Admixture Mapping Development and Testing in AA SLE

AA SLE 中的混合物映射开发和测试

• 批准号: 6930197
• 负责人: Michael F. Seldin
• 金额: $ 49.96万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930197
• 关键词: African American; clinical research; computer simulation; genetic mapping; genetic markers; genetic models; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; immunogenetics; mathematical model; patient oriented research; systemic lupus erythematosus

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.

描述（由申请人提供）：混合作图是寻找复杂遗传疾病中疾病易感基因的潜在强大工具。该方法依赖于不同种族群体之间最近的混合，其易感基因分布存在差异，并且可以在混合群体中区分染色体区域的祖先。我们相信，这种方法将是对全基因组连锁研究的有用补充，这些研究通常缺乏动力和基于关联的方法，难以在全基因组范围内应用。为了提供混合作图适用性的证据，有必要 1) 识别一组区分祖先的标记； 2) 开发并应用多位点统计测试，以在存在祖先关联的情况下进行连锁分析，以模拟真实的基因分型数据； 3）在真实疾病中提供该方法的实际演示。这些是本提案的主要目标。我们小组以及其他研究人员的初步研究表明，非裔美国人是一个庞大的混合人群，混合制图可能适用。流行病学研究表明，系统性红斑狼疮是一种对非洲裔人群影响尤为严重的疾病。初步研究表明，祖先信息标记 (AIM) 可以识别非洲血统和欧洲血统，并且与其他标记相比，绝大多数 AIM 在欧洲和非洲创始人群中仅存在很小的种族内差异。 此外，包括 Perlegen Sciences 筛选超过 160 万个 SNP 在内的多个小组的当前结果表明，足够大的全基因组 AIM 集现在可用于稳健的统计分析。该提案将建立一个包含超过 4000 个 AIM 的全基因组集合，这些 AIM 在非洲、欧洲裔美国人和非裔美国人群体中具有特征。对 950 名非裔美国人 SLE 病例和 500 名匹配的非裔美国人对照进行分型将为模拟和测试提供必要的数据，并有机会探索该方法对于对非裔美国人健康至关重要的疾病的有用性。