Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci
Identifieur interne : 000F67 ( Ncbi/Merge ); précédent : 000F66; suivant : 000F68Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci
Auteurs : Sonia L Pez [Espagne] ; Alfonso Buil [Espagne] ; Juan Carlos Souto [Espagne] ; Jordi Casademont [Espagne] ; John Blangero [États-Unis] ; Angel Martinez-Perez [Espagne] ; Jordi Fontcuberta [Espagne] ; Mark Lathrop [France] ; Laura Almasy [États-Unis] ; Jose Manuel Soria [Espagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p = 1.82e-05). We identified a QTL on Chromosome 2 (LOD = 2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD = 3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD = 2.67), whereas in males a QTL was identified on Chromosome 1 (LOD = 2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene
Url:
DOI: 10.1371/journal.pone.0042711
PubMed: 22916149
PubMed Central: 3423410
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000810
- to stream Pmc, to step Curation: 000807
- to stream Pmc, to step Checkpoint: 000569
Links to Exploration step
PMC:3423410Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci</title><author><name sortKey="L Pez, Sonia" sort="L Pez, Sonia" uniqKey="L Pez S" first="Sonia" last="L Pez">Sonia L Pez</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Buil, Alfonso" sort="Buil, Alfonso" uniqKey="Buil A" first="Alfonso" last="Buil">Alfonso Buil</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Souto, Juan Carlos" sort="Souto, Juan Carlos" uniqKey="Souto J" first="Juan Carlos" last="Souto">Juan Carlos Souto</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Casademont, Jordi" sort="Casademont, Jordi" uniqKey="Casademont J" first="Jordi" last="Casademont">Jordi Casademont</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Martinez Perez, Angel" sort="Martinez Perez, Angel" uniqKey="Martinez Perez A" first="Angel" last="Martinez-Perez">Angel Martinez-Perez</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Fontcuberta, Jordi" sort="Fontcuberta, Jordi" uniqKey="Fontcuberta J" first="Jordi" last="Fontcuberta">Jordi Fontcuberta</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Institut de Génomique, Centre National de Génotypage, Evry, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Almasy, Laura" sort="Almasy, Laura" uniqKey="Almasy L" first="Laura" last="Almasy">Laura Almasy</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Soria, Jose Manuel" sort="Soria, Jose Manuel" uniqKey="Soria J" first="Jose Manuel" last="Soria">Jose Manuel Soria</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22916149</idno><idno type="pmc">3423410</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423410</idno><idno type="RBID">PMC:3423410</idno><idno type="doi">10.1371/journal.pone.0042711</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000810</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000810</idno><idno type="wicri:Area/Pmc/Curation">000807</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000807</idno><idno type="wicri:Area/Pmc/Checkpoint">000569</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000569</idno><idno type="wicri:Area/Ncbi/Merge">000F67</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci</title><author><name sortKey="L Pez, Sonia" sort="L Pez, Sonia" uniqKey="L Pez S" first="Sonia" last="L Pez">Sonia L Pez</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Buil, Alfonso" sort="Buil, Alfonso" uniqKey="Buil A" first="Alfonso" last="Buil">Alfonso Buil</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Souto, Juan Carlos" sort="Souto, Juan Carlos" uniqKey="Souto J" first="Juan Carlos" last="Souto">Juan Carlos Souto</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Casademont, Jordi" sort="Casademont, Jordi" uniqKey="Casademont J" first="Jordi" last="Casademont">Jordi Casademont</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Martinez Perez, Angel" sort="Martinez Perez, Angel" uniqKey="Martinez Perez A" first="Angel" last="Martinez-Perez">Angel Martinez-Perez</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Fontcuberta, Jordi" sort="Fontcuberta, Jordi" uniqKey="Fontcuberta J" first="Jordi" last="Fontcuberta">Jordi Fontcuberta</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Institut de Génomique, Centre National de Génotypage, Evry, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Almasy, Laura" sort="Almasy, Laura" uniqKey="Almasy L" first="Laura" last="Almasy">Laura Almasy</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Soria, Jose Manuel" sort="Soria, Jose Manuel" uniqKey="Soria J" first="Jose Manuel" last="Soria">Jose Manuel Soria</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p = 1.82e-05). We identified a QTL on Chromosome 2 (LOD = 2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD = 3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD = 2.67), whereas in males a QTL was identified on Chromosome 1 (LOD = 2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene <italic>MRPL37</italic>, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene <italic>CMPK2</italic>, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kushnareva, Y" uniqKey="Kushnareva Y">Y Kushnareva</name></author><author><name sortKey="Newmeyer, Dd" uniqKey="Newmeyer D">DD Newmeyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author><author><name sortKey="Koczan, D" uniqKey="Koczan D">D Koczan</name></author><author><name sortKey="Sulonen, Am" uniqKey="Sulonen A">AM Sulonen</name></author><author><name sortKey="Akkad, Da" uniqKey="Akkad D">DA Akkad</name></author><author><name sortKey="Kroner, A" uniqKey="Kroner A">A Kroner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Czarnecka, Am" uniqKey="Czarnecka A">AM Czarnecka</name></author><author><name sortKey="Klemba, A" uniqKey="Klemba A">A Klemba</name></author><author><name sortKey="Krawczyk, T" uniqKey="Krawczyk T">T Krawczyk</name></author><author><name sortKey="Zdrozny, M" uniqKey="Zdrozny M">M Zdrozny</name></author><author><name sortKey="Arnold, Rs" uniqKey="Arnold R">RS Arnold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, R" uniqKey="Zhang R">R Zhang</name></author><author><name sortKey="Zhang, F" uniqKey="Zhang F">F Zhang</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C Wang</name></author><author><name sortKey="Wang, S" uniqKey="Wang S">S Wang</name></author><author><name sortKey="Shiao, Yh" uniqKey="Shiao Y">YH Shiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moreno Loshuertos, R" uniqKey="Moreno Loshuertos R">R Moreno-Loshuertos</name></author><author><name sortKey="Acin Perez, R" uniqKey="Acin Perez R">R Acin-Perez</name></author><author><name sortKey="Fernandez Silva, P" uniqKey="Fernandez Silva P">P Fernandez-Silva</name></author><author><name sortKey="Movilla, N" uniqKey="Movilla N">N Movilla</name></author><author><name sortKey="Perez Martos, A" uniqKey="Perez Martos A">A Perez-Martos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, Gj" uniqKey="Song G">GJ Song</name></author><author><name sortKey="Lewis, V" uniqKey="Lewis V">V Lewis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weng, Sw" uniqKey="Weng S">SW Weng</name></author><author><name sortKey="Lin, Tk" uniqKey="Lin T">TK Lin</name></author><author><name sortKey="Liou, Cw" uniqKey="Liou C">CW Liou</name></author><author><name sortKey="Chen, Sd" uniqKey="Chen S">SD Chen</name></author><author><name sortKey="Wei, Yh" uniqKey="Wei Y">YH Wei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Cs" uniqKey="Liu C">CS Liu</name></author><author><name sortKey="Kuo, Cl" uniqKey="Kuo C">CL Kuo</name></author><author><name sortKey="Cheng, Wl" uniqKey="Cheng W">WL Cheng</name></author><author><name sortKey="Huang, Cs" uniqKey="Huang C">CS Huang</name></author><author><name sortKey="Lee, Cf" uniqKey="Lee C">CF Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Hc" uniqKey="Lee H">HC Lee</name></author><author><name sortKey="Li, Sh" uniqKey="Li S">SH Li</name></author><author><name sortKey="Lin, Jc" uniqKey="Lin J">JC Lin</name></author><author><name sortKey="Wu, Cc" uniqKey="Wu C">CC Wu</name></author><author><name sortKey="Yeh, Dc" uniqKey="Yeh D">DC