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arXiv 1206.4745q-bio.PE
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Wright-Fisher模型中世系共享同一性的方差

The variance of identity-by-descent sharing in the Wright-Fisher model

Shai Carmi, Pier Francesco Palamara, Vladimir Vacic, Todd Lencz, Ariel Darvasi, Itsik Pe'er

摘要:

广泛共享的长,相同的血统(IBD)遗传片段是一个标志的人口经历了最近的遗传漂变。这些IBD片段的检测最近已变得可行,使得从定相和估算到人口统计推断的广泛应用成为可能。在这里,我们研究了在Wright-Fisher模型中IBD共享的分布。具体来说,使用溯祖理论,我们计算随机对个体之间的总共享的方差。然后,我们研究了群体平均共享:一个人和其他群体之间的平均总共享。我们发现,对于较大的队列,队列平均共享近似正态分布。令人惊讶的是,这种分布的方差即使在大的群体中也不会消失,这意味着存在“超共享”个体。这类个体的存在对测序研究的设计具有影响,因为如果选择他们进行全基因组测序,则随后可以对更大比例的队列进行插补。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IBD的插补能力的预期增益,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共享和近交系兄弟姐妹之间共享的方差的人口规模估计量的方差。最后,我们研究了IBD共享混合脉冲模型,并表明,在德系犹太人人口的混合分数与队列平均共享。

英文摘要:

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 "hyper-sharing" 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 hyper-sharing 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.

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