Power of deep, all-exon resequencing for discovery of human trait genes
Power of deep, all-exon resequencing for discovery of human trait genes
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DOI：
10.1073/pnas.0812824106
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发表时间：
2009-03-10
影响因子：
11.1
通讯作者：
Sunyaev, Shamil R.
中科院分区：
文献类型：
--
作者：
Kryukov, Gregory V.;Shpunt, Alexander;Sunyaev, Shamil R.
给定个体基因组的所有编码区域成本效益的所有编码区域的能力都快速接近，并且有可能将全基因组重新置于不远的范围内。目前正在为数十万个主要人类特征的人进行倡议。在这里，我们确定从从头发现与人类性状相关的基因的能力，通过重塑临床人群中的所有人类外显子。我们分析了基因发现策略的潜力，该基因发现策略结合了来自同一基因的多种稀有变体，并将基因而不是单个等位基因视为关联测试的单位。通过使用基于对欧洲人群的深度重新纠正数据的计算机模拟，我们表明可以有意义地影响人类性状的基因以公正的方式确定，尽管需要大量样本量以实现实质性的能力。
The ability to sequence cost-effectively all of the coding regions of a given individual genome is rapidly approaching, with the potential for whole-genome resequencing not far behind. Initiatives are currently underway to phenotype hundreds of thousands of individuals for major human traits. Here, we determine the power for de novo discovery of genes related to human traits by resequencing all human exons in a clinical population. We analyze the potential of the gene discovery strategy that combines multiple rare variants from the same gene and treats genes, rather than individual alleles, as the units for the association test. By using computer simulations based on deep resequencing data for the European population, we show that genes meaningfully affecting a human trait can be identified in an unbiased fashion, although large sample sizes would be required to achieve substantial power.