Study: JGAS00000000002




TitleRapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing.
AbstractLong expansions of short tandem repeats (STRs); i.e., DNA repeats of 2-6 nucleotides, are associated with some genetic diseases. Cost-efficient high throughput sequencing can quickly produce billions of short reads that would be useful for uncovering disease-associated STRs. However, enumerating STRs in short reads remains largely unexplored because of the difficulty in elucidating STRs much longer than 100 bp, the typical length of short reads. We propose ab initio procedures for sensing and locating long STRs promptly by utilizing the frequency distribution of all STRs and paired-end read information. We validated the reproducibility of this method using biological replicates and used it to locate an STR associated with a brain disease (SCA31). Subsequently, we sequenced this STR site in eleven SCA31 samples using SMRT™ sequencing (Pacific Biosciences), determined 2.3-3.1 kb sequences at nucleotide resolution, and revealed that (TGGAA)- and (TAAAATAGAA)-repeat expansions determined the instability of the repeat expansions associated with SCA31. Our method could also identify common STRs, (AAAG)- and (AAAAG)-repeat expansions, which are remarkably expanded at four positions in an SCA31 sample. This is the first proposed method for rapidly finding disease-associated long STRs in personal genomes using hybrid sequencing of short and long reads.
Study Type 1
Study TypeWhole Genome Sequencing
Study Type 2
Study TypeCase Set


TitleGrant-in-Aid for Scientific Research on Innovative Areas
AgencyMinistry of Education, Culture, Sports, Science and Technology (MEXT)
Grant ID22129008


PubMed ID24215022
Publication Statuspublished
Accession Title Dataset type Data objects Policy
JGAD00000000002 whole genome data of SCA31 affected sample Whole genome shotgun sequencing 1 JGAP00000000001