Tandem repeats (TRs) are one of the largest sources of polymorphism, and their length is associated with gene regulation. Although previous studies reported several tandem repeats regulating gene splicing in cis (spl-TRs), no large-scale study has been conducted. In this study, we established a genome-wide catalog of 9537 spl-TRs with a total of 58,290 significant TR–splicing associations across 49 tissues (false discovery rate 5%) by using Genotype-Tissue expression (GTex) Project data. Regression models explaining splicing variation by using spl-TRs and other flanking variants suggest that at least some of the spl-TRs directly modulate splicing. In our catalog, two spl-TRs are known loci for repeat expansion diseases, spinocerebellar ataxia 6 (SCA6) and 12 (SCA12). Splicing alterations by these spl-TRs were compatible with those observed in SCA6 and SCA12. Thus, our comprehensive spl-TR catalog may help elucidate the pathomechanism of genetic diseases.

中文翻译：

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对人类 49 个组织中与剪接变异相关的串联重复进行全基因组鉴定

串联重复序列（TR）是多态性的最大来源之一，其长度与基因调控相关。尽管之前的研究报道了几个串联重复序列调节顺式基因剪接（ spl-TRs），但尚未进行大规模研究。在这项研究中，我们利用基因型组织表达（GTex）项目数据建立了一个包含 9537 个 spl-TR 的全基因组目录，其中包含 49 个组织中总共 58,290 个显着的 TR 剪接关联（错误发现率 5%）。使用 spl-TR 和其他侧翼变体解释剪接变异的回归模型表明，至少有一些 spl-TR 直接调节剪接。在我们的目录中，两个 spl-TR 是重复扩张疾病、脊髓小脑共济失调 6 (SCA6) 和 12 (SCA12) 的已知位点。这些 spl-TR 的剪接改变与 SCA6 和 SCA12 中观察到的剪接改变一致。因此，我们全面的 spl-TR 目录可能有助于阐明遗传病的病理机制。