Abstract

We apply transcriptome-wide RNA sequencing in postmortem autism spectrum disorder (ASD) brain and controls and identify convergent alterations in the noncoding transcriptome, including primate specific lncRNA, and transcript splicing in ASD cerebral cortex, but not cerebellum. We characterize an attenuation of patterning between frontal and temporal cortex in ASD and identify SOX5, a transcription factor involved in cortical neuron fate specification, as a likely driver of this pattern. We further show that a genetically defined subtype of ASD, Duplication 15q Syndrome, shares the core transcriptomic signature of idiopathic ASD, indicating that observed molecular convergence in autism brain is the likely consequence of manifold genetic alterations. Using co-expression network analysis, we show that diverse forms of genetic risk for ASD affect convergent, independently replicated, biological pathways and provide an unprecedented resource for understanding the molecular alterations associated with ASD in humans.