Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing.

Abstract

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.

• Authors: Swaraj Basu, Xie Xie, Jay P Uhler, Carola Hedberg-Oldfors, Dusanka Milenkovic, Olivier R Baris, Sammy Kimoloi, Stanka Matic, James B Stewart, Nils-Göran Larsson, Rudolf J Wiesner, Anders Oldfors, Claes M Gustafsson, Maria Falkenberg, Erik Larsson
• Journal: PLoS genetics (PLoS Genet) Vol. 16 Issue 12 Pg. e1009242 (12 2020) ISSN: 1553-7404 [Electronic] United States
• PMID: 33315859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Mitochondrial

Topics

• Animals
• DNA, Mitochondrial (chemistry, genetics)
• Gene Deletion
• Gene Duplication
• High-Throughput Nucleotide Sequencing (methods, standards)
• Mice
• Reproducibility of Results
• Sequence Analysis, DNA (methods, standards)