RT Journal Article
SR Electronic
T1 Global changes in patterning, splicing and primate specific lncRNAs in autism brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 077057
DO 10.1101/077057
A1 Neelroop N. Parikshak
A1 Vivek Swarup
A1 T. Grant Belgard
A1 Michael Gandal
A1 Manuel Irimia
A1 Virpi Leppa
A1 Jennifer K. Lowe
A1 Robert Johnson
A1 Benjamin J. Blencowe
A1 Steve Horvath
A1 Daniel H. Geschwind
YR 2016
UL http://biorxiv.org/content/early/2016/09/25/077057.abstract
AB 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.