Genome-wide identification of tandem repeats associated with splicing variation across 49 tissues in humans

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 (spl-TRs), no large-scale study has been conducted. In this study, we established a genome-w...

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Bibliographic Details
Published in:Genome research 2023-03, Vol.33 (3), p.435-447
Main Authors: Hamanaka, Kohei, Yamauchi, Daisuke, Koshimizu, Eriko, Watase, Kei, Mogushi, Kaoru, Ishikawa, Kinya, Mizusawa, Hidehiro, Tsuchida, Naomi, Uchiyama, Yuri, Fujita, Atsushi, Misawa, Kazuharu, Mizuguchi, Takeshi, Miyatake, Satoko, Matsumoto, Naomichi
Format: Article
Language:English
Subjects:
Gene polymorphism
Gene regulation
Genetic disorders
Genetic Engineering
Genomes
Humans
Polymorphism, Genetic
Regression analysis
Resources
RNA Splicing
Spinocerebellar ataxia
Splicing
Tandem Repeat Sequences
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Summary: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 (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.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.277335.122