IBD Gene Mapping by Clinical and Population Subsets

按临床和人群亚群划分的 IBD 基因图谱

• 批准号: 7123089
• 负责人: Steven R Brant
• 金额: $ 33.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123089
• 关键词: African American; MHC class I antigen; biotechnology; clinical research; cooperative study; family genetics; gene expression; gene mutation; genetic mapping; genetic susceptibility; genotype; human population genetics; human subject; inflammatory bowel diseases; linkage disequilibriums; medical outreach /case finding; medically underserved population

DESCRIPTION (provided by applicant): Genetic heterogeneity has been a major obstacle for identifying genes for the complex genetic disorder, inflammatory bowel disease. We have demonstrated that stratified analysis by age at onset and severity can markedly reduce genetic heterogeneity for the IBD1 locus. Further stratified analysis based on clinical and epidemiological covariates may have great power to identify and narrow loci. Despite the large African American population with IBD in North America, no genetic studies have included African Americans, perhaps in part to reduce problems of genetic heterogeneity and inadequate sample availability. African ancestral populations however may have greater power to reduce problems of extensive linkage disequilibrium that has plagued narrowing the IBD 3 and 1BD5 loci. We have developed two proposals that take advantage of the large number of IBD patients to be made available for Genetic Research Centers of the proposed NIH lBD Genetics Research Consortium: (A) Sub-analyses, of present and future genome wide and locus specific linkage data, as based on defined clinical and epidemiological characteristics to identify, confirm and/or refine IBD loci. (B) Recruitment, phenotypic characterization and genotyping of African American IBD patients for locus specific linkage disequilibrium studies in the three loci where linkage disequilibrium has already been identified, IBD1, IBD3 and IBD5. We will perform one of these proposals as directed by the consortium steering committee and in collaboration with other consortium investigators.

描述（由申请人提供）： 遗传异质性一直是识别复杂遗传性疾病炎症性肠病基因的主要障碍。我们已经证明，按发病年龄和严重程度进行分层分析可以显着降低 IBD1 基因座的遗传异质性。基于临床和流行病学协变量的进一步分层分析可能具有识别和缩小基因座范围的强大能力。尽管北美有大量患有 IBD 的非裔美国人，但没有任何遗传学研究包括非裔美国人，这可能部分是为了减少遗传异质性和样本可用性不足的问题。然而，非洲祖先群体可能有更大的能力来减少广泛连锁不平衡问题，这种不平衡问题一直困扰着缩小 IBD 3 和 1BD5 位点。我们制定了两项提案，利用大量 IBD 患者，供拟议的 NIH IBD 遗传学研究联盟的遗传研究中心使用：(A) 对当前和未来全基因组和位点特异性连锁数据进行亚分析，根据定义的临床和流行病学特征来识别、确认和/或完善 IBD 基因座。 (B) 非洲裔美国 IBD 患者的招募、表型特征和基因分型，以在已鉴定连锁不平衡的三个基因座（IBD1、IBD3 和 IBD5）中进行基因座特异性连锁不平衡研究。我们将按照联盟指导委员会的指示并与其他联盟研究人员合作执行其中一项提案。