Inferring admixture histories of human populations using linkage disequilibrium.
Inferring admixture histories of human populations using linkage disequilibrium.
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DOI：
10.1534/genetics.112.147330
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发表时间：
2013-04
期刊：
影响因子：
3.3
通讯作者：
Berger B
中科院分区：
文献类型：
--
作者：
Loh PR;Lipson M;Patterson N;Moorjani P;Pickrell JK;Reich D;Berger B
长距离的迁徙和由此产生的种群间的混合一直是塑造人类遗传多样性的重要力量。现有的大多数检测和重建历史混合事件的方法都是基于混合个体染色体上的等位基因频率差异或祖先片段的模式。一种新的方法利用了混合诱导的连锁不平衡(LD)作为遗传距离的函数的指数衰减。在这里，我们全面地将基于LD的推理开发成一个通用的工具来研究混合体。我们提出了一种新的加权LD统计量，与以前的方法相比，它可以用来推断混合比例以及对参考总体的限制较少的日期。我们定义了一种基于LD的三总体混合测试，并确定了它可以检测到以前的正式测试无法检测到的混合事件的场景。我们进一步表明，我们可以通过比较使用一组参考文献获得的加权LD曲线来揭示种群之间的系统发育关系。最后，我们描述了对加权LD曲线的计算和拟合的几点改进，这些改进大大提高了计算的稳健性和速度。我们在一个名为ALDER的软件包中实现了所有这些改进，我们在模拟中验证了该软件包，并将其应用于测试人类基因组多样性项目(HGDP)中所有种群的混合，突出了对中非俾格米人、撒丁岛人和日本人混合历史的洞察。
Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.