Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Aberrant DNA methylation has been observed in ASD but the mechanisms remain largely unknown. Here, we employed discordant monozygotic twins to investigate the contribution of DNA methylation to ASD etiology. Genome-wide DNA methylation analysis was performed using samples obtained from five pairs of ASD-discordant monozygotic twins, which revealed a total of 2,397 differentially methylated genes. Further, such gene list was annotated with Kyoto Encyclopedia of Genes and Genomes and demonstrated predominant activation of neurotrophin signaling pathway in ASD-discordant monozygotic twins. The methylation of SH2B1 gene was further confirmed in the ASD-discordant, ASD-concordant monozygotic twins, and a set of 30 pairs of sporadic case-control by bisulfite-pyrosequencing. The results showed that there was a greater DNA methylation difference in ASD-discordant monozygotic twins than ASD-concordant monozygotic twins. Further, verification of the Chr.16:28856743 of SH2B1 showed significant differences in DNA methylation between case and control. These results suggest abnormal methylation of SH2B1 is associated with ASD etiology. Our data suggest that it might be worthwhile to further explore the functions of SH2B1 and related genes of neurotrophin signaling pathway in ASD.

Highlights

  • Autism spectrum disorder (ASD) is a group of serious neurodevelopmental disorders defined in an individual by deficits in social interaction and communication, accompanied by restricted interests and stereotypical repetitive behaviors

  • A high correlation was observed in genome-wide DNA methylation within each MZ twin, indicating that ASD is not co-related with systemic changes in epigenetic programming (Figure 1A)

  • In order to further verify the similarities observed in methylation status within five ASD-discordant MZ twins, an integrated heat map was generated, which displayed no significant differences in global DNA methylation profile (Figure 1B)

Read more

Summary

Introduction

Autism spectrum disorder (ASD) is a group of serious neurodevelopmental disorders defined in an individual by deficits in social interaction and communication, accompanied by restricted interests and stereotypical repetitive behaviors. The etiology for ASD mainly attributed to different genetic variants such as de novo mutations, copy number variations (CNV), Epigenome Changes in ASD Twins and single-nucleotide polymorphisms (SNP) (State and Levitt, 2011; Neale et al, 2012). Focuses on research efforts have grown in intensity during the past decade and due to the highly clinical and etiological heterogeneous nature of ASD, no findings of biological or clinical markers have been definitively identified. This shows that additional epigenetic or environmental factors are an underlying cause for the susceptibility to ASD. A large survey of over 14,000 children with ASD in Sweden revealed that heritable factors were found to contribute to about half of ASD risk and the other half were contributed from undetected genetic factors, environmental effects and/or stochastic effects

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call