Inferring the ancestry of parents and grandparents from genetic data
Inferring the ancestry of parents and grandparents from genetic data
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DOI：
10.1371/journal.pcbi.1008065
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发表时间：
2020-08-01
影响因子：
4.3
通讯作者：
Wu, Yufeng
中科院分区：
文献类型：
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作者：
Pei, Jingwen;Zhang, Yiming;Wu, Yufeng
混合比例的推断是群体遗传学中的一个经典统计问题。标准方法隐含地假设个体的双亲具有相同的混合分数。然而，在真实的数据中，情况很少如此。在本文中，我们表明，在一个基因组中的混合道长度的分布包含的信息的混合比例的祖先的个人。我们开发了一个隐马尔可夫模型（HMM）的框架，用于估计的混合比例的直接祖先的个人，即一种类型的分解一个人的混合比例到进一步的子集的祖先的祖先比例。基于混合道的谱系模型，我们开发了一种有效的算法，用于计算从单个个体的基因组的采样概率，作为该个体的祖先的混合比例的函数。这使我们能够仅使用现存个体的基因组来执行祖先混合比例的概率推断。我们进行了广泛的模拟，以量化在各种条件下的祖先混合比例的估计误差。为了说明该方法的实用性，我们将其应用到真实的遗传data.Author摘要血统推断是遗传学中的一个重要问题，并被商业上使用的一些公司影响数百万消费者的遗传血统测试。在本文中，我们表明，这是可能的，不仅要估计一个人的祖先分数，但也有一定的不确定性，估计一个人的最近的祖先的祖先分数。例如，如果一个人将他/她的祖先50%追溯到亚洲，50%追溯到欧洲，则可以区分具有两个父母的个体，每个父母都是亚洲和欧洲血统的50：50复合物，或者一个父母来自亚洲，一个来自欧洲。同样也可以对祖父母进行推论。我们提出了一种计算效率高的方法，使这样的推论称为PedMix。PedMix基于后代和最近祖先的概率模型。PedMix使用焦点个体的全基因组遗传变异数据推断最近祖先（父母，祖父母甚至曾祖父母）的混合比例。模拟和真实的数据的结果表明，PedMix在大多数情况下表现相当不错。
Inference of admixture proportions is a classical statistical problem in population genetics. Standard methods implicitly assume that both parents of an individual have the same admixture fraction. However, this is rarely the case in real data. In this paper we show that the distribution of admixture tract lengths in a genome contains information about the admixture proportions of the ancestors of an individual. We develop a Hidden Markov Model (HMM) framework for estimating the admixture proportions of the immediate ancestors of an individual, i.e. a type of decomposition of an individual's admixture proportions into further subsets of ancestral proportions in the ancestors. Based on a genealogical model for admixture tracts, we develop an efficient algorithm for computing the sampling probability of the genome from a single individual, as a function of the admixture proportions of the ancestors of this individual. This allows us to perform probabilistic inference of admixture proportions of ancestors only using the genome of an extant individual. We perform extensive simulations to quantify the error in the estimation of ancestral admixture proportions under various conditions. To illustrate the utility of the method, we apply it to real genetic data.Author summary Ancestry inference is an important problem in genetics and is used commercially by a number of companies affecting millions of consumers of genetic ancestry tests. In this paper, we show that it is possible, not only to estimate the ancestry fractions of an individual, but also, with some uncertainty, to estimate the ancestry fractions of an individual's recent ancestors. For example, if an individual traces his/her ancestry 50% to Asia and 50% to Europe, it is possible to distinguish between the individual having two parents that each are 50:50 composites of Asian and European ancestry, or one parent from Asia and one from Europe. It is likewise also possible to make inferences about grandparents. We present a computationally efficient method for making such inferences called PedMix. PedMix is based on a probabilistic model for the descendant and the recent ancestors. PedMix infers admixture proportions of recent ancestors (parents, grandparents or even great grandparents) using whole-genome genetic variation data from a focal individual. Results on both simulated and real data show that PedMix performs reasonably well in most scenarios.