Universität zu Köln

Basu, Swaraj, Xie, Xie, Uhler, Jay P., Hedberg-Oldfors, Carola, Milenkovic, Dusanka, Baris, Olivier R., Kimoloi, Sammy, Matic, Stanka, Stewart, James B., Larsson, Nils-Goran ORCID: 0000-0001-5100-996X, Wiesner, Rudolf J., Oldfors, Anders, Gustafsson, Claes M., Falkenberg, Maria and Larsson, Erik (2020). Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing. PLoS Genet., 16 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

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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. Author summary Deletions in the mitochondrial genome cause a wide variety of rare disorders, but are also linked to more common conditions such as neurodegeneration, diabetes type 2, and the normal ageing process. There is also a growing awareness that mtDNA duplications, which are also relevant for human disease, may be more common than previously thought. Despite their clinical importance, our current knowledge about the abundance, characteristics and diversity of mtDNA deletions and duplications is fragmented, and based to large extent on a limited view provided by traditional low-throughput analyses. Here, we describe a bioinformatics method, MitoSAlt, that can accurately map and classify mtDNA deletions and duplications using high-throughput sequencing. Application of this methodology to mouse models of mitochondrial deficiencies revealed a large number of duplications, suggesting that these may previously have been underestimated.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Basu, Swaraj UNSPECIFIED UNSPECIFIED UNSPECIFIED Xie, Xie UNSPECIFIED UNSPECIFIED UNSPECIFIED Uhler, Jay P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedberg-Oldfors, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED Milenkovic, Dusanka UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kimoloi, Sammy UNSPECIFIED UNSPECIFIED UNSPECIFIED Matic, Stanka UNSPECIFIED UNSPECIFIED UNSPECIFIED Stewart, James B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Larsson, Nils-Goran UNSPECIFIED orcid.org/0000-0001-5100-996X UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oldfors, Anders UNSPECIFIED UNSPECIFIED UNSPECIFIED Gustafsson, Claes M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Falkenberg, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Larsson, Erik UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-309850
DOI:	10.1371/journal.pgen.1009242
Journal or Publication Title:	PLoS Genet.
Volume:	16
Number:	12
Date:	2020
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; MTDNA REPLICATION; MUTATIONS; GENOME; DEFICIENCY; INCREASE; TWINKLE; DISEASE; HISAT; POLG Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30985