The Variance of Identity-by-Descent Sharing in the Wright-Fisher Model
The Variance of Identity-by-Descent Sharing in the Wright-Fisher Model
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DOI：
10.1534/genetics.112.147215
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发表时间：
2013-03-01
期刊：
影响因子：
3.3
通讯作者：
Pe'er, Itsik
中科院分区：
文献类型：
--
作者：
Carmi, Shai;Palamara, Pier Francesco;Pe'er, Itsik
广泛共享长而相同的血统（IBD）基因片段是最近经历遗传漂变的种群的标志。这些IBD片段的检测最近变得可行，从而实现了从相位和imputation到人口统计推断的广泛应用。本文研究了Wright-Fisher模型中IBD共享的分布。具体来说，利用聚结理论，我们计算了随机个体对之间的总共享方差。然后，我们研究了队列平均分享：一个人与队列其他成员之间的平均总分享。我们发现，对于较大的队列，队列平均份额近似正态分布。令人惊讶的是，即使在大的队列中，这种分布的差异也不会消失，这意味着存在“超级分享”个体。这些个体的存在对测序研究的设计有影响，因为如果选择他们进行全基因组测序，那么随后可以推算出更大比例的队列。当个体被随机选择或被特别选择为超共享个体时，我们计算了IBD的imputation能力的预期增益，以及随后检测关联的能力。使用我们的框架，我们还计算了基于平均IBD共享的种群大小估计量的方差和近亲兄弟姐妹之间共享的方差。最后，我们在混合脉冲模型中研究了IBD共享，并表明在德系犹太人群体中，混合分数与队列平均共享相关。
Widespread sharing of long, identical-by-descent (IBD) genetic segments is a hallmark of populations that have experienced recent genetic drift. Detection of these IBD segments has recently become feasible, enabling a wide range of applications from phasing and imputation to demographic inference. Here, we study the distribution of IBD sharing in the Wright-Fisher model. Specifically, using coalescent theory, we calculate the variance of the total sharing between random pairs of individuals. We then investigate the cohort-averaged sharing: the average total sharing between one individual and the rest of the cohort. We find that for large cohorts, the cohort-averaged sharing is distributed approximately normally. Surprisingly, the variance of this distribution does not vanish even for large cohorts, implying the existence of "hypersharing" individuals. The presence of such individuals has consequences for the design of sequencing studies, since, if they are selected for whole-genome sequencing, a larger fraction of the cohort can be subsequently imputed. We calculate the expected gain in power of imputation by IBD and subsequently in power to detect an association, when individuals are either randomly selected or specifically chosen to be the hypersharing individuals. Using our framework, we also compute the variance of an estimator of the population size that is based on the mean IBD sharing and the variance in the sharing between inbred siblings. Finally, we study IBD sharing in an admixture pulse model and show that in the Ashkenazi Jewish population the admixture fraction is correlated with the cohort-averaged sharing.