Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism Associated Family Genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. is one of the most common autism causative genes. Twenty-four mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete transcript structure. We applied an integrative approach combining cDNA-capture and long-read sequencing to profile the transcriptome in human and mice. We unexpectedly discovered an extremely complex transcriptome. Specific transcripts were altered in mutant mice and postmortem brains tissues from individuals with ASD. The enhanced transcriptome significantly improved the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest the stochastic transcription of genome associated with family genes.