MitoBreak: the Mitochondrial DNA Breakpoints Database

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Oct 31

PMID 24170808

Citations 33

Authors

Joana Damas

Joao Carneiro

Antonio Amorim

Filipe Pereira

Affiliations

Soon will be listed here.

Abstract

Mitochondrial DNA (mtDNA) rearrangements are key events in the development of many diseases. Investigations of mtDNA regions affected by rearrangements (i.e. breakpoints) can lead to important discoveries about rearrangement mechanisms and can offer important clues about the causes of mitochondrial diseases. Here, we present the mitochondrial DNA breakpoints database (MitoBreak; http://mitobreak.portugene.com), a free, web-accessible comprehensive list of breakpoints from three classes of somatic mtDNA rearrangements: circular deleted (deletions), circular partially duplicated (duplications) and linear mtDNAs. Currently, MitoBreak contains >1400 mtDNA rearrangements from seven species (Homo sapiens, Mus musculus, Rattus norvegicus, Macaca mulatta, Drosophila melanogaster, Caenorhabditis elegans and Podospora anserina) and their associated phenotypic information collected from nearly 400 publications. The database allows researchers to perform multiple types of data analyses through user-friendly interfaces with full or partial datasets. It also permits the download of curated data and the submission of new mtDNA rearrangements. For each reported case, MitoBreak also documents the precise breakpoint positions, junction sequences, disease or associated symptoms and links to the related publications, providing a useful resource to study the causes and consequences of mtDNA structural alterations.

Citing Articles

High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.

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The genomic mosaic of mitochondrial dysfunction: Decoding nuclear and mitochondrial epigenetic contributions to maternally inherited diabetes and deafness pathogenesis.

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Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.

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Common mitochondrial deletions in RNA-Seq: evaluation of bulk, single-cell, and spatial transcriptomic datasets.

Omidsalar A, McCullough C, Xu L, Boedijono S, Gerke D, Webb M Commun Biol. 2024; 7(1):200.

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Secondary structure of the human mitochondrial genome affects formation of deletions.

Shamanskiy V, Mikhailova A, Tretiakov E, Ushakova K, Mikhailova A, Oreshkov S BMC Biol. 2023; 21(1):103.

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References

Clayton D . Replication of animal mitochondrial DNA. Cell. 1982; 28(4):693-705. DOI: 10.1016/0092-8674(82)90049-6. View

Hixson J, Wong T, Clayton D . Both the conserved stem-loop and divergent 5'-flanking sequences are required for initiation at the human mitochondrial origin of light-strand DNA replication. J Biol Chem. 1986; 261(5):2384-90. View

Lupski J . Genomic rearrangements and sporadic disease. Nat Genet. 2007; 39(7 Suppl):S43-7. DOI: 10.1038/ng2084. View

Damas J, Carneiro J, Goncalves J, Stewart J, Samuels D, Amorim A . Mitochondrial DNA deletions are associated with non-B DNA conformations. Nucleic Acids Res. 2012; 40(16):7606-21. PMC: 3439893. DOI: 10.1093/nar/gks500. View

Damas J, Samuels D, Carneiro J, Amorim A, Pereira F . Mitochondrial DNA rearrangements in health and disease--a comprehensive study. Hum Mutat. 2013; 35(1):1-14. DOI: 10.1002/humu.22452. View

Robberson D, Kasamatsu H, Vinograd J . Replication of mitochondrial DNA. Circular replicative intermediates in mouse L cells. Proc Natl Acad Sci U S A. 1972; 69(3):737-41. PMC: 426547. DOI: 10.1073/pnas.69.3.737. View

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D . Circos: an information aesthetic for comparative genomics. Genome Res. 2009; 19(9):1639-45. PMC: 2752132. DOI: 10.1101/gr.092759.109. View

Srivastava S, Moraes C . Double-strand breaks of mouse muscle mtDNA promote large deletions similar to multiple mtDNA deletions in humans. Hum Mol Genet. 2005; 14(7):893-902. PMC: 1242110. DOI: 10.1093/hmg/ddi082. View

Berk A, Clayton D . Mechanism of mitochondrial DNA replication in mouse L-cells: asynchronous replication of strands, segregation of circular daughter molecules, aspects of topology and turnover of an initiation sequence. J Mol Biol. 1974; 86(4):801-24. DOI: 10.1016/0022-2836(74)90355-6. View

10.

Burger G, Gray M, Lang B . Mitochondrial genomes: anything goes. Trends Genet. 2003; 19(12):709-16. DOI: 10.1016/j.tig.2003.10.012. View

11.

Manfredi G, Vu T, Bonilla E, Schon E, DiMauro S, Arnaudo E . Association of myopathy with large-scale mitochondrial DNA duplications and deletions: which is pathogenic?. Ann Neurol. 1997; 42(2):180-8. DOI: 10.1002/ana.410420208. View

12.

Poulton J, Morten K, Marchington D, Weber K, Brown G, Rotig A . Duplications of mitochondrial DNA in Kearns-Sayre syndrome. Muscle Nerve Suppl. 1995; 3:S154-8. DOI: 10.1002/mus.880181430. View

13.

Zhao S, Shetty J, Hou L, Delcher A, Zhu B, Osoegawa K . Human, mouse, and rat genome large-scale rearrangements: stability versus speciation. Genome Res. 2004; 14(10A):1851-60. PMC: 524408. DOI: 10.1101/gr.2663304. View

14.

Cooper D, Bacolla A, Ferec C, Vasquez K, Kehrer-Sawatzki H, Chen J . On the sequence-directed nature of human gene mutation: the role of genomic architecture and the local DNA sequence environment in mediating gene mutations underlying human inherited disease. Hum Mutat. 2011; 32(10):1075-99. PMC: 3177966. DOI: 10.1002/humu.21557. View

15.

Gray M, Burger G, Lang B . Mitochondrial evolution. Science. 1999; 283(5407):1476-81. DOI: 10.1126/science.283.5407.1476. View

16.

Fan L, Yao Y . An update to MitoTool: using a new scoring system for faster mtDNA haplogroup determination. Mitochondrion. 2013; 13(4):360-3. DOI: 10.1016/j.mito.2013.04.011. View

17.

Ikebe S, Tanaka M, Ohno K, Sato W, Hattori K, Kondo T . Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. Biochem Biophys Res Commun. 1990; 170(3):1044-8. DOI: 10.1016/0006-291x(90)90497-b. View

18.

Moslemi A, Lindberg C, Oldfors A . Analysis of multiple mitochondrial DNA deletions in inclusion body myositis. Hum Mutat. 1997; 10(5):381-6. DOI: 10.1002/(SICI)1098-1004(1997)10:5<381::AID-HUMU8>3.0.CO;2-I. View

19.

Bodyak N, Nekhaeva E, Wei J, Khrapko K . Quantification and sequencing of somatic deleted mtDNA in single cells: evidence for partially duplicated mtDNA in aged human tissues. Hum Mol Genet. 2001; 10(1):17-24. DOI: 10.1093/hmg/10.1.17. View

20.

Poulton J, Deadman M, Gardiner R . Tandem direct duplications of mitochondrial DNA in mitochondrial myopathy: analysis of nucleotide sequence and tissue distribution. Nucleic Acids Res. 1989; 17(24):10223-9. PMC: 335296. DOI: 10.1093/nar/17.24.10223. View