自闭症患者大脑中CpG甲基化异常升高。
Exaggerated CpH methylation in the autism-affected brain.
作者信息
Ellis Shannon E, Gupta Simone, Moes Anna, West Andrew B, Arking Dan E
机构信息
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
出版信息
Mol Autism. 2017 Feb 17;8:6. doi: 10.1186/s13229-017-0119-y. eCollection 2017.
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 < 0.05 cutoff, = 0.002).
CONCLUSIONS
These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism.
背景
自闭症是一种复杂的、可遗传的神经发育障碍，其病因在很大程度上仍未得到解释。鉴于自闭症存在无法解释的风险，且近期有证据支持表观遗传机制在自闭症发展过程中发挥作用，我们探讨了自闭症相关大脑皮质组织中CpG和CpH（H = A、C或T）甲基化的作用。
方法
完成了简化代表性亚硫酸氢盐测序（RRBS），并对来自29名自闭症患者和34名对照个体的63份死后大脑皮质样本（布罗德曼19区）进行了分析。进行了分析以识别差异甲基化的单个位点，并识别全基因组中CpG或CpH位点的任何整体甲基化改变。
结果
我们报告称，经过多重检验校正后，没有单个甲基化位点或区域与自闭症显著相关，但甲基化的CpH二核苷酸在自闭症相关大脑中显著富集（在<0.05的临界值时约为2倍富集，P = 0.002）。
结论
这些结果进一步表明表观遗传改变参与了自闭症潜在的病理生物学机制。
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