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. 2019 Jul 17:13:712.
doi: 10.3389/fnins.2019.00712. eCollection 2019.

Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder

Shuang Liang  1 , Zhenzhi Li  2 , Yihan Wang  3 , Xiaodan Li  1 , Xiaolei Yang  1 , Xiaolei Zhan  1 , Yan Huang  1 , Zhaomin Gao  1 , Min Zhang  3 , Caihong Sun  1 , Yan Zhang  3 , Lijie Wu  1
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Free PMC article

Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder

Shuang Liang et al. Front Neurosci. .
Free PMC article

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.

Keywords: DNA methylation; SH2B1; autism spectrum disorder; discordant; monozygotic twins.

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Figures

FIGURE 1
FIGURE 1
DNA methylation levels of five ASD-discordant monozygotic twins obtained in 450K array and RRBS. (A) Scatter plots for sample pairs. Scatter plots of % methylation values for each pair in five ASD-discordant monozygotic twins. Numbers on upper right corner denote pair-wise Pearson’s correlation scores. The histograms on the diagonal are % methylation histograms per cytosine for each sample. Most of the bases have either high or low methylation. (B) Heat map of methylation CpG sites of five ASD-discordant monozygotic twins. Scaled methylation values are color-coded according to the legend on the right.
FIGURE 2
FIGURE 2
Functional enrichment analysis of the 2,397 intersected differential genes. (A) Relevant pathway enriched of 2,397 intersected differential genes in KEGG pathway. (B) Intersected differential genes enriched in the neurotrophin signaling pathway. Red star: different methylation genes.
FIGURE 3
FIGURE 3
Different methylation loci status of SH2B1 in autism and controls by pyrosequencing (pair t-test). (A) Methylation level of Chr.16:28856729 of SH2B1 in case and control. (B) Methylation level of Chr.16:28856735 of SH2B1 in case and control. (C) Methylation level of Chr.16:28856743 of SH2B1 in case and control. Green, case and yellow, control.
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References

    1. Akalin A., Kormaksson M., Li S., Garrett-Bakelman F. E., Figueroa M. E., Melnick A., et al. (2012). methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 13:R87. 10.1186/gb-2012-13-10-r87 - DOI - PMC - PubMed
    1. Bachmann-Gagescu R., Mefford H. C., Cowan C., Glew G. M., Hing A. V., Wallace S., et al. (2010). Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genet. Med. 12 641–647. 10.1097/GIM.0b013e3181ef4286 - DOI - PubMed
    1. Bochukova E. G., Huang N., Keogh J., Henning E., Purmann C., Blaszczyk K., et al. (2010). Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 463 666–670. 10.1038/nature08689 - DOI - PMC - PubMed
    1. Chen K. W., Chang Y. J., Chen L. (2015). SH2B1 orchestrates signaling events to filopodium formation during neurite outgrowth. Commun. Integr. Biol. 8:e1044189. 10.1080/19420889.2015.1044189 - DOI - PMC - PubMed
    1. Criado K. K., Sharp W. G., McCracken C. E., De Vinck-Baroody O., Dong L., Aman M. G., et al. (2017). Overweight and obese status in children with autism spectrum disorder and disruptive behavior. Autism 22 450–459. 10.1177/1362361316683888 - DOI - PMC - PubMed

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