期刊
EPIGENOMICS
卷 14, 期 17, 页码 1015-1027出版社
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2022-0184
关键词
autism spectrum disorder; DNA methylation; epimutations; haploinsufficiency; peroxisome biogenesis; function; triplosensitivity
资金
- Centre for Human Disease Research (CHDR)
- CHDR of BITS Pilani Hyderabad Campus
- Deprtment of Biotechnology
- BITS Pilani
Large DNA methylation changes were found in the gene promoters of cerebellum tissues of patients with autism spectrum disorder (ASD), including genes involved in peroxisome function. This supports the hypothesis that impaired peroxisome function/biogenesis is associated with ASD. Similar approaches could be used to identify rare epimutations in ASD and other complex disorders.
Plain language summary Genetic susceptibility of autism spectrum disorder (ASD) is well recognized but found only in one among 30-50% of identical twins. Epigenetic modifications such as DNA methylation underlie differences in gene function without alteration in the sequence. In this study, we identified large DNA methylation changes in nine gene promoters in cerebellum tissues of patients with ASD. Several were already implicated in ASD and other neuropsychiatric disorders. Promoters of two genes (SERHL and CAT) involved in peroxisome function showed increased methylation and low-level expression. The two abnormalities identified support the hypothesis associating ASD with defects in peroxisomes that are involved in detoxification of reactive oxygen species. Aim: We tested the hypothesis that a subset of patients with autism spectrum disorder (ASD) contains candidate genes with high DNA methylation differences (effective values) that potentially affect one of the two alleles. Materials & methods: Genome-wide DNA methylation comparisons were made on cerebellum samples from 30 patients and 45 controls. Results: 12 genes with high effective values, including GSDMD, MMACHC, SLC6A5 and NKX6-2, implicated in ASD and other neuropsychiatric disorders were identified. Monoallelic promoter methylation and downregulation were observed for SERHL (serine hydrolase-like) and CAT (catalase) genes associated with peroxisome function. Conclusion: These data are consistent with the hypothesis implicating impaired peroxisome function/biogenesis for ASD. A similar approach holds promise for identifying rare epimutations in ASD and other complex disorders.
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