Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Perron Institute for Neurological and Translational Science, Perth, WA 6009, Australia.
Exp Biol Med (Maywood). 2021 Jun;246(12):1368-1376. doi: 10.1177/15353702211003511. Epub 2021 Apr 1.
Understanding the mechanisms regulating tissue specific and stimulus inducible regulation is at the heart of understanding human biology and how this translates to wellbeing, the ageing process, and disease progression. Polymorphic DNA variation is superimposed as an extra layer of complexity in such processes which underpin our individuality and are the focus of personalized medicine. This review focuses on the role and action of repetitive DNA, specifically variable number tandem repeats and SINE-VNTR- domains, highlighting their role in modification of gene structure and gene expression in addition to their polymorphic nature being a genetic modifier of disease risk and progression. Although the literature focuses on their role in disease, it illustrates their potential to be major contributors to normal physiological function. To date, these elements have been under-reported in genomic analysis due to the difficulties in their characterization with short read DNA sequencing methods. However, recent advances in long read sequencing methods should resolve these problems allowing for a greater understanding of their contribution to a host of genomic and functional mechanisms underlying physiology and disease.
理解调节组织特异性和刺激诱导调节的机制是理解人类生物学的核心，也是理解如何转化为健康、衰老过程和疾病进展的关键。多态性 DNA 变异是这些过程中的一个额外复杂层，这些过程是我们个性的基础，也是个性化医学的重点。本综述重点介绍重复 DNA，特别是可变数串联重复和 SINE-VNTR 结构域的作用和功能，强调它们在修饰基因结构和基因表达中的作用，以及它们的多态性作为疾病风险和进展的遗传修饰因子的作用。尽管文献主要关注它们在疾病中的作用，但它也说明了它们有可能成为正常生理功能的主要贡献者。迄今为止，由于短读 DNA 测序方法难以对这些元件进行特征描述，因此在基因组分析中对这些元件的报道较少。然而，长读测序方法的最新进展应该可以解决这些问题，从而更好地了解它们对基因组和功能机制的贡献，这些机制是生理学和疾病的基础。
