GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 结节病是一种病因不明的多系统肉芽肿性炎症性疾病。关于家族聚集性和某些种族群体，特别是非裔美国人的高患病率的报道表明，遗传性结节病易感性。肉芽肿性炎症性疾病Blau综合征和克罗恩病的候选基因已经定位在16号染色体的着丝粒区域。我们在这个一般区域没有发现连锁的证据，并可能从中排除相对风险至少为5的显性基因或相对风险至少为3的隐性基因，从而导致结节病。一项对易感基因进行全基因组扫描的多中心研究已经完成，并对6个候选区域(1p22、2p25、5p15-13、5q11、5q35、9q34、11p15和20q13)进行了精细定位，其中最显著的峰值位于染色体5q11上的D5S2500(P=0.0005)。我们在5号染色体上进行了SNP分型，证实该区域存在易感等位基因。此外，利用种群结构，我们已经分离出一组独特的、最有可能藏匿致病基因的家庭。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African-Americans. Candidate genes for the granulomatous inflammatory disorders Blau syndrome and Crohn's disease have been localized to the centrometric region of chromosome 16. We found no evidence of linkage in this general region, and could exclude from it a dominant gene with relative risk at least 5, or a recessive gene with relative risk at least 3, causing sarcoidosis. A multicenter study to perform a whole genome scan in the search for susceptibility genes has been completed, as has fine mapping of six candidate regions (1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13) with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We have conducted SNP typing on chromosome 5, confirming the presence of a susceptibility allele in this region. Further, using population structure we have isolated a unique set of families most likely to harbor the disease causing locus.