Yeh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Hc" uniqKey="Lee H">HC Lee</name></author><author><name sortKey="Yin, Ph" uniqKey="Yin P">PH Yin</name></author><author><name sortKey="Lin, Jc" uniqKey="Lin J">JC Lin</name></author><author><name sortKey="Wu, Cc" uniqKey="Wu C">CC Wu</name></author><author><name sortKey="Chen, Cy" uniqKey="Chen C">CY Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Liu, Vw" uniqKey="Liu V">VW Liu</name></author><author><name sortKey="Xue, Wc" uniqKey="Xue W">WC Xue</name></author><author><name sortKey="Tsang, Pc" uniqKey="Tsang P">PC Tsang</name></author><author><name sortKey="Cheung, An" uniqKey="Cheung A">AN Cheung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamada, S" uniqKey="Yamada S">S Yamada</name></author><author><name sortKey="Nomoto, S" uniqKey="Nomoto S">S Nomoto</name></author><author><name sortKey="Fujii, T" uniqKey="Fujii T">T Fujii</name></author><author><name sortKey="Kaneko, T" uniqKey="Kaneko T">T Kaneko</name></author><author><name sortKey="Takeda, S" uniqKey="Takeda S">S Takeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, M" uniqKey="Yu M">M Yu</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name></author><author><name sortKey="Ning, L" uniqKey="Ning L">L Ning</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hosgood, Hd" uniqKey="Hosgood H">HD Hosgood</name></author><author><name sortKey="Liu, Cs" uniqKey="Liu C">CS Liu</name></author><author><name sortKey="Rothman, N" uniqKey="Rothman N">N Rothman</name></author><author><name sortKey="Weinstein, Sj" uniqKey="Weinstein S">SJ Weinstein</name></author><author><name sortKey="Bonner, Mr" uniqKey="Bonner M">MR Bonner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lan, Q" uniqKey="Lan Q">Q Lan</name></author><author><name sortKey="Lim, U" uniqKey="Lim U">U Lim</name></author><author><name sortKey="Liu, Cs" uniqKey="Liu C">CS Liu</name></author><author><name sortKey="Weinstein, Sj" uniqKey="Weinstein S">SJ Weinstein</name></author><author><name sortKey="Chanock, S" uniqKey="Chanock S">S Chanock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burhans, Wc" uniqKey="Burhans W">WC Burhans</name></author><author><name sortKey="Weinberger, M" uniqKey="Weinberger M">M Weinberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Mt" uniqKey="Lin M">MT Lin</name></author><author><name sortKey="Beal, Mf" uniqKey="Beal M">MF Beal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wallace, Dc" uniqKey="Wallace D">DC Wallace</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Madamanchi, Nr" uniqKey="Madamanchi N">NR Madamanchi</name></author><author><name sortKey="Vendrov, A" uniqKey="Vendrov A">A Vendrov</name></author><author><name sortKey="Runge, Ms" uniqKey="Runge M">MS Runge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonomini, F" uniqKey="Bonomini F">F Bonomini</name></author><author><name sortKey="Tengattini, S" uniqKey="Tengattini S">S Tengattini</name></author><author><name sortKey="Fabiano, A" uniqKey="Fabiano A">A Fabiano</name></author><author><name sortKey="Bianchi, R" uniqKey="Bianchi R">R Bianchi</name></author><author><name sortKey="Rezzani, R" uniqKey="Rezzani R">R Rezzani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gutierrez, J" uniqKey="Gutierrez J">J Gutierrez</name></author><author><name sortKey="Ballinger, Sw" uniqKey="Ballinger S">SW Ballinger</name></author><author><name sortKey="Darley Usmar, Vm" uniqKey="Darley Usmar V">VM Darley-Usmar</name></author><author><name sortKey="Landar, A" uniqKey="Landar A">A Landar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Souto, Jc" uniqKey="Souto J">JC Souto</name></author><author><name sortKey="Almasy, L" uniqKey="Almasy L">L Almasy</name></author><author><name sortKey="Borrell, M" uniqKey="Borrell M">M Borrell</name></author><author><name sortKey="Gari, M" uniqKey="Gari M">M Gari</name></author><author><name sortKey="Martinez, E" uniqKey="Martinez E">E Martinez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, Sa" uniqKey="Miller S">SA Miller</name></author><author><name sortKey="Dykes, Dd" uniqKey="Dykes D">DD