GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

非裔美国人结节病的遗传流行病学

• 批准号: 7723436
• 负责人: MICHAEL C IANNUZZI
• 金额: $ 0.45万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723436
• 关键词: 11p15; 1p22; 20q13; 2p25; 5q11; 5q35; 9q34; Admixture; African; African American; Alleles; Candidate Disease Gene; Chromosomes; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 5; Computer Retrieval of Information on Scientific Projects Database; Crohn' s disease; Disease; Dominant Genes; Ethnic group; Etiology; Family; Funding; Genomics; Grant; Granulomatous; High Prevalence; Inflammatory; Inherited; Institution; Localized; Maps; Multicenter Studies; Phenotype; Population; Predisposition; Recessive Genes; Relative Risks; Reporting; Research; Research Personnel; Resources; Sarcoidosis; Source; Structure; Susceptibility Gene; Syndrome; United States National Institutes of Health; genetic epidemiology; genome wide association study

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 结节病是一种病因不明的多系统肉芽肿性炎症性疾病。家族聚集性报告表明结节病具有遗传易感性，并且在某些种族群体（尤其是非裔美国人）中患病率较高。肉芽肿性炎症性疾病布劳综合征和克罗恩病的候选基因已定位于 16 号染色体的中心区。我们在这个一般区域中没有发现连锁的证据，并且可以从中排除相对风险至少为 5 的显性基因，或者相对风险至少为 3 的隐性基因，导致结节病。 一项旨在寻找易感基因的全基因组扫描多中心研究已经完成，六个候选区域（1p22、2p25、5p15-13、5q11、5q35、9q34、11p15 和 20q13）的精细定位也已完成，其中最突出的区域峰值位于染色体 5q11 上的 D5S2500 (P=0.0005)。 我们对 5 号染色体进行了 SNP 分型，确认该区域存在易感等位基因。 此外，利用人口结构，我们分离出了一组最有可能携带致病位点的独特家庭。 在新的资助下，我们目前正在进行混合分析，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。