Exaggerated CpH methylation in the autism-affected brain.
The etiology of autism, a complex, heritable, neurodevelopmental disorder, remains largely unexplained. Given the unexplained risk and recent evidence supporting a role for epigenetic mechanisms in the development of autism, we explored the role of CpG and CpH (H = A, C, or T) methylation within the autism-affected cortical brain tissue.



Reduced representation bisulfite sequencing (RRBS) was completed, and analysis was carried out in 63 post-mortem cortical brain samples (Brodmann area 19) from 29 autism-affected and 34 control individuals. Analyses to identify single sites that were differentially methylated and to identify any global methylation alterations at either CpG or CpH sites throughout the genome were carried out.



We report that while no individual site or region of methylation was significantly associated with autism after multi-test correction, methylated CpH dinucleotides were markedly enriched in autism-affected brains (~2-fold enrichment atp< 0.05 cutoff,p= 0.002).



These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Shannon E
SE
Ellis
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Simone
S
Gupta
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Anna
A
Moes
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
Andrew B
AB
West
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Dan E
DE
Arking
D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D001344:Autopsy; D001482:Base Composition; D001923:Brain Chemistry; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D017422:Sequence Analysis, DNA / Q000379:methods*
Autism; Bisulfite sequencing; Brains; Methylation; RRBS