Dating genomic variants and shared ancestry in population-scale sequencing data
Dating genomic variants and shared ancestry in population-scale sequencing data
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DOI：
10.1371/journal.pbio.3000586
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发表时间：
2020-01-01
期刊：
影响因子：
9.8
通讯作者：
McVean, Gil
中科院分区：
文献类型：
--
作者：
Albers, Patrick K.;McVean, Gil
物种内新突变的起源和命运是进化的基本过程。然而，虽然很多注意力都集中在表征遗传变异的存在、频率和表型影响上，但大多数变异的进化史在很大程度上还没有被探索。我们开发了一种非参数方法，用于在大规模测序数据集中估计遗传变异的起源日期。通过仿真验证了该方法的准确性和鲁棒性。利用两个公开可用的人类基因组多样性资源的数据，我们估计了人类基因组中超过4500万个单核苷酸多态(SNPs)的年龄，并发布了作为公共在线数据库的变异年龄图集。我们描述了不同地理区域的变异年龄与频率的关系，并展示了年龄信息在解释具有功能和选择重要性的变异中的价值。最后，我们使用等位基因年龄估计来推动一种快速的方法来推断个体基因组之间共享的祖先，量化过去不同时间点的系谱关系，以及描述和探索现代人类群体的进化史。
The origin and fate of new mutations within species is the fundamental process underlying evolution. However, while much attention has been focused on characterizing the presence, frequency, and phenotypic impact of genetic variation, the evolutionary histories of most variants are largely unexplored. We have developed a nonparametric approach for estimating the date of origin of genetic variants in large-scale sequencing data sets. The accuracy and robustness of the approach is demonstrated through simulation. Using data from two publicly available human genomic diversity resources, we estimated the age of more than 45 million single-nucleotide polymorphisms (SNPs) in the human genome and release the Atlas of Variant Age as a public online database. We characterize the relationship between variant age and frequency in different geographical regions and demonstrate the value of age information in interpreting variants of functional and selective importance. Finally, we use allele age estimates to power a rapid approach for inferring the ancestry shared between individual genomes and to quantify genealogical relationships at different points in the past, as well as to describe and explore the evolutionary history of modern human populations.