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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 结节病是一种未知病因的多系统肉芽肿性炎症性疾病。在某些族裔，尤其是非裔美国人的家庭聚类和较高患病率的报道中，提出了遗传性对结节病的敏感性。肉芽肿性炎症性疾病BLAU综合征和克罗恩病的候选基因已定位在16号染色体的中心计时区域。我们发现在该一般地区没有任何联系的证据，并且可以从中排除具有相对风险的主要风险，或者至少有5个具有相对风险的基因，或者至少有3个具有相对风险的基因，至少是3个，可导致肌人员的相对风险。 一项在寻找易感基因的全基因组扫描的多中心研究已经完成，对六个候选区域进行了精细的映射（1p22、2p25、5p15-15-13，5q11，5q35，5q35，9q34，9q34，11p15和20q13），最突出的峰值在D5S2500上是Chromos 5q11（posos 5q11）。 我们已经在5号染色体上进行了SNP打字，证实了该区域中易感性等位基因的存在。 此外，使用种群结构，我们隔离了一组最有可能藏有疾病的独特家庭。 在新的资金下，我们目前正在进行混合分析，以分离可能具有非洲起源等位基因的基因组区域，并与一组无关的控制群体进行比较，以分离结节症和结节型表型特异性基因型。