Autism is a complex disease whose etiology remains elusive. We\nintegrated previously and newly generated data and developed a\nsystems framework involving the interactome, gene expression and\ngenome sequencing to identify a protein interaction module with\nmembers strongly enriched for autism candidate genes. Sequencing\nof 25 patients confirmed the involvement of this module in autism,\nwhich was subsequently validated using an independent cohort of\nover 500 patients. Expression of this module was dichotomized with\na ubiquitously expressed subcomponent and another subcomponent\npreferentially expressed in the corpus callosum, which was\nsignificantly affected by our identified mutations in the network\ncenter. RNA-sequencing of the corpus callosum from patients with\nautism exhibited extensive gene mis-expression in this module, and\nour immunochemical analysis showed that the human corpus\ncallosum is predominantly populated by oligodendrocyte cells.\nAnalysis of functional genomic data further revealed a significant\ninvolvement of this module in the development of oligodendrocyte\ncells in mouse brain. Our analysis delineates a natural network\ninvolved in autism, helps uncover novel candidate genes for this\ndisease and improves our understanding of its molecular pathology.
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