Mitochondrial DNA Rearrangements in Health and Disease-A Comprehensive Study
2013; Wiley; Volume: 35; Issue: 1 Linguagem: Inglês
10.1002/humu.22452
ISSN1098-1004
AutoresJoana Damas, David C. Samuels, João Carneiro, António Amorim, Filipe Pereira,
Tópico(s)Metalloenzymes and iron-sulfur proteins
ResumoHuman MutationVolume 35, Issue 1 p. 1-14 Review Mitochondrial DNA Rearrangements in Health and Disease—A Comprehensive Study Joana Damas, Joana Damas Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, PortugalSearch for more papers by this authorDavid C. Samuels, David C. Samuels Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TennesseeSearch for more papers by this authorJoão Carneiro, João Carneiro Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, PortugalSearch for more papers by this authorAntónio Amorim, António Amorim Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, Portugal Faculty of Sciences, University of Porto, Rua do Campo Alegre, s/n, Porto, PortugalSearch for more papers by this authorFilipe Pereira, Corresponding Author Filipe Pereira Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, Portugal Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Porto, PortugalCorrespondence to: Filipe Pereira, CIIMAR/CIMAR, University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. E-mail: fpereirapt@gmail.comSearch for more papers by this author Joana Damas, Joana Damas Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, PortugalSearch for more papers by this authorDavid C. Samuels, David C. Samuels Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TennesseeSearch for more papers by this authorJoão Carneiro, João Carneiro Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, PortugalSearch for more papers by this authorAntónio Amorim, António Amorim Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, Portugal Faculty of Sciences, University of Porto, Rua do Campo Alegre, s/n, Porto, PortugalSearch for more papers by this authorFilipe Pereira, Corresponding Author Filipe Pereira Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, Porto, Portugal Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Porto, PortugalCorrespondence to: Filipe Pereira, CIIMAR/CIMAR, University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. E-mail: fpereirapt@gmail.comSearch for more papers by this author First published: 01 October 2013 https://doi.org/10.1002/humu.22452Citations: 56 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). Communicated by William S. Oetting Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat 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 (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). Citing Literature Supporting Information Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. Filename Description humu22452-sup-0001-SuppMat.pdf1.1 MB Figure S1. Possible locations of the junction site in the presence of a perfect direct repeat (bold underlined nucleotides) at 5’ and 3’ breakpoints Figure S2. Distribution of deletions and duplications breakpoints throughout the human mtDNA. Figure S3. Two-dimensional scatterplots showing the location of the 730 mtDNA deletions (black dots) and 37 mtDNA duplications (red dots) in the seven groups. Figure S4. Two-dimensional scatterplots showing the breakpoints of the 730 mtDNA deletions (A and B) and 37 duplications (C and D). Figure S5. Distribution of 5’ and 3’ deletion (blue and red bars) and duplication (yellow and green bars) breakpoints in the human mtDNA. The frequency of missing sites (grey area) is defined as the number of times that each mtDNA L-strand position is missing in the 730 different mtDNA deletions. Figure S6. The distribution of deletions (top graph) and duplications (bottom graph) is depicted for all combination of 500-nt windows from the mitochondrial genome. Table S1. General features of mtDNA deletions and duplications Table S2. Description of the seven mtDNA duplications exclusively located inside the control region Table S3. Description of the seven mtDNA deletions and duplications with equal breakpoints Table S4. Distribution of mtDNA deletions and duplications according to the length of the perfect direct repeat (DR) present at breakpoints Table S5. List of all mtDNA deletions detected in four or more groups Table S6. Length of perfect direct repeats (DR) present in all combinations of flanking regions of the 730 deletions and 37 duplications reported in human mtDNA Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume35, Issue1January 2014Pages 1-14 RelatedInformation
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