM_016081PF00047IPR000634 2070a IPR007110 CaMax:trembl~AB

2073b 012223 CaMax:Transcript 2073b :ENST000 CaMax:A8A1 NM 006095PF00702IPR001687 Tmhmm ATP8A1 H

2074b UMAN PF00122IPR001757 CaMax: NM_178043PF05383IPR001199 2075a NM 032239 CaMax:ENST000 2076c 00324643 CaMax:SEP7_HU 603151NM_001788PF00735IPR001687 CDC10 2078a MAN IPR000038 CaMax: NM_020830PF00400IPR001680 WDFY1 2083e NM 178350PF01363IPR000306 CaMax: ~ NM_182543PF01189IPR001678 2088a CaMax:gpnew~37 2092c 790758 CaMax:ENST000 2095a 00258969 CaMax:swissnew~

2099a SF30_HU

MAN

CaMax:ENST000 2099a 00239010 CaMax:trembl~BC

20a 001284_1 CaMax:ENST000 20a 00318446 CaMax:FBNl 134797NM 000138PF00008IPR000152Sigp FBN1 H ' 2100b UMAN 154700 PF00683IPR006209 CaMax:ENST000 2105a 00319412 CaMax:Transcript 2108b :ENST000 CaMax:ENST000 2109a 00324450 CaMax:2345 NM 003419PF00096IPR007087 ZNF345 HU

2110a MAN IPR007086 CaMax:ENST000 2113a 00324450 CaMax:MRP1 158343NM_004996PF00664IPR001687 Tmhmm ABCC1 H

211b~ UMAN NM_019901PF00005IPR000719 NM_019902 IPR003439 NM_019898 IPR001140 NM_019862 NM_019900 CaMax:ENST000 2122a 00321873 CaMax: NM_145648PF00854IPR001117 Tmhmm SLC15A4 2123a IPR000109 CaMax: NM_020239PF00786IPR000095 2129a CaMax:ENST000 2132a 00175091 CaMax:ENST000 2135d 00325604 CaMax:ENST000 2136b 00294665 CaMax:ENSMUS

2141a T0000000 CaMax:Genscan:

2142a CAAA010 04319.1.1.

45274.201 6.41736 CaMax:ENST000 2160a~~~~00285599 CaMax: NM_178043PF05383IPR001199 2161 NM_032239 c CaMax:ENST000 2165a 00244769 CaMax:ENST000 2167a 00278483 CaMax:ENST000 2189b 00309655 CaMax:ENSMUS

2198b T0000000 CaMax:ENST000 2201a 00244769 CaMax:ENST000 2201a 00244769 CaMax:ENST000 2205a 00274054 CaMax:ENST000 2210a 00244769 CaMax: PF00168IPR000008 Tmhmm 2222b CaMax:Transcript 2223a :ENST000 CaMax:_ 604283NM_005807PF01033IPR000585Sigp PRG4 2224a PF05001IPR001212 CaMax: PF01436IPR001258 2225b IPR006663 CaMax:TRFR_M ' NM_013696PF00001IPR000276 Tmhmm Trhr 2234a OUSE IPR002120 CaMax:ENST000 2235a 00296412 CaMax:ENST000 2235a 00296412 CaMax:CN3A_H 123805NM 000921PF00233IPR002073. Tmhmm PDE3A

2238a UMAN IPR005829 CaMax:CN3A_H 123805NM 000921PF00233IPR002073 Tmhmm PDE3A

2241a UMAN IPR005829 CaMax:CN3A_H 123805NM 000921PF00233IPR002073 Tmhmm PDE3A

2238a UMAN IPR005829 CaMax:trembl~HS

224a F8L1B_1 CaMax:swiss~LIN

2251d 1 NYCC

O

CaMax: NM 018359 2252b CaMax:ENST000 2258a 00245479 CaMax:ENST000 2258a 00245479 CaMax:ENST000 ~~

2258a 00245479 CaMax:gp~373618 225a 16 CaMax:ENSMUS

2264b T0000000 CaMax:ENSMUS

2264b T0000000 CaMax:ENST000 2266b 00306715 CaMax:TSP1 188060NM_003246PF02210IPR006209Sigp THBS1 HU

2267a MAN PF00093IPR001007 CaMax:ENST000 231a 00317584 CaMax:ENST000 2331c 00296412 CaMax:

2341b CaMax:ENST000 2351c 00319965 CaMax:ENST000 2351c 00319965 CaMax:CN3A_H 123805NM_000921PF00233IPR002073 Tmhmm PDE3A

2241a UMAN IPR005829 CaMax:Genscan:

235a RNOR010 69968.119 47.48582 CaMax:TSP1 188060NM_003246PF02210IPR006209Sigp THBS1 HLT

2374a MAN PF00093IPR001007 CaMax:Genscan:

238a AC01660 1.7.1.1452 64.1553.2 CaMax:SPCN_H 182810NM 003127PF00435IPR002048 SPTAN1 239a UMAN PF00018IPR000276 CaMax:GME1 604409NM_006582PF01342IPR000770 GMEB1 H

23a UMAN NM_024482 CaMax: NM_032811PF05964 240a PF05965 CaMax:trembl~AB

243a 012223 CaMax: NM_144972PF00056IPR001557 245a PF02866IPR001236 CaMax: NM 018211PF00076IPR000504 248a IPR001064 ~

CaMax:ENST000 24a 00239392 CaMax:gpnew~37 258a 790758 CaMax:gp~373618 261c 50 CaMax:ENST000 261c 00322543 CaMax:TENA 187380NM_002160PF00008I1'R006209Sigp Tmhmm TNC
H

267d UMAN PF00041IPR002049 CaMax: NM_018696PF00753IPR001279 ELAC1 272d CaMax:ENSRNO

27a T0000000 CaMax:Genscan:

28s NA26110.

1.701.151 CaMax:YCE7 NM 016077PF01981IPR002833Sigp Tmhmm H

307b UMAN

CaMax: 180069NM 000329PF03055IPR004294 RPE65 308c CaMax:M172 M

310h OUSE

CaMax:ENST000 311c 00315874 CaMax:Genscan:

313a AL136225 .8.1.42171 .4910.172 CaMax:ENST000 314a 00303575 CaMax:ENSRNO

319b T0000002 CaMax:SEC3_HCT607879NM_018261 320a MAN NM 178237 CaMax:SEC3_HU

320a MAN

CaMax:ENSRNO

322a T0000002 CaMax: NM_020935PF00443IPR001394 USP37 324a PF02809Il'R003903 CaMax:SPC4 NM_019951PF00461IPR000508Sigp Tmhmm Spcl8-M

326e OUSE IPR001733 endin CaMax:gp~373600 327f 62 CaMax:ENST000 327f 00315821 CaMax: NM_016081PF00047IPR000634 328b ' IPR007110 CaMax:

336a CaMax:trembl~BC

33a 024093_1 CaMax:ENSRNO

33a T0000000 CaMax:swiss~PTN

340a 3 HUMA

N

CaMax:ENST000 340a 00262539 CaMax:trembl~AK

343b 033094_1 CaMax:ENST000 343b 00269073 CaMax:gp~345348 34a 17 CaMax:ENST000 34a 00316410 CaMax:FRIH_HU 134770NM_002032PF00210IPR001519. FTH1 106a MAN

CaMax:FRIH_HU 134770NM_002032PF00210IPR001519 FTHl 106a MAN

CaMax:tremblnew 360a ~AK09446 CaMax:ENST000 360a 00291220 CaMax:EWS HU 133450NM 005243PF00076IPR001064 EWSR1 364a MAN NM_013986PF00641IPR000504 CaMax:COX1_C

370a ANFA

CaMax:A32B NM_006401PF00560IPR001611 ANP32B
HU

374a MAN

CaMax:COXl C

375d ANFA

CaMax:ENST000 379a 00278407 CaMax: 607686NM_030917PF05182IPR007854 FIP1L1 38a CaMax:ENST000 391a 00293648 CaMax:tremblnew 392a ~BC03413 CaMax:ENST000 392a 00319311 CaMax:trembl~BC

395a 051886_1 CaMax:ENST000 395a 00323751 CaMax:ALU7_H

397b UMAN

CaMax:

3c CaMax:swiss~CO

406a-rX3_CAN

FA

CaMax:Transcript _77_ 406a-r :ENST000 CaMax: ALU1 H

408a UMAN

CaMax: ALU1 H

409a UMAN

CaMax: IF2A_HU603907NM_004094PF00575IPR003029 EIF2S

415b MAN

CaMax: gpnew~37 421a 790758 CaMax: IPR000694Sigp Tmhmm 43a CaMax: ENST000 446f 00239392 CaMaX: ixembl~AK

44c 019226_1 CaMax: ENST000 44c 00264258 CaMax: trembl~AK

45.1b 007837_1 CaMax: ENST000 45.1b 00314138 CaMax: tremblnew 450a ~HSM805 132_1 CaMax: ENST000 450a 00325086 CaMax: ENST000 452a 00218713 CaMax: trembl~BC

455c 028178_1 CaMax: ENST000 455c 00317856 CaMax: trembl~HS

4.57c U93569_1 CaMax: NFTS_HU604708NM_006599PF00554IPR000451 NFATS

459a MAN NM_138713PF01833IPR002909 NM_13 IPR001472 NM_173214 CaMax: swissnew~

461a SF30_HU

MAN

CaMax: ENST000 461a 00239010 CaMax: PURA_H 103060NM_001126PF00709IPR001114 ADSS

464b UMAN

CaMax: NM_016952PF00047IPR003961 Tmhmm CDON

465b PF00041IPR007110 CaMax: ENST000 46a 00282493 CaMax: tremblnew 472a ~BC01981 CaMax: ENST000 472a 00327301 CaMax: TCTL_H 300302NM_006520PF03645IPR005334 TCTE1L

478a UMAN

CaMax: TCTL_H 300302NM 006520PF03645IPR005334 TCTE1L

479c UMAN

_ 78 _ CaMax: Genscan:

482a AP005117 .2.1.14879 0.13386.9 CaMax: ARH2 607560NM 004723PF00130 IPR002219 ARHGEF2 H

487a UMAN PF00621 IPR001849 CaMax: HXK2_H 601125NM_000189PF00349 IPR001312 HK2 488a UMAN PF03727 CaMax: trembl~AK

48b 019226_1 CaMax: ENST000 48b 00264258 CaMax: trembl~AK

490c 088660_1 CaMax: ENSRNO

490c T0000002 CaMax: trembl~HS

494a AB461_1 CaMax: ENST000 494a 00324722 CaMax: ENSRNO

498a T0000001 CaMax: swiss~RL3 50.1c 1 HUMA

N

CaMax: ENST000 50.1c 00264258 CaMax: ENSMUS

501b T0000005 CaMax: ENST000 504a 00267434 CaMax: ENST000 505b 00248673 CaMax: ENSRNO

507a T0000001 CaMax: Transcript 516c :ENST000 CaMax: Transcript 517c :ENST000 CaMax: trembl~AY

51a 072691_1 CaMax: ENST000 51a 00321758 CaMax: NM 017658PF00651 IPR000210 BTBDS

520a CaMax: MEFC_H 600662NM_002397PF00319 IPR002100 MEF2C

521b UMAN

CaMax: ENST000 523a 00300162 CaMax: ENST000 52a 00242208 CaMax: PSA3_HU 176843NM_152132PF00227 IPR000426 PSMA3 530b MAN 176845NM 002788 IPR001353 CaMax:ENST000 538a 00283629 CaMax: PF00069IPR000719 539a IPR002290 CaMax:pironly~JU , 540a 0033 CaMax:gp~345338 543a 74 CaMax: 605861NM_014255 IPR000886Sigp TMEM4 545a IPR008139 CaMax: NM_014827PF00642IPR000571 547c IPR001472-.

CaMax: NM_014827PF00642IPR000571 548c IPR001472 ~

CaMax: 605975NM 005839PF01480IPR002965 SRRMl 550a IPR002483 CaMax:ENST000 552a 00318468 CaMax: NM_031208PF01557IPR002529 553b CaMax: 605653NM_012158PF00646IPR001810 FBXL3A

555b FBXI,3B

CaMax:tremblnew 556b ~HSM805 CaMax:NSF_HU

557b MAN

CaMax:trembl~AF

558a 352051_1 CaMax:ENST000 558a 00319272 CaMax:RBB2_H

560b UMAN

CaMax:ENST000 561b 00296499 CaMax:trembl~CF

568a A388522_ 1 '.

CaMax:ENST000 568a 00225430 CaMax:gpnew~38 56a 511552 CaMax:ENST000 56a 00202773 CaMax:_ 607442NM_019063PF03451IPR002048 EML4 H

571a UMAN PF00400IPR001254 CaMax:ENST000 574a 00296412 CaMax:SFR6_HU 601944NM_006275PF00076IPR000504 SFRS6 579a MAN IPR001472 CaMax:ITA6_HU 147556NM 000210PF01839IPR000413Sigp Tmhmm ITGA6 57a MAN 226730 PF00357 CaMax: NM_014553PF04516IPR007604 581a CaMax: PF00039IPR006209 Fn l 583e PF00041IPR000083 CaMax:ENST000 58a 00313783 CaMax:FALZ_H 601819NM_182641PF02791IPR001687 FALZ

597c UMAN NM_004459PF00628IPR000345 CaMax:swissnew~

59a SMOZ_M

OUSE

CaMax:ENST000 59a 00230324 CaMax:Genscan:

609a RNORO10 94784.371 6.7206 CaMax:Transcript 611a :ENST000 CaMax:gp~345323.

622a 52 CaMax:Genscan:

622a AC10793 9.5.1.1452 64.83212.

CaMax:IQG1 603379NM_003870PF00307IPR001936 IQGAP1 HLT

623a MAN P F00397 IPR001202 CaMax:ENSMUS

624b T0000005 CaMax:trembl~BC

626a 046507_1 CaMax:ENST000 626a 00261631 CaMax:I~RMl NM_153379PF00431IPR000859 Tmhmm KREMEN1 H

628a UMAN NM 032045 CaMax: 605975NM_005839PF01480IPR002965 SRRMl 635a IPR002483 CaMax:TCTL_H 300302NM 006520PF03645IPR005334 TCTElL

638b UMAN

CaMax:ENST000 639a 00309558 CaMax:trembl~AY

63a 259036 CaMax:Transcript 63a :ENST000 CaMax:Y121 HLT

64.2a MAN

CaMax:U183_HU NM_025187PF03676IPR005373 685a MAN

CaMax:ENST000 690a 00244411 CaMax:ENST000 690a 00244411 CaMax: NM_145702PF04218IPR004875 TIGD1 692a PF03184IPR006695 CaMax: PF00443IPR005479 697a IPR001394 CaMax:Z216_MO

6b USE

CaMax: NM_146000 IPR001472 D030060M

701a llRik CaMax: 243305NM_014425PF00023IPR002110 INVS

704b PF00612IPR000048 CaMax: 243305NM_014425PF00023IPR002110 INVS

704b PF00612IPR000048 CaMax:ENST000 70d 00323467 CaMax:CAlA_H 120110NM_000493PF01391IPR001073Sigp COL10A1 710a UMAN 156500 PF00386IPR008160 CaMax:trembI~AK

711a 019226_1 CaMax:ENST000 711a 00264258 CaMax:trembl~BC

713a 008338_1 CaMax:ENST000 713a 00012559 CaMax:Genscan:

714a AL391495 .16.1.1429 52.28457.

CaMax:ENST000 718a 00299020 CaMax:NU4M_C

720a ANFA

CaMax: PF00063IPR001687 725a PF00612IPR001609 CaMax:GDC_HU 139080NM_152707PF00153IPR001993 SLC25A16 726b MAN IPR002167 CaMax:trembl~AK

72a 007442_1 CaMax:ENST000 72a 00250454 CaMax:trembl~HS

731a DNAW_1 CaMax:ENST000 731a 00275603 CaMax:ATDA 313020NM_002970PF00583IPR000182 SAT
H

736a UMAN

CaMax: NM_133375PF00773IPR001900 739a CaMax:KE4_HU 601416NM_006979PF02535IPR002395Sigp Tmhmm HKE4 73b MAN IPR003689 _8~_ CaMax: ENST000 745a 00315919 CaMax: NM_133433 747a NM 015384 ' .

CaMax: ENST000 749a 00294890 CaMax: ENSRNO

74c T0000002 CaMax: NM_025685PF01410IPR000885 5730512J0 753b 2Rik CaMax: trembl~AX

759b 704781_1 CaMax: ENST000 759b 00261981 CaMax: trembl~AK

764b 002413_1 CaMax: ENSRNO

764b T0000000 CaMax: IPR001687 765a CaMax: ENST000 768a 00325727 CaMax: ENST000 ~76b 00275248 CaMax: PRIO_HU176640NM 000311PF03991IPR000817Sigp Tmhmm PRNP

785b MAN 123400 PF00377 CaMax: ENSMUS

788a T0000002 CaMax: Tmlimm NDFIP2 789a CaMax: SSPN_HU601599NM_005086 Tmhmm SSPN

794a MAN

CaMax: NM_017812PF05300IPR007964 795a CaMax: Y379_HU PF00023IPR002110 810a MAN

CaMax: ENST000 813a 00222567 CaMax: Transcript 815a :ENST000 CaMax: ENST000 81a 00252102 CaMax: ti-embl~AB

820a 012223_1 CaMax: ENST000 820a 00325761 CaMax: trembl~AX

827b 147999_1 CaMax: ENST000 827b 00269485 CaMax: ENST000 828a 00265264 CaMax: ENST000 82b 00252102 CaMax: trembl~AK

831a 019226_1 CaMax: ENST000 831a 00264258 CaMax: PF00039IPR006209 Fn 1 832a PF00041IPR000083 CaMax: 607838NM_032520 Sigp 833a CaMax: LIN1 IVY

835c CCO

CaMax: PF00400IPR001680 839a CaMax: trembl~AY

841b 072691_1 CaMax: ENST000 841b 00321758 CaMax: trembl~AY

847a 170044 CalViax: NM_014301PF01592IPR002871 85.1c CaMax: Sigp Tmhmm 85.2b CaMax: Genscan:

850a AP000813 .4.1.21081 6.38383.4 CaMax: Genscan:

851a AP000813 .4.1.21081 6.38383.4 CaMax: BCAT_H 113520NM_005504PF01063IPR001544 BCAT1 856c UMAN

CaMax: SLUG_M NM_011415PF00096IPR007087 Snai2 863c OUSE IPR007086 CaMax: RB6A 179513NM_002869PF00071IPR001687 RAB6A
H

890a UMAN IPR001806 CaMax: ENST000 i 8a 00254942 CaMax: ENST000 905a 00231061 CaMax: gpnew~37 906a 790758 CaMax: MANR_H

907a UMAN

CaMax: AMD_HU 170270NM_000919PF01082IPR002086Sigp Tmhmm PAM

909a MAN NM_138766PF03712IPR000323 NM_138822PF01436IPR000720 CaMax: HS9B_M NM_008302PF02518IPR001404 Hspcb 90c OUSE PF00183IPR003594 CaMax: trembl~AB

911a 012223 CaMax: ENST000 911a 00292530 CaMaX: gp~345354 912b 83 CaMax: gp~345342 914a 29 CaMax: ENST000 914a 00273342 CaMax: swiss~AL

915a U6_HUM

AN

CaMax: ENST000 915a 00262877 -CaMax: NM_016132PF00076IPR000504 MYEF2 919b CaMax: trembl~S7 91f 8694_1 CaMax: ENST000 91f 00231004 CaMax: NM_016132PF00076IPR000504 MYEF2 919b CaMax: 602691NM_147233PF00010IPR001092 NCOA1 92c NM_003743PF00989IPR000014 NM_147223 IPR001472 CaMax: CHUR_H NM_145165 IPR000345 Cl4orf52 935b UMAN

CaMax: trembl~BT

936b 008233_1 CaMax: ENST000 936b 00316232 CaMax: PF00076IPR000504 945a CaMax: trembl~AY

947a 310153_1 CaMax: ENSRNO

947a T0000000 CaMax: NM_152396 IPR001601 949c IPR000051 CaMax: 68MP NM_027360 Tmhmm 2010107E0 M

953a OUSE 4Rik CaMax: 607204NM_014676PF00806IPR001313 PUM1 963c CaMax: RL32_HU

96e MAN

CaMax: gpnew~37 981a 790758 CaMax: pironly~JC

984a 7185 CaMax: ENSMUS

984a T0000004 CaMax: CGD2_H 123833NM_001759PF00134IPR006671 CCND2 986a UMAN PF02984IPR004367 CaMax: SOX9_H 114290NM_000346PF00505IPR000910 SOX9 990a UMAN IPR001472 CaMax: tremblnew 992a ~AK09640 CaMax: 606457NM 015525PF00023IPR001687 994b PF00415IPR000408 IPROb0210 CaMax:RS20_HU 603682~ 001023 PF00338IPR001687 RPS20 996a MAN IPR001848 [0052] One embodiment of the invention relates to a combination comprising two or more polynucleotide molecules selected from SEQ >D NOs:l-1558, or fragments thereof.
Preferably, the combination comprises about 10 or more polynucleotide'molecules, more preferably about 50 or more polynucleotide molecules, more preferably about 200 or more polynucleotide molecules, more preferably about 400 or more polynucleotide molecules, more preferably about 1000 or more polynucleotide molecules.
[0053] In a preferred embodiment, the invention relates to a combination of differentially expressed polynucleotide molecules, whose sequences are represented by SEQ ID
NOs:1-396. Table 3 identifies a list of gene sequences determined from clinical samples to be differentially expressed in OA versus normal subjects to a degree that is statistically significant (p < 0.05). Table 3 includes the gene IDs, expression values, standard deviations, and fold difference of expression (OA versus normal). Preferably, the combination comprises two or more of polynucleotide molecules selected from SEQ ID NOs:l-396 or fragments thereof.
[0054] In a particularly preferred embodiment, the invention relates to a combination of 217 differentially expressed polynucleotide molecules, whose sequences are represented by SEQ
ID NOs:l-217. Table 4 identifies a list of gene sequences determined from clinical samples to be differentially expressed in OA versus normal subjects to a degree that is highly significant (p < 0.01). Table 4 includes the gene IDs, expression values, standard deviations, and fold difference of expression (OA versus normal). Preferably, the combination comprises two or more of polynucleotide molecules selected from SEQ ID NOs:l-217 or fragments thereof.
[0055] According to an aspect of the invention, one or more oligonucleotide or polynucleotide probes for interrogating a sample may be prepared using the sequence information set forth herein for any of the 1558 isolated gene fragments (SEQ
D7 NOs:1-1558).
According to another aspect of the invention, probes may be prepared using the sequence information available for any of the genes or gene fragments identified in .
The probes should be of sufficient length to specifically hybridize substantially exclusively with appropriate complementary genes or transcripts. Preferably, the oligonucleotide probes will be at least about 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some embodiments, longer probes of at least about 30, 40, 50, 60, 70, 80, 90 or 100 nucleotides are desirable, and probes longer than about 100 nucleotides may be suitable in some embodiments. Preferably, a collection of two or more nucleic acid probes for detecting expression of gene products differentially expressed in OA is provided, more preferably a collection of about 10 or more probes, more preferably a collection of about 50 or more probes, more preferably a collection of about 200 or more probes, more preferably a collection of about 400 or more probes, more preferably a collection of about 1000 or more probes.
[0056] In a preferred embodiment of the invention, one or more oligonucleotide or polynucleotide probes may be prepared using the sequence information set forth for any of SEQ
ID NOs:l-396. Preferably, one or more oligonucleotide or polynucleotide probes may be prepared using the sequence information set forth for any of SEQ ID NOs: l-217.
[0057] In certain preferred embodiments of the present invention, immobilized nucleic acid probes may be used for the rapid and specific detection of nucleic acid molecules and their expression patterns. Typically, a nucleic acid probe is linked to a solid support and a target nucleic acid (e.g., a genomic nucleic acid, an amplicon, or, most commonly, an amplified mixture) is hybridized to the probe. Either the probe, or the target, or both, can be labeled, typically with a fluorophore or other tag, such as streptavidin. Where the target is labeled, hybridization may be detected by detecting bound fluorescence. Where the probe is labeled, hybridization is typically detected by quenching of the label. Where both the probe and the target are labeled, detection of hybridization is typically performed by monitoring a color shift resulting from proximity of the two bound labels. A variety of labeling strategies, labels, and the like, particularly for fluorescent based applications, are known in the art.

[0058] Another aspect of the invention relates to one or more probes comprising polypeptide binding agents that specifically bind to polypeptides produced by expression of one or more nucleic acid molecules comprising sequences selected from SEQ ID NOs:1-1558 or fragments thereof. According to another aspect of the invention, protein binding probes may be prepared using the sequence information available for any of the genes or gene fragments identified in Table 2. Preferably, a collection of two or more polypeptide probes for detecting expression of gene products differentially expressed in OA is provided, more preferably a collection of about 10 or more probes, more preferably a collection of about 50 or more probes, more preferably a collection of about 200 or more probes, more preferably a collection of about 400 or more probes, more preferably a collection of about 1000 or more probes.

[0059] In a preferred embodiment of the invention, probes comprising polypeptide binding agents specifically bind to polypeptides produced by nucleic acid molecules comprising sequences selected from SEQ ID NOs:l-396. In a particularly preferred embodiment, probes _87_ comprising polypeptide binding agents specifically bind to polypeptides produced by nucleic acid molecules comprising sequences selected from SEQ ID NOs: l-217.

[0060] Assay techniques that can be used to determine levels of a protein in a sample are also well known to those of skill in the art. Such assay methods include radioimmunoassays, competitive-binding assays, Western blot analysis and ELISA assays. In the assay methods utilizing antibodies, both polyclonal and monoclonal antibodies are suitable for use in the present invention. Such antibodies may be immunologically specific for a particular protein, or an epitope of the protein, or a protein fragment, as would be well understood by those of skill in the art. Methods of making polyclonal and monoclonal antibodies immunologically specific for a protein or peptide are also well known in the art.

[0061] Preferred embodiments of the present invention may utilize antibodies for the detection and quantification of proteins produced by expression of the polynucleotides described herein. Though proteins may be detected by immunoprecipitation, affinity separation, Western blot analysis and the like, a preferred method utilizes ELISA-type methodology wherein the r antibody is immobilized on a solid support and a target protein or peptide is exposed to the immobilized antibody. Either the probe, or the target, or both, can be labeled. A variety of labeling strategies, labels, and the like, are known in the art.

[0062] ' In particularly preferred embodiments of the invention, expression patterns or profiles of a plurality of genes differentially expressed in osteoarthritis are observed utilizing arrays' of probes for detecting target nucleic acids or proteins. In one embodiment, arrays of oligonucleotide or polynucleotide probes may be utilized, whereas another embodiment may utilize arrays of antibodies or other proteins that bind specifically to the differentially expressed gene products. Such arrays are commercially available (e.g,. through Affymetrix, Inc., Applied Biosystems, Inc., Agilent, Inc.), or they may be custom made according to known methods, such as, for example, in-situ synthesis on a solid support or attachment of pre-synthesized probes to a solid support via micro-printing techniques. In preferred embodiments, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the 1558 differentially expressed genes or gene fragments described herein. In one embodiment of the invention, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the genes or gene fragments identified in Table 2. In a preferred embodiment, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the 396 differentially expressed genes or gene fragments identified in Table 3. In a preferred embodiment, arrays of nucleic acid or protein-binding probes are custom made to _88_ specifically detect transcripts or proteins produced by two or more of the 217 differentially . expressed genes or gene fragments identified in Table 4.

[0063] Preferably, a collection of two or more nucleic acid or polypeptide probes for detecting expression of gene products differentially expressed in OA is immobilized on a support in discrete locations, more preferably a collection of about 10 or more probes, more preferably a collection of about 50 or more probes, more preferably a collection of about 200 or more probes, more preferably a collection of about 400 or more probes, more preferably a collection of about 1000 or more probes.

[0064] Since chondrocytes represent the cellular component of cartilage, a tissue affected by OA, the construction of a chondrocyte array may represent a powerful tool to study the gene expression profile of osteoarthritic chondrocytes. The use of differential display for transcript selection was used by the present inventors to enrich the clones represented on an array for transcripts associated with OA. , [0065] In one aspect of the invention, methods are provided for assaying OA-associated nucleic acids in a sample. Preferably, a combination comprising one or more polynucleotide molecules selected from SEQ ID NOs:l-1558, more preferably selected from SEQ
ID NOs:l-396, more preferably selected from SEQ ID NOs:l-217, are used to prepare probes that are hybridized with nucleic acids of a test sample, forming hybridization complexes that are detected and compared with those of a standard, such that differences between the sample and standard hybridization complexes are indicative of differential expression of nucleic acids in the sample.
In a preferred embodiment, nucleic acid probes are made to specifically detect transcripts or fragments thereof produced by one or more of the genes or gene fragments identified in Table 2.
In certain preferred embodiments, the nucleic acids of the sample may be amplified prior to hybridization.

[0066] In another aspect of the invention, methods are provided for assaying OA-associated polypeptides in a sample. Preferably, polynucleotide sequences selected from SEQ
ID NOs:1-1558, more preferably selected from SEQ ID NOs:l-396, more preferably selected from SEQ ID NOs:l-217 are used to prepare protein-binding probes that specifically bind to translation products of those polypeptides or fragments thereof. These probes are reacted with a test sample, forming binding complexes that are detected and compared with those of a standard, such that differences between the sample and standard binding complexes are indicative of differential expression of polypeptides in the sample. In a preferred embodiment, protein-binding probes are made to specifically detect polypeptides or fragments thereof produced by one or more of the genes or gene fragments identified in Table 2.

[0067] According to certain preferred embodiments of the invention, the assays . described herein for the detection of OA-associated transcription and translation products may be used in methods useful for determining a diagnosis and/or prognosis for osteoarthritis in a patient. According to an embodiment of the invention, a typical diagnostic test will comprise obtaining a sample of cells or tissue from a patient in which OA-associated gene expression is expected to occur. Such cells or tissues include, but are not limited to, cartilage tissue and chondrocytes. The sample is then analyzed for either 1) increased or decreased expression of one or more selected genes, via detection of mRNA or protein, or 2) a particular gene expression profile, for example, via gene or protein array technology, as described herein. Such a diagnostic procedure should lead to a determination of whether indications of osteoarthritis are present in the patient. , [0068] In another embodiment of the invention, the diagnostic procedures described herein may also be extended to provide prognostic information regarding a patient's recovery from OA, or to monitor a patient's progress in response to a therapeutic regimen. In these situations, the diagnostic assay is performed at intervals during the patient's recovery or course of treatment, and a change in expression of a target gene, or a particular change in the pattern of gene expression, is indicative of the patient's level of recovery or improvement.
,, [0069] In one aspect of the invention, assays are provided for identifying substances effective in treatment modalities for osteoarthritis. In one embodiment of the invention, a method is provided for measuring the effect of a test substance on the expression profile of genes differentially expressed in osteoarthritis, comprising the steps of: a) obtaining a standard expression profile from a first sample by measuring transcription or translation products of two or more genes corresponding to two or more genes or gene fragments identified in Tables 1 and/or 2 in the absence of the test substance; b) obtaining a test expression profile from a second sample by measuring the transcription or translation products of two or genes or gene fragments identified in Tables 1 and/or 2 expressed in the presence of the test substance; c) comparing the standard expression profile the test expression profile, wherein a change in the test expression profile compared to the standard expression profile is indicative of an effect of the test substance on the expression profile of genes differentially expressed in osteoarthritis compared to a non-osteoarthritic condition. Preferably, the two or more genes ~or gene fragments correspond to two or more of the genes or gene fragments identified in Table 3 (SEQ ID NOs:1-396). More preferably, the two or more genes or gene fragments correspond to two or more of the genes or gene fragments identified in Table 4 (SEQ m NOs:l-217). In certain preferred embodiments, the samples are obtained from cultured cells. In this case, the standard expression profile is obtained from cells that have not been contacted with the test substance, while the test expression profile is obtained from cells that have been contacted with a test substance.

[0070] Test compounds may include proteins, polypeptides, nucleic acids, small molecule pharmaceuticals, vitamins, minerals, fatty acids, polysaccharides, extracts, nutriceuticals, and the like. In a preferred embodiment, the test compounds are nutrients that may be added to food or other dietary substances, or that may be taken as a dietary supplement.
As exemplified herein, such nutrients include, but are not limited to, fatty acids such as omega-3 fatty acids (e.g., eicosapentaenoic acid) and omega-6 fatty acids (e.g., arachidonic acid), glucosamine, chondroitin sulfate and vitamin D derivatives such as 1a,25-dihydroxyvitamin D3 and 248,25-dihydroxyvitamin D3.

[0071] One type of assay according to an embodiment of the invention involves measuring the activity of the protein encoded by one of the aforementioned OA-associated genes in the presence or absence of a candidate substance. Such activity assays are well known in the art. If a cell-free activity assay is available for the selected protein, such an assay is simply conducted on the purified protein in the presence or absence of the test substance. Candidate substances are selected based on their ability to positively or negatively regulate activity of the purified protein. It should be noted that assays of this type may be performed, for example, in a recombinant cellular system, as described below. They can also be performed, for example, in a cell-free system in some instances.

[0072] For such in vitro activity assays, it is desirable to have a source of the purified protein of interest. One or more of the protein products of the genes mentioned above may be commercially available, or purifiable in significant quantities from an appropriate biological source, e.g., cultured cells. Alternatively, the proteins may be recombinantly produced from an isolated gene or cDNA by expression in a suitable procaryotic or eucaryotic expression system, and thereafter purified, as is also well known in the art.

[0073] Another embodiment of the invention comprises in vitro cellular assays for expression of OA-associated genes or activity of their encoded proteins. For these embodiments, a nucleic acid construct comprising an OA-associated gene according to an aspect of the invention is introduced into host cells. In a preferred embodiment, mammalian cell lines are utilized. Host cells contemplated for use include, but are not limited, to NIH3T3, CHO, HELA, and COS, as well as non-mammalian cells such as yeast, bacteria and insect cells. The coding sequences are operably linked to' appropriate regulatory expression elements suitable for the pal-ticular host cell to be utilized. Methods for introducing nucleic acids into host cells are well known in the art. Such methods include, but are not limited to, transfection, transformation, calcium phosphate precipitation, electroporation and lipofection. The recombinant cells may be used to identify compounds which modulate expression of the OA-associated genes or activity of their encoded proteins.

[0074] For gene expression assays, it is preferred to prepare an artificial construct comprising the promoter of a selected OA-associated gene, operably linked to a reporter gene.
The reporter construct may be introduced a cultured cell, including, without limitation, the standard host cell lines described above, or other suitable cells, for example, cartilage-related cells such as chondrocytes. The assay is performed by monitoring expression of the reporter gene in the presence or absence of a test compound. Candidate substances are selected based on their ability to positively or negatively affect expression of the gene.

[0075] In another embodiment of the invention, OA-associated genes and gene fragments described herein may be used to manipulate the genome of non-human animal subjects. Methods of manipulating the genomes of a variety of animals are known to those of skill in the art. Such methods may include, without limitation, the production of transgenic and gene-knockout animals. In a preferred embodiment of the invention, a gene or gene fragment identified in Table 2 is used to prepare a construct that is used to disrupt or "knock out" the corresponding endogenous gene in an animal, thus producing an animal having a null mutation for that gene locus. In some embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:l-1558. In some embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NO: 1-396. In some embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes having a nucleic acid sequence selected from SEQ ~ NO: 1-217. In other embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes shown in Table 6. The transgenic animals are preferably mammals. In some embodiments, the transgenic animals are rodents (e.g., mice and rats). In other embodiments, the animals are, for example, goats, cats, dogs, cows, pigs, sheep, horses, non-human primates, rabbits, and guinea pigs. In some embodiments, small interfering RNAs are used to functionally disrupt the genes. Briefly, gene expression is inhibited by a short interfering RNA (siRNA) through RNA interference (RNAi) or post-transcriptional gene silencing (PTGS) (see, for example, Ketting et al. (2001) Genes Develop.
15:2654-2659).
siRNA molecules can target homologous mRNA molecules for destruction by cleaving the mRNA molecule within the region spanned by the siRNA molecule. Accordingly;
siRNAs capable of targeting and cleaving mRNA of the gene products shown in Table 6 may be used to decrease or eliminate expression of one or more of these genes. In other embodiments, siRNAs capable of targeting and cleaving mRNA of one or more of the genes shown in Table 1 (SEQ ID
NOS:1-1558) may be used to decrease or eliminate expression of one or more of these genes.

[0076] In another embodiment of the invention, OA-associated genes and gene fragments described herein are used to design molecules that may be used to interfere with the expression of one or more OA-associated genes; such molecules may include, without limitation, RNA interference probes and antisense molecules.

[0077] Another aspect of the invention features compositions of matter to facilitate practice of the assays described above. These compositions may comprise collections of two or more probes or primers for use in detecting differentially expressed OA-related genes, gene fragments and encoded proteins according to certain aspects of the invention.
In one embodiment, the compositions may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with nucleic acid molecules selected from SEQ ID
NOS:l-1558. Preferably, the compositions may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with nucleic acid molecules selected from SEQ )D NOS:1-396. More preferably, the compositions may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with nucleic acid molecules selected from SEQ ID NOS:l-217. Preferably, the composition may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with genes and/or gene fragments selected from the genes 'and gene fragments identified in Table 2.
The collection may comprise a primer pair for amplifying the sequence. In certain preferred embodiments, amplification may be performed using Polymerase Chain Reaction (PCR), more preferably quantitative PCR (qPCR). In a preferred embodiment, the collection comprises a larger plurality of probes, e.g., about 10, 50, 200, 400, 1000 or more probes, each of which hybridizes specifically with part or all of one of the sequences of SEQ ID
NOS:1-1558. In a preferred embodiment, nucleic acid probes are immobilized on a solid support.
In a particularly preferred embodiment, they are immobilized in an array format, most preferably in a miniature or micro-array. Such micro-arrays are known in the art, and are sometimes referred to as "DNA
chips," "microchips," "biological chips" and other similar terms, and may contain the entire array of genes or gene fragments altered by OA, in addition to those represented in Tables 1 and 2.

[0078] In another embodiment, these compositions comprise two or more protein binding substances capable of specifically binding proteins or protein fragments encoded by the genes and gene fragments identified in Tables 1 and 2. In a preferred embodiment the binding substances are antibodies and the collection comprises two or more antibodies for detecting two or more proteins or peptides encoded by SEQ ID NOS:l-1558, respectively.
Preferably, these compositions comprise two or more protein binding substances capable of specifically binding proteins or protein fragments encoded by the genes and gene fragments of SEQ
ID NOS:1-396.
More preferably, these compositions comprise two or more protein binding substances capable of specifically binding proteins or protein fragments encoded by the genes and gene fragments of SEQ ID NOS:1-217. Such binding substances may be any molecule to which the protein or peptide specifically binds, including DNA (for DNA binding proteins), antibodies, cell membrane receptors, peptides, cofactors, lectins, sugars, polysaccharides, cells, cell membranes, organelles and organellar membranes. In a preferred embodiment, the collection comprises a larger plurality of antibodies, e.g., about 10, 50, 200, 400, 1000 or more, each of which binds immunospecifically with part or all of a protein or peptide encoded by genes or gene fragments identified in Tables 1 and/or 2. In a preferred embodiment, the antibodies are immobilized on a solid support. In a particularly preferred embodiment, they are immobilized in an array format, most preferably in a miniature or micro-array, as described above for oligonucleotide probes, and may contain the entire array of proteins altered by OA, in addition to genes or gene fragments identified in Tables 1 and 2.

[0079] Another embodiment of the present invention relates to substances or compounds identified in any of the methods described herein as having an effect on the expression profile of genes differentially expressed in OA. Preferably, such substances will be effective in the treatment andlor prevention of OA.

[0080] Still another aspect of the invention features test kits for use in one or more of the assays described herein. One type of kit comprises one or more pairs of primers for amplifying nucleic acids corresponding to the OA-associated genes and gene fragments described herein. The kit may further comprise samples of total mRNA derived from tissue of various physiological states, for use as controls. The kit may also comprise buffers, nucleotide bases, and other compositions to be used in hybridization and/or amplification reactions. Each solution or composition may be contained in a vial or bottle and all vials held in close confinement in a box for commercial sale.

[0081] Another type of kit comprises one or more nucleic acid or protein-binding probes, wherein the nucleic acid probe hybridizes specifically with a OA-associated gene or gene fragment according to certain aspects of the invention, or the protein-binding probe specifically binds to a protein encoded by the OA-associated gene or gene fragment.
Preferably, the protein-binding probe is an antibody that is immunologically specific for the protein encoded by the OA-associated gene or gene fragment. In preferred embodiments, the nucleic acid or protein-binding probes are immobilized on a solid support. In a particularly preferred embodiment, the kit comprises immobilized arrays of nucleic acid or protein-binding probes, the arrays comprising probes specific for a plurality of the OA-associated genes or gene fragments described herein, or proteins encoded thereby. These kits also may contain appropriate control samples of mRNA or protein from tissues of known physiological state, to be used as controls in the assays. They may further comprise buffers and reagents for performing the assays. Each solution, reagent or composition in the kit may be contained in a vial or bottle and all vials held in close confinement in a box for commercial sale. Preferably, kits may further comprise instructions for performing an assay of gene expression.

[0082] In another aspect, the invention provides a method for altering biological profile of cells through inducing a change in the gene expression profile of the cells with respect to genes involved in OA. The method involves administering to cells an effective amount of a compound that alters the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:l-1558. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:l-396. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:l-217. In other embodiments, the compound affects the expression of one or more genes having the gene products shown in Table 6. The invention also provides a method of affecting the expression of genes involved in OA
comprising exposing cells to an effective amount of a compound that modulates expression of one or more genes having a sequence selected from SEQ ID NOs:1-1558. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ
ID NOs: 1-396. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs: 1-217. In other embodiments, the compound affects the expression of one or more genes having the gene products shown in Table 6.

[0083] In some embodiments the cells are cells associated with symptoms of osteoarthritis. In some embodiments the cells are chondrocytes. In some embodiments the compounds are administered to cells ifa vitro. In other embodiments the compounds are administered to cells ifz vivo. The compounds may be administered to subjects via any route of administration. Preferably, the subjects are vertebrates. More preferably, the subjects are mammals including dogs, cats and humans.

[0084] The change in gene expression is preferably at least a 1.01 fold difference.
More preferably, it is at least a 1.05, 1.10, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.0, 3.25, 3.50, 3.75, 4.0 fold difference or more.

[0085] Chondroitin sulfate was shown to have an effect on a wide variety of OA-associated genes as shown in detail in Tables 7-12. Glucosamine was also found to have an effect on a variety of OA-associated genes as shown in detail in Tables 13-18.
1a,25-dihydroxyvitamin D3 and 248,25-dihydroxyvitamin D3 also affected the expression of OA-related genes as shown in Tables 19-20. Eicosapentaenoic acid (EPA) and arachidonic acid (AA) were also shown to affect OA-related genes as shown in Tables 21-23.

[0086] The following examples are provided to describe the invention in greater detail.
They are intended to illustrate, not to limit, the invention.

Extraction of RNA from chondrocytes [0087] Normal and osteoarthritic canine cartilage chondrocytes (N2-flash frozen) were obtained and stored at -80°C. Osteoarthritic chondrocytes originated from canines clinically diagnosed with osteoarthritis undergoing total hip replacement. 300 to 500 mg were ground in N2 (mortar and pestle) and transferred to a clean, pre-chilled, 50 ml tube.
Trizol (2ml/100mg) was added and the mixture was homogenized using a Polytron for 2 x 30 seconds, and 1 minute (high speed). The homogenate was then centrifuged at 10,000 x g for 10 minutes at 4° C. The supernatant was removed and 0.2 volumes chloroform added to the supernatant, vortexed, and centrifuged at 10,000 x g for 15 minutes at 4° C. The upper aqueous phase was removed and 5 volumes of 4 M Guanidine thiocyanate, 25 mM sodium citrate, 0.5% sarkosyl, 0.1 M beta-mercaptoethanol and .475 volumes of 100 % ethanol were added to the upper aqueous phase.
The solution was then applied to Qiagen RNAqueous mini-columns (cat # 74104), using a vacuum manifold (according to the manufacture's directions) for further purification ~of the RNA. The purified RNA was then ethanol precipitated to concentrate, resuspended in DEPC
water and DNAse I treated to remove residual DNA. The DNA freeTM DNAse Treatment kit from Ambion (cat #1906) was used for DNAse I treatment according to the manufacture's directions.

[0088] RNA was quantitated in a Beckman DU 640B spectrophotometer at 260 nm (Beckman Coulter, Inc.,4300 N. Harbor Boulevard, P.O. Box 3100, Fullerton, CA
92834-3100).
Absorbance of 1 at 260nm is equivalent to 40 ~,g RNA/ml. Typical yields were 0.65 to 0.8 ~,g/~,1. Quality of RNA was determined by the absorbance at 260 nm/280 nm with a typical ratio of 1.7 - 2Ø Quality was also assessed by electrophoresis in a 1 % agarose gel/formaldehyde/Tris-borate-EDTA (TBE), pH 7.8 buffer (90mM Tris, 90mM boric acid, 2mM
EDTA). Approximately 1 to 3.5 ~,g RNA was loaded (2 to 5 ~l) after being mixed with 15 ~,l gel loading solution (lOmM Tris pH 7.5, 1mM EDTA, 0.02% bromophenol blue, 10%
glycerol).
The gel was run at 50 Volts for 3-4 hours, stained with SYBR Green I
(Molecular Probes, Inc., PO Box 22010 ,Eugene, OR 97402-0469, 4849 Pitchford Ave., Eugene, OR 97402-9165 ) at a dilution of 1:10,000 for 30 minutes in the dark and scanned using a Hitachi FMBIO II
Fluorescent scanner at 505 nm (Hitachi Genetic Systems, 1201 Harbor Bay Parkway Ste. 150, Alameda, CA 94502).
Example 2 Differential Display [0089] Fluorescent differential display was performed using one of three anchored primers in combination with one of 80 arbitrary primers (GenHunter). In all, 240 PCR reactions were carried out. Reactions were separated using PAGE and visualized using a fluorescent scanner (FMBIOII, Hitachi). Bands representing differentially expressed genes were excised, reamplified and run on an agarose gel to verify size. These were subsequently subcloned (PCR-TRAP, GenHunter) and sequenced.

[0090] Differential display was performed using GenHunter's RNAimage~ kit or RNAspectra~ green fluorescent mRNA differential display systems (GenHunter Corporation, 624 Grassmere Park Drive, Suite 17, Nashville, TN 37211). Approximately 200 ng of RNA was reverse transcribed in the following reaction (final concentration): RT buffer (25 mM Tris-Cl, pH
8.3, 37.6 mM KCI, 1.5 mM MgCl2, 5 mM DTT), 625 ~.M ea. dNTP, 50 pmol H-T11G
primer (GenHunter) (5'AAGCTTTTTTTTTTTG 3') (SEQ ~ N0:1559), or H-T11C primer (GenHunter) (5'AAGCTTTTTTTTTTTC 3') (SEQ ~ N0:1560), or H-T11A primer (GenHunter) (5'AAGCTTTTTTTTTTTA 3') (SEQ m N0:1561), in a total volume of 19 p,1. 1~,1 (100 units/~,1) of MMLV reverse transcriptase was added ten minutes into the 37°C step in a thermocycler (GeneAmp PCR System 9700, PE Applied Biosystems, 850 Lincoln Center Dr., Foster CA 94404) and the following reaction performed: 65°C 5 minutes, 37°C 60 minutes, 75°C
minutes followed by a hold at 4°C. Two p,1 of the reverse transcription reaction was used in the following polymerase chain reaction: PCR buffer (lOmM Tris-Cl, pH 8.4, 50 mM KCl, 1.5 mM MgCl2, 0.001% gelatin), 50 ~,M each dNTP, 5 pmol Fluorescein-labeled H-T11G
primer (GenHunter) (Fluorescein-labeled primer, 5' AAGCTTTTTTTTTTTG 3') (SEQ ID
N0:1562), or Fluorescein-labeled H-T11C primer (GenHunter) (Fluorescein-labeled primer, 5' AAGCTTTTTTTTTTTC 3') (SEQ ID N0:1563) or Fluorescein-labeled H-T11A primer (GenHunter) (Fluorescein-labeled primer, 5' AAGCTTTTTTTTTTTA 3' ) (SEQ m NO:1564) one of the H-AP primers provided in the kit at 200 pM, 1 unit of Amplitaq DNA
polymerase (PE
Applied Biosystems, 850 Lincoln Center Dr., Foster CA 94404 ) in a total of 20 ~,1.

[0091] The following thermocycler reaction was used: 40 cycles of 94°C
15 seconds, 40°C 2 minutes, 72°C 30 seconds, followed by 72°C 5 minutes and a 4°C hold.

[0092] 5 ~1 of each PCR sample was mixed with 5 ~Zl blue dextran loading buffer and (~1 deionized formamide and electrophoresed on a 6% polyacrylamide gel at 55 watts for 3 hours in TBE buffer. The gel was scanned using a Hitachi FMBIO II at 505 nm.
cDNA bands differentially expressed were excised with a razor, placed in a 1.5 ml tube, soaked in 100 ~,l sterile water for 10 minutes and then boiled for 15 minutes. Tubes were centrifuged for 2 minutes at 10,000 x g and the supernatant transferred to a new tube. 10 ~,l 3M
sodium acetate, 5 ~l glycogen (10 mg/ml) and 450 ~,l 100% ethanol was added to the supernatant and the tubes were placed at -80°C overnight. Samples were centrifuged at 10,000 x g for 10 minutes at 4 °C
and the supernatant was removed. cDNA pellets were washed with cold (-20°C) 85% ethanol, spun as above for 1 minute and the supernatant was removed. cDNA pellets were resuspended in 10 ~,1 sterile water.

[0093] Four p1 samples of the cDNA extracts were amplified the same as in the above PCR reaction with the following exceptions: 40 ~.1 total reaction volume; 20 ~.M ea. dNTP; 200 pM unlabeled primer H-T11G , H-T11C , or H-T11A (Genl3unter) and 2 units of Amplitaq DNA
polymerase (PE Applied Biosystems). PCR conditions were the same as above. 15 p,1 of the amplified cDNA extracts were mixed with 3 ~16X loading dye (0.25% bromophenol blue, 0.25% xylene cyanol FF, 30% glycerol) and electrophoresed in a 1.5% agarose gel. The gel was run at 100 volts for 2 to 3 hours in TBE buffer, stained/visualized the same as above. Bands were excised with a razor and cDNA extracted according to Qiagen's QIAEX~ II
Gel Extraction I~it (Qiagen, Inc., 28159 Avenue Stanford, Valencia, CA 91355). Three hundred ~,l QX1 buffer and 10 ~,l QIAEXO II suspension was added to each gel slice in a 1.5 ml tube and incubated at 50°C for 10 minutes. Tubes were vortexed every 2 minutes during incubation. Tubes were centrifuged 10,000 x g for 30 seconds and the supernatant was discarded.
Pellets were washed once with 500 ~l Buffer QX1 and twice with buffer PE (vortexing and centrifuging as above for each wash). Pellet was air dried for 10 minutes and 20 ~.1 sterile water was added. Tubes were incubated for 5 minutes at room temperature and cDNA was eluted by centrifugation as above for 30 seconds. Supernatant was then transferred to a new 1.5 ml tube and stored at -20°C.

[0094] Amplified gel purified cDNA was subcloned according to GenHunter's PCR-TRAP~ Cloning System I~it (GenHunter Corporation, 624 Grassmere Park Drive, Suite 17, Nashville, TN 37211). 5 ~,l amplified gel purified cDNA was added to 300 ng PCR-TRAP~
vector, ligase buffer (50 mM Tris-Cl, ,.pH 7.8, 10 mM MgCl2, 10 mM DTT, 10 mM
ATP, 5 ~,g BSA) and 200 units T4 DNA ligase, mixed, and incubated overnight at 16°C. GH competent cells (E. coli del(lac pro) ara tl2i (cp80dlacZde1M15)) were transformed with ligation reaction by mixing 10 ~.l ligation reaction to 100 ~,1 GH competent cells on ice in 1.5 ml tubes. Tubes were incubated on ice for 45 minutes, heat shocked at 42°C for 2 minutes and then incubated on ice for 2 minutes. 400 ~l LB broth (Luria-Bertani, Difco) was added to each tube and the tubes were incubated at 37°C for 1 hour with shaking (250 rpm). 200 [u1 of these transformations were plated onto LB-agar-tet plates (LB-agar, Difco, tetracycline 20 ~,g/ml) and incubated overnight at 37°C.

[0095] Colonies were checked for insert using GenHunter's colony lysate PCR
protocol. Colonies were picked with a clean pipette tip and placed in 50 ~,l colony lysate buffer (GenHunter, TE with 0.1 % Tween 20) in a microfuge tube. Tubes were boiled for 10 minutes, centrifuged at 10,000 x g for 2 minutes and the corresponding lysate (supernatant) was transferred to a new microfuge tube. 2.0 ~1 of lysate was added to PCR buffer, 20 ~,M ea. dNTP, 200~pmo1 ea. of Lgh (5' CGACAACACCGATAATC) (SEQ ID N0:1565) and Rgh (5' GACGCGAACGAAGCAAC) (SEQ ID N0:1566) primers and 1 unit of Amplitaq DNA
polymerase (PE Applied Biosystems) in a total volume of 20 ~,1. The following thermocycler reaction was used: 30 cycles of 94°C for 30 seconds, 52°C for 40 seconds and 72°C for 1 minute followed by 72°C for 5 minutes and a 4°C hold. PCR products were analyzed in a 1.5% agarose gel the same as above.

[0096] 3-5 ml LB broth was inoculated with appropriate colonies and incubated overnight at 37°C at 250 rpm. Plasmids were isolated according to Qiagen's QIAprep Plasmid protocol. Bacteria were pelleted (10,000 x g, 30 seconds) using 2 x 1.5 ml inoculated broth and the supernatant was removed. Pelleted bacteria were resuspended in 250 ~1 buffer P1, 250 p,1 buffer P2 was then added and tubes were mixed by gentle inversion. 350 ~,1 buffer N3 was added, tubes were mixed by gentle inversion and then centrifuged for 10 minutes. Supernatants were added to a QIAprep column and centrifuged for 30 seconds. Flow-throughs were discarded, 0.5 ml of buffer PB was added to column and tubes were centrifuged for 30 seconds. Columns were washed with 0.75 ml buffer PE and centrifuged for 30 seconds. Flow-throughs were discarded and tubes were spun an additional minute. DNA was eluted from the column by adding 50 ~l sterile water to the column. The column was incubated at room temperature for 1 minute and then centrifuged for 1 minute. Resulting supernatant containing plasmid DNA was quantitated as above (absorbance of 1 at 260 nm equals 50 [~g/ml) with a typical yield of 350 ~,g/ml and a 260nm/280nm ratio of 1.8.

[0097] Sequencing reactions used 200 to 500 ng plasmid DNA in the ABI Prism BigDye Terminator Cycle Sequencing Ready Reaction Kit (PE Applied Biosystems, 850 Lincoln Center Dr., Foster CA 94404). 0.8 ~.1 of primer (0.16 ~,m final concentration of either Lgh or Rgh, GenHunter) was added to plasmid DNA along with 4.0 ~,1 Teminator Reaction Mix (containing AmpliTaq DNA Polymerase, FS, deoxynucleoside triphosphates, MgCl2, Tris-HCL
buffer, pH 9.0, A-Dye Terminator labeled with dichloro(R6G), C-Dye Terminator labeled with dichloro(ROX), G-Dye Terminator labeled with dichloro(R110) and T-Dye Terminator labeled with dichloro(TAMRA)) and brought to a final volume of 10 ~.1 with sterile water. The following thermocycler reaction was used: 25 cycles of 96°C for 10 seconds, 50°C for 5 seconds, 60°C for 4 minutes followed by a 4°C hold.

[0098] Unincorporated dye-terminators were removed from the sequencing reactions according to Qiagen's DyeEx 'spin protocol. Prepared DyeEx spin columns were placed in 2.0 ml microfuge tubes and centrifuged at 750 x g for 3 minutes. Columns were placed in new tubes, sequencing reactions were added to columns and centrifuged, as above, for 3 minutes. The eluate was placed at 74°C until dry.

[0099] 5 ~,1 of formamide/blue dextran (5:1 ratio) was added to each dried sequencing pellets. 1.5 ~,1 to 2.0 ~,1 was then added to a 5% polyacrylamide gel (in TBE
buffer) on a Perkin Elmer ABI Prism 377 automated DNA sequencer.

[0100] Each isolated plasmid clone was sequenced 2-6 times (2-6 different sequencing reactions, 1-3 times for each primer, Lgh or Rgh). Sequence files from the ABI
377 sequencer were transferred to Genetic Computer Group's Wisconsin Package and a corresponding consensus sequence was determined.

[0101] Approximately 1750 clones were isolated using differential display. All genes that appeared to be differentially expressed were selected. A representational polyacrylamide gel image is shown in Figure 1. Panel A represents the gel prior to band excision and panel B
represents the same gel after band excision. Sizes of clones ranged from 90 b.p. to 1150 b.p., with an average size of 300 b.p. After filtering the sequences for redundant sequences, dimers, E.
coli fragments, fragments <100 b.p. etc., 1558 remained. Sequences obtained (SEQ ID NOs:1-1558) are shown in Table 1, which is appended herewith and which forms part of the present specification.

[0102] The sequences obtained were BLASTed against the human, mouse and dog public domain genomes to get a first hit. To be considered a hit at this stage, the match had to cover more than 50% of the sequence and an Expect value (E value) of less than 0.002. The first hits were used to extend the sequence using the respective genome. The sequences were either extended 2kb to the 5' or 3' side of the hit. The extended sequences were then used to BLAST
against public domain protein databases (Ensembl, swissprot/trembl). The respective hits (those with an Expect value of less than 0.002, in this case) were consolidated and used for the annotations. In some cases, this strategy did not give hits, and in these situations the original sequences were BLASTed directly against swissprot/trembl or Ensembl proteins.
In this case, hits were considered when the Expect value was less than 0.002.

[0103] Results of BLAST analysis (as of 1/28/04) of sequences isolated by differential display are shown in Table 2, which is appended herewith and which forms part of the present specification. The sequences are listed in the leftmost column by the gene ID
designations (clone numbers) employed by the inventors herein. Many sequences matched with a Description of a previously-identified gene; the Description column also includes the source database and the corresponding database accession number. Table 2 includes additional information from a number of databases, including Ensemble Gene IDs, Ensemble Transcript IDs, Swissprot/Ensemble, OMIM (Online Mendelian Inheritance in Man), RefSeq, Pfam, InterPro and HUGO. Information is also shown regarding Chromosome Number (#) and Chromosome Location for many of the sequences. Additionally, the column labeled "Signal peptide" indicates the sequences for which a predicted signal peptide occurs in the amino acid sequence; the column labeled "TMHMM" (Transmembrane Hidden Markov Model) indicates sequences for which a predicted transrnembrane region occurs in a protein sequence.
Table 6 lists clones demonstrating homology to previously-identified genes.
Table 6 CaMax Description SEQ ID
NO

Gene ID

CaMax:BUTYRATE RESPONSE FACTOR 2 (TIS 11D PROTEIN) 1360 (EGF-1006b RESPONSE FACTOR 2) (ERF-2). [Source:SWISSPROT;Acc:P47974]

CaMax:BUTYRATE RESPONSE FACTOR 2 (TIS11D PROTEIN) 1361 (EGF-1007a RESPONSE FACTOR 2) (ERF-2). [Source:SWISSPROT;Acc:P47974]

CaMax:GRAVE'S DISEASE CARRIER PROTEIN (GDC) (GRAVE'S905 DISEASE

1009c AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE CARRIER

PROTEIN HOMOLOG). [Source:SWISSPROT;Acc:P16260]

CaMax:ZINC FINGER PROTEIN 333. [Source:SWISSPROT;Acc:Q96JL9]934 1019a CaMax:CALCITONIN GENE-RELATED PEPTIDE TYPE 1 RECEPTOR

1020a PRECURSOR (CGRP TYPE 1 RECEPTOR). 935 [Source:SWISSPROT;Acc:Q16602]

CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY938 (MOUSE) 1029a HOMOLOG-LIKE. [Source:RefSe ;Acc:NM 145702]

CaMax: POLY [ADP-RIBOSE] POLYMERASE-3 (EC 2.4.2.30) (PARP-3) 1044c (NAD(+) ADP- RIBOSYLTRANSFERASE-3) (POLY[ADP-RIBOSE]1363 SYNTHETASE-3) (PADPRT-3) (HPARP-3) (IRT1).

[Source:SWISSPROT;Acc:Q9Y6F1]

CaMax: HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN H 439 (HNRNP

104a H). [Source:SWISSPROT;Acc:P31943]

CaMax: LEUKEMIA-ASSOCIATED PROTEIN WITH A CXXC DOMAIN.1160 1061a [Source:SPTREMBL;Acc:Q8NFU7]

CaMax: FERRITIN HEAVY CHAIN (FERRITIN H SUBUNIT). 440 106a [Source:SWISSPROT;Acc:P02794]

CaMax: RAS-RELATED PROTEIN RAB-14. [Source:SWISSPROT;Acc:P35287]1320 1105a CaMax: STAR-RELATED LIPID TRANSFER PROTEIN 13 (STARD13) (START

1108a DOMAIN- CONTAII~TING PROTEIN 13) (46H23.2). 1262 [Source:SWISSPROT;Acc:Q9Y3M8]

CaMax: SESTRIN 1 (P53-REGULATED PROTEIN PA26). 898 1111b [Source:SWISSPROT;Acc:Q9Y6P5]

CaMax: GOLGI PHOSPHOPROTEIN 3; GOLGI PROTEIN; GOLGI

1120a PERIPHERAL MEMBRANE PROTEIN 1, 34 KDA; GOLGI-1366 ASSOCIATED PROTEIN; COAT-PROTEIN.

[Source:RefSe ;Acc:NM 022130]

CaMax: MYOCYTE-SPECIFIC ENHANCER FACTOR 2C. 1172 1134a [Source:SWISSPROT;Acc:Q06413]

CaMax: FORKHEAD BOX PROTEIN P2 (CAG REPEAT PROTEIN
44) 1135a (TRINUCLEOTIDE REPEAT- CONTAINING GENE 10 1173 PROTEIN).

[Source:SWISSPROT;Acc:015409]

CaMax: COLLAGEN ALPHA 1(XV) CHAIN PRECURSOR. 1436 1145a [Source:SWISSPROT;Acc:P39059]

CaMax: HETEROGENEOUS NUCLEAR RIBONUCLEOPROTE1N H 439 (HNRNP

104a H). [Source:SWISSPROT;Acc:P31943]

CaMax: TROPOMYOS1N 1 ALPHA CHAIN (ALPHA-TROPOMYOSIN).1322 1169b [Source:SWISSPROT;Acc:P09493]

CaMax: DYNEIN HEAVY CHAIN, CYTOSOLIC (DYHC) (CYTOPLASMIC

1177c DYNEIN HEAVY CHAIN 1) (DHC1) (FRAGMENT). 943 , ' [Source:SWISSPROT;Acc: Q 14204]

CaMax: T-LYMPHOMA INVASION AND METASTASIS INDUCING 885 PROTEIN

1184a 1 (TIAM1 PROTEIN). [Source:SWISSPROT;Acc:Q13009]

CaMax: VAV-3 PROTEIN. [Source:SWISSPROT;Acc:Q9UKW4]1324 1213d CaMax: WD-REPEAT PROTEIN 3. [Source:SWISSPROT;Acc:Q9UNX4]908 1243a CaMax: PROPIONYL-COA CARBOXYLASE ALPHA CHAIN, 1267a MITOCHONDRIAL PRECURSOR (EC 6.4.1.3) (PCCASE874 ALPHA

SUBUNIT) (PROPANOYL-COA:CARBON DIOXIDE LIGASE
ALPHA

SUBUNIT). [Source:SWISSPROT;Acc:P05165]

CaMax: PROPIONYL-COA CARBOXYLASE ALPHA CHAIN, 1267a MITOCHONDRIAL PRECURSOR (EC 6.4.1.3) (PCCASE874 ALPHA

SUBUNIT) (PROPANOYL-COA:CARBON DIOXIDE LIGASE
ALPHA

SUBUNIT). [Source:SWISSPROT;Acc:P05165]

CaMax: PROTEIN TRANSPORT PROTEIN SEC24A (SEC24-RELATED872 1272a PROTEIN A) (FRAGMENT). [Source:SWISSPROT;Acc:095486]

CaMax: IDN3 PROTEIN ISOFORM A. [Source:RefSeq;Acc:NM_133433]952 1287c CaMax: IDN3 PROTEIN ISOFORM A. [Source:RefSeq;Acc:NM_133433]63 1288a CaMax: HEAT SHOCK PROTEIN HSP 90-BETA (HSP 84) (TUMOR
SPECIFIC

128a TRANSPLANTATION 84 KDA ANTIGEN) (TSTA). 234 [Source:SWISSPROT;Acc:P11499]

CaMax: ATP-DEPENDENT DNA HELICASE II, 80 KDA SUBUNIT
(LUPUS KU

1292c AUTOANTIGEN PROTEIN P86) (KU86) (KU80) (86 KDA SUBUNIT OF

KU ANTIGEN) (THYROID- LUPUS AUTOANTIGEN) 44 (TLAA) (CTC

BOX BINDING FACTOR 85 KDA SUBUNIT) (CTCBF) (CTC85) (NUCLEAR FACTOR IV) (DNA-REPAIR PROTEIN XRCCS).

[Source: SWISSPROT;Acc:P 13010]

CaMax: BIFUNCTIONAL AMINOACYL-TRNA SYNTHETASE [INCLUDES:

1294b GLUTAMYL-TRNA SYNTHETASE (EC 6.1.1.17) (GLUTAMATE--1245 TRNA LIGASE); PROLYL-TRNA SYNTHETASE (EC
6.1.1.15) (PROLINE--TRNA LIGASE)]. [Source:SWISSPROT;Acc:P07814]

CaMax: WD REPEAT AND FYVE DOMAIN CONTAINING 3 ISOFORM316 1.

1299c [Source:RefSe ;Acc:NM 014991]

CaMax: AMISYN; SYNTAXIN BINDING PROTEIN 6. 1371 1304a [Source:RefSe ;Acc:NM 014178]

CaMax: UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N-1322c ACETYLGLUCOSAMINYLTRANSFERASE 110 KDA SUBUNIT1372 (EC

2.4.1.-) (O-GLCNAC TRANSFERASE P110 SUBUNIT).

[Source:SWISSPROT;Acc:P56558]

CaMax: CYSTEINE KNOT SUPERFAMILY 1, BMP ANTAGONIST 1269 1;

1341a GREMLIN. [Source:RefSe ;Acc:NM_013372]

CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY370 (MOUSE) 1354a HOMOLOG-LIKE. [Source:RefSe ;Acc:NM 145702]

CaMax: ALPHA-(1,6)-FUCOSYLTRANSFERASE (EC 2.4.1.68) 1361a (GLYCOPROTEIN 6-ALPHA-L-FUCOSYLTRANSFERASE) (GDP-FUCOSE--GLYCOPROTEIN FUCOSYLTRANSFERASE) 1189 (GDP-L-FUC:N-ACETYL-BETA-D-GLUCOSAMINIDE ALPHA1,6-FUCOSYLTRANSFERASE) (ALPHAl-6FUCT) (FUCOSYLTRANSFERASE 8). [Source:SWISSPROT;Acc:Q9BYC5]

CaMax: CONNECTIVE TISSUE GROWTH FACTOR-LIKE PROTEIN

1366a PRECURSOR (CTGF-L) (WNT1 INDUCIBLE SIGNALING209 PATHWAY

PROTEIN 2) (WISP-2) (CONNECTIVE TISSUE GROWTH
FACTOR-RELATED PROTEIN 58). [Source:SWISSPROT;Acc:076076]

CaMax: CATENIN (CADHERIN-ASSOCIATED PROTEIN), ALPHA-LIKE392 1;

1371a ALPHA-CATULIN. [Source:RefSe ;Acc:NM_003798]

CaMax: M-PHASE PHOSPHOPROTEIN 8 (FRAGMENT). 491 137b [Source:SWISSPROT;Acc:Q99549]

CaMax: ECOTROPIC VIRAL INTEGRATION SITE 5; NEUROBLASTOMA911 1383a STAGE 4S GENE. [Source:RefSe ;Acc:NM 005665]

CaMax: ACYL-COA DESATURASE (EC 1.14.19.1) (STEAROYL-COA

1384a DESATURASE) (FATTY ACID DESATURASE) (DELTA(9)-1330 DESATURASE). [Source:SWISSPROT;Acc:000767]

CaMax: NUCLEAR RECEPTOR COACTIVATOR 7; ESTROGEN 858 RECEPTOR

1397b ASSOCIATED PROTEIN 140 KDA. [Source:RefSe ;Acc:NM 181782]

CaMax: PDZ DOMAIN CONTAINING GUANINE NUCLEOTIDE
EXCHANGE

1401c FACTOR (GEF) 1; RA(RAS/RAP1A-ASSOCIATING)-GEF;
PDZ

DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE

FACTOR(GEF)1; RA(RAS/RAP1A-ASSOCIATING)-GEF;306 PDZ

DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE

FACTOR(GEF)1. [Source:RefSe ;Acc:NM 014247]

CaMax: BAG-FAMILY MOLECULAR CHAPERONE REGULATOR-5 853 (BAG-5).

