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估计混合人群中的遗传相关性。

Estimating Genetic Relatedness in Admixed Populations.

作者信息

Sethuraman Arun

机构信息

Department of Biological Sciences, California State University San Marcos, CA 92096

出版信息

G3 (Bethesda). 2018 Oct 3;8(10):3203-3220. doi: 10.1534/g3.118.200485.

Abstract

Estimating genetic relatedness, and inbreeding coefficients is important to the fields of quantitative genetics, conservation, genome-wide association studies (GWAS), and population genetics. Traditional estimators of genetic relatedness assume an underlying model of population structure. Each individual is assigned to a population, depending on assumptions about geographical location of sampling, proximity, or genetic similarity. But often, this population assignment is unknown and assumptions about assignment can lead to erroneous estimates of genetic relatedness. I develop a generalized method of estimating relatedness in admixed populations, to account for (1) multi-allelic genomic data, (2) including all nine Identity By Descent (IBD) states, and implement a maximum likelihood based estimator of pairwise genetic relatedness in structured populations, part of the software, InRelate. Replicated estimations of genetic relatedness between admixed full sib (FS), half sib (HS), first cousin (FC), parent-offspring (PO) and unrelated (UR) dyads in simulated and empirical data from the HGDP-CEPH panel show considerably low bias and error while using InRelate, compared to several previously developed methods. I also propose a bootstrap scheme, and a series of Wald Tests to assign relatedness categories to pairs of individuals.

摘要

估计遗传相关性和近亲繁殖系数对于数量遗传学、保护生物学、全基因组关联研究(GWAS)以及群体遗传学领域而言至关重要。传统的遗传相关性估计方法假定了一种潜在的群体结构模型。根据关于采样地理位置、亲缘关系或遗传相似性的假设,将每个个体分配到一个群体中。但通常情况下,这种群体分配是未知的,而且关于分配的假设可能会导致遗传相关性的错误估计。我开发了一种用于估计混合群体中相关性的通用方法,以考虑(1)多等位基因基因组数据,(2)包括所有九种同源状态,并在结构化群体中实现了基于最大似然的成对遗传相关性估计器,这是软件InRelate的一部分。与之前开发的几种方法相比,在来自HGDP-CEPH面板的模拟和实证数据中,对混合全同胞(FS)、半同胞(HS)、一级表亲(FC)、亲子(PO)和无亲缘关系(UR)二元组之间的遗传相关性进行重复估计时,使用InRelate显示出相当低的偏差和误差。我还提出了一种自助抽样方案以及一系列Wald检验,用于为个体对分配相关性类别。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3616/6169378/315392a8b1d6/3203f1.jpg

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