Siu Michelle T, Weksberg Rosanna
Program in Genetics and Genome Biology, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
Adv Exp Med Biol. 2017;978:63-90. doi: 10.1007/978-3-319-53889-1_4.
Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development. In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.
自闭症谱系障碍（ASD）是最常见的儿童神经发育障碍（NDDs）之一，每68名儿童中就有1名被诊断为此病。ASD在临床和病因学上都具有极大的异质性。已知ASD的病因发病机制很复杂，包括遗传、环境和表观遗传因素。可通过遗传和环境暴露进行修饰的正常表观遗传标记会导致表观遗传改变，从而破坏基因表达的调控，对大脑发育重要的生物学途径产生负面影响。在本章中，我们旨在总结一些重要文献，这些文献支持表观遗传学在ASD潜在分子机制中所起的作用。我们提供了来自遗传学研究、环境暴露研究的证据，最后还提供了来自最近旨在直接确定ASD特异性表观遗传模式的研究证据，主要聚焦于DNA甲基化（DNAm）。最后，我们简要讨论了当前研究对潜在表观遗传治疗靶点的一些影响以及未来工作的新途径。
