Insights from ancient and recent population mixture relevant to medical genetics

与医学遗传学相关的古代和现代人口混合的见解

• 批准号: 8202901
• 负责人: Katarzyna Bryc
• 金额: $ 4.63万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-26 至 2014-08-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8202901
• 关键词: Accounting; Admixture; African; African American; Alleles; Americas; Chromosome Mapping; Collaborations; Complex; Data; Disease; European; Event; Faculty; Family; Generations; Genes; Genetic Materials; Genetic Recombination; Genome; Genotype; Germany; Goals; Health; Heart; Height; Hispanics; Human; Human Gene Mapping; Immigration; Individual; Institutes; Kidney; Laboratories; Latino; Lead; Length; Location; Maps; Medical; Medical Genetics; Mentors; Methods; Minority; Minority Groups; Mississippi; Native Americans; Natural Selections; Nature; Paper; Pattern; Phenotype; Population; Population Genetics; Positioning Attribute; Postdoctoral Fellow; Prostate; Recording of previous events; Research Design; Resolution; Role; South Asian; Stretching; Structure; Testing; Time; United States; United States National Institutes of Health; Variant; Weight; Work; design; disorder risk; gene discovery; genetic pedigree; genetic risk factor; genetic variant; genome sequencing; genome wide association study; graduate student; human disease; human migration; improved; insight; interest; medically underserved population; migration; trait

DESCRIPTION (provided by applicant): African Americans and Hispanic/Latinos - two of the largest minority groups in the U.S. - are admixed populations with ancestry from multiple ancestral populations. This proposal outlines several population genetic methods using admixed populations that will facilitate medical genetics. The first proposed method seeks to improve estimation of the time course of admixture of Africans and Europeans giving rise to African American populations. Delineating the waves of migration in the admixture will improve understanding of the complex structure of African Americans and may provide insights into how to better the design of admixture studies that may boost power to detect variants associated with disease. The second proposed method will leverage sequence data to fine map ancestry breakpoints in local ancestry estimation of admixed individuals. This method can lead to an increased resolution of ancestry, and can extend local ancestry estimation to populations with older admixture, increasing the number of populations that can be utilized for admixture mapping. It may also allow the construction of a fine- scale human genetic map without family or pedigree data. The third method outlined in this proposal will examine the health impact of variants introduced into modern human populations through ancient admixture. The new genetic variants introduced by gene flow, from one population into another, have the potential to be adaptive or to have an impact on traits. This aim of the proposal will explore whether ancient admixture introduced variants that have undergone positive selection or that are associated with height, weight, or disease. In particular, this proposal will examine the recently discovered gene flow from Neandertals into non-African populations, to examine whether the highly-diverged Neandertal variants were adaptive and have undergone positive selection, or whether these variants are associated with morphometric phenotypes or disease. PUBLIC HEALTH RELEVANCE: Medical genetics leverages population genetic methods to perform admixture mapping to find disease genes. This proposal outlines three new population genetic methods, designed for studying admixed populations (populations with ancestry from multiple ancestral populations, such as African Americans), that will provide insights to improve admixture mapping study design, expand admixture mapping to populations with older admixture, and examine the impact of admixture on human disease risk.

描述(申请人提供)：非洲裔美国人和西班牙裔/拉美裔美国人--美国最大的两个少数群体--是有多个祖先的混血群体。这项提案概述了几种使用混合种群的种群遗传学方法，这将促进医学遗传学。第一种提议的方法试图改进对非洲人和欧洲人混杂产生非裔美国人人口的时间进程的估计。描绘混合物中的迁徙浪潮将提高对非裔美国人复杂结构的理解，并可能为如何更好地设计混合物研究提供见解，从而提高检测与疾病相关的变异的能力。第二种方法将利用序列数据在混合个体的局部祖先估计中精细地映射祖先断裂点。这种方法可以提高祖先的分辨率，并可以将本地祖先估计扩展到具有较老混合的种群，增加了可用于混合映射的种群数量。它还可以在没有家族或谱系数据的情况下构建精细的人类基因图谱。这项提案中概述的第三种方法将检查通过古代混合物引入现代人的变异对健康的影响。由基因流引入的新的遗传变异，从一个种群进入另一个种群，具有适应能力或对特征产生影响的潜力。该提案的这一目的将探索古代混合物是否引入了经过正向选择的变异，或与身高、体重或疾病有关的变异。特别是，这项建议将检查最近发现的从尼安德特人进入非非洲人口的基因流，以检查高度分化的尼安德特人变体是否具有适应性并经历了正向选择，或者这些变体是否与形态表型或疾病有关。 公共卫生相关性：医学遗传学利用群体遗传学方法进行混合作图，以发现疾病基因。这项提案概述了三种新的群体遗传学方法，旨在研究混合群体(具有多个祖先群体的群体，如非裔美国人)，这将为改进混合图谱研究设计、将混合图谱扩展到具有较老混合物的群体以及检验混合对人类疾病风险的影响提供见解。