Genome-Wide Analysis of DNA Methylation, Copy Number Variation, and Gene Expression in Monozygotic Twins Discordant for Primary Biliary Cirrhosis
Identifieur interne : 001C46 ( Main/Exploration ); précédent : 001C45; suivant : 001C47Genome-Wide Analysis of DNA Methylation, Copy Number Variation, and Gene Expression in Monozygotic Twins Discordant for Primary Biliary Cirrhosis
Auteurs : Carlo Selmi [Italie, États-Unis] ; Francesca Cavaciocchi [Italie] ; Ana Lleo [Italie] ; Cristina Cheroni [Italie] ; Raffaele De Francesco [Italie] ; Simone A. Lombardi [Italie] ; Maria De Santis [Italie] ; Francesca Meda [Italie] ; Maria Gabriella Raimondo [Italie] ; Chiara Crotti [Italie] ; Marco Folci [Italie] ; Luca Zammataro [Italie] ; Marlyn J. Mayo [États-Unis] ; Nancy Bach [États-Unis] ; Shinji Shimoda [Japon] ; Stuart C. Gordon [États-Unis] ; Monica Miozzo [Italie] ; Pietro Invernizzi [Italie] ; Mauro Podda [Italie] ; Rossana Scavelli [Italie] ; Michelle R. Martin [États-Unis] ; Michael F. Seldin [États-Unis] ; Janine M. Lasalle [États-Unis] ; M. Eric Gershwin [États-Unis]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2014.
Abstract
Primary biliary cirrhosis (PBC) is an uncommon autoimmune disease with a homogeneous clinical phenotype that reflects incomplete disease concordance in monozygotic (MZ) twins. We have taken advantage of a unique collection consisting of genomic DNA and mRNA from peripheral blood cells of female MZ twins (
Url:
DOI: 10.3389/fimmu.2014.00128
PubMed: 24734033
PubMed Central: 3975093
Affiliations:
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Mayo</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>University of Texas Southwestern</institution>,<addr-line>Dallas, TX</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bach, Nancy" sort="Bach, Nancy" uniqKey="Bach N" first="Nancy" last="Bach">Nancy Bach</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Mt. Sinai University</institution>,<addr-line>New York, NY</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shimoda, Shinji" sort="Shimoda, Shinji" uniqKey="Shimoda S" first="Shinji" last="Shimoda">Shinji Shimoda</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Clinical Research Center, National Nagasaki Medical Center</institution>,<addr-line>Nagasaki</addr-line>,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gordon, Stuart C" sort="Gordon, Stuart C" uniqKey="Gordon S" first="Stuart C." last="Gordon">Stuart C. 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Martin</name><affiliation wicri:level="1"><nlm:aff id="aff12"><institution>Genome Center and M.I.N.D. Institute, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Seldin, Michael F" sort="Seldin, Michael F" uniqKey="Seldin M" first="Michael F." last="Seldin">Michael F. 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type="wicri:Area/Main/Exploration">001C46</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-Wide Analysis of DNA Methylation, Copy Number Variation, and Gene Expression in Monozygotic Twins Discordant for Primary Biliary Cirrhosis</title><author><name sortKey="Selmi, Carlo" sort="Selmi, Carlo" uniqKey="Selmi C" first="Carlo" last="Selmi">Carlo Selmi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cavaciocchi, Francesca" sort="Cavaciocchi, Francesca" uniqKey="Cavaciocchi F" first="Francesca" last="Cavaciocchi">Francesca Cavaciocchi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>BIOMETRA Department, University of Milan</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lleo, Ana" sort="Lleo, Ana" uniqKey="Lleo A" first="Ana" last="Lleo">Ana Lleo</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cheroni, Cristina" sort="Cheroni, Cristina" uniqKey="Cheroni C" first="Cristina" last="Cheroni">Cristina Cheroni</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>National Institute of Molecular Genetics (INGM)</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Francesco, Raffaele" sort="De Francesco, Raffaele" uniqKey="De Francesco R" first="Raffaele" last="De Francesco">Raffaele De Francesco</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>National Institute of Molecular Genetics (INGM)</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lombardi, Simone A" sort="Lombardi, Simone A" uniqKey="Lombardi S" first="Simone A." last="Lombardi">Simone A. Lombardi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Santis, Maria" sort="De Santis, Maria" uniqKey="De Santis M" first="Maria" last="De Santis">Maria De Santis</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>BIOMETRA Department, University of Milan</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meda, Francesca" sort="Meda, Francesca" uniqKey="Meda F" first="Francesca" last="Meda">Francesca Meda</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Raimondo, Maria Gabriella" sort="Raimondo, Maria Gabriella" uniqKey="Raimondo M" first="Maria Gabriella" last="Raimondo">Maria Gabriella Raimondo</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Crotti, Chiara" sort="Crotti, Chiara" uniqKey="Crotti C" first="Chiara" last="Crotti">Chiara Crotti</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Folci, Marco" sort="Folci, Marco" uniqKey="Folci M" first="Marco" last="Folci">Marco Folci</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zammataro, Luca" sort="Zammataro, Luca" uniqKey="Zammataro L" first="Luca" last="Zammataro">Luca Zammataro</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mayo, Marlyn J" sort="Mayo, Marlyn J" uniqKey="Mayo M" first="Marlyn J." last="Mayo">Marlyn J. Mayo</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>University of Texas Southwestern</institution>,<addr-line>Dallas, TX</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bach, Nancy" sort="Bach, Nancy" uniqKey="Bach N" first="Nancy" last="Bach">Nancy Bach</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Mt. Sinai University</institution>,<addr-line>New York, NY</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shimoda, Shinji" sort="Shimoda, Shinji" uniqKey="Shimoda S" first="Shinji" last="Shimoda">Shinji Shimoda</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Clinical Research Center, National Nagasaki Medical Center</institution>,<addr-line>Nagasaki</addr-line>,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gordon, Stuart C" sort="Gordon, Stuart C" uniqKey="Gordon S" first="Stuart C." last="Gordon">Stuart C. Gordon</name><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Henry Ford Hospital</institution>,<addr-line>Detroit, MI</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Miozzo, Monica" sort="Miozzo, Monica" uniqKey="Miozzo M" first="Monica" last="Miozzo">Monica Miozzo</name><affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Pathophysiology and Transplantation, University of Milan</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff11"><institution>Division of Pathology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Invernizzi, Pietro" sort="Invernizzi, Pietro" uniqKey="Invernizzi P" first="Pietro" last="Invernizzi">Pietro Invernizzi</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Podda, Mauro" sort="Podda, Mauro" uniqKey="Podda M" first="Mauro" last="Podda">Mauro Podda</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Scavelli, Rossana" sort="Scavelli, Rossana" uniqKey="Scavelli R" first="Rossana" last="Scavelli">Rossana Scavelli</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>National Institute of Molecular Genetics (INGM)</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Michelle R" sort="Martin, Michelle R" uniqKey="Martin M" first="Michelle R." last="Martin">Michelle R. Martin</name><affiliation wicri:level="1"><nlm:aff id="aff12"><institution>Genome Center and M.I.N.D. Institute, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Seldin, Michael F" sort="Seldin, Michael F" uniqKey="Seldin M" first="Michael F." last="Seldin">Michael F. Seldin</name><affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Department of Biochemistry and Molecular Medicine, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Internal Medicine, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lasalle, Janine M" sort="Lasalle, Janine M" uniqKey="Lasalle J" first="Janine M." last="Lasalle">Janine M. Lasalle</name><affiliation wicri:level="1"><nlm:aff id="aff12"><institution>Genome Center and M.I.N.D. Institute, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gershwin, M Eric" sort="Gershwin, M Eric" uniqKey="Gershwin M" first="M. Eric" last="Gershwin">M. Eric Gershwin</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis</institution>,<addr-line>Davis, CA</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Primary biliary cirrhosis (PBC) is an uncommon autoimmune disease with a homogeneous clinical phenotype that reflects incomplete disease concordance in monozygotic (MZ) twins. We have taken advantage of a unique collection consisting of genomic DNA and mRNA from peripheral blood cells of female MZ twins (<italic>n</italic> = 3 sets) and sisters of similar age (<italic>n</italic> = 8 pairs) discordant for disease. We performed a genome-wide study to investigate differences in (i) DNA methylation (using a custom tiled four-plex array containing tiled 50-mers 19,084 randomly chosen methylation sites), (ii) copy number variation (CNV) (with a chip including markers derived from the 1000 Genomes Project, all three HapMap phases, and recently published studies), and/or (iii) gene expression (by whole-genome expression arrays). Based on the results obtained from these three approaches we utilized quantitative PCR to compare the expression of candidate genes. Importantly, our data support consistent differences in discordant twins and siblings for the (i) methylation profiles of 60 gene regions, (ii) CNV of 10 genes, and (iii) the expression of 2 interferon-dependent genes. Quantitative PCR analysis showed that 17 of these genes are differentially expressed in discordant sibling pairs. In conclusion, we report that MZ twins and sisters discordant for PBC manifest particular epigenetic differences and highlight the value of the epigenetic study of twins.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Selmi, C" uniqKey="Selmi C">C Selmi</name></author><author><name sortKey="Bowlus, Cl" uniqKey="Bowlus C">CL Bowlus</name></author><author><name sortKey="Gershwin, Me" uniqKey="Gershwin M">ME Gershwin</name></author><author><name sortKey="Coppel, Rl" uniqKey="Coppel R">RL Coppel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Germolec, D" uniqKey="Germolec D">D Germolec</name></author><author><name sortKey="Kono, Dh" uniqKey="Kono D">DH Kono</name></author><author><name sortKey="Pfau, Jc" uniqKey="Pfau J">JC Pfau</name></author><author><name sortKey="Pollard, Km" uniqKey="Pollard K">KM Pollard</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Chu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Italie</li><li>Japon</li><li>États-Unis</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Selmi, Carlo" sort="Selmi, Carlo" uniqKey="Selmi C" first="Carlo" last="Selmi">Carlo Selmi</name></noRegion><name sortKey="Cavaciocchi, Francesca" sort="Cavaciocchi, Francesca" uniqKey="Cavaciocchi F" first="Francesca" last="Cavaciocchi">Francesca Cavaciocchi</name><name sortKey="Cavaciocchi, Francesca" sort="Cavaciocchi, Francesca" uniqKey="Cavaciocchi F" first="Francesca" last="Cavaciocchi">Francesca Cavaciocchi</name><name sortKey="Cheroni, Cristina" sort="Cheroni, Cristina" uniqKey="Cheroni C" first="Cristina" last="Cheroni">Cristina Cheroni</name><name sortKey="Crotti, Chiara" sort="Crotti, Chiara" uniqKey="Crotti C" first="Chiara" last="Crotti">Chiara Crotti</name><name sortKey="De Francesco, Raffaele" sort="De Francesco, Raffaele" uniqKey="De Francesco R" 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Eric" last="Gershwin">M. Eric Gershwin</name><name sortKey="Gordon, Stuart C" sort="Gordon, Stuart C" uniqKey="Gordon S" first="Stuart C." last="Gordon">Stuart C. Gordon</name><name sortKey="Lasalle, Janine M" sort="Lasalle, Janine M" uniqKey="Lasalle J" first="Janine M." last="Lasalle">Janine M. Lasalle</name><name sortKey="Martin, Michelle R" sort="Martin, Michelle R" uniqKey="Martin M" first="Michelle R." last="Martin">Michelle R. Martin</name><name sortKey="Mayo, Marlyn J" sort="Mayo, Marlyn J" uniqKey="Mayo M" first="Marlyn J." last="Mayo">Marlyn J. Mayo</name><name sortKey="Seldin, Michael F" sort="Seldin, Michael F" uniqKey="Seldin M" first="Michael F." last="Seldin">Michael F. Seldin</name><name sortKey="Seldin, Michael F" sort="Seldin, Michael F" uniqKey="Seldin M" first="Michael F." last="Seldin">Michael F. Seldin</name></country><country name="Japon"><noRegion><name sortKey="Shimoda, Shinji" sort="Shimoda, Shinji" uniqKey="Shimoda S" first="Shinji" last="Shimoda">Shinji Shimoda</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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