Dykes</name></author><author><name sortKey="Polesky, Hf" uniqKey="Polesky H">HF Polesky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soria, Jm" uniqKey="Soria J">JM Soria</name></author><author><name sortKey="Almasy, L" uniqKey="Almasy L">L Almasy</name></author><author><name sortKey="Souto, Jc" uniqKey="Souto J">JC Souto</name></author><author><name sortKey="Bacq, D" uniqKey="Bacq D">D Bacq</name></author><author><name sortKey="Buil, A" uniqKey="Buil A">A Buil</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Morrison, Tb" uniqKey="Morrison T">TB Morrison</name></author><author><name sortKey="Weis, Jj" uniqKey="Weis J">JJ Weis</name></author><author><name sortKey="Wittwer, Ct" uniqKey="Wittwer C">CT Wittwer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ririe, Km" uniqKey="Ririe K">KM Ririe</name></author><author><name sortKey="Rasmussen, Rp" uniqKey="Rasmussen R">RP Rasmussen</name></author><author><name sortKey="Wittwer, Ct" uniqKey="Wittwer C">CT Wittwer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cote, Hc" uniqKey="Cote H">HC Cote</name></author><author><name sortKey="Brumme, Zl" uniqKey="Brumme Z">ZL Brumme</name></author><author><name sortKey="Craib, Kj" uniqKey="Craib K">KJ Craib</name></author><author><name sortKey="Alexander, Cs" uniqKey="Alexander C">CS Alexander</name></author><author><name sortKey="Wynhoven, B" uniqKey="Wynhoven B">B Wynhoven</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cote, Hc" uniqKey="Cote H">HC Cote</name></author><author><name sortKey="Gerschenson, M" uniqKey="Gerschenson M">M Gerschenson</name></author><author><name sortKey="Walker, Ua" uniqKey="Walker U">UA Walker</name></author><author><name sortKey="Miro, O" uniqKey="Miro O">O Miro</name></author><author><name sortKey="Garrabou, G" uniqKey="Garrabou G">G Garrabou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almasy, L" uniqKey="Almasy L">L Almasy</name></author><author><name sortKey="Blangero, J" uniqKey="Blangero J">J Blangero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allison, Db" uniqKey="Allison D">DB Allison</name></author><author><name sortKey="Neale, Mc" uniqKey="Neale M">MC Neale</name></author><author><name sortKey="Zannolli, R" uniqKey="Zannolli R">R Zannolli</name></author><author><name sortKey="Schork, Nj" uniqKey="Schork N">NJ Schork</name></author><author><name sortKey="Amos, Ci" uniqKey="Amos C">CI Amos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blangero, J" uniqKey="Blangero J">J Blangero</name></author><author><name sortKey="Williams, Jt" uniqKey="Williams J">JT Williams</name></author><author><name sortKey="Almasy, L" uniqKey="Almasy L">L Almasy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boehnke, M" uniqKey="Boehnke M">M Boehnke</name></author><author><name sortKey="Lange, K" uniqKey="Lange K">K Lange</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feingold, E" uniqKey="Feingold E">E Feingold</name></author><author><name sortKey="Brown, Po" uniqKey="Brown P">PO Brown</name></author><author><name sortKey="Siegmund, D" uniqKey="Siegmund D">D Siegmund</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boerwinkle, E" uniqKey="Boerwinkle E">E Boerwinkle</name></author><author><name sortKey="Chakraborty, R" uniqKey="Chakraborty R">R Chakraborty</name></author><author><name sortKey="Sing, Cf" uniqKey="Sing C">CF Sing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benjamini, Y" uniqKey="Benjamini Y">Y Benjamini</name></author><author><name sortKey="Hochberg, Y" uniqKey="Hochberg Y">Y Hochberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moraes, Ct" uniqKey="Moraes C">CT Moraes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xing, J" uniqKey="Xing J">J Xing</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Wood, Cg" uniqKey="Wood C">CG Wood</name></author><author><name sortKey="Lin, J" uniqKey="Lin J">J Lin</name></author><author><name sortKey="Spitz, Mr" uniqKey="Spitz M">MR Spitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Curran, Je" uniqKey="Curran J">JE Curran</name></author><author><name sortKey="Johnson, Mp" uniqKey="Johnson M">MP