Date: 19 Apr 2023

A research group led by Assistant Professor Kohei Hamanaka and Professor Naomichi Matsumoto of the Department of Human Genetics in the Graduate School of Medicine has succeeded in genome-wide identification of tandem repeats that regulate gene splicing, reporting its findings in the journal Genome Research.

Scattered throughout the human genome, tandem repeats are regions where the same base sequence unit is repeated in tandem. The length (number of repetitions) varies by individual and may affect genome function, but the complete picture is not clear. Several examples have been reported in which tandem repeat length regulates gene splicing, but an exhaustive search of tandem repeats through the whole human genome has yet to be performed.

The team’s research used data from the Genotype-Tissue Expression (GTEx) project, which aggregates genome and whole-body tissue transcriptome data from the human general population, to identify 9,537 splicing-regulating tandem repeats across 49 tissues. Included in these are multiple instances of repeats that cause repeat expansion diseases, a general term for diseases that arise when specific repeats are abnormally elongated compared to the general population. By comparing the general population represented in the GTEx project with repeat expansion disease patients, the team showed that the sort of splicing changes found in repeat expansion disease patients are also caused in the general population by repeats, although to a slighter degree. These findings confirm the potential for using general population data to predict the pathological mechanisms of repeat expansion diseases.

The 9,537 splicing-regulating tandem repeats identified in the research have been made publicly available on the research data repository Zenodo. The study is expected to aid in elucidating the pathological mechanisms of repeat expansion diseases.

Published paper

A conceptual image from the research was featured on the cover of the April 13, 2023 issue of the journal Genome Research. The regulation of splicing is depicted as the process by which a kimono is made from a bolt of cloth known as a tanmono. The tanmono represents the genome, the seams the tandem repeats, and the kimono the mRNA. Different stitch lengths (tandem repeat lengths) cause changes in the cut-off (spliced) pieces (exons), yielding different kimono (mRNA) patterns.