Strong association of de novo copy number mutations with autism
Strong association of de novo copy number mutations with autism
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DOI：
10.1126/science.1138659
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发表时间：
2007-04-20
期刊：
影响因子：
56.9
通讯作者：
Wigler, Michael
中科院分区：
文献类型：
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作者：
Sebat, Jonathan;Lakshmi, B.;Wigler, Michael
我们检验了从头拷贝数变化（CNV）与自闭症谱系障碍（ASDS）相关的假设。我们对患者的基因组DNA和未受影响的受试者进行了比较基因组杂交（CGH），以检测其各自父母中不存在的拷贝数变异。候选基因组区域通过高分辨率CGH，亲子鉴定，细胞遗传学，原位杂交和微卫星基因分型验证。确认的从头CNV与自闭症显着相关（p = 0.0005）。在118例（10％）的偶发自闭症患者中，有12例（10％）中有12例（3％（3％）（3％）患有受影响的一级亲戚的患者中有12例（10％），在196（1％）中，有2例（3％）（1％），在对照组中发现了这种CNV。 。大多数从头CNV小于显微镜分辨率。受影响的基因组区域是高度异质性的，包括单基因的突变。这些发现确立了从头种系突变，它是ASD比以前认识到的更重要的危险因素。
We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism ( P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.