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Y. Kraytsberg, A. Nicholas, K. Khrapko (2007)
Are somatic mitochondrial DNA mutations relevant to our health? A challenge for mutation analysis techniques.Expert opinion on medical diagnostics, 1 1
M. Nass (1966)
The circularity of mitochondrial DNA.Proceedings of the National Academy of Sciences of the United States of America, 56 4
M. Woischnik, C. Moraes (2002)
Pattern of organization of human mitochondrial pseudogenes in the nuclear genome.Genome research, 12 6
Robert Taylor, M. Barron, G. Borthwick, A. Gospel, P. Chinnery, D. Samuels, G. Taylor, S. Plusa, S. Needham, Laura Greaves, T. Kirkwood, D. Turnbull (2003)
Mitochondrial DNA mutations in human colonic crypt stem cells.The Journal of clinical investigation, 112 9
(2005)
Mitochondrial DNA mutations in human diseaseNat Rev Genet, 6
G. Cortopassi, N. Arnheim (1990)
Detection of a specific mitochondrial DNA deletion in tissues of older humans.Nucleic acids research, 18 23
Y. Kraytsberg, K. Khrapko (2005)
Single-molecule PCR: an artifact-free PCR approach for the analysis of somatic mutationsExpert Review of Molecular Diagnostics, 5
G. Kujoth, A. Hiona, T. Pugh, Shinichi Someya, K. Panzer, S. Wohlgemuth, T. Hofer, Arnold Seo, R. Sullivan, Wendy Jobling, J. Morrow, H. Remmen, J. Sedivy, Tatsuya Yamasoba, M. Tanokura, R. Weindruch, C. Leeuwenburgh, T. Prolla (2005)
Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian AgingScience, 309
Y. Kraytsberg, A. Nicholas, P. Caro, K. Khrapko (2008)
Single molecule PCR in mtDNA mutational analysis: Genuine mutations vs. damage bypass-derived artifacts.Methods, 46 4
S. Old, Margaret Johnson (1989)
Methods of microphotometric assay of succinate dehydrogenase and cytochromec oxidase activities for use on human skeletal muscleThe Histochemical Journal, 21
R. Smigrodzki, J. Parks, W. Parker (2004)
High frequency of mitochondrial complex I mutations in Parkinson’s disease and agingNeurobiology of Aging, 25
M. Vermulst, J. Bielas, G. Kujoth, W. Ladiges, P. Rabinovitch, T. Prolla, L. Loeb (2007)
Mitochondrial point mutations do not limit the natural lifespan of miceNature Genetics, 39
S. Anderson, A. Bankier, B. Barrell, M. Bruijn, A. Coulson, J. Drouin, J. Drouin, I. Eperon, D. Nierlich, D. Nierlich, B. Roe, B. Roe, F. Sanger, P. Schreier, A. Smith, R. Staden, I. Young, I. Young (1981)
Sequence and organization of the human mitochondrial genomeNature, 290
C. Wilding, K. Cadwell, E. Tawn, C. Relton, G. Taylor, P. Chinnery, D. Turnbull (2006)
Mitochondrial DNA Mutations in Individuals Occupationally Exposed to Ionizing Radiation, 165
J. Miquel, A. Economos, J. Fleming, J. Johnson (1980)
Mitochondrial role in cell agingExperimental Gerontology, 15
Ekaterina Nekhaeva, N. Bodyak, Y. Kraytsberg, S. McGrath, N. Orsouw, A. Pluzhnikov, Jeanne Wei, J. Vijg, K. Khrapko (2002)
Clonally expanded mtDNA point mutations are abundant in individual cells of human tissuesProceedings of the National Academy of Sciences of the United States of America, 99
D. Simon, M. Lin, C. Ahn, G. Liu, G. Gibson, M. Beal, D. Johns (2001)
Low mutational burden of individual acquired mitochondrial DNA mutations in brain.Genomics, 73 1
D. Cottrell, E. Blakely, Margaret Johnson, P. Ince, G. Borthwick, D. Turnbull (2001)
Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with ageNeurobiology of Aging, 22
K. Khrapko, P. André, R. Cha, G. Hu, W. Thilly (1994)
Mutational spectrometry: means and ends.Progress in nucleic acid research and molecular biology, 49
Laura Greaves, S. Preston, P. Tadrous, Robert Taylor, M. Barron, D. Oukrif, S. Leedham, M. Deheragoda, P. Sasieni, M. Novelli, J. Jankowski, D. Turnbull, N. Wright, S. McDonald (2006)
Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.Proceedings of the National Academy of Sciences of the United States of America, 103 3
Laura Greaves, Robert Taylor (2006)
Mitochondrial DNA mutations in human diseaseIUBMB Life, 58
A. Trifunovic, A. Wredenberg, M. Falkenberg, J. Spelbrink, A. Rovio, C. Bruder, M. Bohlooly-y, S. Gidlöf, A. Oldfors, R. Wibom, J. Törnell, H. Jacobs, N. Larsson (2004)
Premature ageing in mice expressing defective mitochondrial DNA polymeraseNature, 429
(2009)
Quantification of mitochondrial DNA mutation load
R. Bo, A. Bordoni, F. Boneschi, M. Crimi, M. Sciacco, N. Bresolin, G. Scarlato, G. Comi (2002)
Evidence and age-related distribution of mtDNA D-loop point mutations in skeletal muscle from healthy subjects and mitochondrial patientsJournal of the Neurological Sciences, 202
(2004)
Analysis of somatic mutations via long-distance single molecule PCR. DNA amplification: Current technologies and applications
J. Cooper, V. Mann, A. Schapira, A. Schapira (1992)
Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: Effect of ageingJournal of the Neurological Sciences, 113
SummaryMitochondrial DNA (mtDNA) mutations are an important cause of genetic disease and have been proposed to play a role in the ageing process. Quantification of total mtDNA mutation load in ageing tissues is difficult as mutational events are rare in a background of wild-type molecules, and detection of individual mutated molecules is beyond the sensitivity of most sequencing based techniques. The methods currently most commonly used to document the incidence of mtDNA point mutations in ageing include post-PCR cloning, single-molecule PCR and the random mutation capture assay. The mtDNA mutation load obtained by these different techniques varies by orders of magnitude, but direct comparison of the three techniques on the same ageing human tissue has not been performed. We assess the procedures and practicalities involved in each of these three assays and discuss the results obtained by investigation of mutation loads in colonic mucosal biopsies from ten human subjects.
Aging Cell – Wiley
Published: Oct 1, 2009
Keywords: ageing; cloning; colon; human; mitochondria; mitochondrial DNA; mutation load; polymerase chain reaction
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