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健康与疾病中的可移动DNA
Mobile DNA in Health and Disease


Haig H. Kazazian ... 肿瘤 其他 • 2017.07.27

男性生育力与可移动DNA互惠互利


Partha S. Saha, Simon J. Newkirk, Changfeng Yao, Wenfeng An*

Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA

*通讯作者

 

《新英格兰医学杂志》2017年7月27日发表了一篇关于可移动DNA与人类疾病的综述1。近年来,我们对可移动DNA元件在多种人类疾病中的作用有了越来越丰富的认识,因此这篇综述的发表非常及时。在该综述中,作者Kazazian和Moran涵盖了许多重要的主题,包括:①人类基因组中可移动DNA的种类。②作为诱变剂的逆转座子。③逆转座的机制。④逆转座介导的基因组重排。⑤体细胞与癌症中的逆转座事件。⑥宿主抵御可移动子的机制。

在这篇对该综述的评论中,我们主要讨论了发育期间可移动DNA的活性,特别是这类DNA与人类繁衍之间千丝万缕的联系。

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人类基因组计划1的完成识别了许多基因,包括致病的变异体2-4。其中一项知名度较低但十分重要的发现是,人类基因组的一半以上源自称为转座元件的可移动DNA片段(俗称“跳跃基因”)。60多年前,Barbara McClintock在玉米中发现了转座元件5,但很少有人能猜到,这些序列的总长度超过编码蛋白的外显子40多倍(图1)。尽管大多数转座元件来源的DNA都是其前体的残余且不能转座,但一些转座元件来源的DNA保留了移动能力11,12。在配子或早期胚胎的DNA中插入可移动元件会破坏基因,导致散发疾病病例13,而可移动元件插入体细胞的DNA可能促成癌症和神经精神疾病9,14。无疑,可移动DNA一直在塑造人类基因组的结构、功能和进化上发挥作用。在本文中,我们会从生物学上讨论可移动DNA,并着重于解释这些DNA如何导致人类疾病方面的关键发现。





作者信息

Haig H. Kazazian, Jr., M.D., and John V. Moran, Ph.D.
From the McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore (H.H.K.), and the Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor (J.V.M.). Address reprint requests to Dr. Kazazian at hkazazi1@jhmi.edu; or to Dr. Moran at moranj@umich.edu.

 

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