0 10 Pancreatic pancreatic JJ 11 16 islet islet NN 17 27 expression expression NN 28 35 studies study NNS 36 39 and and CC 40 51 polymorphic polymorphic JJ 52 55 DNA dna NN 56 63 markers marker NNS 64 66 in in IN 67 70 the the DT 71 76 genes gene NNS 77 85 encoding encode VBG 86 96 hepatocyte hepatocyte NN 97 104 nuclear nuclear JJ 105 118 factor-3alpha factor-3alpha NN 118 119 , , , 120 126 -3beta -3beta NN 126 127 , , , 128 135 -3gamma -3gamma NN 135 136 , , , 137 144 -4gamma -4gamma NN 144 145 , , , 146 149 and and CC 150 152 -6 -6 CD 152 153 . . . 155 158 The the DT 159 164 genes gene NNS 165 173 encoding encode VBG 174 177 the the DT 178 190 functionally functionally RB 191 198 related related JJ 199 209 hepatocyte hepatocyte NN 210 217 nuclear nuclear JJ 218 225 factors factor NNS 226 236 HNF-1alpha HNF-1alpha NNP 237 240 and and CC 241 251 HNF-4alpha HNF-4alpha NNP 252 256 play play VBP 257 258 a a DT 259 267 critical critical JJ 268 272 role role NN 273 275 in in IN 276 282 normal normal JJ 283 293 pancreatic pancreatic JJ 294 303 beta-cell beta-cell NN 304 312 function function NN 312 313 . . . 314 323 Mutations mutation NNS 324 326 in in IN 327 332 these these DT 333 347 liver-enriched liver-enriched JJ 348 361 transcription transcription NN 362 369 factors factor NNS 370 376 result result VBP 377 379 in in IN 380 383 two two CD 384 389 forms form NNS 390 392 of of IN 393 404 early-onset early-onset JJ 405 409 type type NN 410 411 2 2 CD 412 420 diabetes diabete NNS 421 422 ( ( ( 422 436 maturity-onset maturity-onset JJ 437 445 diabetes diabete NNS 446 448 of of IN 449 452 the the DT 453 458 young young JJ 459 460 [ [ ( 460 464 MODY MODY NNP 464 465 ] ] ) 465 466 ) ) ) 466 467 , , , 468 473 MODY3 MODY3 NNP 474 477 and and CC 478 483 MODY1 MODY1 NNP 483 484 , , , 485 490 which which WDT 491 494 are be VBP 495 508 characterized characterize VBN 509 511 by by IN 512 520 impaired impaired JJ 521 539 glucose-stimulated glucose-stimulated JJ 540 547 insulin insulin NN 548 557 secretion secretion NN 557 558 , , , 559 564 early early JJ 565 572 disease disease NN 573 578 onset onset NN 578 579 , , , 580 583 and and CC 584 593 autosomal autosomal JJ 594 602 dominant dominant JJ 603 614 inheritance inheritance NN 614 615 . . . 616 619 The the DT 620 635 transcriptional transcriptional JJ 636 645 hierarchy hierarchy NN 646 648 of of IN 649 653 HNFs HNF NNP 654 662 suggests suggest VBZ 663 667 that that IN 668 673 other other JJ 674 682 proteins protein NNS 683 685 of of IN 686 689 the the DT 690 700 regulatory regulatory JJ 701 708 cascade cascade NN 709 714 might might MD 715 717 be be VB 718 729 responsible responsible JJ 730 733 for for IN 734 739 other other JJ 740 745 forms form NNS 746 748 of of IN 749 753 MODY MODY NNP 754 760 and/or and/or CC 761 771 late-onset late-onset JJ 772 776 type type NN 777 778 2 2 CD 779 787 diabetes diabete NNS 787 788 . . . 789 791 In in IN 792 796 this this DT 797 802 study study NN 802 803 , , , 804 806 we we PRP 807 811 show show VBP 812 816 that that IN 817 827 HNF-3alpha HNF-3alpha NNP 827 828 , , , 829 835 -3beta -3beta NN 835 836 , , , 837 844 -3gamma -3gamma NN 844 845 , , , 846 853 -4gamma -4gamma NN 853 854 , , , 855 858 and and CC 859 861 -6 -6 CD 862 865 are be VBP 866 875 expressed express VBN 876 878 in in IN 879 889 pancreatic pancreatic JJ 890 900 beta-cells beta-cell NNS 900 901 . . . 902 904 We we PRP 905 911 report report VBP 912 915 the the DT 916 930 identification identification NN 931 934 and and CC 935 951 characterization characterization NN 952 954 of of IN 955 961 simple simple JJ 962 968 tandem tandem JJ 969 975 repeat repeat NN 976 979 DNA dna NN 980 993 polymorphisms polymorphism NNS 994 996 in in IN 997 1000 the the DT 1001 1006 genes gene NNS 1007 1015 encoding encode VBG 1016 1026 HNF-3alpha HNF-3alpha NNP 1026 1027 , , , 1028 1034 -3beta -3beta NN 1034 1035 , , , 1036 1043 -3gamma -3gamma NN 1043 1044 , , , 1045 1052 -4gamma -4gamma NN 1052 1053 , , , 1054 1057 and and CC 1058 1060 -6 -6 CD 1061 1064 and and CC 1065 1068 the the DT 1069 1076 mapping mapping NN 1077 1079 of of IN 1080 1085 HNF-6 hnf-6 NN 1086 1088 to to TO 1089 1099 chromosome chromosome NN 1100 1105 bands band NNS 1106 1118 15q21.1-21.2 15q21.1-21.2 NN 1119 1121 by by IN 1122 1134 fluorescence fluorescence NN 1135 1137 in in FW 1138 1142 situ situ FW 1143 1156 hybridization hybridization NN 1156 1157 . . . 1158 1163 These these DT 1164 1171 markers marker NNS 1172 1176 will will MD 1177 1179 be be VB 1180 1186 useful useful JJ 1187 1189 to to TO 1190 1195 study study VB 1196 1199 the the DT 1200 1204 role role NN 1205 1207 of of IN 1208 1215 genetic genetic JJ 1216 1225 variation variation NN 1226 1228 in in IN 1229 1234 these these DT 1235 1240 genes gene NNS 1241 1243 in in IN 1244 1247 the the DT 1248 1260 pathogenesis pathogenesis NN 1261 1263 of of IN 1264 1268 type type NN 1269 1270 2 2 CD 1271 1279 diabetes diabete NNS 1279 1280 . . .