Genome-wide Comparison of African-Ancestry Populations from CARe and Other Cohorts Reveals Signals of Natural Selection
Genome-wide Comparison of African-Ancestry Populations from CARe and Other Cohorts Reveals Signals of Natural Selection
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DOI：
10.1016/j.ajhg.2011.07.025
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发表时间：
2011-09-09
影响因子：
9.8
通讯作者：
Price, Alkes L.
中科院分区：
文献类型：
--
作者：
Bhatia, Gaurav;Patterson, Nick;Price, Alkes L.
人类种群中近代自然选择的研究对人类历史和医学有重要的应用。积极的自然选择推动了有益等位基因的增加，并在解释人类种群的多样性方面发挥了作用。通过发现受正选择影响的性状，我们可以更好地理解种群水平对包括传染病在内的环境压力的反应。我们的研究考察了三个大数据集之间不寻常的种群差异，以检测自然选择。非洲裔美国人、尼日利亚人和冈比亚人被研究的人群在基因上彼此接近（所有对的F-ST < 0.01），即使等位基因频率发生适度变化，我们也能检测到选择。我们还开发了一种基于树的方法来确定选择发生的种群，结合种群间的信息。我们的全基因组显著结果证实了先前报道的在非洲人中进行选择的位点，包括HBB和CD36。在6号染色体上的HLA位点，结果表明存在多个独立的群体特异性选择压力靶点。此外，我们报告了前列腺干细胞抗原（PSCA）基因的全基因组显著（p = 1.36 × 10(-11)）选择信号。在我们的分析中，分化最显著的标记rs2920283在非洲和东亚都是高度分化的，并且与膀胱癌和胃癌具有先前的全基因组显著关联。
The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (F-ST < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 x 10(-11)) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers.