Estimating the mutation load in human genomes.
Estimating the mutation load in human genomes.
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DOI：
10.1038/nrg3931
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发表时间：
2015-06
期刊：
影响因子：
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通讯作者：
Gravel S
中科院分区：
文献类型：
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作者：
Henn BM;Botigué LR;Bustamante CD;Clark AG;Gravel S
下一代测序技术促进了人类基因组中数百万个变异的发现。这些等位基因中有相当大一部分被认为是有害的。我们回顾了基因组数据中确定的有害等位基因的模式，并询问人群在预测的有害等位基因负担方面是否存在差异，这种现象称为“突变负荷”。我们讨论了预计会影响突变负荷的三种人口统计模型，并将这些模型与不同人类基因组中纯化选择功效变化的证据（或缺乏证据）联系起来。我们还讨论了为什么突变负载的准确估计取决于有关显性和选择系数分布的假设，这些数量对于当前基因组数据集来说很难表征。
Next-generation sequencing technology has facilitated the discovery of millions of variants in human genomes. A sizeable fraction of these alleles are thought to be deleterious. We review the pattern of deleterious alleles as ascertained in genomic data and ask whether human populations differ in their predicted burden of deleterious alleles, a phenomenon known as “mutation load.” We discuss three demographic models that are predicted to affect mutation load and relate these models to the evidence (or the lack thereof) for variation in the efficacy of purifying selection in diverse human genomes. We also discuss why accurate estimation of mutation load depends on assumptions regarding the distribution of dominance and selection coefficients, quantities that are poorly characterized for current genomic datasets.