Mitochondrial DNA mutations in human colonic crypt stem cells
The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role...
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Veröffentlicht in: | The Journal of clinical investigation 2003-11, Vol.112 (9), p.1351-1360 |
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creator | Taylor, Robert W Barron, Martin J Borthwick, Gillian M Gospel, Amy Chinnery, Patrick F Samuels, David C Taylor, Geoffrey A Plusa, Stefan M Needham, Stephanie J Greaves, Laura C Kirkwood, Thomas B L Turnbull, Douglass M |
description | The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell. |
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Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci19435</identifier><identifier>PMID: 14597761</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Bats ; Biomedical research ; Cancer ; Colon - cytology ; Colon - metabolism ; Cytochrome ; Dehydrogenases ; Disease ; DNA Replication ; DNA, Mitochondrial - genetics ; Electron Transport ; Genomes ; Humans ; Mathematics ; Middle Aged ; Mitochondria ; Mitochondrial DNA ; Models, Genetic ; Mutation ; Phosphorylation ; Proteins ; Stem cells ; Stem Cells - metabolism ; Transfer RNA ; Tumors</subject><ispartof>The Journal of clinical investigation, 2003-11, Vol.112 (9), p.1351-1360</ispartof><rights>Copyright American Society for Clinical Investigation Nov 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3605-1ffcd1ae416f198c73be9a021091bb01f459bb76e4141d3e301d0539d61bb7043</citedby><cites>FETCH-LOGICAL-c3605-1ffcd1ae416f198c73be9a021091bb01f459bb76e4141d3e301d0539d61bb7043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14597761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taylor, Robert W</creatorcontrib><creatorcontrib>Barron, Martin J</creatorcontrib><creatorcontrib>Borthwick, Gillian M</creatorcontrib><creatorcontrib>Gospel, Amy</creatorcontrib><creatorcontrib>Chinnery, Patrick F</creatorcontrib><creatorcontrib>Samuels, David C</creatorcontrib><creatorcontrib>Taylor, Geoffrey A</creatorcontrib><creatorcontrib>Plusa, Stefan M</creatorcontrib><creatorcontrib>Needham, Stephanie J</creatorcontrib><creatorcontrib>Greaves, Laura C</creatorcontrib><creatorcontrib>Kirkwood, Thomas B L</creatorcontrib><creatorcontrib>Turnbull, Douglass M</creatorcontrib><title>Mitochondrial DNA mutations in human colonic crypt stem cells</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Bats</subject><subject>Biomedical research</subject><subject>Cancer</subject><subject>Colon - cytology</subject><subject>Colon - metabolism</subject><subject>Cytochrome</subject><subject>Dehydrogenases</subject><subject>Disease</subject><subject>DNA Replication</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Electron Transport</subject><subject>Genomes</subject><subject>Humans</subject><subject>Mathematics</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondrial DNA</subject><subject>Models, Genetic</subject><subject>Mutation</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Stem Cells - 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cytology</topic><topic>Colon - metabolism</topic><topic>Cytochrome</topic><topic>Dehydrogenases</topic><topic>Disease</topic><topic>DNA Replication</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Electron Transport</topic><topic>Genomes</topic><topic>Humans</topic><topic>Mathematics</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>Mitochondrial DNA</topic><topic>Models, Genetic</topic><topic>Mutation</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Transfer RNA</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taylor, Robert W</creatorcontrib><creatorcontrib>Barron, Martin J</creatorcontrib><creatorcontrib>Borthwick, Gillian M</creatorcontrib><creatorcontrib>Gospel, Amy</creatorcontrib><creatorcontrib>Chinnery, Patrick F</creatorcontrib><creatorcontrib>Samuels, David C</creatorcontrib><creatorcontrib>Taylor, Geoffrey A</creatorcontrib><creatorcontrib>Plusa, Stefan M</creatorcontrib><creatorcontrib>Needham, Stephanie J</creatorcontrib><creatorcontrib>Greaves, Laura C</creatorcontrib><creatorcontrib>Kirkwood, Thomas B L</creatorcontrib><creatorcontrib>Turnbull, Douglass M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taylor, Robert W</au><au>Barron, Martin J</au><au>Borthwick, Gillian M</au><au>Gospel, Amy</au><au>Chinnery, Patrick F</au><au>Samuels, David C</au><au>Taylor, Geoffrey A</au><au>Plusa, Stefan M</au><au>Needham, Stephanie J</au><au>Greaves, Laura C</au><au>Kirkwood, Thomas B L</au><au>Turnbull, Douglass M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial DNA mutations in human colonic crypt stem cells</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2003-11</date><risdate>2003</risdate><volume>112</volume><issue>9</issue><spage>1351</spage><epage>1360</epage><pages>1351-1360</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. 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subjects | Aged Aged, 80 and over Aging Bats Biomedical research Cancer Colon - cytology Colon - metabolism Cytochrome Dehydrogenases Disease DNA Replication DNA, Mitochondrial - genetics Electron Transport Genomes Humans Mathematics Middle Aged Mitochondria Mitochondrial DNA Models, Genetic Mutation Phosphorylation Proteins Stem cells Stem Cells - metabolism Transfer RNA Tumors |
title | Mitochondrial DNA mutations in human colonic crypt stem cells |
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