Johnson</name></author><author><name sortKey="Dyer, Td" uniqKey="Dyer T">TD Dyer</name></author><author><name sortKey="Goring, Hh" uniqKey="Goring H">HH Goring</name></author><author><name sortKey="Kent, Jw" uniqKey="Kent J">JW Kent</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobs, Ht" uniqKey="Jacobs H">HT Jacobs</name></author><author><name sortKey="Turnbull, Dm" uniqKey="Turnbull D">DM Turnbull</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Johansson, M" uniqKey="Johansson M">M Johansson</name></author><author><name sortKey="Karlsson, A" uniqKey="Karlsson A">A Karlsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dalakas, Mc" uniqKey="Dalakas M">MC Dalakas</name></author><author><name sortKey="Semino Mora, C" uniqKey="Semino Mora C">C Semino-Mora</name></author><author><name sortKey="Leon Monzon, M" uniqKey="Leon Monzon M">M Leon-Monzon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marti, R" uniqKey="Marti R">R Marti</name></author><author><name sortKey="Nascimento, A" uniqKey="Nascimento A">A Nascimento</name></author><author><name sortKey="Colomer, J" uniqKey="Colomer J">J Colomer</name></author><author><name sortKey="Lara, Mc" uniqKey="Lara M">MC Lara</name></author><author><name sortKey="Lopez Gallardo, E" uniqKey="Lopez Gallardo E">E Lopez-Gallardo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Freisinger, P" uniqKey="Freisinger P">P Freisinger</name></author><author><name sortKey="Futterer, N" uniqKey="Futterer N">N Futterer</name></author><author><name sortKey="Lankes, E" uniqKey="Lankes E">E Lankes</name></author><author><name sortKey="Gempel, K" uniqKey="Gempel K">K Gempel</name></author><author><name sortKey="Berger, Tm" uniqKey="Berger T">TM Berger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cerritelli, Sm" uniqKey="Cerritelli S">SM Cerritelli</name></author><author><name sortKey="Crouch, Rj" uniqKey="Crouch R">RJ Crouch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, La" uniqKey="Weiss L">LA Weiss</name></author><author><name sortKey="Pan, L" uniqKey="Pan L">L Pan</name></author><author><name sortKey="Abney, M" uniqKey="Abney M">M Abney</name></author><author><name sortKey="Ober, C" uniqKey="Ober C">C Ober</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seda, O" uniqKey="Seda O">O Seda</name></author><author><name sortKey="Tremblay, J" uniqKey="Tremblay J">J Tremblay</name></author><author><name sortKey="Gaudet, D" uniqKey="Gaudet D">D Gaudet</name></author><author><name sortKey="Brunelle, Pl" uniqKey="Brunelle P">PL Brunelle</name></author><author><name sortKey="Gurau, A" uniqKey="Gurau A">A Gurau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiu, Yf" uniqKey="Chiu Y">YF Chiu</name></author><author><name sortKey="Chuang, Lm" uniqKey="Chuang L">LM Chuang</name></author><author><name sortKey="Kao, Hy" uniqKey="Kao H">HY Kao</name></author><author><name sortKey="Shih, Kc" uniqKey="Shih K">KC Shih</name></author><author><name sortKey="Lin, Mw" uniqKey="Lin M">MW Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carter, Am" uniqKey="Carter A">AM Carter</name></author><author><name sortKey="Catto, Aj" uniqKey="Catto A">AJ Catto</name></author><author><name sortKey="Bamford, Jm" uniqKey="Bamford J">JM Bamford</name></author><author><name sortKey="Grant, Pj" uniqKey="Grant P">PJ Grant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guevara, R" uniqKey="Guevara R">R Guevara</name></author><author><name sortKey="Santandreu, Fm" uniqKey="Santandreu F">FM Santandreu</name></author><author><name sortKey="Valle, A" uniqKey="Valle A">A Valle</name></author><author><name sortKey="Gianotti, M" uniqKey="Gianotti M">M Gianotti</name></author><author><name sortKey="Oliver, J" uniqKey="Oliver J">J Oliver</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Colom, B" uniqKey="Colom B">B Colom</name></author><author><name sortKey="Alcolea, Mp" uniqKey="Alcolea M">MP Alcolea</name></author><author><name sortKey="Valle, A" uniqKey="Valle A">A Valle</name></author><author><name sortKey="Oliver, J" uniqKey="Oliver J">J Oliver</name></author><author><name