Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.

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...

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Autores principales:	Sonia López, Alfonso Buil, Juan Carlos Souto, Jordi Casademont, John Blangero, Angel Martinez-Perez, Jordi Fontcuberta, Mark Lathrop, Laura Almasy, Jose Manuel Soria
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/813c9936137a49e9ab8a79252a269ab3
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spelling	oai:doaj.org-article:813c9936137a49e9ab8a79252a269ab32021-11-18T07:08:16ZSex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.1932-620310.1371/journal.pone.0042711https://doaj.org/article/813c9936137a49e9ab8a79252a269ab32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22916149/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Altered 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 MRPL37, 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 CMPK2, 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.Sonia LópezAlfonso BuilJuan Carlos SoutoJordi CasademontJohn BlangeroAngel Martinez-PerezJordi FontcubertaMark LathropLaura AlmasyJose Manuel SoriaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42711 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sonia López Alfonso Buil Juan Carlos Souto Jordi Casademont John Blangero Angel Martinez-Perez Jordi Fontcuberta Mark Lathrop Laura Almasy Jose Manuel Soria Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.
description	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 MRPL37, 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 CMPK2, 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.
format	article
author	Sonia López Alfonso Buil Juan Carlos Souto Jordi Casademont John Blangero Angel Martinez-Perez Jordi Fontcuberta Mark Lathrop Laura Almasy Jose Manuel Soria
author_facet	Sonia López Alfonso Buil Juan Carlos Souto Jordi Casademont John Blangero Angel Martinez-Perez Jordi Fontcuberta Mark Lathrop Laura Almasy Jose Manuel Soria
author_sort	Sonia López
title	Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.
title_short	Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.
title_full	Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.
title_fullStr	Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.
title_full_unstemmed	Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.
title_sort	sex-specific regulation of mitochondrial dna levels: genome-wide linkage analysis to identify quantitative trait loci.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/813c9936137a49e9ab8a79252a269ab3
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Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.

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