Analysis of 6,515 exomes reveals a recent origin of most human protein-coding variants
Analysis of 6,515 exomes reveals a recent origin of most human protein-coding variants
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发表时间：
2013
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通讯作者：
Wenqing Fu;T. O’Connor;G. Jun;H. Kang;G. Abecasis;S. Leal;S. Gabriel;D. Altshuler;J. Shendure-J.-She
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作者：
Wenqing Fu;T. O’Connor;G. Jun;H. Kang;G. Abecasis;S. Leal;S. Gabriel;D. Altshuler;J. Shendure-J.-She
确定当代人类种群中每个突变分离的年龄对于充分理解我们的进化史1、2非常重要，并将有助于开发新的疾病基因发现方法3。对人类遗传变异的大规模调查报告了最近人口爆炸性增长的迹象，以稀有基因变异的过剩而闻名，定性地表明，许多突变是最近出现的。为了更定量地评估突变年龄的分布，我们对6,515名欧洲人(n=4,298)和非洲人(n=2,217)美国血统的15,336个基因进行了重新测序，并推断出1,146,401个常染色体单核苷酸变体(SNV)的年龄。我们估计，大约73%的蛋白质编码SNV和~86%的SNV预测是有害的，发生在过去的5000-10000年间。有害SNV的平均年龄在不同的分子途径和疾病中差异很大
Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history 1,2 and will help facilitate the development of new approaches for disease gene discovery 3 . Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth 4-6 , notable for an excess of rare genetic variants, qualitatively suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European (n=4,298) and African (n=2,217) American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that ~73% of all protein-coding SNVs and ~86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease