Contract grant sponsors: Portuguese Foundation for Science and Technology, Fundo Social Europeu and Programa Operacional Potencial Humano (SFRH/BPD/44637/2008, PTDC/CVT/100881/2008, Investigator FCT program); European Regional Development Fund (ERDF) (PEst-C/MAR/LA0015/2013).
Mitochondrial DNA Rearrangements in Health and Disease—A Comprehensive Study
Article first published online: 18 OCT 2013
© 2013 WILEY PERIODICALS, INC.
Volume 35, Issue 1, pages 1–14, January 2014
How to Cite
Damas, J., Samuels, D. C., Carneiro, J., Amorim, A. and Pereira, F. (2014), Mitochondrial DNA Rearrangements in Health and Disease—A Comprehensive Study. Hum. Mutat., 35: 1–14. doi: 10.1002/humu.22452
Communicated by William S. Oetting
- Issue published online: 18 DEC 2013
- Article first published online: 18 OCT 2013
- Accepted manuscript online: 1 OCT 2013 03:14PM EST
- Manuscript Accepted: 19 SEP 2013
- Manuscript Received: 7 MAY 2013
- Portuguese Foundation for Science and Technology, Fundo Social Europeu and Programa Operacional Potencial Humano. Grant Number: SFRH/BPD/44637/2008, PTDC/CVT/100881/2008
- Investigator FCT program
- European Regional Development Fund (ERDF). Grant Number: PEst-C/MAR/LA0015/2013
- mitochondrial DNA;
- breakage hotspots;
- mitochondrial disease;
Mitochondrial DNA (mtDNA) rearrangements cause a wide variety of highly debilitating and often fatal disorders and have been implicated in aging and age-associated disease. Here, we present a meta-analytical study of mtDNA deletions (n = 730) and partial duplications (n = 37) using information from more than 300 studies published over the last 30 years. We show that both classes of mtDNA rearrangements are unequally distributed among disorders and their breakpoints have different genomic locations. We also demonstrate that 100% of cases with sporadic mtDNA deletions and 97.3% with duplications have no breakpoints in the 16,071 breakage hotspot site, in contrast with deletions from healthy and aged tissues. Notably, most deletions removing a section of the D-loop are found in tumors. Deleted mtDNA molecules lacking the origin of L-strand replication (OL) represent only 9.5% of all reported cases, whereas extra origins of replication occur in all duplications. As previously shown for deletions, imperfect stretches of homology are common in duplication breakpoints. Finally, we provide a dedicated Website with detailed information on deleted/duplicated mtDNA regions to facilitate the design of efficient methods for identification and screening of rearranged mitochondrial genomes (available at http://www.portugene.com/mtDNArearrangements.html).