Detecting recent positive selection in the human genome from haplotype structure
Detecting recent positive selection in the human genome from haplotype structure
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DOI：
10.1038/nature01140
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发表时间：
2002-10-24
期刊：
影响因子：
64.8
通讯作者：
Lander, ES
中科院分区：
文献类型：
--
作者：
Sabeti, PC;Reich, DE;Lander, ES
发现人类群体中最近的自然选择的能力将对人类历史和医学的研究产生深远的影响。在这里，我们介绍了一个框架，通过分析人类群体中的长距离单倍型来检测最近的正选择的遗传印记。我们首先在感兴趣的基因座处鉴定单倍型（核心单倍型）。然后，我们评估每个核心单倍型的年龄，其关联的衰减等位基因在不同的距离，从基因座，测量扩展单倍型纯合性（EHH）。具有异常高的EHH和高群体频率的核心单倍型表明存在突变，该突变在人类基因库中比在中性进化下预期的更快地上升到突出地位。我们应用这种方法来研究对两个携带与抗疟疾有关的常见变体的基因的选择：G6PD（1）和CD40配体（2）。在这两个位点，核心单倍型携带拟议的保护性突变脱颖而出，并显示出显着的选择证据。更一般地说，这种方法可以用来扫描整个基因组，寻找最近正选择的证据。
The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD(1) and CD40 ligand(2). At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.