1409b [Source:SWISSPROT;Acc:Q9UL15]

CaMax: PROTEIN PHOSPHATASE 1, REGULATORY (INHIBITOR)1247 SUBUNIT

1411a 12A; MYOSIN PHOSPHATASE, TARGET SUBUNIT 1.

[Source:RefSe ;Acc:NM 002480]

CaMax: CELL CYCLE PROGRESSION 8 PROTEIN. 981 1420c [Source:RefSe ;Acc:NM 020739]

CaMax: MUCOSA ASSOCIATED LYMPHOID TISSUE LYMPHOMA

1421a TRANSLOCATION PROTEIN 1 (EC 3.4.22.-) (MALT-LYMPHOMA1248 ASSOCIATED TRANSLOCATION) (PARACASPASE).

[Source:SWISSPROT;Acc:Q9UDY8]

CaMax:SPARC-LIKE PROTEIN 1 PRECURSOR (HIGH ENDOTHELIAL

143.2cVENULE PROTEIN) (HEVIN) (MAST 9). 145 [Source:SWISSPROT;Acc:Q14515]

CaMax:SPARC-LIKE PROTEIN 1 PRECURSOR (HIGH ENDOTHELIAL

143.2cVENULE PROTEIN) (HEVIN) (MAST 9). 145 [Source:SWISSPROT;Acc:Q14515]

CaMax:TESTICAN-3 PRECURSOR. [Source:SWISSPROT;Acc:Q9BQ16]969 1448a CaMax:ZINC FINGER PROTEIN CLONE 647. 1270 1449a [Source:SWISSPROT;Acc:P15622]

CaMax:CYTOKINE-LIKE PROTEIN C17 PRECURSOR. 1450 1450a [Source:SWISSPROT;Acc:Q9NRR1]

CaMax:ACTIVATED RNA POLYMERASE II TRANSCRIPTIONAL 850 1459c COACTIVATOR P15 (PC4) (P14). [Source:SWISSPROT;Acc:P53999]

CaMax:60S RIBOSOMAL PROTEIN L10 (QM PROTEIN) (TUMOR

145b SUPPRESSOR QM) (LAMININ RECEPTOR HOMOLOG). 455 [Source:SWISSPROT;Acc:P27635]

CaMax:UPREGULATED DURING SKELETAL MUSCLE GROWTH 847 5.

1469a [Source:RefSe ;Acc:NM 023211]

CaMax:UPREGULATED DURING SKELETAL MUSCLE GROWTH 847 5.

1469a [Source:RefSe ;Acc:NM_023211]

CaMax:DNA-BINDING PROTEIN INHIBITOR ID-4. 846 1476a [Source:SWISSPROT;Acc:P47928]

CaMax:BTG2 PROTEIN (NGF-INDUCIBLE ANTI-PROLIFERATIVE276 PROTEIN

1477a PC3). [Source:SWISSPROT;Acc:P78543]

CaMax:HOMEOBOX PROTEIN HOX-A3 (HOX-lE). 23 1481c [Source:SWISSPROT;Acc:043365]

CaMax:HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS A2/B195 1488b (IINRNP A2 l HNRNP B 1). [Source:SWISSPROT;Acc:P22626]

CaMax:NADP-DEPENDENT LEUKOTRIENE B4 12-150a HYDROXYDEHYDROGENASE (EC 1.1.1.-). 458 [Source:SWISSPROT;Acc:Q14914]

CaMax:PROTEIN PHOSPHATASE METHYLESTERASE-1. 147 1521b [Source:RefSe ;Acc:NM 016147]

CaMax:CYSTINE/GLUTAMATE TRANSPORTER (AMINO ACID

1546b TRANSPORT SYSTEM XC-) (XCT) (CALCIUM CHANNEL 1199 BLOCKER

RESISTANCE PROTEIN CCBR1). [Source:SWISSPROT;Acc:Q9UPY5]

CaMax:BTB (POZ) DOMAIN CONTAINING 5. 223 1551a [Source:RefSe ;Acc:NM 017658]

CaMax:TRANSMEMBRANE PROTEIN 4. [Source:RefSeq;Acc:NM_014255]1464 1577a CaMax:UNC-51-LIKE KINASE 2. [Source:RefSeq;Aec:NM_014683]119 1631d CaMax:UNC-51-LIKE KINASE 2. [Source:RefSeq;Acc:NM_014683]1550 1635a CaMax:UNC-51-LIKE KINASE 2. [Source:RefSeq;Acc:NM_014683]1550 1635a CaMax:MACROPHAGE INFLAMMATORY PROTEIN-2-BETA PRECURSOR465 164c (MIP2-BETA) (CXCL3) (GROWTH REGULATED PROTEIN
GAMMA) (GRO-GAMMA). [Source:SWISSPROT;Acc:P19876]

CaMax:CYTOCHROME C OXIDASE SUBUNIT IV ISOFORM 1, 1690a MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (COX 1379 IV-1)' (CYTOCHROME C OXIDASE POLYPEPTIDE IV).

[Souree:SWISSPROT;Acc:P 10888]

CaMax:CYTOCHROME C OXIDASE SUBUNIT IV ISOFORM 1, 1692a MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (COX 1380 IV-1) (CYTOCHROME C OXIDASE POLYPEPTIDE IV).

[Source:SWISSPROT;Acc:P 10888]

CaMax:FIBROBLAST GROWTH FACTOR RECEPTOR 2 PRECURSOR
(EC

1693b 2.7.1.112) (FGFR-2) (KERATINOCYTE GROWTH 1333 FACTOR

RECEPTOR 2). [Source:SWISSPROT;Acc:P21802]

CaMax: CASPASE RECRUITMENT DOMAIN PROTEIN 6. 1132 1705a [Source:SWISSPROT;Acc:Q9BX69]

CaMax: T-CELL ACTIVATION PROTEIN. [Source:RefSeq;Acc:NM_033296]1060 -1717a CaMax: LEUKOCYTE ELASTASE INHIBITOR (LEI) 1721a (MONOCYTE/NEUTROPHIL ELASTASE INHIBITOR) 1064 (M/NEI) (EI).

[ Source:SWISSPROT;Acc:P30740]

CaMax: GOLGI AUTOANTIGEN, GOLGIN SUBFAMILY A MEMBER

1722a (TRANS-GOLGI P230) (256 KDA GOLGIN) (GOLGIN-245)1065 (72.1 PROTEIN). [Source:SWISSPROT;Acc:Q13439]

CaMax: G-PROTEIN COUPLED RECEPTOR. [Source:RefSeq;Acc:NM_153832]1066 1724a CaMax: EGF-LIKE MODULE-CONTAINING MUCIN-LIKE RECEPTOR29 1727a ISOFORM A. [Source:RefSe ;Acc:NM 032571]

CaMax: LEUCINE-RICH REPEAT-CONTAINING G PROTEIN-COUPLED

1744a RECEPTOR 4 PRECURSOR (G PROTEIN-COUPLED RECEPTOR325 48).

[Source:SWISSPROT;Acc:Q9BXB 1]

CaMax: TRANSCRIPTION INITIATION FACTOR IIF, BETA
SUBUNIT (TFIIF-174a BETA) (TRANSCRIPTION INITIATION FACTOR RAP30).243 [Source:SWISSPROT;Acc:P13984]

CaMax: U1 SMALL NUCLEAR RIBONUCLEOPROTEIN 70 KDA 340 (U1 SNRNP

1758a 70 KDA) (SNRNP70) (U1-70K). [Source:SWISSPROT;Acc:P08621]

CaMax: BTB (POZ) DOMAIN CONTAINING 5. 1479 1759b [Source:RefSe ;Acc:NM 017658]

CaMax: GOLGI COILED COIL PROTEIN 1. [Source:SWISSPROT;Acc:Q96CN9]1481 .

1775a CaMax: GOLGI COILED COIL PROTEIN 1. [Source:SWISSPROT;Acc:Q96CN9]1481 1775a CaMax: OK/SW-CL.87. [Source:SPTREMBL;Acc:Q8NI68] 1136 1782b CaMax: TRANSCRIPTION FACTOR CP2; TRANSCRIPTION FACTOR295 CP2, 178a ALPHA GLOBIN. [Source:RefSe ;Acc:NM 005653]

CaMax: ATP-DEPENDENT CLP PROTEASE ATP-BINDING SUBUNIT
CLPX-1801b LIKE, MITOCHONDRIAL PRECURSOR. 89 [Source:SWISSPROT;Acc:076031]

CaIVIax:TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY472 (MOUSE) 180a HOMOLOG-LIKE. [Source:RefSe ;Acc:NM 145702]

CaMax: SIALIC ACID BINDING IG-LIKE LECTIN 6 PRECURSOR
(SIGLEC-6) 1812b (OBESITY- BINDING PROTEIN 1) (OB-BP1) (CD33 272 ANTIGEN-LIKE

1). [Source:SWISSPROT;Acc:043699]

CaMax: PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE39 1814c PRECURSOR (EC 1.14.17.3) (PAM). [Source:SWISSPROT;Acc:P19021]

CaMax: PROTEOGLYCAN LINK PROTEIN PRECURSOR (CARTIL,AGE1283 LINK

1828b PROTEIN) (LP). [Source:SWISSPROT;Acc:Q9QUP5]

CaMax: SPLICEOSOMAL PROTEIN SAP155 (FRAGMENT). 263 1853a [Source:SPTREMBL;Acc:Q9ET34]

CaMax: CYTOCHROME B5. [Source:SWISSPROT;Acc:P00173]15 1857c CaMax: MYELOID/LYMPHOID OR MIXED-LINEAGE LEUKEMIA 983 3; ALR-1859a LIKE PROTEIN. [Source:RefSe ;Acc:NM 021230]

CaMax: SNF2 HISTONE LINKER PHD RING HELICASE. 133 1917f [Source:RefSe ;Acc:NM 173082]

CaMax: ENDOTHELIAL AND SMOOTH MUSCLE CELL-DERIVED

1919a NEUROPILIN-LIKE PROTEIN; COAGULATION FACTOR 150 V/VIII-HOMOLOGY DOMAINS PROTEIN 1. [Source:RefSe ;Acc:NM 080927]

CaMax: BETA-TUBULIN COFACTOR E. [Source:RefSeq;Acc:NM24 003193]

1940e CaMax: CDW92 ANTIGEN; CHOLINE TRANSPORTER-LIKE PROTEIN.314 1941e [Source:RefSe ;Acc:NM 080546]

CaMax: ALPHA-ACTININ-2-ASSOCIATED LIM PROTEIN; ENIGMA338 1943a HOMOLOG. [Source:RefSe ;Acc:NM 014476]

CaMax: VAV-3 PROTEIN. [Source:SWISSPROT;Acc:Q9UKW4]1293 1950a CaMax: NGFI-A BINDING PROTEIN 1 (EGR-1 BINDING PROTEIN
1) 1953a (TRANSCRIPTIONAL REGULATORY PROTEIN P54). 371 [Source:SWISSPROT;Acc:Q13506]

CaMax: MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG

1961e INTERACTING PROTEIN (MADH-INTERACTING PROTEIN)1494 (SMAD

ANCHOR FOR RECEPTOR ACTIVATION) (RECEPTOR
ACTIVATION

ANCHOR) (HSARA) (NOVEL SERINE PROTEASE) (NSP).

[Source:SWISSPROT;Acc:095405]

CaMax: ANTIGEN PEPTIDE TRANSPORTER 2 (APT2) (PEPTIDE

1967a TRANSPORTER TAP2) (PEPTIDE TRANSPORTER PSF2)1083 (PEPTIDE

SUPPLY FACTOR 2) (PSF-2) (PEPTIDE TRANSPORTER
INVOLVED

IN ANTIGEN PROCESSING 2). [Source:SWISSPROT;Acc:Q03519]

CaMax: PELLINO PROTEIN. [Source:RefSeq;Acc:NM_020651]1084 1968a CaMax: COLLAGEN ALPHA 1(XI) CHAIN PRECURSOR. 1088 1982a [Source:SWISSPROT;Acc:P12107]

CaMax: MICROTUBULE-ASSOCIATED PROTEIN, RP/EB FAMILY, MEMBER

1990a 2; T-CELL ACTIVATION PROTEIN, EB 1 FAMILY; 1092 APC-BINDING

PROTEINEBl. [Source:RefSe ;Acc:NM 014268]

CaMax: PINS. [Source:RefSeq;Acc:NM_029522] 1498 2008a CaMax: NUCLEAR FACTOR RIP140 (NUCLEAR RECEPTOR INTERACTING1499 2013a PROTEIN 1). [Source:SWISSPROT;Acc:P48552]

CaMax: 60S RIBOSOMAL PROTEIN L4 (L1). [Source:SWISSPROT;Acc:P36578]233 2015e CaIVIax:MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE

2020b KINASE 3 (EC 2.7.1.37) (MAPK/ERK KINASE KINASE
KINASE 3) (MEK KINASE KINASE 3) (MEKKK 3) (GERMINAL 284 CENTER KINASE

RELATED PROTEIN KINASE) (GLK).

[Source:SWISSPROT;Acc:Q8IVH8]

CaMax: LATE ENVELOPE PROTEIN 4. [Source:RefSeq;Acc:NM_178352]1501 2034a CaMax: DNA-DIRECTED RNA POLYMERASES III 12.5 KDA
POLYPEPTIDE

2035d (EC 2.7.7.6) (RNA POLYMERASE III C11 SUBUNIT)149 (HSC11P) (HRPC11) (MY010 PROTEIN). [Source:SWISSPROT;Acc:Q9Y2Y1]

CaMax: POTENTIAL HELICASE WITH ZINC-FINGER DOMAIN. 1305 2056d [Source:SWISSPROT;Acc:P42694]

CaMax: PALLADIN; CGI-151 PROTEIN. [Source:RefSeq;Acc:NM1307 016081]

2070a CaMax: POTENTIAL PHOSPHOLIPID-TRANSPORTING ATPASE
IA (EC

2074b 3.6.3.1) (CHROMAFFIN GRANULE ATPASE II) (ATPASE99 CLASS I

TYPE 8A MEMBER 1). [Source:SWISSPROT;Acc:Q9Y2Q0]

CaMax: SEPTIN 7 (CDC10 PROTEIN HOMOLOG). 1098 2078a [Source:SWISSPROT;Acc:Q16181]

CaMax: WD REPEAT AND FYVE DOMAIN CONTAINING 1 ISOFORM
1;

2083e PHOSPHOINOSITIDE-BINDING PROTEIN SRl; WD40 113 AND FYVE

DOMAIN CONTAINING 1. [Source:RefSe ;Acc:NM
020830]

CaMax: FIBRILLIN 1 PRECURSOR. [Source:SWISSPROT;Acc:P35555]1104 2100b CaMax: ZINC FINGER PROTEIN 345 (ZINC FINGER PROTEIN989 HZF10).

2110a [Source:SWISSPROT;Acc:Q14585]

CaMax: MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 1. 505 211b [Source:SWISSPROT;Acc:P33527]

CaMax: PEPTIDE-HISTIDINE TRANSPORTER 4. 1557 2123a [Source:RefSe ;Acc:NM 145648]

CaMax: SMALL PROTEIN EFFECTOR 1 OF CDC42. 990 2129a [Source:RefSe ;Acc:NM 020239]

CaMax: PROTEOGLYCAN 4; MEGAKARYOCYTE STIMULATING
FACTOR;

2224a PROTEOGLYCAN 4, (MEGAKARYOCYTE STIMULATING
FACTOR, ARTICULAR SUPERFICIAL ZONE PROTEIN); JACOBS 215 CAMPTODACTYLY-ARTHROPATHY-PERICARDITIS SYNDROME;

CAMPTODACTYLY, ARTHROPATHY, COXA VARA, PERICARDITIS

SYNDROME. [Source:RefSe ;Acc:NM 005807]

CaMax: THYROTROPIN-RELEASING HORMONE RECEPTOR (TRH-R)994 2234a (THYROLIBERIN RECEPTOR). [Source:SWISSPROT;Acc:P21761]

CaMax: CGMP-INHIBITED 3',5'-CYCLIC PHOSPHODIESTERASE
A (EC

2238a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE996 A) (CGI-PDE A). [Source:SWISSPROT;Acc:Q14432]

CaMax: CGMP-INHIBITED 3',5'-CYCLIC PHOSPHODIESTERASE188 A (EC , 2241a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE
A) (CGI-PDE A). [Source:SWISSPROT;Acc:Q14432]

CaMax: CGMP-INHIBITED 3',5'-CYCLIC PHOSPHODIESTERASE
A (EC

2238a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE996 A) (CGI-PDE A). [Source:SWISSPROT;Acc:Q14432]

CaMax: THROMBOSPONDIN 1 PRECURSOR. 999 2267a [Source:SWISSPROT;Acc:P07996]

CaMax: CGMP-INHIBITED 3',5'-CYCLIC PHOSPHODIESTERASE
A (EC

2241a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE188 A) (CGI-PDE A). [Source:SWISSPROT;Acc:Q14432]

CaMax: THROMBOSPONDIN 1 PRECURSOR. 206 2374a [Source:SWISSPROT;Acc:P07996]

CaMax: SPECTRIN ALPHA CHAIN, BRAIN (SPECTRIN, NON-ERYTHROID

239a ALPHA CHAIN) (ALPHA-II SPECTRIN) (FODRIN 530 ALPHA CHAIN).

[Source:SWISSPROT;Acc:Q13813]

CaMax: GLUCOCORTICOID MODULATORY ELEMENT BINDING 90 ' PROTEIN

23a 1 (GMEB-1) (PARVOVIRUS INITIATION FACTOR
P96) (PIF P96) (DNA BINDING PROTEIN P96PIF). [Source:SWISSPROT;Acc:Q9Y692]

CaMax: TENASCIN PRECURSOR (TN) (HEXABRACHION) (CYTOTACTIN) 267d (NEURONECTIN) (GMEM) (JI) (MIOTENDINOUS ANTIGEN)553 (GLIOMA-ASSOCIATED-EXTRACELLULAR MATRIX ANTIGEN) (GP 150-225) (TENASCIN-C) (TN-C). [Source:SWISSPROT;Acc:P24821]

CaMax: ELAC HOMOLOG 1. [Source:RefSeq;Acc:NM_018696]116 272d CaMax: PROTEIN CGI-147. [Source:SWISSPROT;Acc:Q9Y3E5]598 307b CaMax: RETINAL PIGMENT EPITHELIUM-SPECIFIC PROTEIN
65KDA;

308c RETINAL PIGMENT EPITHELIUM-SPECIFIC PROTEIN 597 (65KI?);

RETINITIS PIGMENTOSA 20 (AUTOSOMAL RECESSIVE).

[Source:RefSe ;Acc:NM 000329]

CaMax: EXOCYST COMPLEX COMPONENT SEC3 (BM-012). 1532 320a [Source:SWISSPROT;Acc:Q9NV70]

CaMax: MICROSOMAL SIGNAL PEPTIDASE 18 KDA SUBUNIT
(EC 3.4.-.-) 326e (SPASE 18 KDA SUBUNIT) (SPC18) (ENDOPEPTIDASE71 SP18).

[Source:SWISSPROT;Acc:Q9ROP6]

CaMax: PALLADIN; CGI-151 PROTEIN. [Source:RefSeq;Acc:NM_016081]591 328b CaMax: FERRITIN HEAVY CHAIN (FERRITIN H SUBUNIT). 440 106a [Source:SWISSPROT;Acc:P02794]

CaMax: RNA-BINDING PROTEIN EWS (EWS ONCOGENE) (EWING

364a SARCOMA BREAKPOINT REGION 1 PROTEIN). 640 [Source:SWISSPROT;Acc:Q01844]

CaMax: ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN

374a MEMBER B (PHAPI2 PROTEIN) (SIL,VER-STAINABLE644 PROTEIN

SSP29) (ACIDIC PROTEIN RICH IN LEUCINES).

[Source:SWISSPROT;Acc:Q92688]

CaMax: FIP1-LIKE 1; REARRANGED IN HYPEREOSINOPHILIA.423 38a [Source:RefSe ;Acc:NM 030917]

CaMax: EUKARYOTIC TRANSLATION INITIATION FACTOR 2 415b (EUKARYOTIC TRANSLATION INITIATION FACTOR 913 SUBUNIT) (EIF-2-ALPHA) (EIF- 2ALPHA) (EIF-2A).

[Source:SWISSPROT;Acc:P05198]

CaMax: NUCLEAR FACTOR OF ACTIVATED T CELLS 5 (T CELL658 459a TRANSCRIPTION FACTOR NFATS) (NF-AT5) (TONICITY-RESPONSIVE ENHANCER-BINDING PROTEIN) (TONE-BINDING

PROTEIN) (TONEBP). [Source:SWISSPROT;Acc:094916]

CaMax: ADENYLOSUCCINATE SYNTHETASE (EC 6.3.4.4) (IMP--464b ASPARTATE LIGASE) (ADSS) (AMPSASE). 292 [Source:SWISSPROT;Acc:P30520]

CaMax: SURFACE GLYCOPROTEIN, IG SUPERFAMILY MEMBER. 193 465b [Source:RefSe ;Acc:NM 016952]

CaMax: T-COMPLEX ASSOCIATED-TESTIS-EXPRESSED 1-LIKE 662 (PROTEIN

478a 91/23). [Source:SWISSPROT;Acc:P51808]

CaMax: T-COMPLEX ASSOCIATED-TESTIS-EXPRESSED 1-LIKE 129 (PROTEIN

479c 91/23). [Source:SWISSPROT;Acc:P51808]

CaMax: RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 2 (GEF-Hl 487a PROTEIN) (PROLIFERATING CELL NUCLEOLAR ANTIGEN668 P40).

[Source:SWISSPROT;Acc:Q92974]

CaMax: HEXOKINASE, TYPE II (EC 2.7.1.1) (HK II) (MUSCLE669 FORM

488a HEXOKINASE). [Source:SWISSPROT;Acc:P52789]

CaMax: BTB (POZ) DOMAIN CONTAINING 5. ~ 622 520a [Source:RefSe ;Acc:NM 017658]

CaMax: MYOCYTE-SPECIFIC ENHANCER FACTOR 2C. 621 521b [Source:SWISSPROT;Acc:Q06413]

CaMax: PROTEASOME SUBUNIT ALPHA TYPE 3 (EC 3.4.25.1) 530b (PROTEASOME COMPONENT C8) (MACROPAIN SUBUNIT 9 C8) (MULTICATALYTIC ENDOPEPTIDASE COMPLEX SUBUNIT
C8).

[Source:SWISSPROT;Acc:P25788]

CaMax: HDCMD38P. [Source:SPTREMBL;Acc:Q9P1S5] 612 539a CaMax: TRANSMEMBRANE PROTEIN 4. [Source:RefSeq;Acc:NM_014255]670 545a CaMax: SER/ARG-RELATED NUCLEAR MATRIX PROTEIN (PLENTY
OF

550a PROLINES 101-L; SER/ARG-RELATED NUCLEAR MATRIX1403 PROTEIN (PLENTY OF PROLINES 101-LIKE).

[Source:RefSe ;Acc:NM 005839]

CaMax: F-BOX AND LEUCINE-RICH REPEAT PROTEIN 3A; 114 F-BOX PROTEIN

555b FBL3A. [Source:RefSe ;Acc:NM 012158]

CaMax: ECHINODERM MICROTUBULE-ASSOCIATED PROTEIN-LIKE

571a (EMAP-4) (RESTRICTEDLY OVEREXPRESSED PROLIFERATION-673 ASSOCIATED PROTEIN) (ROPP 120).

[Source:SWISSPROT;Acc:Q9HC35]

CaMax: SPLICING FACTOR, ARGININE/SERINE-RICH 6 (PRE-MRNA676 579a SPLICING FACTORSRP55). [Source:SWISSPROT;Acc:Q13247]

CaMax: INTEGRIN ALPHA-6 PRECURSOR (VLA-6) (CD49F). 417 57a [Source:SWISSPROT;Acc:P23229]

CaMax: LBP-9. [Source:RefSeq;Acc:NM_014553] 80 581a CaMax: FETAL ALZHEIMER ANTIGEN (FETAL ALZ-50-REACTIVE312 CLONE

597c 1). [Source:SWISSPROT;Acc:Q12830]

CaMax: RAS GTPASE-ACTIVATING-LIKE PROTEIN IQGAP1 1022 (P195).

623a [Source:SWISSPROT;Acc:P46940]

CaMax: KREMEN PROTEIN 1 PRECURSOR (KRINGLE-CONTAINING

628a PROTEIN MARKING THE EYE AND THE NOSE) (DICKKOPF1046 RECEPTOR). [Source:SWISSPROT;Acc:Q96MU8]

CaMax: SER/ARG-RELATED NUCLEAR MATRIX PROTEIN (PLENTY
OF

635a PROLINES 101-L; SER/ARG-RELATED NUCLEAR MATRIX1404 PROTEIN (PLENTY OF PROLINES 101-LIKE).

[Source:RefSeq;Acc:NM 005839]

CaMax: T-COMPLEX ASSOCIATED-TESTIS-EXPRESSED 1-LIKE261 (PROTEIN

638b 91/23). [Source:SWISSPROT;Acc:P51808]

CaMax: UPF0183 PROTEIN. [Source:SWISSPROT;Acc:Q9BSU1]683 685a CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY688 (MOUSE) 692a HOMOLOG-LIKE. [Source:RefSe ;Acc:NM 145702]

CaMax: INVERSIN. [Source:RefSeq;Acc:NM_014425] 697 704b ~

CaMax: INVERSIN. [Source:RefSeq;Acc:NM_014425] 697 704b CaMax: COLLAGEN ALPHA 1(X) CHAIN PRECURSOR. 701 710a [Source:SWISSPROT;Acc:Q03692]

CaMax: GRAVE'S DISEASE CARRIER PROTEIN (GDC) (GRAVE'S
DISEASE

726b AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE 1405 CARRIER

PROTEIN HOMOLOG). [Source:SWISSPROT;Acc:P16260]

CaMax: DIAMINE ACETYLTRANSFERASE (EC 2.3.1.57) 736a (SPERMIDINE/SPERMINE N(1)- ACETYLTRANSFERASE)142 (SSAT) (PUTRESCINE ACETYLTRANSFERASE).

[Source:SWISSPROT;Acc:P21673]

CaMax: HISTIDINE-RICH MEMBRANE PROTEIN KE4. 408 73b [Source:SWISSPROT;Acc:Q92504]

CaMax: IDN3 PROTEIN ISOFORM A. [Source:RefSeq;Acc:NM_133433]126 747a CaMax: MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30)268 (PRP33-35C) 785b (ASCR) (CD230 ANTIGEN). [Source:SWISSPROT;Acc:P04156]

CaMax: SARCOSPAN (K-RAS ONCOGENE-ASSOCIATED PROTEIN) 794a (KIRSTEN-RAS-ASSOCIATED PROTEIN). 372 [Source:SWISSPROT;Acc:Q 14714]

CaMax: NITROGEN FIXATION CLUSTER-LIKE. 72 85.1c [Source:RefSe ;Acc:NM 014301]

CaMax: BRANCHED-CHAIN AMINO ACID AMINOTRANSFERASE, 856c CYTOSOLIC (EC 2.6.1.42) (BCAT(C)) (ECA39 1130 PROTEIN).

[Source:SWISSPROT;Acc:P54687] ' CaMax: ZINC FINGER PROTEIN SLUG (NEURAL CREST TRANSCRIPTION

863c FACTOR SLUG) (SNAIL HOMOLOG 2). 916 [Source:SWIS'SPROT;Acc:P97469]

CaMax: RAS-RELATED PROTEIN RAB-6A (RAB-6). 161 890a [Source:SWISSPROT;Acc:P20340]

CaMax: PEPTIDYL-GLYCINE ALPHA-AMIDAT1NG MONOOXYGENASE786 909a PRECURSOR (EC 1.14.17.3) (PAM). [Source:SWISSPROT;Acc:P19021]

CaMax: HEAT SHOCK PROTEIN HSP 90-BETA (HSP 84) (TUMOR
SPECIFIC

90c TRANSPLANTATION 84 KDA ANTIGEN) (TSTA). 400 [Source:SWISSPROT;Acc:P11499]

CaMax: MYELIN GENE EXPRESSION FACTOR 2. 777 919b [Source:RefSe ;Acc:NM 016132]

CaMax: NUCLEAR RECEPTOR COACTIVATOR 1 ISOFORM 1. 398 92c [Source:RefSe ;Acc:NM 003743]

CaMax: CHURCHILL PROTEIN (MY015 PROTEIN). 767 935b [Source:SWISSPROT;Acc:Q8WUH1]

CaMax: 6.8 KDA MITOCHONDRIAL PROTEOLIPID. 759 953a [Source:SWISSPROT;Acc:P56379]

CaMax: PUMILIO HOMOLOG 1. [Source:RefSeq;Acc:NM_014676]755 963c CaMax: G1/S-SPECIFIC CYCLIN D2. [Source:SWISSPROT;Acc:P30279]1423 986a CaMax: TRANSCRIPTION FACTOR SOX-9. [Source:SWISSPROT;Acc:P48436]194 990a CaMax: INHIBITOR OF BRUTON'S TYRSOINE KINASE; BTK-BINDING257 994b PROTEIN. [Source:RefSe ;Acc:NM 015525]

CaMax:40S RIBOSOMAL PROTEIN 520. [Source:SWISSPROT;Acc:P17075]930 996a Preparation of Microarray [0104] Microarray probes were generated by PCR-amplifying clones isolated from differential display. Probes were spotted in duplicate onto poly-L-lysine coated slides using a GMS417 (Affymetrix) arrayer. Osteoarthritic cartilage samples were obtained from the femoral heads of clinically diagnosed canines undergoing total hip replacement. RNA
was hybridized to the slides using the HC ExpressArray (Digene) kit and visualized using a GMS418 (Affymetrix) scanner. The Imagene (Biodiscovery) program was used for spot finding and subsequent data analysis was performed using GeneSight (Biodiscovery). Expression levels are represented after background subtraction, log (base 2) transformation and global slide signal normalization.
Microarray clone preparation [0105] Culture blocks containing 1.5 mLs of Magnificent Broth (MB) plus tetracycline (50 mg/mL) were inoculated with appropriate clones from glycerol stocks and grown overnight with shaking at 37°C. These cultures were used to inoculate a second culture block that was grown for approximately 6 hours with shaking at 37°C. These 6-hour cultures were used to inoculate 2 replicate culture blocks which were grown overnight with shaking at 37°C. Cultures were centrifuged to pellet cells and plasmids isolated using the Qiagen 96-well culture system (Qiagen). Plasmid concentrations were determined using a spectrophotometer by measuring the absorbance at 260nm. All cDNA plasmid clones were amplified in duplicate using the following PCR reaction (final concentration): 10X PCR buffer (lOmM Tris-HCI, pH 8.3, 50mM KCI, 2.5mM MgCl2), 500uM ea. dNTP, 600 nM Rgh primer, 600 nM Lgh primer, lp,L
(5units/~L) of Eppendorf Taq polymerase and 1~.L (~100ng/~,L) cDNA template in a total of 100~,L. The reaction was performed in the following conditions: 94°C 30 seconds, 52°C 40 seconds, 72°C 1 minute for 40 cycles, followed by 72°C - 5min and 4°C - hold.
Amplified products were verified on 1.5% agarose gel and purified using Minelute (Qiagen) protocol.
The 200~,L of PCR
was added to the filter plate and vacuum was turned on to pull through all' PCR reagents and liquid leaving only the cDNA bound to the filter. 30~L molecular grade water was added to the filter plate and incubated at room temperature on an orbital shaker at 900 rpm for 5 minutes. The supernatant containing the purified cDNA was aspirated from the filter plate.
The cDNA's were dried for 2hrs or to completion in a speed.vac at 45°C. 30~,L Corning Universal Printing Buffer was added to all cDNA's and resuspended over night at room temperature on an orbital shaker.
2~L's transferred for concentration analysis and the appropriate amount of Corning Universal Printing Buffer was added for a final concentration of 200 to 500 ng/uL.
Plates were stored at -20 °C until and after each array printing.
Clone arraying [0106] Microscope slides (Goldseal cat# 3010) were submerged in a 10% NaOH
(Fisher cat#5318-500) 57% EtOH solution and incubated at room temperature in an orbital shaker at 50rpm for 2 hours. Slides were rinsed in Milli-Q water 5X for 30 seconds each. While the slides remain in the last water rinse a 10% Poly-L-Lysine (Sigma cat#P8920), 10% 1X PBS
(GibcoBRL cat#70013-032) was brought to 700mLs using Milli-Q water in plastic ware. Slides were submerged in coating solution and incubated at room temperature in orbital shaker at 50rpm for 1 hour. Slides were rinsed in Milli-Q water 5X for 30 seconds each and spun at 500rpm for 1 minute. Slides were incubated in 55°C oven for 10 min and kept in dessicator for at least 14 days and no longer than 3 months prior to arraying. cDNA clones were arrayed using the GMS 417 arrayer (Affymetrix). All slides were placed in a room temperature dessicator to dry overnight. The slides were rehydrated over boiling Milli-Q water (steam) and snap dried DNA side up on an 80°C heat block. To ensure efficient cross-linking the slides were baked for 2 hours at 80°C in an oven and then cross-linked with Stratalinker (120mJ, Stratagene). All slides were stored in a room temperature dessicator until used for cDNA
hybridization.
cDNA microarray hybridization [0107] All RNA samples were reverse transcribed using the following reaction:

Superscript II First Strand Buffer (Invitrogen), luL (lpmole/uL) of RT primer (Genisphere), luL
Superase-Ins Rnase inhibitor, luL lOmM ea. DNTP, 2uL 0.1 M DTT, luL
Superscript II and 5ug total RNA. The reaction was performed at 42°C for 2hrs. The reac7tion was stopped by adding 3.5uL of 0.5 M NaOH/50 mM EDTA and incubating at 65°C for 10 minutes. The reaction was neutralized by adding 5uL of 1M Tris-HCL, pH 7.5. 101.5uL of lOmM
Tris, pH 8, 1mM EDTA was added and the cDNA was purified and concentrated by following the Microcon YM-30 (Millipore) protocol. The concentrated cDNA was brought to a final volume of lOuL
with Nuclease-free water and the following reagents added: 20u1 of 2X
hybridization buffer (Genisphere), 2uL dT LNA blocker and 8uL Nuclease-free water for a total of 40uL. The hybridization mixture was heated at 80°C for 10 minutes and loaded onto the microarray slide at the edge of the lifterSlip. The slide was then placed into a GeneMachines dual hybridization chamber and placed in a 60°C water bath overnight. The following day the slides were processed according to the 3DNA Array 350 (Genisphere) protocol. Briefly, the slides were washed (2XSSC-.2%SDS, 2X SSC, .2X SSC), spun dry at 1000rpm for 1 min and the capture hybridization performed. The slides were washed (2XSSC-.2%SDS, 2X SSC, .2X SSC) spun dry at 1000rpm for 1 min and scanned using a GMS 418 array scanner (Affymetrix).
Microarray analysis [0108] , Scanned images representing RNA transcripts bound to specific clones were quantified and checked for spot quality control using Imagene analysis software (BioDiscovery).
Quantified images were analyzed using Genesight analysis software (BioDiscovery). The analysis represented subtraction of background surrounding the spots, averaging spot replicates, deletion of clone information representing clone hybridization signals not greater than 200 above background on all samples, log (base 2) transformation and global normalization of each slide (values expressed as percent of average spot intensity).

Expression Analysis Using Microarray [0109] RNA was extracted from cartilage as described, supra. Microarray analysis (described supra) was performed on 8 osteoarthritic cartilage samples from clinically diagnosed canines undergoing total hip replacement and 8 normal cartilage samples. A
standard T-test (two categories) was performed on the final hybridization signals for osteoarthritic characterization of cartilage samples (p<0.05 and p<0.01, results shown in Tables 3 and 4, respectively).

Gene OA A STD Normal AVG STD DIF(OA-N) Fold ID G
V

1028c _ 0.75 0.24 0.94 1.57 2.96 _ 1.81 ~

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1545b -1.84 0.48 -1.22 0.50 -0.63 1.54 2173a 2.84 0.40 3.47 0.49 -0.63 1.55 1676a -1.90 0.07 -1.27 0.47 -0.63 : 1.55 581a -1.77 0.16 -1.14 0.25 -0_.63 1.55 472a 4.26 0.7_4 4.89 0.42 -0.63 1.55 1695a _0.22 _0.3_0 0.85 0.59 -0.63 1.55 1414b -0.28 0.42 0.35 0.39 -0.64 1.55 151b 0.13 0.48 0.77 0.28 -0.64 1.55 112d 0.04 0.49 0.68 0.40 -0.64 1.56 461a -1.37 0.49 -0.73 0.24 -0.64 1.56 1557a -1.79 0.28 -1.I5 0.76 -0.64 , 1.56 1615b -1.61 0.56 -0.97 0.34 -0.64 1.56 489c I.BI 0.65 2.46 0.29 -0.64 1.56 310h -1.41 0.50 -0.76 0.25 -0.64 1.56 297a -1.13 0.38 -0.48 0.25 -0.64 1.56 1495a -1.30 0.64 -0.66 0.46 -0.64 1.56 1801b -0.24 0.28 0.41 0.38 -0.65 1.56 23a -1.60 0.45 -0.96 0.22 -0.6~ 1.56 1739a -0.50 0.43 0.14 0.36 -0.65 1:57 170a 1.94 0.28 2.59 0.22 -0.65 1.57 1955a -1.57 0.30 -0.93 0.52 -0.65 1.57 1302a -2.16 0.80 -1.51 0.42 -0.65 1.57 2088a -0.75 0.46 -0.10 0.29 -0.65 1.57 I8a 0.01 0.67 0.66 0.39 -0.65 1.57 182a -1.80 0.28 -1.15 0.55 -0.65 1.57 2243b -2.44 0.24 -1.78 0.30 -0.65 1.57 1440a 1.14 0.42 1.79 0.36 -0.65 1.57 2351c -1.39 0.37 -0.74 0.32 -0.65 1.57 1415b -0.73 0.33 -0.07 0.32 -0.66 1.58 2074b -1.62 0.48 -0.96 0.38 -0.66 1.58 2250a -2.15 0.21 -1.49 0.39 -0.66 1.58 1740a -1.62 0.49 -0.96 0.36 -0.66 1.58 81a 0.76 0.18 1.42 0.31 -0.66 1.58 1248b 0.18 0.52 0.85 0.18 -0.67 1.59 82b 0.44 0.58 1.10 0.26 -0.67 1.59 991b -1.16 0.56 -0.50 0.70 -0.67 1.59 1513b -2.06 0.40 -1.39 0.59 -0.67 1.59 992a -1.22 0.54 -0.55 0.71 -0.67 1.59 1147a -1.35 0.32 -0.68 0.29 -0.67 1.60 12a -1.59 0.21 -0.92 0.39 -0.67 1.60 2201a -1.89 0.24 -1.21 0.27 -0.68 1.60 1032d -0.81 0.78 -0.12 0.27 -0.69 1.61 1373a -2.37 0.22 -1.68 0.46 -0.69 1.61 2266b -1.26 0.33 -0.57 0.27 -0.69 1.61 795a -1.16 0.32 -0.47 0.19 -0.69 1.61 206a -1.93 0.37 -1.25 0.52 -0.69 1.61 1400a 1.27 0.78 1.96 0.47 -0.69 1.61 327f -0.25 0.63 0.44 0.23 -0.69 I.61 212a -1.81 0.33 -1.I2 0.27 -0.69 1.61 2083e -1.73 0.39 -1.04 0.28 -0.69 1.61 555b 0.58 0.33 1.28 0.16 -0.69 1.62 1296a -2.22 0.41 -1.53 0.34 -0.69 1.62 226a -2.32 0.72 -1.63 0.44 -0.69 1.62 272d -2.17 0.22 -1.48 0.29 -0.69 1.62 1709a -2.13 0.40 -1.43 0.34 -0.70 1.62 1945a 4.78 0.43 5.47 0.28 -0.70 1.62 1631d 2.12 0.58 2.82 0.28 -0.70 1.62 1354a -2.29 0.66 -1.59 0.38 -0.70 1.62 24a -1.08 0.39 -0.38 0.35 -0.70 1.63 1284a -0.15 0.44 0.55 0.25 -0.71 1.63 184a -1.80 0.27 -1.09 0.35 -0.71 1.63 936b I.54 0.58 2.25 0.17 -0.71 I.63 1a 4.14 0.55 4.85 0.50 -0.71 1.63 1677b 5.86 0.55 6.57 0.26 -0.71 1.64 747a -1.04 0.62 -0.33 0.21 -0.71 1.64 737a 0.67 0.46 1.38 0.48 -0.71 1.64 1953a -1.46 0.35 -0.74 0.75 -0.72 1.64 794a -0.98 0.85 -0.26 0.46 -0.72- 1.65 2166a -1.84 0.39 -1.12 0.33 -0.73 1.65 1604a -2.12 0.49 -1.39 0.36 -0.73 1.66 479c -1.62 0.45 -0.89 0.24 -0.73 1.66 1245b -2.05 0.38 -1.32 0.56 -0.73 1.66 2040d -2.46 0.37 -1.73 0.23 -0.73 1.66 1502a -1.69 0.42 -0.95 0.38 -0.74 1.67 72a -0.5I 0.39 0.24 0.35 -0.74 1.68 1917f -1.03 0.41 -0.28 0.44 -0.75 1.69 1650a -1.85 0.41 -1.09 0.40 -0.76 1.69 192a -1.83 0.41 -1.07 0.79 -0.76 1.69 1620a -1.99 0.27 -1.23 0.43 -0.76 1.69 1951a -1.81 0.32 -1.05 0.69 -0.76 1.70 1398a -2.82 0.45 -2.05 0.43 -0.77 1.70 2355c -1.79 0.48 -1.02 0.30 -0.77 1.70 1394b 1.65 0.77 2.42 0.24 -0.77 1.71 1651a -2.01 0.24 -1.24 0.66 -0.77 1.71 2071a -2.70 0.03 -1.93 0.28 -0.78 1.71 340a -2.01 0.24 -I.23 0.38 -0.78 1.72 368b -0.08 0.51 0.70 0.26 -0.78 1.72 736a 2.45 0.61 3.24 ' 0.54 -0.79 1.73 64.2a 1.87 0.88 2.66 0.56 -0.79 1.73 17a 0.06 0.68 0.86 0.32 -0.80 1.74 1475a -1.53 0.33 -0.73 0.39 -0.80 1.74 2161c -1.79 0.44 -0.99 0.70 -0.80 1.74 143.2c 1.35 0.33 2.16 0.23 -0.81 1.75 1540a -1.64 0.43 -0.83 0.57 -0.81 1.76 1521b -1.05 0.59 -0.23 0.15 -0.82 1.76 2156c -2.35 0.36 -1.53 0.39 -0.82 1.76 2035d 0.44 0.71 1.26 0.43 -0.82 I.77 1618b 0.76 0.88 1.59 0.38 -0.82 1.77 r~r ,~tr;w-~.~.
i516a .,. :~'6'' _1.55 0.45 -0.83 1.78 ~~ '~-~'.3$ ", 1803a -1.30 0.55 -0.46 0.85 -0.83 1.78 . ~

1593b -2.07 0.66 -1.23 0.31 -0.84 1.79 1919x -1.03 0.43 -0.19 0.48 -0.84 1.79 1648x -2.08 0.43 -1.24 0.56 -0.84 1.79 2109a 3.09 0.81 3.94 0.81 -0.84 1.79 1241x -0.64 0.38 0.22 0.80 -0.86 1.82 392a 0.29 0.94 1.16 0.35 -0.86 1.82 1713x -2.09 0.40 -1.23 0.42 -0.86 1.82 144.2a 0.63 0.27 1.50 0.27 -0.86 1.82 2255x -1.13 0.35 -0.26 0.46 -0.87 1.83 1533x -2.04 0.70 -1.17 0.37 -0.87 1.83 690x -0.08 0.56 0.79 0.19 -0.87 1.83 1317x -2.69 0.92 -1.82 0.61 -0.88 1.83 2163x -1.44 0.74 -0.56 0.38 -0.88 1.84 979a 1.91 0.69 2.78 0.52 -0.88 1.84 1747x -2.25 0.79 -1.37 0.41 -0.88 1.84 507x -0.37 0.46 0.51 0.81 -0.88 1.84 890a -0.61 0.58 0.28 0.39 -0.88 1.85 1137b -0.71 1.21 0.18 0.36 -0.89 1.85 395x -2.00 0.46 -l.ll 0.29 -0.89 ' 1.85 51x -0.61 0.76 0.28 0.60 -0.89 1.85 1309b -2.56 0.05 -1.66 0.23 -0.90 1.86 1462x -0.23 0.28 0.68 0.39 -0.92 1.89 1708x -1.09 0.57 -0.17 0.85 -0.92 1.89 1086c -1.08 0.45 -0.16 0.74 -0.92 1.89 1313x -2.71 0.38 -1.78 0.33 -0.93 1.91 1439b -0.90 0.30 0.04 0.36 -0.94 1.91 153b -0.48 0.31 0.46 0.95 -0.94 1.92 1790x -2.28 0.33 -1.33 0.54 -0.95 1.93 961x -0.73 0.63 0.22 0.43 -0.95 1.93 493a 0.99 0.89 1.94 0.28 -0.96 1.94 1463x -0.08 0.21 0.88 0.17 -0.96 1.94 172a 2.00 0.43 2.97 0.35 -0.97 1.96 1454d -1.78! 0.39 -0.80 0.21 -0.97 1.96 1143d -1.02 0.47 -0.05 0.52 -0.98 1.97 862c -1.96 1.22 -0.98 0.56 -0.98 1.97 766b -1.85 0.31 -0.86 0.50 -0.99 1.99 1412b 1.90 0.29 2.89 0.49 -0.99 1.99 1423b 3.55 0.77 4.54 0.20 -0.99 1.99 850x -0.14 0.42 0.87 0.59 -1.01 2.02 148x -0.73 0.40 0.32 0.27 -1.05 2.07 1696a 3.70 0.51 4.75 0.31 -1.05 2.07 1396b -2.51 0.36 -1.45 0.49 -1.06 2.08 2141a 1.46 0.40 2.53 0.64 -1.07 2.10 1503c -0.13 0.75 0.95 0.30 -1.08 2.11 639x -1.04 0.62 0.04 0.50 -1.08 2.12 1682x -0.59 0.32 0.50 0.38 -1.09 2.13 2153x -0.83 0.49 0.26 0.41 -1.09 2.13 H ", ~~ 2241a-0.24 0.39 0.86 0.48 -1.10 2.15 ~ ~~~~~

2263b -1.18 0.52 -0.08 0.42 -1.10 2.15 1438a 3.02 0.39 4.17 0.43 -1.15 2.22 2059b -1.36 0.47 -0.13 0.49 -1.22 2.34 1646a 1.35 0.79 2.58 0.51 -1.23 2.35 851d -1.81 0.47 -0.58 0.63 -1.23 2.35 465b -1.16 0.37 0.08 0.68 -1.25 2.37 990a 2.62 0.67 3.87 0.96 -1.25 2.38 1488b 0.21 0.78 1.46 0.66 -1.25 2.38 1452a 2.09 0.61 3.35 0.28 -1.26 2.40 1270a -1.47 0.36 -0.19 0.54 -1.28 2.43 2142a 0.23 0.57 1.52 1.18 -1.29 2.45 1371a -3.40 1.22 -2.10 0.45 -1.30 2.46 945a 0.76 0.68 2.06 0.30 -1.30 2.47 2117b 2.31 1.27 3.62 1.12 -1.31 2.48 1367a 0.92 0.83 2.25 0.65 -1.33 2.51 1818a 2.82 0.88 4.16 1.23 -1.34 2.53 2198b -0.03 0.54 1.32 1.21 -1.34 2.54 1139a 0.17 0.84 1.56 0.96 -1.39 2.61 851a -1.51 0.60 -0.13 0.40 -1.39 2.62__ 1138a 2.33 0.75 3.73 0.88 -1.41 2.65 1008a 2.72 0.80 4.14 0.92 -1.42 2.67 2113a 2.70 1.23 4.13 1.11 -1.43 2.69 552a 0.19 0.55 1.65 0.46 -1.46 2.74 2374a 0.73 0.76 2.21 0.60 -1.48 2.79 1532a -0.57 0.70 0.94 0.70 -1.51 2.85 2118a -0.83 0.68 0.69 0.38 -1.52 2.86 1366a 1.60 0.90 3.14 0.82 -1.53 2.90 1262b -0.27 0.47 1.28 1.13 -1.55 2.93 144.1c 2.31 0.40 4.24 0.49 -1.93 3.80 21a 0.69 0.77 2.95 0.77 -2.26 4.80 1246a 0.28 0.85 3.33 1.44 -3.05 8.29 1253a -1.26 0.64 2.10 1.84 -3.36 10.26 2224a 0.08 0.44 3.48 0.64 -3.40 10.57 1015d -1.04 0.52 3.01 1.83 -4.05 16.52 2252b -0.50 0.58 3.90 1.80 -4.39 21.00 Gene OA AVG STD Normal AVG STD DIF(OA-N) Fold ID

1028c 1.81 0.75 0.24 0.94 1.57 2.96 768a 1.99 0.54 __ 0.55 1.11 2.16 0.88 ~

141c 3.94 0.57 3.01 0.75 0.93 1.90 1548c 5.49 0.41 4.79 0.46 0.69 1.62 1357a -2.01 0.12 -1.73 0.07 -0.28 ' 1.21 168c 5.11 0.19 5.40 0.21 -0.29 1.22 383d -1.78 0.18 -1.47 0.14 -0.30 1.24 2127c 0.08 0.23 0.48 0.31 -0.39 1.31 .~.-~-530b ~~1.39~~ ~~0.2~1~1.78 0.23 -0.40 1.32 ~ ~ ~~~~~ ~~
~ ~

1405c 3.41 0.34 3.81 0.16 -0.41 1.32 1765x -1.60 0.28 -1.19 0.28 -0.41 1.33 166x -0.97 0.34 -0.56 0.25 -0.41 1.33 1797x -1.79 0.25 -1.38 0.30 -0.42 1.33 1729a 3.95 0.37 4.37 0.23 -0.42 1.34 1857c -0.91 0.16 -0.49 0.20 -0.42 1.34 523x -1.36 0.28 -0.93 0.32 -0.43 1.34 2172c -2.54 0.17 -2.11 0.11 -0.43 1.35 58x -0.09 0.22 0.34 0.24 -0.43 1.35 244x -1.91 0.01 -1.47 0.12 -0.44 1.35 70d -1.65 0.30 -1.21 0.34 -0.44 1.36 1472a 0.07 0.40 0.51 0.23 -0.44 1.36 452x -0.80 0.33 -0.36 0.21 -0.45 1.36 1481c -1.53 0.19 -1.09 0.32 -0.45 1.36 1940e -0.44 0.30 0.01 0.20 -0.45 1.36 1930x -2.00 0.27 -1.54 0.37 -0.45 1.37 739x -0.46 0.27 0.00 0.15 -0.46 1.37 1612x -0.56 0.41 -0.09 0.28 -0.47 1.39 14x -0.93 0.24 -0.45 0.30 -0.47 1.39 1727x -1.68 0.31 -1.20 0.27 -0.48 1.39 1220b 2.96 0.46 3.44 0.15 -0.48 1.40 33a 1.31 0.22 1.80 0.35 -0.49 1.40 1146a 0.55 0.33 1.04 0.34 -0.50 1.41 1738b -1.57 0.25 -1.07 0.36 -0.50 1.41 810x -2.11 0.30 -1.61 0.28 -0.50 1.42 1993b -1.33 0.38 -0.82 0.34 -0.51 1.42 2147x -1.63 0.41 -1.11 0.33 -0.52 1.43 1678a 6.05 0.47 6.57 0.26 -0.52 1.44 56a 3.79 0.23 4.32 0.38 -0.53 1.44 1814c -1.03 0.40 -0.49 0.37 -0.54 1.45 129b 0.47 0.26 1.01 0.26 -0.54 1.45 1924x -0.46 0.34 0.08 0.41 -0.54 1.45 557b -1.56 0.24 -1.02 0.39 -0.54 1.45 1254x -0.48 0.46 0.06 0.28 -0.54 1.46 1292c -0.94 0.32 -0.40 0.47 -0.54 1.46 2221c -0.01 0.25 0.53 0.33 -0.54 1.46 490c 4.71 0.34 5.26 0.42 -0.54 1.46 907x -2.23 0.20 -1.68 0.29 -0.55 1.47 469d -0.61 0.31 -0.05 0.29 -0.56 1.47 713x -1.30 0.34 -0.74 0.25 -0.56 1.47 1372a 1.49 0.32 2.05 0.30 -0.56 1.47 482x -1.55 0.25 -0.99 0.39 -0.56 1.48 1098x -2.29 0.30 -1.72 0.31 -0.56 1.48 1785x -2.19 0.09 -1.63 0.27 -0.56 1.48 1624b -0.95 0.39 -0.38 0.36 -0.57 1.48 1441d -1.09 0.29 -0.52 0.50 -0.57 1.48 553b -0.76 0.16 -0.19 0.27 -0.57 1.48 2179x -2.12 0.29 -1.55 0.46 -0.57 1.49 ~",...~,-.~-~""~ ~".,A.-.Y-.-~,.~
... . 0.22 -0.18 0.34 -0.58 . 1.49 ~~1257b -0.76 1506d -1.45 0.32 -0.88 0.36 -0.58 1.49 1939c -2.37 0.07 -1.79 0.36 -0.58 1.49 2007x -1.93 0.29 -1.35 0.20 -0.58 1.49 13x -0.25 0.52 0.33 0.24 -0.58 1.50 1288x -1.12 0.25 -0.53 0.36 -0.58 1.50 1949x -1.40 0.25 -0.82 0.50 -0.59 1.50 142.2c 1.04 0.28 1.63 0.26 -0.59 1.50 1054x -0.73 0.26 -0.14 0.31 -0.59 1.50 1404c 2.76 0.43 3.35 0.29 -0.59 1.51 8a -0.51 0.51 0.08 0.30 -0.60 1.51 46x -0.07 0.54 0.52 , 0.34 -0.60 1.51 1985x -1.92 0.23 -1.33 0.50 -0.60 1.51 326e -0.12 0.25 0.48 0.24 -0.60 1.51 85.1c -0.04 0.40 0.56 0.22 -0.60 1.51 1675x -1.75 0.14 -1.15 0.40 -0.60 1.52 574a 0.54 0.26 1.14 0.47 -0.61 1.52 2159b -2.29 0.29 -1.67 0.44 -0.62 1.53 2108b 0.49 0.54 1.10 0.29 -0.62 1.54 45.1b 4.48 0.51 5.11 0.29 -0.62 1.54 2173a 2.84 0.40 3.47 0.49 -0.63 1.55 1676x -1.90 0.07 -1.27 0.47 -0.63 1.55 581x -1.77 0.16 -1.14 0.25 -0.63 1.55 1695a 0.22 0.30 0.85 0.59 -0.63 1.55 1414b -0.28 0.42 0.35 0.39 -0.64 1.55 151b 0.13 0.48 0.77 0.28 -0.64 1.55 112d 0.04 0.49 0.68 0.40 -0.64 1.56 461x -1.37 0.49 -0.73 0.24 -0.64 1.56 1615b -1.61 0.56 -0.97 0.34 -0.64 1.56 310h -1.41 0.50 -0.76 0.25 -0.64 1.56 297x -1.13 0.38 -0.48 0.25 -0.64 1.56 1801b -0.24 0.28 0.41 0.38 -0.65 1.56 23x -1.60 0.45 -0.96 0.22 -0.65 1.56 1739x -0.50 0.43 0.14 0.36 -0.65 1.57 170a 1.94 0:28 2.59 0.22 -0.65 1.57 1955x -1.57 0.30 -0.93 0.52 -0.65 1.57 2088x -0.75 0.46 -0.10 0.29 -0.65 1.57 2243b -2.44 0.24 -1.78 0.30 -0.65 1.57 1440a 1.14 0.42 1.79 0.36 -0.65 1.57 2351c -1.39 0.37 -0.74 0.32 -0.65 1.57 1415b -0.73 0.33 -0.07 0.32 -0.66 ~ 1.58 2074b -1.62 0.48 -0.96 0.38 -0.66 1.58 2250a -2.15 0.21 -1.49 0.39 -0.66 1.58 1740x -1.62 0.49 -0.96 0.36 -0.66 1.58 81a 0.76 0.18 1.42 0.31 -0.66 1.58 1248b 0.18 0.52 0.85 0.18 -0.67 1.59 82b 0.44 0.58 1.10 0.26 '-0.67 1.59 1147x -1.35 0.32 -0.68 0.29 -0.67 1.60 12x -1.59 0.21 -0.92 0.39 -0.67 1.60 _ , , ~~2201a -1.89 0.24 -1.21 0.27 -0.68 1.60 2266b -1.26 0.33 -0.57 0.27 -0.69 1.61 795a -1.16 0.32 -0.47 0.19 -0.69 1.61 206a -1.93 0.37 -1.25 0.52 -0.69 1.61 327f -0.25 0.63 0.44 0.23 -0.69 1.61 212a -1.81 0.33 -1.12 0.27 -0.69 1.61 2083e -1.73 0.39 -1.04 0.28 -0.69 1.61 555b 0.58 0.33 1.28 0.16 -0.69 1.62 1296a -2.22 0.41 -1.53 0.34 -0.69 1.62 272d -2.17 0.22 -1.48 0.29 -0.69 1.62 1709a -2.13 0.40 -1.43 0.34 -0.70 1.62 1945a 4.78 0.43 5.47 0.28 -0.70 1.62 1631d 2.12 0.58 2.82 0.28 -0.70 1.62 24a -1.08 0.39 -0.38 0.35 -0.70 1.63 1284a -0.15 0.44 0.55 0.25 -0.71 1.63 184a -1.80 0.27 -1.09 0.35 -0.71 1.63 936b 1.54 0.58 2.25 0.17 -0.71 1.63 1a 4.14 0.55 4.85 0.50 -0.71 1.63 1677b 5.86 0.55 6.57 0.26 -0.71 1.64 747a -1.04 0.62 -0.33 0.21 -0.71 1.64 737a 0.67 0.46 1.38 0.48 -0.71 1.64 2166a -1.84 0.39 -1.12 0.33 -0.73 1.65 479c -1.62 0.45 -0.89 0.24 -0.73 1.66 2040d -2.46 0.37 -1.73 0.23 -0.73 1.66 1502a -1.69 0.42 -0.95 0.38 -0.74 1.67 72a -0.51 0.39 0.24 0.35 -0.74 1.68 1917f -1.03 0.41 -0.28 0.44 -0.75 1.69 1650a -1.85 0.41 -1.09 0.40 -0.76 ' 1.69 1620a -1.99 0.27 -1.23 0.43 -0.76 1.69 1951a -1.81 0.32 -1.05 0.69 -0.76 1.70 2355c -1.79 0.48 -1.02 0.30 -0.77 1.70 1394b 1.65 0.77 2.42 0.24 -0.77 1.71 2071a -2.70 0.03 -1.93 0.28 -0.78 1.71 340a -2.01 0.24 -1.23 0.38 -0.78 1.72 368b -0.08 0.51 0.70 0.26 -0.78 1.72 736a 2.45 0.61 3.24 0.54 -0.79 1.73 17a 0.06 0.68 0.86 0.32 -0.80 1.74 1475a -1.53 0.33 -0.73 0.39 -0.80 1.74 143.2c 1.35 0.33 2.16 0.23 -0.81 1.75 1540a -1.64 0.43 -0.83 0.57 -0.81 1.76 1521b -1.05 0.59 -0.23 0.15 -0.82 1.76 2156c -2.35 0.36 -1.53 0.39 -0.82 1.76 2035d 0.44 0.71 1.26 0.43 -0.82 1.77 1919a -1.03 0.43 -0.19 0.48 -0.84 1.79 1648a -2.08 0.43 -1.24 0.56 -0.84 1.79 1241a -0.64 0.38 0.22 0.80 -0.86 1.82 1713a -2.09 0.40 -1.23 0.42 -0.86 1.82 144.2a 0.63 0.27 1.50 0.27 -0.86 1.82 2255a -1.13 0.35 -0.26 0.46 -0.87 1.83 690a -0.08 0.56 0.79 0.19 -0.87 1.83 2163a -1.44 0.74 -0.56 0.38 -0.88 1.84 979a 1.91 0.69 2.78 0.52 -0.88 1.84 1747a -2.25 0.79 -1.37 0.41 -0.88 1.84 507a -0.37 0.46 0.51 0.81 -0.88 1.84 890a -0.61 0.58 0.28 0.39 -0.88 1.85 395a -2.00 0.46 -1.11 0.29 -0.89 1.85 1309b -2.56 0.05 -1.66 0.23 -0.90 1.86 1462a -0.23 0.28 0.68 0.39 -0.92 1.89 1086c -1.08 0.45 -0.16 0.74 -0.92 1.89 1313a -2.71 0.38 -1.78 0.33 -0.93 1.91 1439b -0.90 0.30 0.04 0.36 -0.94 1.91 153b -0.48 0.31 0.46 0.95 -0.94 1.92 1790a -2.28 0.33 -1.33 0.54 -0.95 1.93 961a -0.73 0.63 0.22 0.43 -0.95 1.93 493a 0.99 0.89 1.94 0.28 -0.96 1.94 1463a -0.08 0.21 0.88 0.17 -0.96 1.94 172a 2.00 0.43 2.97 0.35 -0.97 1.96 14544 -1.78 0.39 -0.80 0.21 -0.97 1.96 11434 -1.02 0.47 -0.05 0.52 -0.98 1.97 766b -1.85 0.31 -0.86 0.50 -0.99 1.99 1412b 1.90 0.29 2.89 0.49 -0.99 1.99 1423b 3.55 0.77 4.54 0.20 -0.99 1.99 850a -0.14 0.42 0.87 0.59 -1.01 2.02 148a -0.73 0.40 0.32 0.27 -1.05 2.07 1696a 3.70 0.51 4.75 0.31 -1.05 2.07 1396b -2.51 0.36 -1.45 0.49 -1.06 2.08 2141a 1.46 0.40 2.53 0.64 -1.07 2.10 1503c -0.13 0.75 0.95 0.30 -1.08 2.11 639a -1.04 0.62 0.04 0.50 -1.08 2.12 1682a -0.59 0.32 0.50 0.38 -1.09 2.13 2153a -0.83 0.49 0.26 0.41 -1.09 2.13 2241a -0.24 0.39 0.86 0.48 -1.10 2.15 2263b -1.18 0.52 -0.08 0.42 -1.10 2.15 1438a 3.02 0.39 4.17 0.43 -1.15 2.22 2059b -1.36 0.47 -0.13 0.49 -1.22 2.34 1646a 1.35 0.79 2.58 0.51 -1.23 2.35 8514 -1.81 0.47 -0.58 0.63 -1.23 2.35 465b -1.16 0.37 0.08 0.68 -1.25 2.37 990a 2.62 0.67 3.87 0.96 -1.25 2.38 1488b 0.21 0.78 1.46 0.66 -1.25 2.38 1452a 2.09 0.61 3.35 0.28 -1.26 2.40 1270a -1.47 0.36 -0.19 0.54 -1.28 2.43 2142a 0.23 0.57 1.52 1.18 -1.29 2.45 945a 0.76 0.68 2.06 0.30 -1.30 2.47 1367a 0.92 0.83 2.25 0.65 -1.33 2.51 2198b -0.03 0.54 1.32 1.21 -1.34 2.54 1139a 0.17 0.84 1.56 0.96 -1.39 2.61 1138a 2.33 0.75 3.73 0.88 -1.41 2.65 ~~"1008a2.72 . 0.80 4.14 0.92 -1.42 2.67 552a 0.19 0.55 1.65 0.46 -1.46 2.74 2374a 0.73 0.76 2.21 0.60 -1.48 2.79 1532a -0.57 0.70 0.94 0.70 -1.51 ~ 2.85 2118a -0.83 0.68 0.69 0.38 -1.52 2.86 1366a 1.60 0.90 3.14 0.82 -1.53 2.90 1262b_ -0.27 0.47 1.28 1.13 -1.55 2.93 144.1c 2.31 0.40 4.24 0.49 -1.93 3.80 21 a 0.69 0.77 2.95 0.77 -2.26 4.80 ' 1246a 0.28 0.85 3.33 1.44 -3.05 8.29 1253a -1.26 0.64 2.10 1.84 -3.36 10.26 2224a 0.08 0.44 3.48 0.64 -3.40 10.57 1015d -1.04 0.52 3.01 1.83 -4.05 16.52 2252b -0.50 0.58 3.90 1.80 -4.39 21.00 [0110] The use of differential display to isolate gene transcripts has enabled the present inventors to develop a microarray chip enriched in transcripts involved in osteoarthritis. The use of this chip to analyze samples from canines with osteoarthritis (1) confirms the results from differential display and (2) enables further characterization of canine osteoarthritis at the molecular level. Transcripts analyzed by qPCR (discussed ifZfra) have validated the differential expression analysis from the microarray.

Quantitative Polymerase Chain Reaction (qPCR) [0111] Confirmation of changes in RNA transcripts was performed using quantitative PCR. Reverse transcriptase reactions were performed using Super ScriptTM II
Reverse Transcriptase for RT-PCR (Invitrogen) according to the manufacture's directions. 1 ~.g of RNA
was added to 1.5~,L10 mM dNTP's, 1.5~,L random hexamers and 0.6~,L Oligo dT
primers and brought to a final volume of 15 uL. Samples were incubated at 68°C for 10 minutes and then brought down to 4°C for at least 1 minute using a GeneAmp PCR System 9700 (Applied Biosystems). A portion (0.25X) of the above reaction was removed and used as a minus RT
reaction (Negative Control containing No Super ScriptTM II Reverse Transcriptase). Using the same Super ScriptTM II Reverse Transcriptase kit, a master mix containing 3~,L
of lOX RT
buffer, 6~,L of 25mM MgCl2, 3~,L O.1M DTT and 1.5~,L RNAse Inhibitor was made.
A portion (0.25X) was removed and 0.375~.L H20 was added for the minus RT samples. To the remainder of the Master Mix, 1.125~,L Super ScriptTM II Reverse Transcriptase was added for the positive RT reactions. All reactions were then incubated at 42°C for lhour, boiled at 95°C for 5minutes, and the brought down to 4°C using a GeneAmp PCR System 9700. The samples were then diluted 1 part RT reaction to 29 Parts HZO to create a stock of cDNA for experimentation.

[0112] Primers and 5' nuclease assay probes were designed based on selected sequences from the differential display using Primer Expresses v1.5 (Applied Biosystems Primer Express~ Tutorial for Real Time Quantitative PCR Primer and Probe Design Tutorial). Minor groove Binding probes (ABI Custom Oligo Synthesis Factory) were ordered from ABI. All oligos were reconstituted with TE buffer pH=8.0 (Ambion) to 100~.M stock concentration, and then diluted with TE buffer to a S~,M working stock concentration. TaqMan~
Universal PCR
Master Mix (Applied Biosystems) was used for quantitative PCR reactions according to the manufacture's directions. Primer concentration was 300~.M each and Probe concentration was 200wM (determined optimal from earlier experiments). 4q.1 of RT and minus RT
reactions were used for quantitative PCR reactions. All positive reactions were done in triplicate, and negative controls were performed singly. Standard qPCR conditions were used as described in the TaqMan~ Universal Master Mix (Applied Biosystems, 50.0°C for 2 minutes, 95.0°C for 10 minutes, and 40-50 cycles of 95°C for 15 seconds then 60°C for 1 minute) at 0.5 volumes.
Samples were run on an ABI Prism 7700 Sequence Detector using ABI Sequence Detector Program vl.7a.
[0113] All samples were run singularly against each primer/probe set to determine what standard curve should be used. Standard curves were generated using serial dilutions of liver RNA or RNA from experimental samples. Alternately, if the samples did not fall within either of the curve ranges, the sample with the lowest CT (cycle threshold) would be re-reverse transcribed and a 1:10 serial dilution would be used as the standard curve for that primer/probe set. Values were normalized to G3PDH (glyceraldehyde-3-phoshate dehydrogenase) levels as determined by quantitative PCR. Inductions were calculated from each of the lowest sample's normalized value.
Error bars represent standard error of the means.
[0114] Table 5 shows the primers and probes used for the qPCR analysis.

I. Clone TargetSEQ Primers and Probes (5' - 3') ID
NO:

Fwd - Rev 1568 TGA CAA TCT TGA GGG AGT TGT CA

- Probe 1569 6FAM - CTT CTC ATG GTT CAC GCC CAT CAC AAA
-MGBNFQ

11B - Fwd 1570 TTG ATA CTC CTA GTC TTG TCT ATT CAC TGA

- Rev 1571 TCG AGT TTT TGC TCT TTG GAG AA

- Probe 1572 6FAM - TCA TTC AAC CCA GCA TTG AAC AAG GCT
-MGBNFQ

59A - Fwd 1573 AGC AGG TGT TCA TCC CAG AAT G

- Revf ~ 1574 GGG TGT GAC GCA CCA ACA G

- Probe 1575 6FAM - CCT ACA GCC AGG TGC AGT GTC ACA GC
-MGBNFQ

127B - Fwd 1576 GCA TCC CCG AGC CTC AT

- Rev 1577 GGG TGC TAT ACA GTC CAG GTC AA

- Probe 1578 6FAM - TCT ATC TCC CCA GCT GCT TCC CCA C -MGBNFQ

141C - Fwd 1579 AAG GAA GTC CAA TAA ATT CTT TGT TTG

- Rev 1580 TGC CAG GAT TGT TGG TCT GTT

- Probe 1581 6FAM - CTC CTG CTG TTA CCC CAG TGA AGA GTG
TTT T - MGBNFQ

159A - Fwd 1582 CAG GCT GCC AAC GAA TGG

- Rev 1583 AGA CCG GCT CTT GAG GAC AGA

- Probe 1584 6FAM - TGG CCT GCC TGA CAA GTA CTG AGC TTC
-MGBNFQ

768A - Fwd 1585 CCA TCT TTT CTC CCT CCT CAA CT

- Rev 1586 GGT CTT CAG GTG ATG GTG GG

- Probe 1587 6FAM - TCT TCA GCG GGA CTC CCT CTT GGG -MGBNFQ

794A - Fwd 1588 AGT TTG GCT CCC TAA GTA GAT CAC TT

- Rev 1589 GAA TAC AGC TAC CAC CAA CTT TCA ATT

- Probe 1590 6FAM - CTA AAT GCT TTG GAT GAT TGT CCG CTT
CTC A - MGBNFQ

851D - Fwd 1591 TGA ACA TGC TAA CCT GCG TCT C

- Rev 1592 GAC GTG TTT TCT CGG CTG GA

- Probe 1593 6FAM - CCC ACG TAG TCC GTG GGA GAC CC -MGBNFQ

22528 - Fwd 1594 CAT GTT GGT TCT GAA AAG GTC TGA

- Rev 1595 GGT GAG CCA AAA GCC ATA GCT

Probe 1596 6FAM - CCT TTA CTC CGT GCA GAT CTA CTG CTC
AGC - MGBNFQ

2258A - Fwd 1597 TGT GTT TTG TTT GTT TTG CTT GTT T

Rev 1598 AGA AAG AAA AAA GGA AAG ATG AGT TCA

- Probe 1599 6FAM - CGC CCC CCA AAC CTT TTG TTC TCT C -MGBNFQ

1678A - Fwd 1600 ACT ATT TCA TAC CCT CTC CCA CTA CAA

- Rev 1601 CCC ACA AAT ACA ATT TAT ATT TAG CAG TGA

- Probe 1602 6FAM - TTT CCG TGC AGT TAC CTT TCA TTT TTA
AAG
CAA - MGBNFQ

1466B - Fwd 1603 ACA AGA CAT CCT ACC GCT GGT T

- Rev 1604 CAG CTC AGG ACC CTC GTA GAA

- Probe 1605 6FAM - CTG CAG CAT CGG CCC CAA GTG - MGBNFQ

2141A - Fwd 1606 TGA GAT TCA ACA CTT CCC AGT CAA

- Rev 1607 TGT CCC CAT GGT TAG GTG ACA

- Probe 1608 6FAM - TAT TTA CAT CAG GCA AAG CAG CAT CAG
CAA - MGBNFQ

2267A - Fwd 1609 AAA TAA CAA AAG GTG AAA CTT CTA TAC AAA TAT
T

- Rev 1610 AAG TTT GTA AGA CAC TTA AAC TCT TTC TGC

- Probe 1611 ~ 6FAM - CCA AAA ATT CTT TAC TCA GTC ACA CAA
CAA ATG AGG - MGBNFQ

qPCR analysis of Canine OA Cartilage [0115] qPCR was performed as described, supra, on 6 osteoarthritic cartilage samples from clinically diagnosed canines undergoing total hip replacement and 8 normal cartilage samples. Results are shown in Figure 2 (A-E).

Microarray Analysis of Treated OA Samples A. In Vitro Chondrocyte Cell Culture [0116] Canine cartilage was digested in a 37°C shaking water bath using the following enzymes: trypsin (0.25%) for 25 minutes, hyaluronidase (150U/ml) for 1 hour, and collagenase (0.78%) overnight. Digested cartilage was filtered to obtain chondrocytes.
Dulbecco's Modified Eagle Medium (DMEM) + 2.4% alginate (low melting) + cells were dropped from a lOcc syringe into calcium chloride (102 mM) to form "beads." Chondrocyte beads were cultured in DMEM/F12 + P/S (100 U/mL penicillin and 100 ~ g/mL streptomycin) + 10% Fetal Bovine Serum (FBS). Media was changed every other day. At the end of the treatment (see below), the chondrocyte beads were dissolved in sodium citrate (55mM) and EDTA (30mM).
Suspensions were centrifuged at 1800 rpm for lOminutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion~
RNAqueousT"~) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at -20°C until RNA isolation could be performed.
B. RNA Isolation from Cell Culture [0117] Samples were vortexed and homogenized using a Quiashredder (Qiagen) column according to manufacture's directions. The homogenized lysate was collected and 1 equal volume of 64% ethanol was added to it. This mixture was then applied to an RNAqueousTM
filter cartridge, 700 uL at a time, and centrifuged for 1 minute at 10,000 rpm. The cartridge was washed using 700uL wash solution #1 and 500 uL wash solution #2/3 with centrifugation at 10,000 rpm for 1 minute for each wash. The filter cartridge was dried by centrifugation (10,000 rpm) for 1 minute. RNA was eluted 3 times by centrifugation (as above) using 30 uL aliquots of 95-100°C elution solution. The resulting RNA was DNAse-treated and quantitated as stated previously. Following RNA isolation, the RNA was prepared for microarray hybridization as stated previously.
C. Statistical Analysis of Cell Culture Microarray [0118] Data were transformed to logarithm, base 2. Data were normalized using quantile normalization. After normalization, a concordance correlation was computed.
[0119] Differentially expressed genes were determined using a paired t test (a=0.05) for the EPA vs. AA; EPAstim'vs. AAstim; chondroitin sulfate and glucosamine 100~g vs.
control, 100 g vs. 10~ g and 10~ g vs. control.
[0120] Differentially expressed genes were determined by first using ratios of AAstim vs. AA and EPAstim vs. EPA followed by a paired t test (oc=0.05) for the ratios of AAstim/AA
and EPAstim/EPA.
[0121] Differentially expressed genes following a unidirectional trend for all glucosamine and chondroitin sulfate analyses were determined for each treatment pair where responses to the treatment resulted in increases or decreases, in the same direction, in all three samples.
[0122] Differentially expressed genes were determined using a Welch modified two-sample t test for both 1,25 D3 vs. control and 24,25 D3 vs. control (oc=0.05).
1. Chondroitin Sulfate Treatment [0123] Chondrocytes were treated with chondroitin sulfate based on the recognition of chondroitin sulfate as a joint nutrient. Chondrocyte beads were treated with 100 ~g/mL, 10 ~g/mL or 0 ~g/mL (control) chondroitin sulfate (n=3) for 1 week in DMEM/F12 +
P/S + 10°7o FBS. Media was changed every other day. After one week, the chondrocytes beads were dissolved in sodium citrate (55mM) and EDTA (30mM). Suspensions were centrifuged at 1800 rpm for lOminutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion~ RNAqueousT"~) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at -20°C until RNA isolation could be performed. One sample from the chondroitin sulfate treatment was removed due to poor correlation with the rest of the array data. This reduced this analysis to an n=3. The results are shown in Tables 7-12.
TABLE 7: Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 ~ug/mL and 10 ~ug/mL Chondroitin Sulfate on Chondroc tes ( <0.5) Gene ID DIF (100-10) Fold 1071b -0.21 1.15 1089d 0.23 1.17 1221a -0.19 1.14 1228a -0.44 1.36 1263b -0.22 1.16 1304a -0.14 1.10 143.2c 0.22 1.16 1477a -0.22 1.17 1576a -0.30 1.23 1577a -0.12 1.09 158a -0.23 1.17 1717a -0.29 1.22 1732a -0.10 1.07 1747a -0.16 1.12 1749a -0.49 1.40 1752a -0.30 1.23 1917f -0.43 1.35 2173a -0.63 1.54 2267a -0.55 1.47 2374a -0.54 1.46 322a -0.41 1.33 368b -0.17 1.12 392a -0.07 1.05 508 -0.17 1.12 639a -0.26 1.20 711a -0.24 1.18 720a -0.17 1.12 73b -0.24 1.18 753b -0.26 1.20 831a -0.38 1.30 91f -0.27 1.21 936b -0.21 1.16 997a 0.15 1.11 TABLE 8: Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 ~ug/mL
and 0 ~ug/mL
Chondroitin Sulfate (Control) on Chondroc tes ( <0.5) Gene ID DIF (100-Control)Fold 1044c 0.19 1.14 1136b -0.32 1.25 1137b -0.20 1.15 1212b -0.31 1.24 1248b -0.24 1.18 1254a 0.13 ~ 1.09 ;..,m.,.~.:,.,.~_-.....
.1304a -0.35 1.28 143.2c 0.28 1.21 1450a -0.12 1.09 1457b 0.10 1.07 1524a 0.24 1.18 159a 0.84 1.79 1741 a -0.42 1.34 1801b 0.26 1.20 1880a -0:75 1.68 1911b -0.24 1.18 1930a -0.34 1.27 297 a -0.31 1.24 398b -0.34 1.27 466b -0.38 1.30 487a -0.21 1.16 538x -0.25 1.19 713a -0.20 1.15 720a -0.21 1.16 739a -0.29 1.22 795a -0.43 1.35 831a -0.18 1.13 85.2b -0.25 1.19 961 a -0.31 ' 1.24 995 a -0.60 1.52 999a -0.35 1.27 TABLE 9: Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 10 ~ug/mL
and 0 ~ug/mL
Chondroitin Sulfate (Control) on Chondroc tes ( <0.5) Gene ID DIF (10-Control)Fold 1050a -0.27 1.21 1097c -0.35 1.27 1163d 0.18 1.13 1366a -0.12 1.09 1406a 0.13 1.10 145b 0.35 1.28 1554c -0.73 1.66 170a 0.20 1.15 1764a -0.11 1.08 1911b -0.29 1.23 2088a -0.13 1.10 2105a 0.23 1.17 2205a -0.27 1.20 2266b -0.16 1.12 33a 0.38 1.31 406a-r -0.02 1.01 708a 0.13 1.10 768a .~" 0.81 1.75 840d-r -0.19 1.14 93e 0.14 1.10 TABLE 10: Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 ~ug/mL and ~ug/mL
Chondroitin Sulfate on Chondrocytes;
Dataset shows a Unidirectional Trend in Fold Chan a Across All Sam les Gene ID DIF (100-10) Fold 491 1.21 2.32 498 0.18 1.13 508 -0.17 1.12 1016b 0.36 1.28 1044c 0.33 1.26 1089d 0.23 1.17 1091b 0.18 1.13 1106a -0.25 1.19 llla -0.11 1.08 1129a -0.22 1.17 1133b -0.12 1.09 1137b 0.20 1.15 11b 0.69 1.61 1212b -0.24 1.18 1217a -0.34 1.27 1221a -0.19 1.14 1225b -0.23 1.17 1228a -0.44 1.36 1254a 0.15 1.11 1263b -0.22 1.16 127b 0.31 1.24 128a -0.43 1.35 129b 0.26 1.20 1304a -0.14 1.10 132a -0.35 1.27 1364d 0.29 1.22 1403a -0.25 1.19 1406a -0.14 l . l l 1409b -0.22 ' 1.17 1416a -0.33 1.25 142.1c -0.11 1.08 ~142.2c 0.76 1.70 143.2c 0.22 1.16 144.1c 0.82 1.77 1453a -0.13 1.09 1477a -0.22 1.17 1489a -0.18 1.14 1519a 0.42 1.34 1532a 0.22 1.16 154a 0.04 1.03 1577a -0.12 1.09 158a -0.23 1.17 159a 0.90 1.87 1612a -0.13 1.10 1629a -0.17 1.13 163 a -0.27 1.20 1646a -0.06 1.04 1693b -0.08 1.06 1705 a -0.34 1.26 1717a -0.29 1.22 1732a -0.10 1.07 1739a -0.05 1.03 173 a -0.48 1.40 1741 a -0.21 1.16 1747a -0.16 1.12 1749a -0.49 1.40 1752a -0.30 1.23 1760c -0.09 1.07 1772a -0.36 1.28 186a 0.27 1.21 1874b -0.18 1.13 1880a -0.40 1.32 1881b -0.11 1.08 1892a 0.24 1.18 1945a -0.07 1.05 1989b -0.02 1.02 1990a -0.37 1.29 2002c -0.16 1.12 2008a -0.05 1.03 2013a 0.05 1.04 2023b -0.17 1.12 2047b -0.17 1.13 2083e -0.28 1.21 2095 a -0.48 1.40 2102a -0.64 1.56 2108b -0.13 1.09 2109a -0.41 1.33 2117b -0.37 1.29 211b 0.40 1.32 2148a 0.10 1.07 2173 a -0.63 1.54 2182b 0.26 1.20 2205 a 0.34 1.27 2221 c 0.21 1.16 2223 a -0.22 1.17 2267a _ 1.47 -0.55 ,~12374a -0.54 1.46 27a -0.14 1.10 297a -0.17 1.12 307b 0.15 1.11 309a 0.42 1.34 322a -0.41 1.33 106a ' 0.15 1.11 106a 0.18 1.13 368b ~ -0.17 1.12 379a -0.15 1.11 392a -0.07 1.05 410c -0.22 1.17 425c . -0.25 1.19 455c -0.01 1.01 468f -0.19 1.14 472a -0.46 1.38 483a 0.15 1.11 545a -0.12 1.08 553b 0.38 1.31 596e -0.10 1.07 60a -0.40 1.32 623a 0.64 1.56 639a -0.26 1.20 63a -0:25 1.19 67a -0.56 1.47 704b -0.39 1.31 711a -0.24 1.18 713a -0.26 1.20 718a -0.18 1.14 720a -0.17 1.12 736a -1.16 2.23 737a -0.22 1.16 73b -0.24 1.18 753b -0.26 1.20 759b -0.28 1.21 795a -0.19 1.14 8124-r -0.19 1.14 831a -0.38 1.30 833a -0.28 1.22 84.2c -0.33 1.26 840d-r 0.28 1.22 841b -0.31 1.24 847a -0.18 1.13 87.2b -0.41 1.33 878c -0.25 1.19 8a -0.21 1.16 90c -0.25 1.19 91f -0.27 1.21 929a -0.72 1.64 ~~936b. -0.21 1.16 93e -0.30 1.23 945 a -0.27 1.20 990a -0.19 1.14 995a ' -0.35 1.27 999a -0.12 1.09 TADLE 11: Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 ~ug/mL and 0 ~ug/mL (Control) Chondroitin Sulfate on Chondrocytes;
Dataset shows a Unidirectional Trend in Fold Chan a Across All Sam les Gene ID DIF (100-Control)Fold 1002b -0.18 1.13 1026b -0.11 1.08 1044c 0.19 1.14 106a 0.13 1.10 1133b -0.20 1.15 1136b -0.32 1.25 1137b -0.20 1.15 1138a -0.32 1.25 1159b 0.17 1.12 1183a 0.18 1.13 1189a 0.12 1.09 11b 1.14 2.20 1212b -0.31 1.24 1217a -0.45 1.37 1228a -0.34 1.26 1240a -0.03 1.02 1246a -0.04 1.03 1248b -0.24 1.18 1254a 0.13 1.09 1294b 0.40 1.32 1304a -0.35 1.28 1366a -0.26 1.19 136b -0.41 1.33 1394b -0.19 1.14 1403a -0.28 1.21 1405c -0.02 1.02 1409b -0.15 1.11 141c 0.58 1.50 142.2c 1.01 2.02 1423b -0.12 1.09 143.2c 0.28 1.21 1450a -0.12 1.09 1456b -0.09 1.06 146b 0.27 1.21 "1472a . 0.16 1.12 1477 a -0.45 1.37 1489x -0.37 1.29 1519a 0.18 1.13 154x -0.11 1.08 156b 0.35 1.27 158x -0.27 1.21 159a 0.84 1.79 15b -0.29 1.22 1612x -0.34 1.27 1630b -0.24 1.18 163 ~1 d -0.26 1.20 1632x -0.23 1.17 163x -0.40 1.32 1695a 0.05 1.03 1705 a -0.46 1.37 1715x -0.14 1.10 1717x -0.24 1.18 1732x -0.10 1.07 1734b -0.27 1.21 1740x -0.07 1.05 1741 a -0.42 1.34 ' 1747x -0.10 1.07 1749x -0.36 1.28 1752a -0.26 1.20 1758x -0.21 1.16 1772x -0.06 1.05 181 1b -0.19 1.14 1813b -0.13 1.10 1874b -0.36 1.29 1911b -0.24 1.18 1917f -0.41 1.33 1928a -0.16 1.12 1930x -0.34 1.27 1945 a -0.26 1.20 1948b 0.14 1.10 2013x -0.17 1.12 2035d -0.30 1.24 2047b -0.22 1.17 205 a -0.29 1.22 2088x -0.18 1.14 2129x -0.17 1.12 2136b ~ 0.23 1.17 2154x -0.21 1.16 2266b -0.18 1.14 2267x -0.55 1.47 2374x -0.54 1.45 297x -0.31 1.24 319b -0.39 ~ 1.31 322a -0.36 1.28 32e 0.19 1.14 33a 0.20 1.15 106a 0.32 1.25 106a 0.15 1.11 392a -0.15 1.11 398b -0.34 1.27 401 a -0.20 1.15 406a-r -0.03 1.02 421a -0.19 1.14 425c -0.36 1.28 44a -0.18 1.13 472a -0.29 1.22 487a -0.21 1.16 50.2d -0.25 1.19 538a -0.25 1.19 553b 0.28 1.21 568a -0.15 1.11 57a -0.18 1.13 596e -0.17 1.13 59a 0.39 1.31 60a -0.30 1.23 616a -0.19 1.14 61c -0.14 1.10 639a -0.26 1.20 63a -0.18 1.13 6b 0.18 1.13 713a -0.20 1.15 720a -0.21 1.16 72a -0.22 1.17 736a -0.71 1.63 739a ' -0.29 1.22 749a -0.24 1.18 794a -0.12 1.08 795a -0.43 1.35 828a , -0.49 1.40 82b 0.21 1.16 831a -0.18 1.13 833a -0.26 1.20 84. 1b -0.10 1.07 84.2c -0.35 1.28 844c-r -0.09 1.06 85.2b -0.25 1.19 890a -0.08 1.06 91f -0.15 1.11 936b -0.15 1.11 953a -0.04 1.03 961 a -0.31 1.24 995a -0.60 1.52 ~996a -0.08 1.06 999a - -0.35 1.27 TABLE 12: Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 10 ~ug/mL and 0 ~ug/mL (Control) Chondroitin Sulfate on Chondrocytes;
Dataset shows a Unidirectional Trend in Fold Chan a Across All Sam les Gene ID DIF (10-C) Fold 491 -1.37 2.59 493 -0.05 1.04 498 -0.35 1.27 1016b -0.50 1.42 1050a -0.27 1.21 1072a -0.48 1.40 1089d -0.21 1.15 1105 a -0.40 1.32 1136b -0.32 1.25 1137b -0.39 1.31 1139a -0.07 1.05 1145a -0.11 1.08 1174d -0.45 1.36 1217a -0.11 1.08 1247a -0.20 1.15 1304a -0.21 1.15 131a -0.21 1.16 1366a -0.12 1.09 1406a 0.13 1.10 1409b 0.07 1.05 1411a -0.18 1.13 145b 0.35 1.28 1500b -0.24 1.18 1521b -0.19 1.14 154a -0.15 1.11 1632a -0.20 1.15 1656a 0.16 1.12 1721a -0.19 1.14 1739a 0.07 1.05 173 a 0.37 1.29 1741a -0.21 1.16 1747a 0.07 1.05 1758a -0.19 1.14 1764a -0.11 1.08 1772a 0.29 1.22 1811b -0.16 1.12 1852a 0.38 1.30 1892a -0.35 1.28 1895b 0.06 1.04 1908a -0.12 1.09 1930a -0.22 1.16 1945a -0.19 1.14 1948b 0.19 1.14 2013a -0.22 1.17 2088a -0.13 1.10 2105a 0.23 1.17 2109a 0.68 1.61 2149d -0.14 1.10 2205a -0.27 1.20 2266b -0.16 1.12 307b -0.14 1.10 319b -0.11 1.08 326e 0.22 1.17 32e 0.18 1.14 33a 0.38 1.31 348c 0.15 1.11 379a 0.21 1.16 406a-r -0.02 1.01 413a -0.17 1.12 421a -0.13 1.10 472a 0.17 1.13 489c 0.04 1.03 530b -0.24 1.18 538a -0.48 1.39 56a 0.06 1.04 57a -0.22 1.17 583e -0.22 1.17 64.2a -0.24 1.18 704b 0.23 1.17 708a 0.13 1.10 719a -0.35 1.28 737a 0.11 1.08 749a -0.29 1.23 753b 0.21 1.15 75c 0.24 1.19 795a -0.25 1.19 828a -0.65 1.57 831a 0.20 1.15 840d-r -0.19 1.14 848a 0.09 1.07 87.2b 0.42 1.34 90c 0.27 1.20 91f 0.13 1.09 93e 0.14 1.10 945a 0.26 1.20 961a -0.31 1.24 98d 0.15 1.11 995a -0.25 1.19 ~99a ~ -0.23 1.17 2. Glucosamine Treatment [0124 Glucosamine treatment was used to determine the effect of this joint health nutrient on the differential expression of OA-associated genes. Chondrocyte beads were treated with I00 ~glmL, 10 ~g/mL or 0 ~g/mL (control) glucosamine (n=3) for 1 week in DMEM/F12 +
P/S + 10% FBS. Media was changed every other day. After one week, the chondrocytes beads were dissolved in sodium citrate (55mM) and EDTA (30mM). Suspensions were centrifuged at 1800 rpm for l0minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion0 RNAqueousT"") was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at '20°C until RNA isolation could be performed. The results are shown in Tables 13-18.
TABLE 13: Differential ExpressionA-Associated Genes with Glucosaof O aring the of 100 ~ug/mL mine Treatment Effect and 1 Comp n Chondrocytes 0 ~ug/mL Glucosamine o ( <0.5) Gene ID DIF (100-10) Fold 1044c -1.12 2.17 lOc -0.48 I.39 113 1b -0.80 I .74 1183a -0.43 ~ 1.34 1257b 0.46 1.38 1479a -0.49 1.41 1532a 0.34 1.27 1656a -0.73 1.66 170a -0.56 1.47 1896b -0.59 1.5I

2085c -0.44 1.36 2137b -0.67 1.59 322a 0.41 I.32 687a -0.46 1.38 695 a -0.51 1.42 841b 0.79 1.73 TABLE 14: Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 ~ug/mL and 0 ~ug/mL (Control) Glucosamine on Gene ID I DIF (100-C) . I Fold 1413b -1.73 3.31 1892a 0.94 1.92 TABLE 15: Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 10 ~ug/mL
and 0 ~ug/xnl, (Control) Glucosamine on Chondroc tes ( <0.5) Gene ID DIF (10-C) Fold 1294b -0.55 1.46 1364d -0.67 1.59 1384a 1.61 3.04 150a 1.23 2.34 151b 1.18 2.27 1645a 0.43 1.34 2100b -0.34 1.26 2198b 0.76 1.70 2210a -0.51 1.43 38a -0.57 1.48 457c -1.57 2.96 464b -0.34 1.27 623a ' -0.56 1.47 63a 0.20 1.15 794a -0.24 1.18 TABLE 16: Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 ~ug/mL
and 10 ~tg/mL
Glucosamine on Chondrocytes;
Dataset shows a Unidirectional Trend in Fold Chan a Across All Sam les Gene ID DIF (100-10) Fold 508 -0.41 1.33 1004a -0.68 1.60 1023c -0.58 1.49 1026b -0.52 1.43 1030a -0.70 1.63 1044c -1.12 2.17 1089d -0.42 1.34 1094b -0.35 1.28 1099c -0.66 1.58 10c -0.48 1.39 1104b -0.79 . 1.73 1110b -0.59 1.50 1131b -0.80 1.74 1159b -0.86 1.81 1183a -0.43 1.34 1227b -1.55 2.94 131 a -0.70 1.62 1405c -0.40 1.32 1406a -0.58 1.49 1423b -0.73 1.66 1437a -0.55 1.47 1479a -0.49 1.41 1500b -0.97 1.95 150a -0.72 1.64 1584a -0.80 1.74 1594a -1.04 2.05 159a 0.56 1.48 1626c -0.82 1.77 1639a -0.58 1.50 1656a -0.73 1.66 1669d -0.69 1.61 1670d -1.20 2.30 1849d -0.54 1.45 1895b -0.22 1.16 1896b -0.59 1.51 2085c -0.44 1.36 2092c -0.52 1.43 2104a -0.67 1.59 2117b -1.00 1.99 2137b -0.67 1.59 2167a -0.83 1.77 2267a -1.12 2.18 260c -0.63 1.55 370a 0.24 1.18 ~413a -0.40 1.32 421 a -0.5 8 1.49 48b -0.89 1.85 687a -0.46 1.38 695 a -0.51 1.42 706b -0.39 1.31 720a -0.42 1.34 847 a -0. 50 1.41 863c-r -0.45 1.36 87.2b -0.87 1.83 906a -0.36 1.28 981 a -0.70 1.62 TABLE 17: Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 ~ug/mL and 0 ~ug/mL (Control) Glucosamine on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (100-C) Fold 491 0.56 1.47 1026b -0.30 1.23 1030a -0.50 1.41 1040b -0.63 1.55 106a 0.23 1.17 1094b -0.14 1.10 l l la -0.85 1.81 1227b -1.15 2.23 1413b -1.73 3.31 146b -0.57 1.49 1500b -1.51 2.85 158a -1.07 2.10 1630b -1.23 2.34 1669d -0.24 1.19 1670d -0.26 1.20 2048a -0.27 1.20 2331c -0.74 1.67 283a -0.69 1.62 370a 0.15 1.11 375 d -0.22 1.16 384c -0.39 1.31 TABLE 18: Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 10 ~ug/mL
and 0 ~ug/mL
(Control) Glucosamine on Chondrocytes;
Dataset shows a Unidirectional Trend in Fold Chan a Across All Sam les Gene ID DIF (10-Control)Fold 1006b -0.79 1.73 104a -0.53 1.44 106a 0.24 1.18 1072a 0.52 1.44 1089d 0.63 1.54 111 a -0.29 , 1.22 104a -0.20 1.15 1190b -0.52 1.43 130b 0.35 1.28 1364d -0.67 1.59 1384a 1.61 3.04 1400a -0.66 1.58 1405c 0.66 1.58 1437a 0.56 1.47 1466b -0.75 1.68 146b -0.27 1.20 1469a 0.57 1.48 150a 1.23 2.34 151b 1.18 2.27 1554c -0.34 1.27 1631d 0.48 1.39 1645a 0.43 1.34 1670d 0.94 1.92 1683a -1.36 2.57 1712a 0.18 1.14 1948b 0.25 1.19 1a -1.05 2.07 2095 a -0.94 1.92 2117b 1.14 2.20 262c -0.18 1.14 27 a 0.10 1.07 283a -0.32 1.25 421a 0.55 1.46 45.1b 0.15 1.11 457c -1.57 2.96 459a -0.40 1.32 468f 0.34 1.27 483a -0.37 1.29 489c 0.22 1.16 490c 0.17 1.13 50.2d 0.30 1.23 52a -1.14 2.20 530b -0.24 1.18 553b 0.26 1.20 557b -0.17 1.13 63a 0.20 ~ 1.15 795a 0.28 1.21 986a -0.61 1.52 98d 0.17 1.13 996a 0.77 1.71 3. 1x,25-dihydroxyvitamin D3 (1,25 D3) and 248,25-dihydroxyvitamin D3 (24,25 D3) Treatment [0125] 1,25 D3 and 248,25D3 treatment was applied to chondrocytes based on their known effects on prostaglandin production and differential responses to the vitamin D3 metabolites in chondrocytes to determine the effect of these compounds on OA-associated gene expression. Chondrocyte beads were treated with 10-~M 1,25 D3 or 10-~M 24,25 D3 for 24 hours or without Vitamin D (equivalent ethanol was added to control), (n=3) in DMEM/F12 + P/S +
10% FBS. After 24 hours, the chondrocyte beads were dissolved in sodium citrate (55mM) and EDTA (30mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL
lysis binding solution (Ambion~ RNAqueousT"~) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at -20°C until RNA isolation could be performed.
The results are shown in Tables 19 and 20.

TABLE 19:
Differential Expression of OA-Associated Genes with 1a,25-dih drox vitamin D3 Treatment on Chondroc tes ( <0.5) Gene ID median C median 1,25 DIF (1,~5-Control)Fold vD3 1023c 10.95 10.12 ~ -0.83 1.77 1042a 11.30 10.86 -0.44 1.36 1068a 9.62 8.89 -0.73 1.66 1096a 9.68 9.36 -0.32 1.25 1101a 7.76 7.16 -0.60 1.51 1103a 7.92 ~ 7.29 -0.63 1.55 1120a 8.17 7.77 -0.40 1.32 1147a 8.04 7.43 -0.61 1.52 117.1d 8.60 8.16 -0.44 1.35 1174d 9.66 8.30 -1.36 2.57 1178a 8.12 7.55 -0.57 1.49 1275c 8.72 8.07 -0.64 1.56 1304a 8.92 8:07 -0.85 1.80 1447a 9.67 9.21 -0.46 1.37 1461a 7.89 6.96 -0.92 1.90 1503c 8.86 8.47 -0.40 1.32 1521b 9.79 8.50 -1.29 2.44 153b 8.49 8.03 -0.46 1.37 1554c 9.09 8.49 -0.61 1.52 1576a 8.27 7.66 -0.61 1.52 1582a 8.10 7.62 -0.47 1.39 1592a 8.03 7.35 -0.67 1.59 1601a 7.68 7.30 -0.38 1.30 1612a 10.11 8.71 -1.40 2.64 1779b 7.63 7.09 -0.54 1.45 1813b 11.20 10.19 -1.01 2.02 1849d 11.81 11.31 -0.49 1.41 185a 7.61 7.28 -0.34 1.26 1863c 10.52 9.95 -0.57 1.49 1889a 8.20 7.45 -0.75 1.68 1892a 9.71 8.90 -0.81 1.75 1920a 8.24 7.54 -0.70 1.62 192a 7.84 7.61 -0.23 1.17 1943a 7.71 7.35 -0.36 1.28 1991d 9.36 8.48 -0.88 1.84 2109a 10.56 11.72 1.16 2.23 2117b 9.27 11.06 1.79 3.46 2163a 8.69 7.49 -1.20 2.30 2179a 7.71 7.17 -0.54 1.45 2198b 9.71 8.36 -1.35 2.54 2201 a 8.19 7.74 -0.45 1.37 2223 a 15.42 14.5 8 -0.84 1.79 2263b 8.85 8.11 -0.74 1.67 2266b 8.69 7.92 -0.77 1.71 2337a 13.57 12.62 -0.95 1.93 ~.234a 7.95 7.61 -0.33 ' 1.26 2353a 8.43 7.96 -0.47 I.38 299a 7.62 7.90 0.29 1.22 106a 16.00 15.99 -0.01 1.00 367a 10.83 10.22 -0.61 1.52 388a 7.81 7.52 -0.29 1.22 415b 7.86 7.33 -0.53 1.44 478a 9.24 8.85 -0.38 1.30 5b 10.21 9.71 -0.51 1.42 61c 10.58 9:88 -0.70 1.62 719a 10.62 10.27 -0.35 1.27 -721b 9.08 8.62 -0.46 I 1.38 TABLE 20:
Differential Expression of OA-Associated Genes with 248,25-dih drox vitamin D3 Treatment on Chondroc tes ( <0.5) Gene ID median C median 24,25 DIF (24,25-Control)Fold vD3 I023c 11.11 10.48 -0.64 1.56 1068a 9.68 9.21 -0.47 1.39 1098a 7.01 8.18 1.17 2.25 1285a 7.37 7.69 0.33 I.25 1335b 7.85 7.69 -0.16 1.12 1474a 6.94 7.70 0.76 I.69 1481c 7.70 7.39 -0.31 1.24 1592a 8.09 7.46 -0.63 1.55 16b 8.47 7.73 -0.74 1.67 1726a 7.88 7.37 -0.50 1.42 1779b 7.66 7.32 -0.35 1.27 2330b 8.01 7.74 -0.27 1.21 340a 7.71 8.41 0.69 1.62 371 a 9.33 9.60 0.26 1.20 401a-r 7.17 7.55 0.39 1.31 449a 7.29 7.59 0.30 1.23 70d 7.88 8.23 0.35 1.28 725a 7.42 8.23 0.81 1.75 832a 8.37 9.04 0.67 1.59 996a 14.73 14.52 -0.22 1.16 4. Eicosapentaenoic acid (EPA) and Arachidonic Acid (AA) Treatment [0126] Chondrocytes were treated with eicosapentaenoic acid (EPA) and arachidonic acid (AA) based on the recognition in the literature that EPA acts as an anti-inflammatory. AA
was used as a control to represent a typical western diet. Chondrocytes were enriched with 50pM
EPA or 50pM AA (using albumin as a carrier) for two weeks in DMEM/HAMS + P/S +
10%
FBS. Media was changed every other day. Each set (n=3) was split and half were treated with stimulated monocyte neutrophil conditioned media (SMNCM) for one week with media changed every other day. SMNCM was made by isolating monocytes and neutrophils from canine whole blood using NycoPrepT"" according to the manufacture's directions. Monocytes and neutrophils were stimulated with lipopolysaccharide (20ng/mL) for 72 hours. The resulting supernatant was used as SMNCM in cell culture experimentation (SMNCM made up 10% of media used during experimentation). Chondrocyte beads were dissolved in sodium citrate (55mM) and EDTA
(30mM). Suspensions were centrifuged at 1800 rpm for lOminutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion~ RNAqueousT"") was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at -20°C until RNA isolation could be performed.
One sample from the EPA/AA stim treatment was removed due to poor correlation with the rest of the array data.
This reduced these analyses to an n=3. The results are shown in Tables 21-23.
TABLE
21: Differential A
Expression of OA-Associated Genes Comparing AA Treatment with EP
Treatment of Chondroc tes ( <0.05) Gene ID DIF (AA-EPA) Fold 1190b 0.42 1.34 1381a -0.12 1.08 1391a 0.26 1.20 1450a -0.64 1.56 1451a -0.85 1.80 1466b 0.33 1.26 1678a -0.67 1.60 1730a 0.45 1.36 2095a -0.35 1.28 493 -0.46 1.3 8 708a 0.51 1.43 99b -0.17 1.13 TABLE
22: Differential Expression of OA-Associated Genes with Inflammatory Stimulation Comparing AA Treatment with EPA Treatment of Chondroc tes ( <0.05) Gene ID DIF (AAs-EPAs) Fold 1099c 1.12 2.17 1104b 0.73 1.66 1106a 0.46 1.38 1184a 0.54 1.45 1190b 0.56 1.47 128a -0.68 1.60 1323b-r -0.58 1.50 1339b -1.58 2.98 1391a 0.88 1.84 1425a 0.68 1.61 1459c -0.38 1.30 154a -1.27 2.42 1576a -0.33 1.26 1629a -0.58 1.49 1639a 0.64 1.56 164c -0.69 1.61 166a -0.43 1.35 1752a -0.27 1.20 2035d -0.57 1.48 2113a -0.90 1.86 2120a-r 0.28 1.22 35c -0.19 1.14 65.2a -0.86 1.82 90c -0.61 1.53 TABLE 23:
Differential Expression of OA-Associated Genes with Inflammatory Stimulation Comparing EPA Treatment and AA
Treatment of Chondrocytes ( <0.05) ,Gene ID AAs-AA EPAs-EPA DIF ((AAs-AA)-(EPAs-EPA))Fold 517 0.10 1.08 -0.98 1.97 1007a -2.37 -2.00 -0.37 1.29 1030a 0.25 -0.23 0.48 1.39 1042a 0.89 0.51 0.38 1.30 104a 0.10 0.95 -0.85 1.80 1091b 1.20 0.90 0.30 1.23 1145a -0.41 -0.55 0.14 1.10 1184a 1.48 0.94 0.55 1.46 1227b 1.47 1.13 0.35 1.27 1270a 0.19 -1.04 1.23 2.35 1339b -1.91 0.09 -2.00 4.00 134b 0.83 0.16 0.66 1.58 1381a -1.65 -2.22 0.56 1.47 1406a 0.46 0.09 0.37 1.29 1469a 0.77 1.36 -0.59 1.51 1549a 0.13 0.15 -0.02 1.01 154a 2.97 4.48 -1.51 2.85 1585b 0.28 -0.21 0.49 1.40 1598a 0.19 -0.09 0.27 1.21 1656a 1.28 0.36 0.92 1.89 1659a 0.19 0.03 0.16 1.12 1670d 1.52 ' 0.68 0.84 1.79 1678a -1.27 -1.76 0.49 1.40 1741a 0.02 -0.64 0.66 1.58 1895b 0.89 0.42 0.46 1.38 1929c 0.35 0.23 0.12 1.09 1930a 0.59 0.34 0.25 1.19 1981'a -0.04 -0.30 0.27 1.21 2008a 0.44 0.03 0.41 1.33 2255a 0.16 -0.08 0.25 1.19 253b -0.18 0.19 -0.37 1.29 342a 0.02 0.13 -0.11 1.08 350b -0.79 0.09 -0.87 1.83 364a 0.20 0.28 -0.08 1.06 3 84c 0.13 -0.19 0.31 1.24 465b -0.13 -0.84 0.71 1.64 490c -0.45 0.09 -0.54 1.45 516c 0.04 1.09 -1.05 2.07 687a 1.16 0.74 0.42 1.34 706b 0.70 -0.44 1.14 2.20 709a 0.53 0.09 0.44 1.36 758b 0.09 -0.18 0.27 1.21 89c 0.55 1.25 -0.70 1.62 981a 1.11 0.52 0.59 1.51 [0127] The experiments demonstrated that various treatments can affect the expression of OA-associated genes. In some cases, the effect on gene expression was statistically significant (p<0.05). In other cases, although the change could not be demonstrated to be statistically significant due to the variability of expression, there was a definite trend for expression to be changed in one direction only (either increased expression or decreased expression). This unidirectional change is considered to be both biologically relevant and significant. In some cases, it is believed that down-regulation of expression of certain genes will have a beneficial biological effect on OA. For other genes, increased expression will have a beneficial biological effect. The invention allows the identification of genes that correlate with beneficial effects as demonstrated by regulation of compounds known to be involved in anti-inflammatory processes, for example. The invention also permits the identification of new compounds which should have beneficial effects based on their regulation of gene expression of the OA-associated genes described in this invention.
[0128] The results demonstrate that one can affect the biology of the cells with various treatments and have a direct impact on gene expression of OA-associated genes.
The invention permits the rapid and powerful screening of compounds to identify candidate treatments and preventatives of OA in animals, particularly humans.
[0129] The disclosures of each patent, patent application, publication and accession number to database sequences cited or described in this document are hereby incorporated herein by reference, in their entirety.
[0130] Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description.
Such modifications are also intended to fall within the scope of the appended claims.

Claims (21)

1. A combination comprising a plurality of polynucleotide molecules wherein the polynucleotide molecules are differentially expressed in an osteoarthritic subject or in a pre-osteoarthritic subject compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic.

2. The combination of claim 1, wherein the plurality of polynucleotide molecules comprises two or more molecules selected from SEQ ID NOs:1-1558 or fragments thereof.

3. A method for the detection of differential expression of nucleic acids in a sample, comprising the steps of:
a) hybridizing a combination comprising a plurality of polynucleotide molecules wherein the polynucleotide molecules are differentially expressed in an osteoarthritic subject or in a pre-osteoarthritic subject compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic with nucleic acids of the sample, thereby forming one or more hybridization complexes;
b) detecting the hybridization complexes; and c) comparing the hybridization complexes with those of a standard, wherein differences between the standard and sample hybridization complexes indicate differential expression of nucleic acids in the sample.

4. The method of claim 3, wherein the polynucleotide molecules hybridize with nucleic acid sequences selected from SEQ ID NOs:1-1558 or fragments thereof.

5. The method of claim 3, wherein the polynucleotide molecules hybridize with nucleic acid sequences selected from gene sequences identified in Table 2 or fragments thereof.

6. A method for the detection of differential expression of polypeptides in a sample, comprising the steps of:
a) reacting a combination comprising a plurality of protein binding molecules with polypeptides of the sample, thereby allowing specific binding to occur, wherein the proteins bound by the protein-binding molecules are differentially expressed in an osteoarthritic subject or in a pre-osteoarthritic subject compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic;
b) detecting specific binding; and c) comparing the specific binding in the sample with that of a standard, wherein differences between the standard and sample specific binding indicate differential expression of polypeptides in the sample.

7. The method of claim 3 or 6, further comprising the step of treating the sample with a test compound, wherein comparison to a standard is indicative of whether treatment with the test compound altered the differential expression of nucleic acids or polypeptides in the sample.

8. A composition of matter comprising a collection of two or more probes for detecting expression of genes differentially expressed in osteoarthritic or pre-osteoarthritic subjects compared to subjects that are not osteoarthritic or pre-osteoarthritic, wherein the probes comprise two or more of:
a) nucleic acid molecules that specifically hybridize to two or more of the genes or gene fragments identified in Tables 1 and 2, or fragments thereof; or b) polypeptide binding agents that specifically bind to polypeptides produced by expression of two or more nucleic acid molecules comprising sequences selected from one or more of genes or gene fragments identified in Tables 1 and 2, or fragments thereof.

9. The composition of claim 8 wherein the genes or gene fragments comprise SEQ
ID NOs:1-1558 or fragments thereof.

10. The composition of claim 8 wherein the gene or gene fragments comprise genes or gene fragments identified in Table 2.

11. A device for detecting expression of a plurality of genes differentially expressed in osteoarthritis, comprising a substrate to which is affixed, at known locations, a plurality of probes, wherein the probes comprise:

a) a plurality of oligonucleotides or polynucleotides, each of which specifically hybridizes to a different sequence selected from any of SEQ ID NOS: 1-1558 or fragments thereof; or b) a plurality of polypeptide binding agents, each of which specifically binds to a different polypeptide or fragment thereof produced by expression of a nucleic acid molecule comprising a sequence selected from the genes or gene fragments comprising any of SEQ ID
NOS: 1-1558 or fragments thereof.

12. A method for measuring the effect of a test compound on the expression of one or more genes differentially expressed in osteoarthritis, comprising the steps of:
a) measuring standard expression by measuring transcription or translation products of one or more of the genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof, in a standard sample in the absence of the test compound;
b) measuring test expression by measuring the transcription or translation products of one or more of the genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof, in a test sample in the presence of the test compound;
c) comparing the standard expression to the test expression, wherein a change in the test expression compared to the standard expression is indicative of an effect of the test compound on the expression of genes differentially expressed in osteoarthritis compared to a non-osteoarthritic condition.

13. The method of claim 12, wherein said measuring utilizes a composition of matter comprising a plurality of probes, wherein the probes comprise two or more of two or more of the genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof.

14. The method of claim 12, wherein the standard and test samples are obtained from at least one mammalian subject.

15. A method for measuring the effect of a test compound on expression of an OA-associated gene, wherein the gene is selected from the group consisting of the genes identified in Table 6, the method comprising measuring production of transcription or translation products produced by expression of the gene in the presence or absence of the test compound, wherein a change in the production of transcription or translation products in the presence of the test compound is indicative of an effect of the test compound on expression of the gene.

16. The method of claim 15, wherein the gene expression is measured by providing a DNA
construct comprising a reporter gene coding sequence operably linked to transcription regulatory sequences of the OA-associated gene, and measuring formation of a reporter gene product in the presence or absence of the test compound.

17. A method to diagnose or develop a prognosis for a subject who exhibits signs of osteoarthritis, the method comprising:
a) obtaining a sample from the subject;
b) measuring in the sample the production of transcription or translation products produced by the expression of one or more OA-associated genes or gene fragments comprising any of SEQ m NOS: 1-1558, or fragments thereof;
c) comparing the transcription or translation products of the sample with that of a standard, wherein a difference in the expression of any of the OA-associated genes or gene fragments is indicative of osteoarthritis.

18. A kit for detecting the presence of osteoarthritis or predisposition for osteoarthritis in a subject comprising one or more oligonucleotides of at least about 10 consecutive nucleotides of a sequence selected from sequences hybridizing to two or more genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof, wherein the oligonucleotides specifically bind to nucleic acids differentially expressed in an osteoarthritic subject or in a subject predisposed to osteoarthritis compared to expression in subjects which are not osteoarthritic or predisposed to osteoarthritis.

19. A kit for assaying the expression of genes differentially expressed in osteoarthritis, comprising a container containing a collection of two or more probes, wherein the probes comprise one or more of:
a) oligonucleotides or polynucleotides that specifically hybridize to two or more genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof; or b) polypeptide binding agents that specifically bind to polypeptides produced by expression of two or more genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof;
and instructions for performing an assay of gene expression.

20. A method of modulating osteoarthritis-associated gene expression in a cell by administering an effective amount of a compound under appropriate conditions to affect the expression of at least one gene associated with osteoarthritis having a sequence selected from SEQ ID NOs:1-1588, or fragments thereof.

21. A method of modulating osteoarthritis-associated gene expression in a cell by administering an effective amount of a compound under appropriate conditions to affect the expression of at least one gene associated with osteoarthritis having a gene product identified in Table 6.
23. The method of claim 21 or 22, wherein the compound is a vitamin, mineral, neutriceutical, small molecule pharmaceutical, protein, polypeptide, nucleic acid, fatty acid or polysaccharide.
24. The method of claim 23, wherein the compound is eicosopentaenoic acid, arachidonic acid, glucosamine, chondroitin sulfate, 1.alpha.,25-dihydroxyvitamin D3, or 248,25-dihydroxyvitamin D3.
25. A method for identifying compounds that modulate osteoarthritis-associated genes comprising:
a) measuring standard expression by measuring transcription or translation products of one or more of the genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof, in a standard sample in the absence of a test compound;
b) measuring test expression by measuring the transcription or translation products of one or more of the genes or gene fragments comprising any of SEQ ID NOS: 1-1558, or fragments thereof, in a test sample in the presence of the test compound; and c) comparing the standard expression to the test expression, wherein a change in the test expression compared to the standard expression is indicative of an effect of the test compound on the expression of genes differentially expressed in osteoarthritis compared to a non-osteoarthritic condition.