Recurrent Tissue-Specific mtDNA Mutations Are Common in Humans
Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively para...
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| Published in | PLoS genetics Vol. 9; no. 11; p. e1003929 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
01.11.2013
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage. |
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| AbstractList | Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage.Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage. Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage. Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage. Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage. DNA mutations are expected to be formed randomly, thus any reproducible pattern of DNA somatic mutations across multiple individuals or even across organs within each individual is highly unexpected. Using next generation sequencing of multiple tissues from the same individuals we found several somatic mutations in mitochondrial DNA that appear in a heteroplasmic state in all individuals examined, but only in particular tissues. These mutations were only found in known regions of replication control for the mitochondrial DNA. These data imply the presence of tissue-specific positive selection for these variants. |
| Audience | Academic |
| Author | Murdock, Deborah G. Mortlock, Douglas P. Torstenson, Eric Thornton-Wells, Tricia A. Moore, Jason H. Hoffman, Robert D. Hughes, Tia M. Samuels, David C. Boyd Clay, Hayley Li, Chun Song, Zhuo Haines, Jonathan L. Rokas, Antonis Williams, Scott M. Li, Bingshan |
| AuthorAffiliation | 1 Center for Human Genetics Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America 2 Center for Human Genetics Research, Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America 3 Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America 5 Dartmouth Medical School, Department of Genetics, Computational Genetics Lab, Lebanon, New Hampshire, United States of America 6 Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America 4 Department of Biological Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America Stanford University School of Medicine, United States of America |
| AuthorAffiliation_xml | – name: 1 Center for Human Genetics Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America – name: 3 Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America – name: 6 Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America – name: 4 Department of Biological Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America – name: 5 Dartmouth Medical School, Department of Genetics, Computational Genetics Lab, Lebanon, New Hampshire, United States of America – name: Stanford University School of Medicine, United States of America – name: 2 Center for Human Genetics Research, Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America |
| Author_xml | – sequence: 1 givenname: David C. surname: Samuels fullname: Samuels, David C. – sequence: 2 givenname: Chun surname: Li fullname: Li, Chun – sequence: 3 givenname: Bingshan surname: Li fullname: Li, Bingshan – sequence: 4 givenname: Zhuo surname: Song fullname: Song, Zhuo – sequence: 5 givenname: Eric surname: Torstenson fullname: Torstenson, Eric – sequence: 6 givenname: Hayley surname: Boyd Clay fullname: Boyd Clay, Hayley – sequence: 7 givenname: Antonis surname: Rokas fullname: Rokas, Antonis – sequence: 8 givenname: Tricia A. surname: Thornton-Wells fullname: Thornton-Wells, Tricia A. – sequence: 9 givenname: Jason H. surname: Moore fullname: Moore, Jason H. – sequence: 10 givenname: Tia M. surname: Hughes fullname: Hughes, Tia M. – sequence: 11 givenname: Robert D. surname: Hoffman fullname: Hoffman, Robert D. – sequence: 12 givenname: Jonathan L. surname: Haines fullname: Haines, Jonathan L. – sequence: 13 givenname: Deborah G. surname: Murdock fullname: Murdock, Deborah G. – sequence: 14 givenname: Douglas P. surname: Mortlock fullname: Mortlock, Douglas P. – sequence: 15 givenname: Scott M. surname: Williams fullname: Williams, Scott M. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24244193$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1055/s-2006-924066 10.1016/j.neurobiolaging.2004.06.014 10.1086/318801 10.1038/nature08802 10.1002/humu.20921 10.1038/88859 10.1146/annurev-biochem-060408-093701 10.1093/nar/gng060 10.1093/hmg/dds245 10.1093/bioinformatics/btp324 10.1073/pnas.061013598 10.1073/pnas.1009687108 10.1007/s00439-002-0708-4 10.1126/science.286.5440.774 10.1023/A:1016707228425 10.1080/07853890510007368 10.1093/hmg/10.22.2469 10.1016/j.cell.2012.09.004 10.1016/j.ajhg.2009.04.013 10.1073/pnas.0403649101 10.1038/ng0597-93 10.1111/j.1556-4029.2006.00136.x 10.1371/journal.pbio.0060010 10.1016/S0022-510X(02)00247-2 10.1016/j.forsciint.2004.06.001 10.1038/ng1073 10.1371/journal.pone.0022332 10.1007/s00414-006-0083-0 10.1016/S0379-0738(03)00181-6 10.1016/j.forsciint.2004.12.021 10.1093/hmg/dds435 10.1126/science.1102077 10.1093/nar/28.21.4350 10.1038/nature09414 10.1073/pnas.0630589100 10.1016/j.molcel.2005.05.002 10.1073/pnas.89.16.7370 10.1016/j.bbadis.2009.03.002 10.1093/molbev/msn225 10.1016/j.jns.2007.07.006 10.1016/S0197-4580(02)00233-6 10.1038/13779 10.1101/gr.107524.110 10.1038/ng.f.94 10.1016/S0960-8966(01)00329-7 10.1038/ng1292-324 |
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| Copyright | COPYRIGHT 2013 Public Library of Science 2013 Samuels et al 2013 Samuels et al 2013 Samuels et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Samuels DC, Li C, Li B, Song Z, Torstenson E, et al. (2013) Recurrent Tissue-Specific mtDNA Mutations Are Common in Humans. PLoS Genet 9(11): e1003929. doi:10.1371/journal.pgen.1003929 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: DCS CL BL JLH DGM DPM SMW. Performed the experiments: DCS CL BL ET HBC TMH DGM DPM. Analyzed the data: DCS CL BL ZS ET AR TATW JHM SMW. Contributed reagents/materials/analysis tools: TMH RDH DPM SMW. Wrote the paper: DCS CL BL AR TATW JHM JLH DGM DPM SMW. The authors have declared that no competing interests exist. |
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| References | T Yamasoba (ref38) 2002; 12 JP Jenuth (ref42) 1997; 16 M Corral-Debrinski (ref12) 1992; 2 BAI Payne (ref25) 2013; 22 AW Duncan (ref44) 2010; 467 HA Coller (ref46) 2001; 28 R Del Bo (ref19) 2002; 202 J Fish (ref15) 2004; 306 T Yasukawa (ref16) 2005; 18 CY Pai (ref29) 2006; 156 H Li (ref5) 2009; 25 PE Coskun (ref39) 2003; 100 Y Wang (ref10) 2001; 98 F Pereira (ref17) 2008; 25 DG Murdock (ref34) 2000; 28 C Barthelemy (ref22) 2002; 110 JL Elson (ref2) 2001; 68 BJ Battersby (ref41) 2001; 10 S Dimauro (ref11) 2005; 37 G Avital (ref21) 2012; 21 LM Cree (ref1) 2009; 1792 PE Coskun (ref35) 2004; 101 GA Cortopassi (ref13) 1992; 89 R Del Bo (ref20) 2003; 24 Y Michikawa (ref33) 1999; 286 JB Stewart (ref47) 2008; 6 KC Chandy (ref48) 2007; 10 A McKenna (ref6) 2010; 20 BJ Battersby (ref40) 2003; 33 NG Larsson (ref3) 2010; 79 MW Allard (ref26) 2005; 148 MW Allard (ref27) 2006; 51 BA Malyarchuk (ref28) 2001; 37 FJ Miller (ref7) 2003; 31 R Suspene (ref45) 2011; 108 G Tully (ref31) 2004; 140 MS Sharpley (ref43) 2012; 151 KJ Krishnan (ref14) 2008; 40 M van Oven (ref49) 2009; 30 CK da Costa (ref24) 2007; 263 L Shu (ref36) 2012; 5 LA Tully (ref32) 2000; 67 YP He (ref9) 2010; 464 A Cormio (ref23) 2005; 26 A Picornell (ref30) 2006; 120 GMC Janssen (ref37) 2006; 114 L Pereira (ref8) 2009; 84 RM Andrews (ref4) 1999; 23 T Andrew (ref18) 2011; 6 24281144 - Nat Rev Genet. 2014 Jan;15(1):4 |
| References_xml | – volume: 114 start-page: 168 year: 2006 ident: ref37 article-title: Novel mitochondrial DNA length variants and genetic instability in a family with diabetes and deafness publication-title: Experimental and Clinical Endocrinology & Diabetes doi: 10.1055/s-2006-924066 – volume: 26 start-page: 655 year: 2005 ident: ref23 article-title: Mitochondrial DNA mutations in RRF of healthy subjects of different age publication-title: Neurobiology of Aging doi: 10.1016/j.neurobiolaging.2004.06.014 – volume: 68 start-page: 802 year: 2001 ident: ref2 article-title: Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age publication-title: American Journal of Human Genetics doi: 10.1086/318801 – volume: 464 start-page: 610 year: 2010 ident: ref9 article-title: Heteroplasmic mitochondrial DNA mutations in normal and tumour cells publication-title: Nature doi: 10.1038/nature08802 – volume: 30 start-page: E386 year: 2009 ident: ref49 article-title: Updated Comprehensive Phylogenetic Tree of Global Human Mitochondrial DNA Variation publication-title: Human Mutation doi: 10.1002/humu.20921 – volume: 28 start-page: 147 year: 2001 ident: ref46 article-title: High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection publication-title: Nature Genetics doi: 10.1038/88859 – volume: 79 start-page: 683 year: 2010 ident: ref3 article-title: Somatic Mitochondrial DNA Mutations in Mammalian Aging publication-title: Annual Review of Biochemistry doi: 10.1146/annurev-biochem-060408-093701 – volume: 31 start-page: e61 issue: (11) year: 2003 ident: ref7 article-title: Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age publication-title: Nucleic Acids Research doi: 10.1093/nar/gng060 – volume: 21 start-page: 4214 year: 2012 ident: ref21 article-title: Mitochondrial DNA heteroplasmy in diabetes and normal adults: role of acquired and inherited mutational patterns in twins publication-title: Human Molecular Genetics doi: 10.1093/hmg/dds245 – volume: 67 start-page: 432 year: 2000 ident: ref32 article-title: A sensitive denaturing gradient-gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region publication-title: American Journal of Human Genetics – volume: 25 start-page: 1754 year: 2009 ident: ref5 article-title: Fast and accurate short read alignment with Burrows-Wheeler transform publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp324 – volume: 98 start-page: 4022 year: 2001 ident: ref10 article-title: Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.061013598 – volume: 5 start-page: 28 year: 2012 ident: ref36 article-title: Complete mitochondrial DNA sequence analysis in two southern Chinese pedigrees with Leber hereditary optic neuropathy revealed secondary mutations along with the primary mutation publication-title: International Journal of Ophthalmology – volume: 108 start-page: 4858 year: 2011 ident: ref45 article-title: Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.1009687108 – volume: 110 start-page: 479 year: 2002 ident: ref22 article-title: D-loop mutations in mitochondrial DNA: link with mitochondrial DNA depletion publication-title: Human Genetics doi: 10.1007/s00439-002-0708-4 – volume: 286 start-page: 774 year: 1999 ident: ref33 article-title: Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication publication-title: Science doi: 10.1126/science.286.5440.774 – volume: 37 start-page: 823 year: 2001 ident: ref28 article-title: Variation of human mitochondrial DNA: Distribution of hot spots in hypervariable segment I of the major noncoding region publication-title: Russian Journal of Genetics doi: 10.1023/A:1016707228425 – volume: 37 start-page: 222 year: 2005 ident: ref11 article-title: Mitochondrial DNA and disease publication-title: Annals of Medicine doi: 10.1080/07853890510007368 – volume: 10 start-page: 2469 year: 2001 ident: ref41 article-title: Selection of a mtDNA sequence variant in hepatocytes of heteroplasmic mice is not due to differences in respiratory chain function or efficiency of replication publication-title: Human Molecular Genetics doi: 10.1093/hmg/10.22.2469 – volume: 151 start-page: 333 year: 2012 ident: ref43 article-title: Heteroplasmy of Mouse mtDNA Is Genetically Unstable and Results in Altered Behavior and Cognition publication-title: Cell doi: 10.1016/j.cell.2012.09.004 – volume: 84 start-page: 628 year: 2009 ident: ref8 article-title: The Diversity Present in 5140 Human Mitochondrial Genomes publication-title: American Journal of Human Genetics doi: 10.1016/j.ajhg.2009.04.013 – volume: 101 start-page: 10726 year: 2004 ident: ref35 article-title: Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.0403649101 – volume: 16 start-page: 93 year: 1997 ident: ref42 article-title: Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice publication-title: Nature Genetics doi: 10.1038/ng0597-93 – volume: 51 start-page: 566 year: 2006 ident: ref27 article-title: Evaluation of variation in control region sequences for Hispanic individuals in the SWGDAM mtDNA data set publication-title: Journal of Forensic Sciences doi: 10.1111/j.1556-4029.2006.00136.x – volume: 6 start-page: 63 year: 2008 ident: ref47 article-title: Strong purifying selection in transmission of mammalian mitochondrial DNA publication-title: Plos Biology doi: 10.1371/journal.pbio.0060010 – volume: 202 start-page: 85 year: 2002 ident: ref19 article-title: Evidence and age-related distribution of mtDNA D-loop point mutations in skeletal muscle from healthy subjects and mitochondrial patients publication-title: Journal of the Neurological Sciences doi: 10.1016/S0022-510X(02)00247-2 – volume: 148 start-page: 169 year: 2005 ident: ref26 article-title: Characterization of human control region sequences of the African American SWGDAM forensic mtDNA data set publication-title: Forensic Science International doi: 10.1016/j.forsciint.2004.06.001 – volume: 33 start-page: 183 year: 2003 ident: ref40 article-title: Nuclear genetic control of mitochondrial DNA segregation publication-title: Nature Genetics doi: 10.1038/ng1073 – volume: 6 start-page: e22332 issue: (8) year: 2011 ident: ref18 article-title: A Twin Study of Mitochondrial DNA Polymorphisms Shows that Heteroplasmy at Multiple Sites Is Associated with mtDNA Variant 16093 but Not with Zygosity publication-title: Plos One doi: 10.1371/journal.pone.0022332 – volume: 120 start-page: 271 year: 2006 ident: ref30 article-title: Mitochondrial DNA sequence variation in Jewish populations publication-title: International Journal of Legal Medicine doi: 10.1007/s00414-006-0083-0 – volume: 140 start-page: 1 year: 2004 ident: ref31 article-title: Results of a collaborative study of the EDNAP group regarding mitochondrial DNA heteroplasmy and segregation in hair shafts publication-title: Forensic Science International doi: 10.1016/S0379-0738(03)00181-6 – volume: 156 start-page: 124 year: 2006 ident: ref29 article-title: Mitochondrial DNA sequence alterations observed between blood and buccal cells within the same individuals having betel quid (BQ)-chewing habit publication-title: Forensic Science International doi: 10.1016/j.forsciint.2004.12.021 – volume: 22 start-page: 384 year: 2013 ident: ref25 article-title: Universal heteroplasmy of human mitochondrial DNA publication-title: Human Molecular Genetics doi: 10.1093/hmg/dds435 – volume: 306 start-page: 2098 year: 2004 ident: ref15 article-title: Discovery of a major D-loop replication origin reveals two modes of human mtDNA synthesis publication-title: Science doi: 10.1126/science.1102077 – volume: 28 start-page: 4350 year: 2000 ident: ref34 article-title: The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method publication-title: Nucleic Acids Research doi: 10.1093/nar/28.21.4350 – volume: 467 start-page: 707 year: 2010 ident: ref44 article-title: The ploidy conveyor of mature hepatocytes