Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders
Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders
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DOI：
10.1016/j.neuron.2011.05.015
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发表时间：
2011-06-09
期刊：
影响因子：
16.2
通讯作者：
Wigler, Michael
中科院分区：
文献类型：
--
作者：
Levy, Dan;Ronennus, Michael;Wigler, Michael
为了探索自闭症谱系障碍（ASD）的遗传贡献，我们研究了一个大的家族中的基因组拷贝数变异，其中有一个受影响的孩子和至少一个未受影响的兄弟姐妹。我们确认了从头缺失和重复的主要贡献，但也发现了遗传性“超稀有”重复的作用的证据。我们的研究结果表明，相对于男性，女性对遗传原因引起的自闭症有更大的抵抗力，这就提出了女性携带者命运的问题。通过分析重复位点的比例和数量，我们将不同靶位点的下限设定为几百个。我们发现了许多新的候选区域，大大增加了潜在的基因靶点，并确认了以前观察到的几个位点。从头变异区域中基因的功能表明了遗传原因的巨大多样性，但也表明了功能趋同。
To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited "ultrarare" duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence.