IBD Gene Mapping by Clinical and Population Subsets

描述（由申请人提供）： 遗传异质性一直是确定复杂遗传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分层分析可以显著降低IBD 1基因座的遗传异质性。进一步分层分析的基础上，临床和流行病学的协变量可能有很大的权力，以确定和缩小基因座。尽管在北美有大量的非裔美国人患有IBD，但没有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力量来减少广泛的连锁不平衡问题，这些问题一直困扰着缩小IBD 3和1BD 5基因座。我们已经开发了两个提案，其利用了大量IBD患者，以供所提议的NIH IBD遗传学研究联盟的遗传研究中心使用：（A）基于所定义的临床和流行病学特征，对当前和未来的全基因组和基因座特异性连锁数据进行子分析，以鉴定、确认和/或细化IBD基因座。(B)在已经确定连锁不平衡的三个位点（IBD 1、IBD 3和IBD 5）中，对非裔美国人IBD患者进行位点特异性连锁不平衡研究的招募、表型表征和基因分型。我们将按照联合体指导委员会的指示，与其他联合体调查人员合作，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.