GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 结节病是一种病因不明的多系统肉芽肿性炎性疾病。结节病的遗传易感性是由家族聚集性和某些种族群体，特别是非洲裔美国人中较高的患病率报告提出的。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于16号染色体的着丝粒区域。我们没有发现在这一区域存在连锁的证据，可以排除引起结节病的相对危险度至少为5的显性基因或相对危险度至少为3的隐性基因。 已完成了一项多中心研究，以进行全基因组扫描，寻找易感基因，并已精细定位6个候选区域（1 p22，2 p25，5 p15 -13，5 q11，5 q35，9 q34，11 p15和20 q13），最突出的峰位于染色体5 q11上的D5 S2500（P=0.0005）。 我们在5号染色体上进行了SNP分型，证实了该区域存在易感等位基因。 此外，使用人口结构，我们已经分离出一组独特的家庭最有可能窝藏致病基因座。 在新的资助下，我们目前正在进行混合物分析，以分离病例中可能含有非洲起源等位基因的基因组区域，并与一组不相关的对照进行比较，以分离结节病和结节病表型特异性位点。

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. Under new funding, we are currently conducting an admixture analysis to isolate genomic regions likely to harbor alleles of African origin in cases and compare to a set of unrelated controls to isolate sarcoidosis and sarcoidosis phenotype specific loci.