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Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with polynomial functions

机译:通过用多项式函数对连锁不平衡的衰减建模来推断多波总体混合

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摘要

To infer the histories of population admixture, one important challenge with methods based on the admixture linkage disequilibrium (ALD) is to remove the effect of source LD (SLD), which is directly inherited from source populations. In previous methods, only the decay curve of weighted LD between pairs of sites whose genetic distance were larger than a certain starting distance was fitted by single or multiple exponential functions, for the inference of recent single- or multiple-wave admixture. However, the effect of SLD has not been well defined and no tool has been developed to estimate the effect of SLD on weighted LD decay. In this study, we defined the SLD in the formularized weighted LD statistic under the two-way admixture model and proposed a polynomial spectrum (p-spectrum) to study the weighted SLD and weighted LD. We also found that reference populations could be used to reduce the SLD in weighted LD statistics. We further developed a method, iMAAPs, to infer multiple-wave admixture by fitting ALD using a p-spectrum. We evaluated the performance of iMAAPs under various admixture models in simulated data and applied iMAAPs to the analysis of genome-wide single nucleotide polymorphism data from the Human Genome Diversity Project and the HapMap Project. We showed that iMAAPs is a considerable improvement over other current methods and further facilitates the inference of histories of complex population admixtures.
机译:要推断种群混合的历史,基于混合链不平衡(ALD)方法的一项重要挑战是消除直接从来源种群继承的来源LD(SLD)的影响。在先前的方法中,只有一对遗传距离大于某个起始距离的位点之间的加权LD衰减曲线才通过单指数或多指数函数拟合,以推断最近的单波或多波混合。但是,SLD的影响尚未明确定义,也没有开发任何工具来估计SLD对加权LD衰减的影响。在这项研究中,我们在双向混合模型下的公式化加权LD统计量中定义了SLD,并提出了多项式频谱(p谱)来研究加权SLD和加权LD。我们还发现,参考人口可用于减少加权LD统计中的SLD。我们进一步开发了一种方法,即iMAAP,通过使用p光谱拟合ALD来推断多波混合。我们在模拟数据中评估了各种混合模型下iMAAP的性能,并将iMAAP应用于分析来自人类基因组多样性计划和HapMap项目的全基因组单核苷酸多态性数据。我们表明,iMAAPs是对其他当前方法的显着改进,并且进一步促进了复杂人口混合物历史的推论。

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