Genome-wide identification of tandem repeats associated with splicing variation across 49 tissues in humans
- Kohei Hamanaka1,
- Daisuke Yamauchi2,
- Eriko Koshimizu1,
- Kei Watase3,
- Kaoru Mogushi4,
- Kinya Ishikawa5,
- Hidehiro Mizusawa6,
- Naomi Tsuchida1,7,
- Yuri Uchiyama1,7,
- Atsushi Fujita1,
- Kazuharu Misawa1,
- Takeshi Mizuguchi1,
- Satoko Miyatake1,8 and
- Naomichi Matsumoto1
- 1Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan;
- 2BITS Company, Limited, Tokyo 101-0062, Japan;
- 3Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;
- 4Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan;
- 5The Center for Personalized Medicine for Healthy Aging, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan;
- 6Department of Neurology, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan;
- 7Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa 236-0004, Japan;
- 8Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa 236-0004, Japan
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.277335.122.
- Received September 17, 2022.
- Accepted February 22, 2023.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
