Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion
Identifieur interne : 000D61 ( Main/Exploration ); précédent : 000D60; suivant : 000D62Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion
Auteurs : Zhengrui Xi [Canada] ; Lorne Zinman [Canada] ; Danielle Moreno [Canada] ; Jennifer Schymick [Canada] ; Yan Liang [Canada] ; Christine Sato [Canada] ; Yonglan Zheng [États-Unis] ; Mahdi Ghani [Canada] ; Samar Dib [Canada] ; Julia Keith [Canada] ; Janice Robertson [Canada] ; Ekaterina Rogaeva [Canada]Source :
- American Journal of Human Genetics [ 0002-9297 ] ; 2013.
Abstract
The G4C2 repeat expansion in
Url:
DOI: 10.1016/j.ajhg.2013.04.017
PubMed: 23731538
PubMed Central: 3675239
Affiliations:
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- to stream Pmc, to step Checkpoint: 000643
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- to stream Ncbi, to step Curation: 001465
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Le document en format XML
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wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Sato, Christine" sort="Sato, Christine" uniqKey="Sato C" first="Christine" last="Sato">Christine Sato</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Zheng, Yonglan" sort="Zheng, Yonglan" uniqKey="Zheng Y" first="Yonglan" last="Zheng">Yonglan Zheng</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Medicine, The University of Chicago, Chicago, IL 60637, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, The University of Chicago, Chicago, IL 60637</wicri:regionArea><wicri:noRegion>IL 60637</wicri:noRegion></affiliation></author><author><name sortKey="Ghani, Mahdi" sort="Ghani, Mahdi" uniqKey="Ghani M" first="Mahdi" last="Ghani">Mahdi Ghani</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Dib, Samar" sort="Dib, Samar" uniqKey="Dib S" first="Samar" last="Dib">Samar Dib</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName 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xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Medicine, Division of Neurology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, Division of Neurology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23731538</idno><idno type="pmc">3675239</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675239</idno><idno type="RBID">PMC:3675239</idno><idno type="doi">10.1016/j.ajhg.2013.04.017</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000353</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000353</idno><idno type="wicri:Area/Pmc/Curation">000353</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000353</idno><idno type="wicri:Area/Pmc/Checkpoint">000643</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000643</idno><idno type="wicri:Area/Ncbi/Merge">001465</idno><idno type="wicri:Area/Ncbi/Curation">001465</idno><idno type="wicri:Area/Ncbi/Checkpoint">001465</idno><idno type="wicri:doubleKey">0002-9297:2013:Xi Z:hypermethylation:of:the</idno><idno type="wicri:Area/Main/Merge">000D72</idno><idno type="wicri:Area/Main/Curation">000D61</idno><idno type="wicri:Area/Main/Exploration">000D61</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hypermethylation of the CpG Island Near the G<sub>4</sub>C<sub>2</sub> Repeat in ALS with a <italic>C9orf72</italic> Expansion</title><author><name sortKey="Xi, Zhengrui" sort="Xi, Zhengrui" uniqKey="Xi Z" first="Zhengrui" last="Xi">Zhengrui Xi</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Zinman, Lorne" sort="Zinman, Lorne" uniqKey="Zinman L" first="Lorne" last="Zinman">Lorne Zinman</name><affiliation wicri:level="1"><nlm:aff id="aff2">Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5</wicri:regionArea><wicri:noRegion>ON M4N 3M5</wicri:noRegion></affiliation></author><author><name sortKey="Moreno, Danielle" sort="Moreno, Danielle" uniqKey="Moreno D" first="Danielle" last="Moreno">Danielle Moreno</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Schymick, Jennifer" sort="Schymick, Jennifer" uniqKey="Schymick J" first="Jennifer" last="Schymick">Jennifer Schymick</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Liang, Yan" sort="Liang, Yan" uniqKey="Liang Y" first="Yan" last="Liang">Yan Liang</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Sato, Christine" sort="Sato, Christine" uniqKey="Sato C" first="Christine" last="Sato">Christine Sato</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Zheng, Yonglan" sort="Zheng, Yonglan" uniqKey="Zheng