Fedorova Larisa, Qiu Shuhao, Dutta Rajib, Fedorov Alexei
GEMA-Biomics, Ottawa Hills, OH,
Program in Bioinformatics and Proteomics/Genomics, University of Toledo Department of Medicine, University of Toledo.
Genome Biol Evol. 2016 Feb 23;8(3):777-90. doi: 10.1093/gbe/evw034.
A novel computational method for detecting identical-by-descent (IBD) chromosomal segments between sequenced genomes is presented. It utilizes the distribution patterns of very rare genetic variants (vrGVs), which have minor allele frequencies <0.2%. Contrary to the existing probabilistic approaches our method is rather deterministic, because it considers a group of very rare events which cannot happen together only by chance. This method has been applied for exhaustive computational search of shared IBD segments among 1,092 sequenced individuals from 14 populations. It demonstrated that clusters of vrGVs are unique and powerful markers of genetic relatedness, that uncover IBD chromosomal segments between and within populations, irrespective of whether divergence was recent or occurred hundreds-to-thousands of years ago. We found that several IBD segments are shared by practically any possible pair of individuals belonging to the same population. Moreover, shared short IBD segments (median size 183 kb) were found in 10% of inter-continental human pairs, each comprising of a person from sub-Saharan Africa and a person from Southern Europe. The shortest shared IBD segments (median size 54 kb) were found in 0.42% of inter-continental pairs composed of individuals from Chinese/Japanese populations and Africans from Kenya and Nigeria. Knowledge of inheritance of IBD segments is important in clinical case-control and cohort studies, since unknown distant familial relationships could compromise interpretation of collected data. Clusters of vrGVs should be useful markers for familial relationship and common multifactorial disorders.
本文提出了一种用于检测测序基因组间同源染色体片段（IBD）的新型计算方法。该方法利用了罕见遗传变异（vrGVs）的分布模式，这些变异的次要等位基因频率小于0.2%。与现有的概率方法不同，我们的方法具有较强的确定性，因为它考虑了一组极罕见的事件，这些事件不可能仅仅偶然同时发生。该方法已应用于对来自14个群体的1092个测序个体间共享IBD片段进行详尽的计算搜索。结果表明，vrGVs簇是遗传相关性的独特且强大的标记，可揭示群体间和群体内的IBD染色体片段，无论分歧是近期发生还是发生在数百至数千年前。我们发现，同一群体中几乎任何可能的个体对都共享若干IBD片段。此外，在10%的洲际人类对中发现了共享的短IBD片段（中位大小183 kb），每对由一名撒哈拉以南非洲人和一名南欧人组成。在由中国/日本人群个体与来自肯尼亚和尼日利亚的非洲人组成的洲际对中，0.42%发现了最短的共享IBD片段（中位大小54 kb）。了解IBD片段的遗传情况在临床病例对照和队列研究中很重要，因为未知的远亲关系可能会影响对收集数据的解释。vrGVs簇应是用于家族关系和常见多因素疾病的有用标记。
