Department of Medical Genetics, The University of British Columbia, and Children's & Women's Hospital, Vancouver, British Columbia, Canada.
Pacific Biosciences, Menlo Park, CA, USA.
Nat Rev Genet. 2024 Jul;25(7):476-499. doi: 10.1038/s41576-024-00696-z. Epub 2024 Mar 11.
Short tandem repeats (STRs) are a class of repetitive elements, composed of tandem arrays of 1-6 base pair sequence motifs, that comprise a substantial fraction of the human genome. STR expansions can cause a wide range of neurological and neuromuscular conditions, known as repeat expansion disorders, whose age of onset, severity, penetrance and/or clinical phenotype are influenced by the length of the repeats and their sequence composition. The presence of non-canonical motifs, depending on the type, frequency and position within the repeat tract, can alter clinical outcomes by modifying somatic and intergenerational repeat stability, gene expression and mutant transcript-mediated and/or protein-mediated toxicities. Here, we review the diverse structural conformations of repeat expansions, technological advances for the characterization of changes in sequence composition, their clinical correlations and the impact on disease mechanisms.
短串联重复序列（STRs）是一类重复元件，由 1-6 个碱基对序列基序的串联阵列组成，占人类基因组的很大一部分。STR 扩展可引起广泛的神经和神经肌肉疾病，称为重复扩展障碍，其发病年龄、严重程度、外显率和/或临床表型受重复长度及其序列组成的影响。非典型基序的存在，取决于其在重复序列中的类型、频率和位置，可通过改变体细胞和世代间重复稳定性、基因表达以及突变转录本介导和/或蛋白介导的毒性来改变临床结局。在这里，我们综述了重复扩展的多种结构构象、用于鉴定序列组成变化的技术进展、它们与临床的相关性以及对疾病机制的影响。