Y" first="Yonglan" last="Zheng">Yonglan Zheng</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Medicine, The University of Chicago, Chicago, IL 60637, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, The University of Chicago, Chicago, IL 60637</wicri:regionArea><wicri:noRegion>IL 60637</wicri:noRegion></affiliation></author><author><name sortKey="Ghani, Mahdi" sort="Ghani, Mahdi" uniqKey="Ghani M" first="Mahdi" last="Ghani">Mahdi Ghani</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Dib, Samar" sort="Dib, Samar" uniqKey="Dib S" first="Samar" last="Dib">Samar Dib</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Keith, Julia" sort="Keith, Julia" uniqKey="Keith J" first="Julia" last="Keith">Julia Keith</name><affiliation wicri:level="1"><nlm:aff id="aff2">Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5</wicri:regionArea><wicri:noRegion>ON M4N 3M5</wicri:noRegion></affiliation></author><author><name sortKey="Robertson, Janice" sort="Robertson, Janice" uniqKey="Robertson J" first="Janice" last="Robertson">Janice Robertson</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation wicri:level="4"><nlm:aff id="aff1">Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, ON M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Medicine, Division of Neurology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, Division of Neurology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">American Journal of Human Genetics</title><idno type="ISSN">0002-9297</idno><idno type="eISSN">1537-6605</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The G<sub>4</sub>C<sub>2</sub> repeat expansion in <italic>C9orf72</italic> is the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We tested the hypothesis that the repeat expansion causes aberrant CpG methylation near the G<sub>4</sub>C<sub>2</sub> repeat, which could be responsible for the downregulation of gene expression. We investigated the CpG methylation profile by two methods using genomic DNA from the blood of individuals with ALS (37 expansion carriers and 64 noncarriers), normal controls (n = 76), and family members of 7 ALS probands with the expansion. We report that hypermethylation of the CpG island 5′ of the G<sub>4</sub>C<sub>2</sub> repeat is associated with the presence of the expansion (p < 0.0001). A higher degree of methylation was significantly correlated with a shorter disease duration (p < 0.01), associated with familial ALS (p = 0.009) and segregated with the expansion in 7 investigated families. Notably, we did not detect methylation for either normal or intermediate alleles (up to 43 repeats), bringing to question the current cutoff of 30 repeats for pathological alleles. Our study raises several important questions for the future investigation of large data sets, such as whether the degree of methylation corresponds to clinical presentation (ALS versus FTLD).</p></div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Xi, Zhengrui" sort="Xi, Zhengrui" uniqKey="Xi Z" first="Zhengrui" last="Xi">Zhengrui Xi</name></region><name sortKey="Dib, Samar" sort="Dib, Samar" uniqKey="Dib S" first="Samar" last="Dib">Samar Dib</name><name sortKey="Ghani, Mahdi" sort="Ghani, Mahdi" uniqKey="Ghani M" first="Mahdi" last="Ghani">Mahdi Ghani</name><name sortKey="Keith, Julia" sort="Keith, Julia" uniqKey="Keith J" first="Julia" last="Keith">Julia Keith</name><name sortKey="Liang, Yan" sort="Liang, Yan" uniqKey="Liang Y" first="Yan" last="Liang">Yan Liang</name><name sortKey="Moreno, Danielle" sort="Moreno, Danielle" uniqKey="Moreno D" first="Danielle" last="Moreno">Danielle Moreno</name><name sortKey="Robertson, Janice" sort="Robertson, Janice" uniqKey="Robertson J" first="Janice" last="Robertson">Janice Robertson</name><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><name sortKey="Sato, Christine" sort="Sato, Christine" uniqKey="Sato C" first="Christine" last="Sato">Christine Sato</name><name sortKey="Schymick, Jennifer" sort="Schymick, Jennifer" uniqKey="Schymick J" first="Jennifer" last="Schymick">Jennifer Schymick</name><name sortKey="Zinman, Lorne" sort="Zinman, Lorne" uniqKey="Zinman L" first="Lorne" last="Zinman">Lorne Zinman</name></country><country name="États-Unis"><noRegion><name sortKey="Zheng, Yonglan" sort="Zheng, Yonglan" uniqKey="Zheng Y" first="Yonglan" last="Zheng">Yonglan Zheng</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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