Copy number variations independently induce autism spectrum disorder

The examination of copy number variation (CNV) is critical to understand the etiology of the CNV-related autism spectrum disorders (ASD). DNA samples were obtained from 64 ASD probands, which were genotyped on an Affymetrix CytoScan HD platform. qPCR or FISH were used as a validation for some novel recurrent CNVs. We further compared the clinical phenotypes of the genes in the Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources (DECIPHER) database with these overlapping genes. Using vast, readily available databases with previously reported clinically relevant CNVs from human populations, the genes were evaluated using Enrichment Analysis and GO Slim Classification. By using the Ploysearch2 software, we identified the interaction relationship between significant genes and known ASD genes. A total of 29 CNVs, overlapping with 520 genes, including 315 OMIM genes, were identified. Additionally, myocyte enhancer factor 2 family (MEF2C) with two cases of CNV overlapping were also identified. Enrichment analysis showed that the 520 genes are most likely to be related to membrane components with protein-binding functions involved in metabolic processes. In the interaction network of those genes, the known ASD genes are mostly at the core position and the significant genes found in our samples are closely related to the known ASD genes. CNVs should be an independent factor to induce autism. With the strategy of our study, we could find the ASDs candidate genes by CNV data and review certain pathogenesis of this disorder. Those CNVs were associated with ASD and they may contribute to ASD by affecting the ASD-related genes.

拷贝数变异（CNV）检测对于理解与CNV相关的自闭症谱系障碍（ASD）的病因至关重要。从64名ASD先证者获取了DNA样本，这些样本在Affymetrix CytoScan HD平台上进行了基因分型。定量聚合酶链反应（qPCR）或荧光原位杂交（FISH）被用于对一些新的反复出现的CNV进行验证。我们进一步将使用Ensembl资源的人类染色体不平衡和表型数据库（DECIPHER）中基因的临床表型与这些重叠基因进行了比较。利用大量现成的、包含先前报道的来自人类群体的临床相关CNV的数据库，使用富集分析和基因本体论精简分类（GO Slim Classification）对基因进行了评估。通过使用Ploysearch2软件，我们确定了显著基因与已知ASD基因之间的相互作用关系。共鉴定出29个CNV，它们与520个基因重叠，包括315个在线人类孟德尔遗传（OMIM）基因。此外，还鉴定出了有两例CNV重叠的肌细胞增强因子2家族（MEF2C）。富集分析表明，520个基因最有可能与参与代谢过程且具有蛋白质结合功能的膜成分相关。在这些基因的相互作用网络中，已知的ASD基因大多处于核心位置，我们样本中发现的显著基因与已知的ASD基因密切相关。CNV应该是诱发自闭症的一个独立因素。通过我们的研究策略，我们可以通过CNV数据找到ASD的候选基因，并审视这种疾病的某些发病机制。那些CNV与ASD相关，它们可能通过影响与ASD相关的基因而导致ASD。