sortKey="Roca, P" uniqKey="Roca P">P Roca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gavrilova Jordan, Lp" uniqKey="Gavrilova Jordan L">LP Gavrilova-Jordan</name></author><author><name sortKey="Price, Tm" uniqKey="Price T">TM Price</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mattingly, Ka" uniqKey="Mattingly K">KA Mattingly</name></author><author><name sortKey="Ivanova, Mm" uniqKey="Ivanova M">MM Ivanova</name></author><author><name sortKey="Riggs, Ka" uniqKey="Riggs K">KA Riggs</name></author><author><name sortKey="Wickramasinghe, Ns" uniqKey="Wickramasinghe N">NS Wickramasinghe</name></author><author><name sortKey="Barch, Mj" uniqKey="Barch M">MJ Barch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klinge, Cm" uniqKey="Klinge C">CM Klinge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Psarra, Am" uniqKey="Psarra A">AM Psarra</name></author><author><name sortKey="Sekeris, Ce" uniqKey="Sekeris C">CE Sekeris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simpkins, Jw" uniqKey="Simpkins J">JW Simpkins</name></author><author><name sortKey="Yang, Sh" uniqKey="Yang S">SH Yang</name></author><author><name sortKey="Sarkar, Sn" uniqKey="Sarkar S">SN Sarkar</name></author><author><name sortKey="Pearce, V" uniqKey="Pearce V">V Pearce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giordano, C" uniqKey="Giordano C">C Giordano</name></author><author><name sortKey="Montopoli, M" uniqKey="Montopoli M">M Montopoli</name></author><author><name sortKey="Perli, E" uniqKey="Perli E">E Perli</name></author><author><name sortKey="Orlandi, M" uniqKey="Orlandi M">M Orlandi</name></author><author><name sortKey="Fantin, M" uniqKey="Fantin M">M Fantin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22916149</article-id><article-id pub-id-type="pmc">3423410</article-id><article-id pub-id-type="publisher-id">PONE-D-12-07247</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0042711</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Bioenergetics</subject><subj-group><subject>Energy-Producing Organelles</subject></subj-group></subj-group></subj-group><subj-group><subject>Genetics</subject><subj-group><subject>Human Genetics</subject><subj-group><subject>Mitochondrial Diseases</subject></subj-group></subj-group></subj-group><subj-group><subject>Genomics</subject><subj-group><subject>Genome Analysis Tools</subject><subj-group><subject>Genetic Screens</subject><subject>Genome Scans</subject><subject>Genome-Wide Association Studies</subject><subject>Linkage Maps</subject><subject>Trait Locus Analysis</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci</article-title><alt-title alt-title-type="running-head">Genetic Architecture of mtDNA Levels</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>López</surname><given-names>Sonia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Buil</surname><given-names>Alfonso</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Souto</surname><given-names>Juan Carlos</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Casademont</surname><given-names>Jordi</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Blangero</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Martinez-Perez</surname><given-names>Angel</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fontcuberta</surname><given-names>Jordi</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lathrop</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Almasy</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Soria</surname><given-names>Jose Manuel</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Unit of Genomic of Complex Diseases, Institute of Biomedical Research of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Haemostasis and Thrombosis Unit, Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Department of Population Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Institut de Génomique, Centre National de Génotypage, Evry, France</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Bai</surname><given-names>Yidong</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Texas Health Science Center at San Antonio, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>jsoria@santpau.cat</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: JC JCS SL JMS. Performed the experiments: SL. Analyzed the data: AB LA JB JMS SL AMP. Contributed reagents/materials/analysis tools: JC JCS JMS JF ML SL LA JB. Wrote the paper: SL JMS.</p></fn></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>20</day><month>8</month><year>2012</year></pub-date><volume>7</volume><issue>8</issue><elocation-id>e42711</elocation-id><history><date date-type="received"><day>10</day><month>3</month><year>2012</year></date><date date-type="accepted"><day>10</day><month>7</month><year>2012</year></date></history><permissions><copyright-year>2012</copyright-year><copyright-holder>López et al</copyright-holder><license><license-p>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.</license-p></license></permissions><abstract><p>Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p = 1.82e-05). We identified a QTL on Chromosome 2 (LOD = 2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD = 3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD = 2.67), whereas in males a QTL was identified on Chromosome 1 (LOD = 2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene <italic>MRPL37</italic>, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene <italic>CMPK2</italic>, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels.</p></abstract><funding-group><funding-statement>This work was supported by the ‘Instituto de Salud Carlos III-Fondo de Investigación Sanitaria’ [PI-11/00184, PI-08/0420, PI-08/0756, RECAVA-RD06/0014]; the ‘Ministerio de Ciencia e Innovación’ [SAF2008/01859]; and the ‘Agència de Gestió d'ajuts Universitaris i de Recerca’ [SGR 2009-1240]. SL was supported by “Contratos Posdoctorales de Perfeccionamiento Sara Borrell” from ‘Instituto de Salud Carlos III-Fondo de Investigación Sanitaria’ (ISCIII-FIS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="11"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Espagne</li><li>France</li><li>États-Unis</li></country><region><li>Catalogne</li><li>Texas</li><li>Île-de-France</li></region><settlement><li>Barcelone</li><li>Évry (Essonne)</li></settlement><orgName><li>Université autonome de Barcelone</li></orgName></list><tree><country name="Espagne"><region name="Catalogne"><name sortKey="L Pez, Sonia" sort="L Pez, Sonia" uniqKey="L Pez S" first="Sonia" last="L Pez">Sonia L Pez</name></region><name sortKey="Buil, Alfonso" sort="Buil, Alfonso" uniqKey="Buil A" first="Alfonso" last="Buil">Alfonso Buil</name><name sortKey="Casademont, Jordi" sort="Casademont, Jordi" uniqKey="Casademont J" first="Jordi" last="Casademont">Jordi Casademont</name><name sortKey="Fontcuberta, Jordi" sort="Fontcuberta, Jordi" uniqKey="Fontcuberta J" first="Jordi" last="Fontcuberta">Jordi Fontcuberta</name><name sortKey="Martinez Perez, Angel" sort="Martinez Perez, Angel" uniqKey="Martinez Perez A" first="Angel" last="Martinez-Perez">Angel Martinez-Perez</name><name sortKey="Soria, Jose Manuel" sort="Soria, Jose Manuel" uniqKey="Soria J" first="Jose Manuel" last="Soria">Jose Manuel Soria</name><name sortKey="Souto, Juan Carlos" sort="Souto, Juan Carlos" uniqKey="Souto J" first="Juan Carlos" last="Souto">Juan Carlos Souto</name></country><country name="États-Unis"><region name="Texas"><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name></region><name sortKey="Almasy, Laura" sort="Almasy, Laura" uniqKey="Almasy L" first="Laura" last="Almasy">Laura Almasy</name></country><country name="France"><region name="Île-de-France"><name sortKey="Lathrop, Mark" sort="Lathrop, Mark" uniqKey="Lathrop M" first="Mark" last="Lathrop">Mark Lathrop</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F67 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000F67 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:3423410
|texte= Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:22916149" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonFranceV1
| This area was generated with Dilib version V0.6.29. |  |