LaSalle Janine M
Department of Medical Microbiology and Immunology, Perinatal Origins of Disparities Center, MIND Institute, Genome Center, Environmental Health Sciences Center, University of California, Davis, Davis, CA, United States.
Front Genet. 2022 Mar 9;13:864848. doi: 10.3389/fgene.2022.864848. eCollection 2022.
The etiology of autism spectrum disorders (ASD) is complex, involving different combinations of genetic and environmental factors. My lab's approach has been to investigate DNA methylation as a tractable genome-wide modification at the interface of these complex interactions, reflecting past and future events in the molecular pathogenesis of ASD. Since X-linked genes were enriched in DNA methylation differences discovered from cord blood from newborns later diagnosed with ASD, this has prompted me to review and revisit the recent advancements in the field of X chromosome inactivation (XCI), particularly in humans and other primates. In this Perspective, I compare XCI mechanisms in different mammalian species, including the finding of the noncoding transcript associated with X chromosome erosion in human pluripotent stem cells and recent findings from non-human primate post-implantation embryos. I focus on the experimentally challenging peri- and post-implantation stages of human development when the timing of XCI is prolonged and imprecise in humans. Collectively, this research has raised some important unanswered questions involving biased sex ratios in human births and the male bias in the incidence of ASD.
自闭症谱系障碍（ASD）的病因复杂，涉及遗传和环境因素的不同组合。我实验室的方法是研究DNA甲基化，将其作为这些复杂相互作用界面上一种易于处理的全基因组修饰，反映ASD分子发病机制中的既往和未来事件。由于在后来被诊断为ASD的新生儿脐带血中发现的DNA甲基化差异中，X连锁基因富集，这促使我回顾和重新审视X染色体失活（XCI）领域的最新进展，特别是在人类和其他灵长类动物中的进展。在这篇观点文章中，我比较了不同哺乳动物物种的XCI机制，包括与人类多能干细胞中X染色体侵蚀相关的非编码转录本的发现以及非人灵长类动物植入后胚胎的最新发现。我关注人类发育中实验上具有挑战性的植入期和植入后期，此时人类XCI的时间延长且不精确。总的来说，这项研究提出了一些重要的未解决问题，涉及人类出生时的性别比例偏差以及ASD发病率中的男性偏差。
