IBD Gene Mapping by Clinical and Population Subsets

描述(由申请人提供)： 遗传异质性一直是寻找炎症性肠病这一复杂遗传疾病基因的主要障碍。我们已经证明，根据发病年龄和严重程度进行分层分析可以显著降低IBD1基因座的遗传异质性。进一步的基于临床和流行病学协变量的分层分析可能对识别和缩小基因座有很大的作用。尽管北美有大量患有IBD的非裔美国人，但还没有包括非裔美国人的基因研究，这可能部分是为了减少遗传异质性和样本供应不足的问题。然而，非洲祖先群体可能有更大的力量来减少困扰IBD3和1BD5基因座缩小的广泛连锁不平衡问题。我们已经制定了两项建议，以利用拟议的NIH LBD遗传学研究联盟的遗传研究中心可利用的大量IBD患者：(A)根据已定义的临床和流行病学特征，对当前和未来的全基因组和特定于基因座的连锁数据进行子分析，以识别、确认和/或改进IBD基因座。(B)对非裔美国人IBD患者进行招募、表型特征和基因分型，以便在已确定连锁不平衡的三个基因座(IBD1、IBD3和IBD5)进行基因座特异性连锁不平衡研究。我们将按照财团指导委员会的指示，并与其他财团调查人员合作，执行其中一项建议。

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.