Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana
Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana
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DOI：
10.1016/j.ajhg.2018.03.010
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发表时间：
2018-05-03
影响因子：
9.8
通讯作者：
Hanchard, Neil A.
中科院分区：
文献类型：
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作者：
Retshabile, Gaone;Mlotshwa, Busisiwe C.;Hanchard, Neil A.
大规模的、基于人群的基因组研究为现代医学遗传学提供了背景。然而，在这些研究中，非洲人口的代表性仍然相对不足。整个非洲大陆的遗传多样性的广度主张探索当地的基因组背景，以促进在非洲蓬勃发展的疾病绘图研究。我们试图描述遗传变异的特征，并评估来自博茨瓦纳的一组HIV阳性儿童的群体结构，博茨瓦纳是一个在基因组数据库中区域代表性不足的南部非洲国家。使用来自164名蝙蝠的全外显子组测序数据，并与150名类似测序的艾滋病毒阳性乌干达儿童进行比较，我们发现蝙蝠中观察到的13%-25%的变异没有被公共数据库捕获。未捕获的变体显著富集（p = 2.2 x 10（-16））具有1%至5%的次要等位基因频率的编码变体，并且包括预测的破坏性非同义变体。在公共数据库中发现的变异体中，相应的等位基因频率变化很大，博茨瓦纳在罕见（
Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa. We sought to characterize genetic variation and to assess population substructure within a cohort of HIV-positive children from Botswana-a Southern African country that is regionally underrepresented in genomic databases. Using whole-exome sequencing data from 164 Batswana and comparisons with 150 similarly sequenced HIV-positive Ugandan children, we found that 13%-25% of variation observed among Batswana was not captured by public databases. Uncaptured variants were significantly enriched (p = 2.2 x 10(-16)) for coding variants with minor allele frequencies between 1% and 5% and included predicted-damaging non-synonymous variants. Among variants found in public databases, corresponding allele frequencies varied widely, with Botswana having significantly higher allele frequencies among rare (