中断影响重复扩张疾病的临床特征，但它们是如何获得和失去的？

IF 16.3 2区生物学 Q1 GENETICS & HEREDITY

Trends in Genetics Pub Date : 2025-08-29 DOI:10.1016/j.tig.2025.07.005

Alys N Aston, Vincent Dion

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引用次数: 0

摘要

扩展串联重复序列中的中断减少了体细胞扩展，并改变了所导致疾病的严重程度。因此，已经做了很多工作来确定人群中的中断并评估其临床影响。然而，如何获得和失去中断是未知的。在这里，我们提出合成依赖的微同源介导的末端连接（SD-MMEJ）可以解释扩展重复序列中中断的大部分动态变化，如果不是全部的话。SD-MMEJ解释了中断的位点特异性，为什么它们出现在扩大的染色体束的5‘和3’端附近，以及复杂等位基因是如何在一代内出现的。了解中断动力学是重复扩张病病因学和治疗发展的基础。

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Interruptions impact clinical features of repeat expansion diseases, but how are they gained and lost?

Interruptions within expanded tandem repeats reduce somatic expansion and alter the severity of the resulting diseases. Consequently, much has been done to identify interruptions in the human population and assess their clinical impact. However, how interruptions are gained and lost is unknown. Here, we propose that synthesis-dependent microhomology-mediated end joining (SD-MMEJ) can account for most, if not all, the dynamic changes in interruptions within expanded repeats. SD-MMEJ explains the locus specificity of interruptions, why they appear near the 5' and 3' ends of expanded tracts, and how complex alleles arise within a single generation. Understanding interruption dynamics is fundamental to repeat expansion disease aetiology and therapeutic development.

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来源期刊

Trends in Genetics 生物-遗传学

CiteScore

20.90

自引率

0.90%

发文量

160

审稿时长

6-12 weeks

期刊介绍： Launched in 1985, Trends in Genetics swiftly established itself as a "must-read" for geneticists, offering concise, accessible articles covering a spectrum of topics from developmental biology to evolution. This reputation endures, making TiG a cherished resource in the genetic research community. While evolving with the field, the journal now embraces new areas like genomics, epigenetics, and computational genetics, alongside its continued coverage of traditional subjects such as transcriptional regulation, population genetics, and chromosome biology. Despite expanding its scope, the core objective of TiG remains steadfast: to furnish researchers and students with high-quality, innovative reviews, commentaries, and discussions, fostering an appreciation for advances in genetic research. Each issue of TiG presents lively and up-to-date Reviews and Opinions, alongside shorter articles like Science & Society and Spotlight pieces. Invited from leading researchers, Reviews objectively chronicle recent developments, Opinions provide a forum for debate and hypothesis, and shorter articles explore the intersection of genetics with science and policy, as well as emerging ideas in the field. All articles undergo rigorous peer-review.