Toomajian Christopher, Ajioka Richard S, Jorde Lynn B, Kushner James P, Kreitman Martin
Committee on Genetics, University of Chicago, Chicago, Illinois 60637, USA.
Genetics. 2003 Sep;165(1):287-97. doi: 10.1093/genetics/165.1.287.
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-associated HFE C282Y mutation. Our results allow us to reject neutral models incorporating plausible human demographic histories for HFE C282Y and one other young but common allele, indicating positive selection at HFE or a linked locus. This method will be useful for scanning the human genome for alleles under selection using the haplotype map now being constructed.
近期通过正向自然选择而频率增加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，通过从连锁位点的单倍型共享程度估计等位基因的年龄来检测近期选择。然后使用中性合并模拟来确定给定等位基因观察频率下该年龄的可能性。我们将此方法应用于一种常见疾病等位基因，即与血色素沉着症相关的HFE C282Y突变。我们的结果使我们能够拒绝纳入HFE C282Y以及另一个年轻但常见等位基因的合理人类人口统计学历史的中性模型，表明HFE或一个连锁位点存在正向选择。这种方法将有助于利用正在构建的单倍型图谱在人类基因组中扫描受选择的等位基因。
