Florey Institute of Neuroscience and Mental Health, University of Melbourne.
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
Nat Rev Genet. 2018 May;19(5):286-298. doi: 10.1038/nrg.2017.115. Epub 2018 Feb 5.
Accumulating evidence suggests that many classes of DNA repeats exhibit attributes that distinguish them from other genetic variants, including the fact that they are more liable to mutation; this enables them to mediate genetic plasticity. The expansion of tandem repeats, particularly of short tandem repeats, can cause a range of disorders (including Huntington disease, various ataxias, motor neuron disease, frontotemporal dementia, fragile X syndrome and other neurological disorders), and emerging data suggest that tandem repeat polymorphisms (TRPs) can also regulate gene expression in healthy individuals. TRPs in human genomes may also contribute to the missing heritability of polygenic disorders. A better understanding of tandem repeats and their associated repeatome, as well as their capacity for genetic plasticity via both germline and somatic mutations, is needed to transform our understanding of the role of TRPs in health and disease.
越来越多的证据表明，许多类别的 DNA 重复序列具有区别于其他遗传变异的特征，包括它们更容易发生突变；这使它们能够介导遗传可塑性。串联重复序列的扩展，特别是短串联重复序列的扩展，可能导致一系列疾病（包括亨廷顿病、各种共济失调、运动神经元疾病、额颞叶痴呆、脆性 X 综合征和其他神经退行性疾病），新出现的数据表明，串联重复多态性（TRP）也可以调节健康个体的基因表达。人类基因组中的 TRP 也可能导致多基因疾病的遗传缺失。为了改变我们对 TRP 在健康和疾病中的作用的理解，需要更好地了解串联重复序列及其相关的重复组，以及它们通过种系和体细胞突变产生遗传可塑性的能力。
