格兰特搜索

自闭症谱系障碍(ASDs)是一组异质障碍，其特征是语言障碍、社会互动和沟通缺陷、刻板行为和兴趣受限。染色体异常，如突变和拷贝数变异(CNVs) -特定染色体区域的缺失或复制，与asd的发病有关。具体来说，16号染色体上的微缺失或微重复(16p11.2)赋予asd易感性。该区域含有约25个基因，其中大部分在人脑中表达。人类神经影像学研究显示16p11.2 CNV携带者的胼胝体异常。既往文献也提示特发性asd中胼胝体异常。然而，目前尚不清楚16p11.2 CNV如何与胼胝体缺陷相关。我们实验室的初步硅质分析表明，某些上游调控因子控制着16p11.2区域的几个基因。这些假定的调节因子之一是胼胝体发育的关键决定因素，以前也与特发性asd有关。本项目探索了这样一种假设，即从16p11.2 CNV携带者获得的诱导多能干细胞(iPSCs)中特定16p11.2基因的“主调控因子”的操纵将允许通过细胞分析描述基因表达模式和功能后果。 Using callosal bioassays such as axon outgrowth and guidance in neurons generated from 16p11.2-CNV carrier and non-carrier derived iPSCs, these studies will replicate the 16p11.2-associated cellular phenotypes and identify potential targets for therapeutic intervention. Finally, target-based strategies will be developed to rescue the phenotype in patient-derived neurons. This will encourage the development of novel strategies for prevention or treatment of ASDs. Once a gene target is identified, future projects will include small molecule screening.