Autism spectrum disorders (ASDs) Psynaptic Genes Targeted Sequencing

Autism spectrum disorders (ASDs) are characterized by deficits in three core behavioral domains: reciprocal social interactions, communication, and restricted interests and/or repetitive behaviors. It remains a challenge to associate these genes with specific core behavioral deficits. In multiplex autism families, affected sibs often show significant differences in severity of individual core phenotypes. We hypothesize that a higher mutation burden contributes to a larger difference in the severity of specific core phenotypes between affected sibs. We tested this hypothesis on social behavioral deficits in autism. We sequenced synaptome genes (n=1,886) in affected male sib-pairs (n=274) in families from the Autism Genetics Research Exchange (AGRE) and identified rare (MAF≤1%) and predicted functional variants.

自闭症谱系障碍（Autism Spectrum Disorders, ASDs）以三大核心行为领域的缺损为特征：互惠社交互动、沟通交流，以及受限兴趣和/或重复刻板行为。将此类基因与特定核心行为缺陷建立关联仍是一项极具挑战性的工作。在多发自闭症家族中，患病同胞往往在个体核心表型的严重程度上存在显著差异。我们提出假说：更高的突变负荷会导致患病同胞之间特定核心表型的严重程度差异更大。我们针对自闭症的社交行为缺陷验证了这一假说。我们对来自自闭症遗传学研究交流库（Autism Genetics Research Exchange, AGRE）的274对患病男性同胞对中的1886个突触组基因（synaptome genes）进行了测序，并鉴定出次要等位基因频率≤1%的罕见变异以及预测具有功能效应的变异。