Construction and Application of a US Admixture Map

美国外加剂图的构建及应用

• 批准号: 6953756
• 负责人: Mark D Shriver
• 金额: $ 28.91万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-24 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6953756
• 关键词: African American; Hispanic Americans; United States; alleles; clinical research; family genetics; gene frequency; genetic mapping; genetic markers; genetic polymorphism; genetic susceptibility; genotype; human data; human genetic material tag; human population genetics; linkage disequilibriums; linkage mapping; mathematical model; model design /development; molecular biology information system; nucleic acid sequence; phenotype; quantitative trait loci; racial /ethnic difference; statistics /biometry

DESCRIPTION (provided by applicant): The European colonial period beginning in the late 1400s brought previously isolated populations together in the New World; thus, many US residents can trace their ancestry to more than one continent. Studying the impact of genetic admixture is important because variation in individual admixture proportions can be a confounding factor in ordinary genetic association studies, and because the genetic structure of admixed populations can facilitate the detection and localization of genes underlying ethnic variation in disease risk. We have demonstrated the usefulness of study designs that exploit the ability to model admixture for: (1) Distinguishing genetic and environmental explanations for ethnic differences in disease risk (and investigating the mode of inheritance), by studying the relationship of disease risk to individual admixture; (2) Controlling for confounding of genetic associations in stratified populations by modeling individual and population admixture; and (3) Admixture mapping: localizing genes that underlie ethnic differences in disease risk. Indeed, one of the greatest areas of promise in admixture studies is gene mapping, which can be accomplished by testing for association between the disease and locus ancestry after conditioning on parental admixture. The advantage of admixture mapping is it has higher statistical power compared to family linkage studies. Application of these approaches to admixed populations such as African Americans, Mexican Americans and Puerto Ricans, not only requires further development of the statistical methods, but also additional markers informative for ancestry. A genome spanning panel of Ancestry Informative Markers (AIMs) is needed for distinguishing European, West African and Native American ancestry. AIMs have the primary feature of large differences in allele frequency between the parental populations. Of the three study designs listed above, typically 100 AIMs from across the genome are needed to estimate individual admixture proportions for (1) and (2). However, design (3) necessitates markers at much higher density because it depends upon inferring ancestry at each locus. From simulation studies, we estimate that about 1000 AIMs will be required for genome-wide mapping with two-way admixture, and about 1500 for admixture between three populations.

描述(由申请人提供)： 从14世纪末开始的欧洲殖民时期将新大陆以前与世隔绝的人口聚集在一起；因此，许多美国居民的祖先可以追溯到不止一个大陆。研究遗传混合的影响很重要，因为个体混合比例的变化可能是普通遗传关联研究中的一个混杂因素，而且混合种群的遗传结构可以促进疾病风险中潜在的种族差异基因的检测和定位。我们已经证明了利用混合建模能力的研究设计的有用性：(1)通过研究疾病风险与个人混合的关系，区分疾病风险种族差异的遗传和环境解释(并调查遗传模式)；(2)通过对个人和群体混合建模，控制分层人口中遗传关联的混淆；以及(3)混合映射：定位疾病风险种族差异的基因。事实上，混合体研究中最有希望的领域之一是基因图谱，这可以通过测试在父母混合体条件作用后疾病与基因座祖先之间的关联来完成。与家族连锁研究相比，混合作图的优势在于它具有更高的统计能力。将这些方法应用于非洲裔美国人、墨西哥裔美国人和波多黎各人等混杂人口，不仅需要进一步发展统计方法，而且还需要更多关于祖先的信息标记。需要一个跨越祖先信息标记(AIMS)的基因组小组来区分欧洲人、西非人和美洲原住民的祖先。AIMS的主要特征是亲本群体之间的等位基因频率差异很大。在上面列出的三个研究设计中，通常需要来自整个基因组的100个目标来估计(1)和(2)的个体混合比例。然而，设计(3)需要更高密度的标记，因为它依赖于推断每个座位的祖先。从模拟研究中，我们估计使用双向混合进行全基因组定位将需要大约1000个AIMS，而对于三个种群之间的混合则需要大约1500个AIMS。