Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes.
Chun-Yen LinKai-Wei ChangChia-Yi LinJia-Ying WuHilary CoonPei-Hsin HuangHong-Nerng HoSchahram AkbarianSusan Shur-Fen GauHsien-Sung HuangPublished in: Scientific reports (2018)
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, and the exact causal mechanism is unknown. Dysregulated allele-specific expression (ASE) has been identified in persons with ASD; however, a comprehensive analysis of ASE has not been conducted in a family quartet with ASD. To fill this gap, we analyzed ASE using genomic DNA from parent and offspring and RNA from offspring's postmortem prefrontal cortex (PFC); one of the two offspring had been diagnosed with ASD. DNA- and RNA-sequencing revealed distinct ASE patterns from the PFC of both offspring. However, only the PFC of the offspring with ASD exhibited a mono-to-biallelic switch for LRP2BP and ZNF407. We also identified a novel site of RNA-editing in KMT2C in addition to new monoallelically-expressed genes and miRNAs. Our results demonstrate the prevalence of ASE in human PFC and ASE abnormalities in the PFC of a person with ASD. Taken together, these findings may provide mechanistic insights into the pathogenesis of ASD.
Keyphrases
- autism spectrum disorder
- intellectual disability
- attention deficit hyperactivity disorder
- high fat diet
- poor prognosis
- prefrontal cortex
- endothelial cells
- crispr cas
- genome wide
- transcription factor
- type diabetes
- single molecule
- dna methylation
- long non coding rna
- density functional theory
- induced pluripotent stem cells
- heat stress
- working memory