Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Transl Psychiatry. 2023 Dec 20;13(1):402. doi: 10.1038/s41398-023-02689-8.
Tandem repeats (TRs) are prevalent throughout the genome, constituting at least 3% of the genome, and often highly polymorphic. The high mutation rate of TRs, which can be orders of magnitude higher than single-nucleotide polymorphisms and indels, indicates that they are likely to make significant contributions to phenotypic variation, yet their contribution to schizophrenia has been largely ignored by recent genome-wide association studies (GWAS). Tandem repeat expansions are already known causative factors for over 50 disorders, while common tandem repeat variation is increasingly being identified as significantly associated with complex disease and gene regulation. The current review summarizes key background concepts of tandem repeat variation as pertains to disease risk, elucidating their potential for schizophrenia association. An overview of next-generation sequencing-based methods that may be applied for TR genome-wide identification is provided, and some key methodological challenges in TR analyses are delineated.
串联重复（TR）在基因组中普遍存在，构成至少 3%的基因组，且通常高度多态性。TR 的高突变率，其可以比单核苷酸多态性和插入缺失高出几个数量级，表明它们可能对表型变异有重大贡献，但最近的全基因组关联研究（GWAS）在很大程度上忽略了它们对精神分裂症的贡献。串联重复扩展已经是 50 多种疾病的致病因素，而常见的串联重复变异越来越被认为与复杂疾病和基因调控显著相关。目前的综述总结了与疾病风险相关的串联重复变异的关键背景概念，阐明了它们与精神分裂症关联的潜力。提供了基于下一代测序的可能适用于 TR 全基因组鉴定的方法概述，并描述了 TR 分析中的一些关键方法学挑战。
