Admixture Mapping Development and Testing in AA SLE

描述（由申请人提供）：混合物图谱是在复杂遗传疾病中发现疾病易感基因的潜在有力工具。该方法依赖于最近的混合物之间的不同种族群体的易感基因的分布存在差异，和祖先的染色体区域可以区分在混合人口。我们相信，这种方法将是一个有用的补充，全基因组的连锁研究，往往缺乏权力和协会为基础的方法，难以适用于全基因组。为了提供混合作图的适用性的证据，有必要1）鉴定一组区分祖先的标记; 2）在存在祖先关联的情况下开发和应用多位点连锁统计检验以模拟真实的基因分型数据;和3）提供该方法在真实的疾病中的实际演示。这些是这项建议的主要目标。我们小组和其他研究人员的初步研究表明，非洲裔美国人是一个大的混合人口，混合映射可能是适用的。流行病学研究表明，系统性红斑狼疮是一种疾病，不成比例地影响个人与非洲遗产。初步的研究提供了信心，一个遗传信息标记（AIM）可以识别非洲与欧洲血统，绝大多数这些AIM相比，其他标记只有很小的种族内差异，在欧洲和非洲的创始人口。 此外，包括Perlegen Sciences筛选的超过160万个SNP在内的几个小组的当前结果表明，现在有足够大的全基因组AIM集可用于稳健的统计分析。该提案将建立一个基因组范围内的一组>4000个AIM，其特征在于非洲人，欧洲人和非洲裔美国人人群。950例非裔美国人SLE病例和500例匹配的非裔美国人对照的分型将为模拟和测试提供必要的数据，并有机会探索这种方法对非裔美国人健康具有重大意义的疾病的有用性。

DESCRIPTION (provided by applicant): Admixture mapping is a potentially powerful tool for finding disease susceptibility genes in complex genetic diseases. The method depends on recent admixture between different ethnic groups for which differences in the distribution of susceptibility genes exist, and ancestry of the chromosomal regions can be distinguished in the admixed population. We believe that this approach will be a useful complement to genome-wide linkage studies that often lack power and association based methodologies that are difficult to apply genome-wide. For providing proof of the applicability of admixture mapping it is necessary to 1) identify a set of markers that distinguish ancestry; 2) develop and apply multilocus statistical tests for linkage in the presence of ancestral association to simulations of real genotyping data; and 3) provide an actual demonstration of the method in a real disease. These are the major objectives of this proposal. Preliminary studies by our group as well as other investigators have shown that African Americans are a large admixed population for which admixture mapping is likely to be applicable. Epidemiological studies suggest that systemic lupus erythematosus is a disease that disproportionately affects individuals with African heritage. Preliminary studies provide confidence that a Ancestry Informative Markers (AIMs) can identify African versus European ancestry and that the vast majority of these AIMs in contrast to other markers have only small intra-ethnic differences within the European and African founding populations. Furthermore, the current results of several groups including the Perlegen Sciences screen of over 1.6 million SNPs suggest that a sufficiently large genome-wide set of AIMs is now available for a robust statistical analysis. This proposal will establish a genome wide set of >4000 AIMs that are characterized in African, European American, and African American populations. The typing of 950 African American SLE cases and 500 matched African American controls will provide the necessary data for simulations and testing as well as the opportunity to explore the usefulness of this method for a disease of major importance to the health of African Americans.