Interrogating a high-density SNP map for signatures of natural selection
Interrogating a high-density SNP map for signatures of natural selection
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DOI：
10.1101/gr.631202
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发表时间：
2002-12-01
期刊：
影响因子：
7
通讯作者：
Shriver, MD
中科院分区：
文献类型：
--
作者：
Akey, JM;Zhang, G;Shriver, MD
识别那些已成为自然选择目标的基因组区域仍然是遗传学研究中最重要且最具挑战性的领域之一。为此，我们报告了对26530个单核苷酸多态性（SNP）的分析，这些SNP的等位基因频率是在三个人群中确定的。具体而言，我们计算了每个基因座的遗传分化度量F - ST，并在基因组、染色体和单个基因水平上检查了它的分布。通过多种分析，我们发现了具有统计学意义的证据，支持选择影响了现存人类遗传变异模式这一假设。重要的是，通过将单个SNP的F - ST与F - ST的全基因组经验分布进行对比，我们的结果不会因对群体人口统计学历史的不可靠假设而混淆。此外，我们已经确定了174个候选基因，其遗传变异分布表明它们已成为选择的目标。我们的工作提供了人类基因组的第一代自然选择图谱，并提供了令人信服的证据，表明选择塑造了现存的人类基因组变异模式。
Identifying genomic regions that have been targets of natural selection remains one of the most important and challenging areas of research in genetics. To this end, we report an analysis of 26,530 single nucleotide polymorphisms (SNPs) with allele frequencies that were determined in three populations. Specifically, we calculated a measure of genetic differentiation, F-ST, for each locus and examined its distribution at the level of the genome, the chromosome, and individual genes. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Importantly, by contrasting the F-ST of individual SNPs to the empirical genome-wide distribution of F-ST, our results are not confounded by tenuous assumptions of population demographic history. Furthermore, we have identified 174 candidate genes with distribution of genetic variation that indicates that they have been targets of selection. Our work provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation.