Characterizing the Global Architecture of Genomic Diversity

这份关于美国国立卫生研究院院长早期独立奖的提案旨在 实现基因组学对改善所有人的健康的承诺 对人类基因组的全球架构有更全面的理解 多样性。这将通过描述全球基因组多样性来实现， 包括序列和结构变化，在人口统计背景下 人类人口的历史。为了实现这一反对意见，我们提出了三个具体的 目标：(1)改善对人类人口历史和全球多样性的描述， (2)评估人口学史对功能变异和推论的影响 古人对人类变异的贡献以及(3)发展基因分型的方法 利用短读测序技术研究基因组结构变异。建议数 研究将提供有关全球流行情况和 未确知变异类型的特征，阐明重要 人类人口历史的特征，并定义了这一现象的持久影响 与现有种群相关的变异的历史，包括混合或 基因组包括来自不同物种的片段的世界性种群 大陆祖先。了解这些全球多样性模式，包括 序列和结构变体，将是正确执行和 对旨在阐明疾病遗传基础的研究的解释 不同人群中的易感性。

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.