Laboratory of Clinical and Developmental Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Gene. 2012 Apr 1;496(2):88-96. doi: 10.1016/j.gene.2012.01.020. Epub 2012 Jan 26.
Autism spectrum disorders (ASDs) are a group of diseases exhibiting impairment in social drive, communication/language skills and stereotyped behaviors. Though an increased number of candidate genes and molecular interactions have been identified by various approaches, the pathogenesis remains elusive. Based on clinical observations, data from accessible GWAS and expression datasets we identified ASDs gene candidates. Integrative gene network and a novel CNV-centric Node Network (CNN) analysis method highlighted ASDs-associated key elements and biological processes. Functional analysis identified neurological functions including synaptic cholinergic receptor (CHRNA) families, dopamine receptor (DRD2), and correlations between social behavior and oxytocin related pathways. CNN analysis of genome-wide genetic and expression data identified inheritance-related clusters related to PTEN/TSC1/FMR1 and mTor/PI3K regulation. Integrative analysis identified potential regulators of networks, specifically TNF and beta-estradiol, suggesting a potential central role in ASDs. Our data provide information on potential disease mechanisms, and key regulators that may generate novel postulations, and diagnostic molecular biomarkers.
自闭症谱系障碍（ASD）是一组表现为社会驱动、沟通/语言技能和刻板行为障碍的疾病。尽管通过各种方法已经确定了越来越多的候选基因和分子相互作用，但发病机制仍不清楚。基于临床观察、可及的 GWAS 和表达数据集的数据，我们确定了 ASD 候选基因。综合基因网络和一种新的 CNV 中心节点网络（CNN）分析方法突出了与 ASD 相关的关键元素和生物学过程。功能分析确定了包括突触胆碱能受体（CHRNA）家族、多巴胺受体（DRD2）在内的神经功能，以及社会行为与催产素相关途径之间的相关性。对全基因组遗传和表达数据的 CNN 分析确定了与 PTEN/TSC1/FMR1 和 mTor/PI3K 调节相关的遗传相关簇。综合分析确定了网络的潜在调节剂，特别是 TNF 和β-雌二醇，表明其在 ASD 中可能具有潜在的核心作用。我们的数据提供了关于潜在疾病机制和关键调节剂的信息，这些调节剂可能会产生新的假说和诊断分子生物标志物。
