Autism spectrum disorder: insights into convergent mechanisms from transcriptomics

Heredity has a major role in autism spectrum disorder (ASD), yet underlying causal genetic variants have been defined only in a fairly small subset of cases. The enormous genetic heterogeneity associated with ASD emphasizes the importance of identifying convergent pathways and molecular mechanisms that are responsible for this disorder. We review how recent transcriptomic analyses have transformed our understanding of pathway convergence in ASD. In particular, deep RNA sequencing coupled with downstream investigations has revealed that a substantial fraction of autistic brains possess distinct transcriptomic signatures. These signatures are in part a consequence of altered neuronal activity and have a particular impact on pre-mRNA alternative splicing patterns.Transcriptome profiling in different brain regions has revealed distinct patterns of gene and non-coding RNA expression, as well as alternative splicing, in autism spectrum disorder (ASD). The authors review these ASD-associated signatures and the resulting mechanistic insights into ASD.