as a source of genetic variation publication-title: Nature doi: 10.1038/nature09414 – volume: 100 start-page: 2174 year: 2003 ident: ref39 article-title: Control region mtDNA variants: Longevity, climatic adaptation, and a forensic conundrum publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.0630589100 – volume: 10 start-page: e402 year: 2007 ident: ref48 article-title: Preparing T cell growth factor from rat splenocytes publication-title: Journal of Visualized Experiments – volume: 18 start-page: 651 year: 2005 ident: ref16 article-title: A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA publication-title: Molecular Cell doi: 10.1016/j.molcel.2005.05.002 – volume: 89 start-page: 7370 year: 1992 ident: ref13 article-title: A Pattern of Accumulation of a Somatic Deletion of Mitochondrial-DNA in Aging Human Tissues publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.89.16.7370 – volume: 1792 start-page: 1097 year: 2009 ident: ref1 article-title: The inheritance of pathogenic mitochondrial DNA mutations publication-title: Biochimica Et Biophysica Acta-Molecular Basis of Disease doi: 10.1016/j.bbadis.2009.03.002 – volume: 25 start-page: 2759 year: 2008 ident: ref17 article-title: Evidence for Variable Selective Pressures at a Large Secondary Structure of the Human Mitochondrial DNA Control Region publication-title: Molecular Biology and Evolution doi: 10.1093/molbev/msn225 – volume: 263 start-page: 139 year: 2007 ident: ref24 article-title: Age-related mitochondrial DNA point mutations in patients with mitochondrial myopathy publication-title: Journal of the Neurological Sciences doi: 10.1016/j.jns.2007.07.006 – volume: 24 start-page: 829 year: 2003 ident: ref20 article-title: High mutational burden in the mtDNA control region from aged muscles: a single-fiber study publication-title: Neurobiology of Aging doi: 10.1016/S0197-4580(02)00233-6 – volume: 23 start-page: 147 year: 1999 ident: ref4 article-title: Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA publication-title: Nature Genetics doi: 10.1038/13779 – volume: 20 start-page: 1297 year: 2010 ident: ref6 article-title: The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data publication-title: Genome Research doi: 10.1101/gr.107524.110 – volume: 40 start-page: 275 year: 2008 ident: ref14 article-title: What causes mitochondrial DNA deletions in human cells publication-title: Nature Genetics doi: 10.1038/ng.f.94 – volume: 12 start-page: 506 year: 2002 ident: ref38 article-title: Atypical muscle pathology and a survey of cis-mutations in deaf patients harboring a 1555 A-to-G point mutation in the mitochondrial ribosomal RNA gene publication-title: Neuromuscular Disorders doi: 10.1016/S0960-8966(01)00329-7 – volume: 2 start-page: 324 year: 1992 ident: ref12 article-title: Mitochondrial-DNA Deletions in Human Brain - Regional Variability and Increase with Advanced Age publication-title: Nature Genetics doi: 10.1038/ng1292-324 – reference: 24281144 - Nat Rev Genet. 2014 Jan;15(1):4 |
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| Snippet | Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to... Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to... |
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| SubjectTerms | Aging Base Sequence Cell division Deoxyribonucleic acid DNA DNA Replication - genetics DNA, Mitochondrial - genetics Gene mutations Genome, Mitochondrial Genomes Humans Mitochondria - genetics Mitochondrial DNA Muscle, Skeletal - metabolism Musculoskeletal system Mutation Mutation - genetics Organ Specificity Physiological aspects Polymorphism, Restriction Fragment Length - genetics Population genetics |
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| Title | Recurrent Tissue-Specific mtDNA Mutations Are Common in Humans |
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