A method for detecting recent selection in the human genome from allele age estimates.
A method for detecting recent selection in the human genome from allele age estimates.
复制标题
一种根据等位基因年龄估计检测人类基因组中最近选择的方法。
DOI：
10.1093/genetics/165.1.287
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发表时间：
2003
期刊：
影响因子：
3.3
通讯作者：
Kreitman,Martin
中科院分区：
文献类型：
--
作者：
Toomajian,Christopher;Ajioka,RichardS;Jorde,LynnB;Kushner,JamesP;Kreitman,Martin
最近通过积极的自然选择而增加频率的突变是影响适应性的自然发生变异的重要组成部分。为了识别此类变异，我们开发了一种方法，通过根据链接位点的单倍型共享程度估计等位基因的年龄来测试最近的选择。然后，根据观察到的等位基因频率，使用中性聚结模拟来确定该年龄的可能性。我们将此方法应用于常见疾病等位基因，即与血色素沉着病相关的 HFEC282Y 突变。我们的结果使我们能够拒绝包含 HFEC282Y 和另一个年轻但常见等位基因的合理人类人口统计历史的中性模型，表明 HFE 或连锁基因座的正选择。该方法可用于使用目前正在构建的单倍型图谱扫描人类基因组以寻找选择的等位基因。
Mutations that have recently increased in frequency by positive natural selection are an important component of naturally occurring variation that affects fitness. To identify such variants, we developed a method to test for recent selection by estimating the age of an allele from the extent of haplotype sharing at linked sites. Neutral coalescent simulations are then used to determine the likelihood of this age given the allele's observed frequency. We applied this method to a common disease allele, the hemochromatosis-associatedHFEC282Y mutation. Our results allow us to reject neutral models incorporating plausible human demographic histories forHFEC282Y and one other young but common allele, indicating positive selection atHFEor a linked locus. This method will be useful for scanning the human genome for alleles under selection using the haplotype map now being constructed.