Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Molecular Autism
Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Research

Exaggerated CpH methylation in the autism-affected brain

Authors: Shannon E. Ellis, Simone Gupta, Anna Moes, Andrew B. West, Dan E. Arking

Published in: Molecular Autism | Issue 1/2017

Login to get access

Abstract

Background

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.

Methods

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.

Results

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 at p < 0.05 cutoff, p = 0.002).

Conclusions

These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism.
Appendix
Available only for authorised users
Literature
1.
2.
de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016;22:345–61.CrossRefPubMedPubMedCentral
3.
4.
Gupta S, et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun. 2014;5:5748.CrossRefPubMedPubMedCentral
5.
6.
Vijayakumar NT, Judy MV. Autism spectrum disorders: integration of the genome, transcriptome and the environment. J Neurol Sci. 2016;364:167–76.CrossRefPubMed
7.
Nagarajan R, Hogart A, Gwye Y, Martin MR, Lasalle JM. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics. 2006;1:172–82.CrossRef
8.
9.
Nguyen A, Rauch TA, Pfeifer GP, Hu VW. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J. 2010;24:3036–51.CrossRefPubMedPubMedCentral
10.
11.
12.
Day K, et al. Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol. 2013;14:R102.CrossRefPubMedPubMedCentral
13.
Leek JT, Storey JD. Capturing heterogeneity in gene expression studies by surrogate variable analysis. Plos Genet. 2007;3:1724–35.CrossRefPubMed
14.
15.
Smith AK, et al. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics. 2014;15:145.CrossRefPubMedPubMedCentral
16.
17.
18.
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. gkv007 (2015). doi:10.​1093/​nar/​gkv007
19.
20.
Aryee MJ, et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–9.CrossRefPubMedPubMedCentral
21.
22.
23.
Meissner A, et al. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res. 2005;33:5868–77.CrossRefPubMedPubMedCentral
24.
25.
26.
27.
Guo JU, et al. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 2014;17:215–22.CrossRefPubMed
28.
Kinde B, Gabel HW, Gilbert CS, Griffith EC, Greenberg ME. Reading the unique DNA methylation landscape of the brain: non-CpG methylation, hydroxymethylation, and MeCP2. Proc Natl Acad Sci U S A. 2015;112:6800–6.CrossRefPubMedPubMedCentral
29.
Wiles ET, Selker EU. H3K27 methylation: a promiscuous repressive chromatin mark. Curr Opin Genet Dev. 2017;43:31–7.CrossRef
30.
31.
32.
Münzel M, et al. Quantification of the sixth DNA base hydroxymethylcytosine in the brain. Angew Chem Int Ed. 2010;49:5375–7.CrossRef
33.
Metadata
Title
Exaggerated CpH methylation in the autism-affected brain
Authors
Shannon E. Ellis
Simone Gupta
Anna Moes
Andrew B. West
Dan E. Arking
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0119-y

Other articles of this Issue 1/2017

Molecular Autism 1/2017 Go to the issue

Research

ADHD-related symptoms and attention profiles in the unaffected siblings of probands with autism spectrum disorder: focus on the subtypes of autism and Asperger’s disorder

Short report

The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis

Short report

No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism

Review

Bio-collections in autism research

Review

Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses

Short report

Initial evidence that non-clinical autistic traits are associated with lower income