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: 7414714
• 负责人: Michael F. Seldin
• 金额: $ 48.81万
• 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/7414714
• 关键词: Admixture; Affect; African; African American; Algorithms; Alleles; American; California; Collaborations; Complement; Complex; Confidence Intervals; DNA; Data; Development; Disease; Disease susceptibility; Ensure; Epidemiologic Studies; Ethnic group; European; Founder Generation; Gene Frequency; Genes; Genetic; Genetic Models; Genome; Genomic Segment; Genotype; Health; Hereditary Disease; Individual; Localized; Lupus; Maps; Methodology; Methods; New York City; Phase; Phenotype; Population; Population Control; Predisposition; Preparation; Principal Investigator; Research Personnel; Sample Size; Sampling; Science; Simulate; Site; Structure; Susceptibility Gene; Systemic Lupus Erythematosus; Systemic disease; Testing; United States; Validation; base; case control; cost effective; ethnic difference; genetic linkage analysis; genome-wide linkage; human disease; models and simulation; novel; programs; segregation; simulation; tool; transmission process

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）：混合图是在复杂遗传疾病中找到疾病易感基因的潜在强大工具。该方法取决于不同种族之间的最新混合，这些种族存在易感基因分布的差异，并且在混合种群中可以区分染色体区域的祖先。我们认为，这种方法将是整个基因组联系研究的有用补充，这种研究通常缺乏难以应用全基因组的基于幂和关联的方法。为了提供混合映射的适用性证明，有必要1）确定一组区分祖先的标记； 2）在存在祖先关联的情况下，开发和应用多焦点统计检验，以与实际基因分型数据的模拟进行联系； 3）实际疾病中提供了该方法的实际证明。这些是该提议的主要目标。我们小组以及其他研究人员的初步研究表明，非洲裔美国人是一个大量的混合人群，可能适用混合映射。流行病学研究表明，全身性红斑狼疮是一种不成比例地影响非洲遗产的人的疾病。初步研究提供了信心，即祖先提供信息标记（AIMS）可以识别非洲与欧洲血统，并且与其他标记相比，绝大多数这些目的与其他欧洲和非洲基金会之间的种族内差异很小。 此外，包括超过160万个SNP的Perlegen Sciences屏幕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目标集可用于强大的统计分析。该提案将建立一组> 4000个目标的基因组，这些目标在非洲，欧美和非裔美国人人口中。 950个非裔美国人SLE案件和500个匹配的非裔美国人控制措施的打字将为模拟和测试提供必要的数据，以及探索这种方法对非裔美国人健康主要重要性疾病的有用性的机会。