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PMID: 30352806 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Targeted genotyping of variable number tandem repeats with adVNTR.

Genome research ·Vol. 28 ·No. 11 ·2018-00-00 ·Pages 1709-1719

Bakhtiari M, Shleizer-Burko S, Gymrek M, Bansal V, Bafna V

Abstract

Whole-genome sequencing is increasingly used to identify Mendelian variants in clinical pipelines. These pipelines focus on single-nucleotide variants (SNVs) and also structural variants, while ignoring more complex repeat sequence variants. Here, we consider the problem of genotyping Variable Number Tandem Repeats (VNTRs), composed of inexact tandem duplications of short (6-100 bp) repeating units. VNTRs span 3% of the human genome, are frequently present in coding regions, and have been implicated in multiple Mendelian disorders. Although existing tools recognize VNTR carrying sequence, genotyping VNTRs (determining repeat unit count and sequence variation) from whole-genome sequencing reads remains challenging. We describe a method, adVNTR, that uses hidden Markov models to model each VNTR, count repeat units, and detect sequence variation. adVNTR models can be developed for short-read (Illumina) and single-molecule (Pacific Biosciences [PacBio]) whole-genome and whole-exome sequencing, and show good results on multiple simulated and real data sets.

MeSH Terms
Genome, Human Genotyping Techniques/methods Humans Markov Chains Minisatellite Repeats Polymorphism, Genetic
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bakhtiari Mehrdad ORCID
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California 92093, USA.
Shleizer-Burko Sharona
Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Gymrek Melissa
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California 92093, USA. | Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Bansal Vikas
Department of Pediatrics, University of California, San Diego, La Jolla, California 92093, USA.
Bafna Vineet
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California 92093, USA.
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1549-5469
DOI
10.1101/gr.235119.118
Published
2018-00-00
Epub
2018-00-23
Pages
1709-1719
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC6211647
Subset
IM
Grants
NIH HHS · DP5 OD024577 · United States
NIGMS NIH HHS · P41 GM103484 · United States
NIGMS NIH HHS · R01 GM114362 · United States
NHGRI NIH HHS · R01 HG010149 · United States
External Links
PubMed source DOI: 10.1101/gr.235119.118 PMC Full Text View journal details
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