Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease
Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease
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DOI：
10.1038/ng.2555
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发表时间：
2013-03-01
期刊：
影响因子：
30.8
通讯作者：
Wray, Naomi R.
中科院分区：
文献类型：
--
作者：
Gratten, Jacob;Visscher, Peter M.;Wray, Naomi R.
系谱、连锁和关联研究与复杂疾病的遗传变异一致，这是由于家族和群体中遗传因素的分离。相比之下，新生突变对复杂性状的遗传力估计只有很小的贡献。尽管如此，已知一些新生变异在疾病病因学中是重要的。鉴定赋予风险的新生变异将有助于发现病因相关的基因和途径，并可能有助于遗传咨询。有相当大的兴趣在复杂的神经精神疾病，主要是由新的基因分型和测序技术驱动的这种突变的作用。已经确定了大的从头拷贝数变异的重要作用。最近，全外显子组测序已被用于扩展从头变异的蛋白质编码区的点突变的调查。在这里，我们考虑了几个挑战，解释这些突变的背景下，他们在神经精神疾病的作用。
Pedigree, linkage and association studies are consistent with heritable variation for complex disease due to the segregation of genetic factors in families and in the population. In contrast, de novo mutations make only minor contributions to heritability estimates for complex traits. Nonetheless, some de novo variants are known to be important in disease etiology. The identification of risk-conferring de novo variants will contribute to the discovery of etiologically relevant genes and pathways and may help in genetic counseling. There is considerable interest in the role of such mutations in complex neuropsychiatric disease, largely driven by new genotyping and sequencing technologies. An important role for large de novo copy number variations has been established. Recently, whole-exome sequencing has been used to extend the investigation of de novo variation to point mutations in protein-coding regions. Here, we consider several challenges for the interpretation of such mutations in the context of their role in neuropsychiatric disease.