Characterizing the Global Architecture of Genomic Diversity

NIH主任早期独立奖的提案旨在 实现基因组学对改善所有人健康的承诺， 更全面地了解人类基因组的整体结构 多样性这将通过表征全球基因组多样性来实现， 包括序列和结构变化，在人口统计学的背景下， 人类的历史。为了实现这一目标，我们提出了三个具体的建议。 目标：（1）改进对人类人口历史和全球多样性的描述， (2)评估人口统计学史对功能变异和推断的影响 对人类变异的古老贡献;（3）开发基因型的方法 基因组结构变异使用短读测序。拟议 研究将提供关于全球流行率的基本信息， 未确知变量类型的特征，澄清重要的 人类历史的特征，并确定这一点的持久影响， 与现存种群相关的变异历史，包括混合或 世界性种群，其基因组包括来自不同 大陆祖先了解这些全球多样性模式，包括 序列和结构变异，将是至关重要的适当执行， 对旨在阐明疾病遗传基础的研究的解释 不同人群的易感性。

This proposal for the NIH Director's Early Independence Award is designed to realize the promise of genomics for improving health of all people by achieving a more complete understanding of the global architecture of human genomic diversity. This will be achieved by characterization global genomic diversity, including sequence and structural variation, in the context of the demographic history of human populations. To achieve this objected we propose three specific aims: (1) improve description of human demographic history and global diversity, (2) assess impact of demographic history on functional variation and inferences of archaic contributions to human variation and (3) develop methods to genotype genomic structural variation using short-read sequencing. The proposed research will provide essential information concerning the global prevalence and characteristics of under-ascertained variant types, clarify important characteristics of human population history, and define the lasting effects of this history on variation that is relevant for extant populations, including admixed or cosmopolitan populations whose genomes include segments from diverse continental ancestries. Understanding these global patterns of diversity, including sequence and structural variants, will be critical for proper execution and interpretation of studies designed to elucidate the genetic basis for disease susceptibility in diverse human populations.