Increased exonic de novo mutation rate in individuals with schizophrenia
Increased exonic de novo mutation rate in individuals with schizophrenia
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DOI：
10.1038/ng.886
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发表时间：
2011-09-01
期刊：
影响因子：
30.8
通讯作者：
Rouleau, Guy A.
中科院分区：
文献类型：
--
作者：
Girard, Simon L.;Gauthier, Julie;Rouleau, Guy A.
精神分裂症是一种严重的精神疾病，深刻影响认知、行为和情感过程。精神分裂症的广泛症状和临床变异表明其存在复杂的遗传病因，这与迄今为止通过连锁、拷贝数变异和关联研究鉴定的众多基因座一致(1-4)。尽管精神分裂症的遗传率可能高达 80%，但导致这种遗传率大部分的基因仍有待确定 (5)。在这里，我们对 14 名精神分裂症先证者及其父母的外显子组进行了测序。我们在 8 个先证者中发现了 15 个从头突变 (DNM)，考虑到之前报道的 DNM 率，这明显多于预期 (6-8)。此外，在 15 个已识别的 DNM 中，有 4 个是无义突变，这超出了偶然的预期(9)。我们的研究支持这样的观点，即 DNM 可能解释了精神分裂症的一些遗传性，同时提供了可能参与疾病发病机制的基因列表。
Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies(1-4). Although schizophrenia heritability may be as high as similar to 80%, the genes responsible for much of this heritability remain to be identified(5). Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate(6-8). In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance(9). Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis.