title: Mitochondrial DNA rearrangements in health and disease--a comprehensive study.
abstract: 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 (O(L)) 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).
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Damas
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: João
authors.initials: J
authors.lastname: Carneiro
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Filipe
authors.initials: F
authors.lastname: Pereira
mesh_terms: D000375:Aging / Q000235:genetics; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D015321:Gene Rearrangement; D054629:Genome, Mitochondrial; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D009690:Nucleic Acid Conformation; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial
keywords: breakage hotspots; deletions; duplications; mitochondrial DNA; mitochondrial disease; tumors