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表观遗传学在人类疾病预防与缓解中的关键作用
The Key Role of Epigenetics in Human Disease Prevention and Mitigation


Andrew P. Feinberg ... 肿瘤 其他 • 2018.04.05

表观遗传学与人类疾病

 

刘贇

复旦大学基础医学院

 

Andrew Feinberg在2018年4月5日出版的《新英格兰医学杂志》发表了一篇综述,回顾并展望了在后基因组时代,表观遗传学在人类常见疾病的诊疗、防治中起到的关键作用1

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能够控制发育、组织分化和细胞响应的核信息构成了表观基因组,在细胞分裂过程中,这样的信息可以遗传。控制表观遗传信息的因素有基因组序列、环境暴露和随机性事件。就此而言,表观遗传学关注的是基因组、发育和环境暴露三者间的相互作用。

身体的所有细胞实际上拥有同样的DNA,然而不同的器官和组织发挥着截然不同的功能,并且当各自细胞分裂时都能保持其特征。这种细胞特征就是表观遗传信息,也就是附加到基因自身的信息。表观遗传学最初由胚胎学家Conrad Waddington在20世纪50年代定义为研究基因及其实现表型的基因产物之间相互作用的生物学分支1。Waddington的这一定义是基于对组织发育最终命运的高度决定论的观点:虽然发育过程由于环境暴露或许会有些差异,但最终结果毫无例外地是由基因而不是环境决定的。Waddington描述了一种 “表观遗传景观”,一个多能细胞在这种“地形”上沿着通往其最终命运的“山谷”滑下去,并在这一过程中获得分化特征。

表观遗传学思想上的一次重大变革来自人们发现环境对发育可塑性有着深刻影响,尤其是在衰老和对常见疾病的易感性方面2。表观遗传学的现代定义将这种可塑性纳入其中:在DNA序列本身以外,DNA及储存信息相关因子的修饰可以在细胞分裂过程中得以保留,也可以受到环境的影响,并导致基因表达方面的稳定变化。因此,比起当初,今天人们以更加动态的观点来看待表观遗传景观3





作者信息

Andrew P. Feinberg, M.D., M.P.H.
From the Department of Medicine, Johns Hopkins University School of Medicine, the Department of Biomedical Engineering, Whiting School of Engineering, and the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health — all in Baltimore. Address reprint requests to Dr. Feinberg at the Department of Medicine, Johns Hopkins University School of Medicine, 855 N. Wolfe St., Rangos 570, Baltimore, MD, or at afeinberg@jhu.edu.

 

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