Local Adaptations in Humans

人类的局部适应

• 批准号: 7922889
• 负责人: Anna Di Rienzo
• 金额: $ 29.58万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922889
• 关键词: Africa; African; African American; Age; Agriculture; Chronology; Classification; Conflict (Psychology); DNA Resequencing; Data; Disease; Disease susceptibility; Environment; Ethnic group; Evolution; Functional RNA; Future; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genome Scan; Geographic Distribution; Geographic Locations; Geography; Goals; Habitats; Haplotypes; Human; Ice; Individual; Learning; Left; Life; Link; Location; Medical; Modeling; Motivation; Natural Selections; Nucleotides; Pattern; Pharmaceutical Preparations; Phenotype; Play; Population; Population Genetics; Prevalence; Recording of previous events; Reporting; Research Personnel; Role; Sampling; Scanning; Shapes; Sickle Cell; Skin Pigmentation; Structure; Testing; Time; Variant; Work; base; genome wide association study; health disparity; insight; interest; novel; pressure; programs; rapid growth; response; trait

DESCRIPTION (provided by applicant): Adaptations to different environments are likely to play an important role in variation in disease prevalence among ethnic groups. Thus, an accurate characterization of local adaptations in humans is of fundamental importance to understanding disease susceptibility, as well as other phenotypes. Currently, it is thought that many local adaptations result from the dispersal of anatomically modern humans from East Africa. If so, patterns of polymorphism from non-African individuals should show the signature of adaptations dating to 40- 100 Kya. To date, however, scans of polymorphism data from a limited number of populations have yielded conflicting results as to both the chronology and geography of local adaptations. To clarify these issues, we propose to: 1) Generate new polymorphism data from non-coding regions and use it together with existing data to infer a sensible demographic model for each of 15 populations. These models will provide a framework within which to reliably assess the evidence for positive selection and estimate its timing. 2) Characterize the timing and geographic distribution of adaptations for a known selected phenotype linked to Out of Africa expansions into new environments, namely skin pigmentation. 3) Characterize the timing and geographic distribution of adaptations for unknown phenotypes in genes reported to have been under selection in one of the HapMap populations. With the rapid growth of polymorphism studies, our work will provide an interpretive framework for large- scale analysis of the signature of selection based on polymorphism data. Moreover, it will yield important insights into the demographic and selective factors that shape disease susceptibility loci.

描述（由申请人提供）：对不同环境的适应可能在族裔群体中疾病患病率的变化中起重要作用。因此，对人类局部适应的准确表征对于理解疾病易感性以及其他表型至关重要。目前，人们认为，许多当地改编是由于来自东非的解剖学现代人的散布而产生的。如果是这样，非非洲个体的多态性模式应显示至40-100 kya的适应性签名。然而，迄今为止，从有限数量的人群中扫描多态性数据，就局部适应的年代学和地理学都产生了矛盾的结果。为了阐明这些问题，我们建议：1）从非编码区域生成新的多态性数据，并将其与现有数据一起使用，以推断15个人群中的每个人的明智人群模型。这些模型将提供一个框架，以可靠地评估积极选择的证据并估算其时间。 2）表征适应的时间和地理分布，用于与非洲扩展到新环境的已知选定表型，即皮肤色素沉着。 3）表征在其中一个HAPMAP种群中，据报道已选择的基因中未知表型适应的时间和地理分布。随着多态性研究的快速增长，我们的工作将为基于多态性数据的选择签名提供大规模分析的解释框架。此外，它将对塑造疾病易感性基因座的人口统计学和选择性因素产生重要的见解。