Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genome Res. 2010 Mar;20(3):393-402. doi: 10.1101/gr.100545.109. Epub 2010 Jan 19.
Selective sweeps can increase genetic differentiation among populations and cause allele frequency spectra to depart from the expectation under neutrality. We present a likelihood method for detecting selective sweeps that involves jointly modeling the multilocus allele frequency differentiation between two populations. We use Brownian motion to model genetic drift under neutrality, and a deterministic model to approximate the effect of a selective sweep on single nucleotide polymorphisms (SNPs) in the vicinity. We test the method with extensive simulated data, and demonstrate that in some scenarios the method provides higher power than previously reported approaches to detect selective sweeps, and can provide surprisingly good localization of the position of a selected allele. A strength of our technique is that it uses allele frequency differentiation between populations, which is much more robust to ascertainment bias in SNP discovery than methods based on the allele frequency spectrum. We apply this method to compare continentally diverse populations, as well as Northern and Southern Europeans. Our analysis identifies a list of loci as candidate targets of selection, including well-known selected loci and new regions that have not been highlighted by previous scans for selection.
选择压力可以增加种群间的遗传分化,并导致等位基因频率谱偏离中性条件下的预期。我们提出了一种检测选择压力的似然方法,该方法涉及联合建模两个种群之间的多位点等位基因频率分化。我们使用布朗运动来模拟中性条件下的遗传漂变,并用确定性模型来近似选择压力对附近单核苷酸多态性(SNP)的影响。我们使用广泛的模拟数据对该方法进行了测试,并证明在某些情况下,该方法比以前报道的检测选择压力的方法具有更高的功效,并且可以对选定等位基因的位置进行令人惊讶的良好定位。我们的技术的一个优势是它使用了种群之间的等位基因频率分化,这比基于等位基因频率谱的方法更能抵抗 SNP 发现中的确认偏差。我们将该方法应用于比较大陆多样化的种群,以及北欧和南欧人群。我们的分析确定了一系列作为选择候选目标的基因座,包括众所周知的选择基因座和以前的选择扫描中未突出显示的新区域。