Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads.


Journal

Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660

Informations de publication

Date de publication:
19 03 2019
Historique:
received: 14 08 2018
accepted: 01 03 2019
entrez: 21 3 2019
pubmed: 21 3 2019
medline: 17 8 2019
Statut: epublish

Résumé

Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. Our method is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we prioritize pathogenic expansions within the top 10 out of 700,000 tandem repeats in whole genome sequencing data. This may help to elucidate the many genetic diseases whose causes remain unknown.

Identifiants

pubmed: 30890163
doi: 10.1186/s13059-019-1667-6
pii: 10.1186/s13059-019-1667-6
pmc: PMC6425644
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Pagination

58

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Auteurs

Satomi Mitsuhashi (S)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004, Japan. satomits@yokohama-cu.ac.jp.

Martin C Frith (MC)

Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-3-26 Aomi, Koto-ku, Tokyo, 135-0064, Japan. mcfrith@edu.k.u-tokyo.ac.jp.
Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan. mcfrith@edu.k.u-tokyo.ac.jp.
Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), AIST, Shinjuku-ku, Tokyo, Japan. mcfrith@edu.k.u-tokyo.ac.jp.

Takeshi Mizuguchi (T)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004, Japan.

Satoko Miyatake (S)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004, Japan.

Tomoko Toyota (T)

Department of Neurology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Fukuoka, Japan.

Hiroaki Adachi (H)

Department of Neurology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Fukuoka, Japan.

Yoko Oma (Y)

Department of Liberal Arts, Faculty of Medicine, Saitama Medical University, Iruma, Saitama, Japan.

Yoshihiro Kino (Y)

Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.

Hiroaki Mitsuhashi (H)

Department of Applied Biochemistry, School of Engineering, Tokai University, Hiratsuka, Kanagawa, Japan.

Naomichi Matsumoto (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004, Japan.

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Classifications MeSH