The role of mutation rate variation and genetic diversity in the architecture of human disease.
The role of mutation rate variation and genetic diversity in the architecture of human disease.
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DOI：
10.1371/journal.pone.0090166
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Eyre-Walker A
中科院分区：
文献类型：
--
作者：
Eyre-Walker YC;Eyre-Walker A
我们研究了基因突变率和基因变异结构在决定基因是否与疾病有关的过程中所起的作用。我们预测，除非所有可能导致疾病的基因都已经被识别出来，否则与疾病相关的基因的突变率及其遗传多样性应该会更高。与我们的预测一致，我们发现与孟德尔病和复杂疾病相关的基因比非疾病基因长得多。然而，我们发现孟德尔和复杂疾病基因都在基因组中突变频率相对较低的区域被发现，这是从人类和黑猩猩之间的内含子差异推断的，并且它们被预测具有与其他基因相似的非同义突变率。最后，我们发现，即使控制了突变率的变异，疾病基因也位于遗传多样性显著提高的区域。然而，影响是很小的。我们的结果表明，基因长度决定了基因是否与疾病相关。然而，在决定基因是否与疾病相关方面，该基因的突变率和遗传结构似乎只起到了很小的作用。
We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Smith, NGC;Eyre-Walker, A
通讯作者：
Eyre-Walker, A
影响因子：
14.9
作者：
Kondrashov, FA;Ogurtsov, AY;Kondrashov, AS
通讯作者：
Kondrashov, AS
影响因子：
7
作者：
McVicker, Graham;Green, Phil
通讯作者：
Green, Phil
影响因子：
10.7
作者：
Pink, Catherine J.;Hurst, Laurence D.
通讯作者：
Hurst, Laurence D.