Hashimoto L, Habita C, Beressi J P, Delepine M, Besse C, Cambon-Thomsen A, Deschamps I, Rotter J I, Djoulah S, James M R
INSERM U. 358, Hôpital St. Louis, Paris, France.
Nature. 1994 Sep 8;371(6493):161-4. doi: 10.1038/371161a0.
Loci in the major histocompatibility complex (MHC) on chromosome 6 and the insulin (INS) region on chromosome 11 have been implicated in susceptibility to insulin-dependent diabetes mellitus (IDDM) through candidate gene investigations, but they may account for less than 50% of genetic risk for the disease. Genome-wide linkage studies have led to localization of more than 10 susceptibility loci for insulin-dependent diabetes in the non-obese diabetic (NOD) mouse and the BB rat. Similar studies are now possible in humans through the development of dense genetic maps of highly informative microsatellite loci obtained using polymerase chain reaction analysis. We have applied microsatellite markers from recent Généthon maps, and other highly informative markers, in a genome-wide linkage study in IDDM. Here we report evidence for the localization of a previously undetected susceptibility locus for IDDM in the region of the FGF3 gene on chromosome 11q. Our results shows the potential of genome-wide linkage studies to detect susceptibility loci in IDDM and other multifactorial disorders.
通过候选基因研究发现,位于6号染色体上的主要组织相容性复合体(MHC)区域以及11号染色体上的胰岛素(INS)区域与胰岛素依赖型糖尿病(IDDM)的易感性有关,但它们可能仅占该疾病遗传风险的不到50%。全基因组连锁研究已在非肥胖糖尿病(NOD)小鼠和BB大鼠中确定了10多个胰岛素依赖型糖尿病易感性位点。现在,通过使用聚合酶链反应分析获得的高信息含量微卫星位点的密集遗传图谱,人类也能够开展类似研究。我们在IDDM的全基因组连锁研究中应用了来自近期Généthon图谱的微卫星标记以及其他高信息含量标记。在此,我们报告了在11q染色体上FGF3基因区域存在一个先前未检测到的IDDM易感性位点的证据。我们的结果显示了全基因组连锁研究在检测IDDM和其他多因素疾病易感性位点方面的潜力。