Cheng Shan, Wang Xiao-Rong, Ding Wei
Sheng Li Ke Xue Jin Zhan. 2016 Feb;47(1):7-13.
Studies in traditional genetics have revealed the molecular causes of many genetic diseases and provided direct clues for their prevention, diagnosis and treatments, as well as for various disorders with genetic background. However, the genetic profiles of most human diseases could not be fully explained with the canonical laws of genetics. Paramutation is one of non-Mendelian inheritance phenomenon, which was found in maize first in 1950s. The absence of alteration in nucleotide sequences in the gene-coding alleles suggested that paramutations might involve epigenetic mechanisms to transmit heritable changes in gene expression and determination of phenotypes. Recently, a novel epigenetic mechanism has been found in paramutation researches, emphasized the importance of DNA methyltransferase II mediated RNA (primarily non-coding RNAs) methylation in the occurrence and maintenance of paramutations. Researches on paramutations and their epigenetic mechnisms will not only expand our understanding in the genetic principles of life, but also help to develop new ideas for bioengineer and disease treatments. The present article reviewed the research highlights on molecular mechanisms of paramutation and discussed the prospects in disease study and therapy.
传统遗传学研究揭示了许多遗传疾病的分子病因,并为其预防、诊断和治疗以及各种具有遗传背景的疾病提供了直接线索。然而,大多数人类疾病的遗传特征无法用经典遗传学定律完全解释。副突变是非孟德尔遗传现象之一,于20世纪50年代首次在玉米中发现。基因编码等位基因中核苷酸序列没有改变,这表明副突变可能涉及表观遗传机制,以传递基因表达的可遗传变化和表型的决定。最近,在副突变研究中发现了一种新的表观遗传机制,强调了DNA甲基转移酶II介导的RNA(主要是非编码RNA)甲基化在副突变的发生和维持中的重要性。对副突变及其表观遗传机制的研究不仅将扩展我们对生命遗传原理的理解,还将有助于为生物工程和疾病治疗开发新的思路。本文综述了副突变分子机制的研究亮点,并讨论了在疾病研究和治疗方面的前景。