Open AccessAccurate mapping of mitochondrial DNA deletions and duplications using deep sequencing
Author(s) -
Swaraj Basu,
Xie Xie,
Jay P. Uhler,
Carola HedbergOldfors,
Dusanka Milenkovic,
Olivier Baris,
Sammy Kimoloi,
Stanka Matic,
James B. Stewart,
Nils-Göran Larsson,
Rudolf J. Wiesner,
Anders Oldfors,
Claes M. Gustafsson,
Maria Falkenberg,
Erik Larsson
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009242
Subject(s) - heteroplasmy , biology , mitochondrial dna , genetics , dna sequencing , computational biology , gene duplication , mitochondrial disease , genomics , deep sequencing , segmental duplication , genome , dna , gene , gene family
Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we establish a computational method, MitoSAlt, for accurate identification, quantification and visualization of mtDNA deletions and duplications from genomic sequencing data. Our method was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy.