Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease
Identifieur interne : 00AF18 ( Main/Exploration ); précédent : 00AF17; suivant : 00AF19Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease
Auteurs : L. Djoussé [États-Unis] ; B. Knowlton [États-Unis] ; M. Hayden ; E. W. Almqvist ; R. Brinkman ; C. Ross [États-Unis] ; R. Margolis [États-Unis] ; A. Rosenblatt [États-Unis] ; A. Durr [France] ; C. Dode [France] ; P. J. Morrison [Royaume-Uni] ; A. Novelletto [Italie] ; M. Frontali [Italie] ; R. J. A. Trent [Australie] ; E. Mccusker [Australie] ; E. G Mez-Tortosa [Espagne] ; D. Mayo [Espagne] ; R. Jones [Géorgie (pays)] ; A. Zanko [États-Unis] ; M. Nance [États-Unis] ; R. Abramson [États-Unis] ; O. Suchowersky ; J. Paulsen [États-Unis] ; M. Harrison [États-Unis] ; Q. Yang [États-Unis] ; L. A. Cupples [États-Unis] ; J. F. Gusella [États-Unis] ; M. E. Macdonald [États-Unis] ; R. H. Myers [États-Unis]Source :
- American Journal of Medical Genetics Part A [ 1552-4825 ] ; 2003-06-15.
Descripteurs français
- Wicri :
- topic : Neurologie.
English descriptors
- KwdEn :
- Allele, Boston university school, British columbia, Cellular toxicity, Chromosome, Cohort, Conneally, England huntington disease center, Expandeda unexpanded, Genet, Glur6 gene, Grant sponsor, Highest tertile, Huntingtin, Huntington, Huntington disease, Interaction term, Medical genetics, Mutant huntingtin, Myers, Neurodegenerative disorder, Neurology, Normal chromosome, Proc natl acad, Size unexpanded, Tertile, Third tertile, Trinucleotide, Unexpanded, Unique families.
- Teeft :
- Allele, Boston university school, British columbia, Cellular toxicity, Chromosome, Cohort, Conneally, England huntington disease center, Expandeda unexpanded, Genet, Glur6 gene, Grant sponsor, Highest tertile, Huntingtin, Huntington, Huntington disease, Interaction term, Medical genetics, Mutant huntingtin, Myers, Neurodegenerative disorder, Neurology, Normal chromosome, Proc natl acad, Size unexpanded, Tertile, Third tertile, Trinucleotide, Unexpanded, Unique families.
Abstract
Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD‐MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47–83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats. © 2003 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/ajmg.a.20190
Affiliations:
- Australie, Espagne, France, Géorgie (pays), Italie, Royaume-Uni, États-Unis
- Californie, Caroline du Sud, Communauté de Madrid, Iowa, Latium, Maryland, Massachusetts, Minnesota, Nouvelle-Galles du Sud, Virginie, Île-de-France
- Madrid, Paris, Rome, Sydney
- Université de Sydney
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000C53
- to stream Istex, to step Curation: 000C53
- to stream Istex, to step Checkpoint: 001B24
- to stream Main, to step Merge: 00BC57
- to stream Main, to step Curation: 00AF18
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease</title><author><name sortKey="Djousse, L" sort="Djousse, L" uniqKey="Djousse L" first="L." last="Djoussé">L. Djoussé</name></author><author><name sortKey="Knowlton, B" sort="Knowlton, B" uniqKey="Knowlton B" first="B." last="Knowlton">B. Knowlton</name></author><author><name sortKey="Hayden, M" sort="Hayden, M" uniqKey="Hayden M" first="M." last="Hayden">M. Hayden</name></author><author><name sortKey="Almqvist, E W" sort="Almqvist, E W" uniqKey="Almqvist E" first="E. W." last="Almqvist">E. W. Almqvist</name></author><author><name sortKey="Brinkman, R" sort="Brinkman, R" uniqKey="Brinkman R" first="R." last="Brinkman">R. Brinkman</name></author><author><name sortKey="Ross, C" sort="Ross, C" uniqKey="Ross C" first="C." last="Ross">C. Ross</name></author><author><name sortKey="Margolis, R" sort="Margolis, R" uniqKey="Margolis R" first="R." last="Margolis">R. Margolis</name></author><author><name sortKey="Rosenblatt, A" sort="Rosenblatt, A" uniqKey="Rosenblatt A" first="A." last="Rosenblatt">A. Rosenblatt</name></author><author><name sortKey="Durr, A" sort="Durr, A" uniqKey="Durr A" first="A." last="Durr">A. Durr</name></author><author><name sortKey="Dode, C" sort="Dode, C" uniqKey="Dode C" first="C." last="Dode">C. Dode</name></author><author><name sortKey="Morrison, P J" sort="Morrison, P J" uniqKey="Morrison P" first="P. J." last="Morrison">P. J. Morrison</name></author><author><name sortKey="Novelletto, A" sort="Novelletto, A" uniqKey="Novelletto A" first="A." last="Novelletto">A. Novelletto</name></author><author><name sortKey="Frontali, M" sort="Frontali, M" uniqKey="Frontali M" first="M." last="Frontali">M. Frontali</name></author><author><name sortKey="Trent, R J A" sort="Trent, R J A" uniqKey="Trent R" first="R. J. A." last="Trent">R. J. A. Trent</name></author><author><name