Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families
Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families
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DOI：
10.1007/s10048-014-0394-0
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发表时间：
2014-05-01
期刊：
影响因子：
2.2
通讯作者：
Vincent, John B.
中科院分区：
文献类型：
--
作者：
Egger, Gerald;Roetzer, Katharina M.;Vincent, John B.
自闭症或自闭症谱系障碍(ASD)是一系列始于儿童早期的神经发育障碍，其特征是沟通和相互社会互动方面的障碍，以及存在受限和重复的行为模式。在双胞胎和家庭研究中，遗传因素对自闭症的贡献是显而易见的。很明显，总的来说，ASD是一种复杂的非孟德尔疾病。最近的研究表明，拷贝数变异(CNV)在ASD的病因学中起重要作用。在目前的工作中，我们从奥地利Styria的73个ASD家庭招募了245名家庭成员。先证者的DNA用Affymetrix单核苷酸多态性(SNP)6.0微阵列进行基因分型，以筛选基因组中的CNV。使用三种不同的算法对微阵列数据进行分析，并将严格呼叫列表与来自超过2357个欧洲血统对照的现有CNV数据进行比较。对于对照组中不存在的严格呼叫，使用定量实时聚合酶链式反应(qRT-PCR)来验证先证者及其家庭成员中的CNV。从这一组中验证了22个CNV(其中5个显然是从头开始的)，其中许多似乎可能扰乱可能被认为是神经精神障碍的良好候选基因，包括DLG2、S100B、ARX、DIP2A、HPCAL1和GPHN。其他几个基因扰乱了以前被认为与自闭症有关的基因，如BDNF、AUTS2、DPP6和C18orf22，我们的数据增加了越来越多的证据表明它们参与了自闭症。
Autism or autism spectrum disorder (ASD) is a range of neurodevelopmental disorders starting in early childhood and is characterized by impairments in communication and reciprocal social interaction and presence of restricted and repetitive patterns of behavior. The contribution of genetic factors to autism is clear in twin and family studies. It is apparent that, overall, ASD is a complex non-Mendelian disorder. Recent studies suggest that copy number variations (CNVs) play a significant role in the etiology of ASD. For the current work, we recruited 245 family members from 73 ASD families from Styria, Austria. The DNA from probands was genotyped with Affymetrix single nucleotide polymorphism (SNP) 6.0 microarrays to screen for CNVs in their genomes. Analysis of the microarray data was performed using three different algorithms, and a list of stringent calls was compared to existing CNV data from over 2,357 controls of European ancestry. For stringent calls not present in controls, quantitative real-time PCR (qRT-PCR) was used to validate the CNVs in the probands and in their family members. Twenty-two CNVs were validated from this set (five of which are apparently de novo), many of which appear likely to disrupt genes that may be considered as good candidates for neuropsychiatric disorders, including DLG2, S100B, ARX, DIP2A, HPCAL1, and GPHN. Several others disrupt genes that have previously been implicated in autism, such as BDNF, AUTS2, DPP6, and C18orf22, and our data add to the growing evidence of their involvement in ASD.