Complete gene knockouts in autism: identification and functional characterization

项目总结 拟议研究的首要目标是提高我们对神经生物学的理解。 自闭症谱系障碍(ASDS)的基础。在这个项目中，我们将分析从TENS收集的测序数据 对数千名患有和不患有ASD的人进行研究，并检查基因敲除(突变)的比率 破坏一个基因的两个功能拷贝)。基因敲除虽然罕见，但可以揭示关键的生物学 向我们传授疾病基础的途径。 我们将在病例和对照之间比较和对比这些基因敲除的比率和模式，研究 性别的影响，并将这些模式与男性自闭症患者的已知优势联系起来。我们还将 使用这些数据来生成特定基因的目录，这些基因在患有 ASD的发病率高于普通人群。最后，从这个目录中，将选出最强的候选基因 神经生物学功能研究，以深入了解功能障碍如何改变大脑发育和 自闭症患者的可塑性。

PROJECT SUMMARY The overarching goal of the proposed research is to improve our understanding of the neurobiological basis of autism spectrum disorders (ASDs). In this project we will analyze sequencing data collected from tens of thousands of individuals with and without ASD, and examine the rate at which gene knockouts (mutations that disrupt both functional copies of a gene) occur. Gene knockouts, while rare, can reveal critical biological pathways that teach us about the basis of disease. We will compare and contrast rates and patterns of these knockouts between cases and controls, study the effect of gender, and relate these patterns to the known preponderance of males with ASD. We will also use this data to generate a catalog of specific genes that are knocked out more frequently in individuals with ASD than in the general population. Finally, from this catalog, the strongest gene candidates will be chosen for neurobiological functional studies, to provide insight into how dysfunction may alter brain development and plasticity in autistic individuals.