sortKey="Mccusker, E" sort="Mccusker, E" uniqKey="Mccusker E" first="E." last="Mccusker">E. Mccusker</name></author><author><name sortKey="G Mez Ortosa, E" sort="G Mez Ortosa, E" uniqKey="G Mez Ortosa E" first="E." last="G Mez-Tortosa">E. G Mez-Tortosa</name></author><author><name sortKey="Mayo, D" sort="Mayo, D" uniqKey="Mayo D" first="D." last="Mayo">D. Mayo</name></author><author><name sortKey="Jones, R" sort="Jones, R" uniqKey="Jones R" first="R." last="Jones">R. Jones</name></author><author><name sortKey="Zanko, A" sort="Zanko, A" uniqKey="Zanko A" first="A." last="Zanko">A. Zanko</name></author><author><name sortKey="Nance, M" sort="Nance, M" uniqKey="Nance M" first="M." last="Nance">M. Nance</name></author><author><name sortKey="Abramson, R" sort="Abramson, R" uniqKey="Abramson R" first="R." last="Abramson">R. Abramson</name></author><author><name sortKey="Suchowersky, O" sort="Suchowersky, O" uniqKey="Suchowersky O" first="O." last="Suchowersky">O. Suchowersky</name></author><author><name sortKey="Paulsen, J" sort="Paulsen, J" uniqKey="Paulsen J" first="J." last="Paulsen">J. Paulsen</name></author><author><name sortKey="Harrison, M" sort="Harrison, M" uniqKey="Harrison M" first="M." last="Harrison">M. Harrison</name></author><author><name sortKey="Yang, Q" sort="Yang, Q" uniqKey="Yang Q" first="Q." last="Yang">Q. Yang</name></author><author><name sortKey="Cupples, L A" sort="Cupples, L A" uniqKey="Cupples L" first="L. A." last="Cupples">L. A. Cupples</name></author><author><name sortKey="Gusella, J F" sort="Gusella, J F" uniqKey="Gusella J" first="J. F." last="Gusella">J. F. Gusella</name></author><author><name sortKey="Macdonald, M E" sort="Macdonald, M E" uniqKey="Macdonald M" first="M. E." last="Macdonald">M. E. Macdonald</name></author><author><name sortKey="Myers, R H" sort="Myers, R H" uniqKey="Myers R" first="R. H." last="Myers">R. H. Myers</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4338708DF83B0821C39E2E5102457BA83D77375B</idno><date when="2003" year="2003">2003</date><idno type="doi">10.1002/ajmg.a.20190</idno><idno type="url">https://api.istex.fr/document/4338708DF83B0821C39E2E5102457BA83D77375B/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000C53</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000C53</idno><idno type="wicri:Area/Istex/Curation">000C53</idno><idno type="wicri:Area/Istex/Checkpoint">001B24</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001B24</idno><idno type="wicri:doubleKey">1552-4825:2003:Djousse L:interaction:of:normal</idno><idno type="wicri:Area/Main/Merge">00BC57</idno><idno type="wicri:Area/Main/Curation">00AF18</idno><idno type="wicri:Area/Main/Exploration">00AF18</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease</title><author><name sortKey="Djousse, L" sort="Djousse, L" uniqKey="Djousse L" first="L." last="Djoussé">L. Djoussé</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Knowlton, B" sort="Knowlton, B" uniqKey="Knowlton B" first="B." last="Knowlton">B. Knowlton</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Department of Neurology, Boston University School of Medicine, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Hayden, M" sort="Hayden, M" uniqKey="Hayden M" first="M." last="Hayden">M. Hayden</name><affiliation><wicri:noCountry code="subField">Columbia</wicri:noCountry></affiliation></author><author><name sortKey="Almqvist, E W" sort="Almqvist, E W" uniqKey="Almqvist E" first="E. W." last="Almqvist">E. W. Almqvist</name><affiliation><wicri:noCountry code="subField">Columbia</wicri:noCountry></affiliation></author><author><name sortKey="Brinkman, R" sort="Brinkman, R" uniqKey="Brinkman R" first="R." last="Brinkman">R. Brinkman</name><affiliation><wicri:noCountry code="subField">Columbia</wicri:noCountry></affiliation></author><author><name sortKey="Ross, C" sort="Ross, C" uniqKey="Ross C" first="C." last="Ross">C. Ross</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>John Hopkins University, Department of Neurology, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Margolis, R" sort="Margolis, R" uniqKey="Margolis R" first="R." last="Margolis">R. Margolis</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>John Hopkins University, Department of Neurology, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Rosenblatt, A" sort="Rosenblatt, A" uniqKey="Rosenblatt A" first="A." last="Rosenblatt">A. Rosenblatt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>John Hopkins University, Department of Neurology, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Durr, A" sort="Durr, A" uniqKey="Durr A" first="A." last="Durr">A. Durr</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hôpital de la Salpetriere, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dode, C" sort="Dode, C" uniqKey="Dode C" first="C." last="Dode">C. Dode</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hôpital de la Salpetriere, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Morrison, P J" sort="Morrison, P J" uniqKey="Morrison P" first="P. J." last="Morrison">P. J. Morrison</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medical Genetics, Belfast City Hospital Trust, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Novelletto, A" sort="Novelletto, A" uniqKey="Novelletto A" first="A." last="Novelletto">A. Novelletto</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology, University of Calabria, Rende</wicri:regionArea><wicri:noRegion>Rende</wicri:noRegion></affiliation></author><author><name sortKey="Frontali, M" sort="Frontali, M" uniqKey="Frontali M" first="M." last="Frontali">M. Frontali</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Experimental Medicine, CNR, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Trent, R J A" sort="Trent, R J A" uniqKey="Trent R" first="R. J. A." last="Trent">R. J. A. Trent</name><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, University of Sydney, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Mccusker, E" sort="Mccusker, E" uniqKey="Mccusker E" first="E." last="Mccusker">E. Mccusker</name><affiliation wicri:level="3"><country xml:lang="fr">Australie</country><wicri:regionArea>Neurology Department, Westmead Hospital, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="G Mez Ortosa, E" sort="G Mez Ortosa, E" uniqKey="G Mez Ortosa E" first="E." last="G Mez-Tortosa">E. G Mez-Tortosa</name><affiliation wicri:level="3"><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Mayo, D" sort="Mayo, D" uniqKey="Mayo D" first="D." last="Mayo">D. Mayo</name><affiliation wicri:level="3"><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Jones, R" sort="Jones, R" uniqKey="Jones R" first="R." last="Jones">R. Jones</name><affiliation wicri:level="1"><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Emory Neurobehavioral Center, Atlanta</wicri:regionArea><wicri:noRegion>Atlanta</wicri:noRegion></affiliation></author><author><name sortKey="Zanko, A" sort="Zanko, A" uniqKey="Zanko A" first="A." last="Zanko">A. Zanko</name><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>UCSF Division of Medical Genetics, San Francisco</wicri:cityArea></affiliation></author><author><name sortKey="Nance, M" sort="Nance, M" uniqKey="Nance M" first="M." last="Nance">M. Nance</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Hennepin County Medical Center, Department of Neurology, Minneapolis</wicri:cityArea></affiliation></author><author><name sortKey="Abramson, R" sort="Abramson, R" uniqKey="Abramson R" first="R." last="Abramson">R. Abramson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>Department of Neuropsychiatry & Behavior, WMS Hall Psychiatric Institute, Columbia</wicri:cityArea></affiliation></author><author><name sortKey="Suchowersky, O" sort="Suchowersky, O" uniqKey="Suchowersky O" first="O." last="Suchowersky">O. Suchowersky</name><affiliation><wicri:noCountry code="subField">Alberta</wicri:noCountry></affiliation></author><author><name sortKey="Paulsen, J" sort="Paulsen, J" uniqKey="Paulsen J" first="J." last="Paulsen">J. Paulsen</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>University of Iowa, Department of Psychiatry, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Harrison, M" sort="Harrison, M" uniqKey="Harrison M" first="M." last="Harrison">M. Harrison</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>University of Virginia, Department of Neurology, Charlottesville</wicri:cityArea></affiliation></author><author><name sortKey="Yang, Q" sort="Yang, Q" uniqKey="Yang Q" first="Q." last="Yang">Q. Yang</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Cupples, L A" sort="Cupples, L A" uniqKey="Cupples L" first="L. A." last="Cupples">L. A. Cupples</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Gusella, J F" sort="Gusella, J F" uniqKey="Gusella J" first="J. F." last="Gusella">J. F. Gusella</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Department of Genetics, Harvard Medical School, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Macdonald, M E" sort="Macdonald, M E" uniqKey="Macdonald M" first="M. E." last="Macdonald">M. E. Macdonald</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Myers, R H" sort="Myers, R H" uniqKey="Myers R" first="R. H." last="Myers">R. H. Myers</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Department of Neurology, