Homo sapiens Transcriptome or Gene expression

Despite its tremendous heterogeneity, autism is characterized by a shared core behavioral phenotype. This suggests a convergence of the pathology on specific neural substrates. We aimed to identify region-specific molecular changes by performing the largest to date meta analysis of RNA-seq data from six cortical regions of autism patients together with DNA methylation profiling of one of the regions. We identified a prominent discordant pattern of gene expression and splicing changes that suggests a hyperactivation of the prefrontal cortex and a hypoactivation of the anterior insular cortex involved in emotional responses. Moreover, we identified a link between DNA methylation, alternative splicing and gene expression changes mediated by the chromatin modifier and high autism risk factor gene CHD8. Finally, analysis of candidate gene expression in different regions of developing human cortex suggested a predominant enrichment of misregulated genes in the layers populated by radial glia cells and producing inhibitory interneurons.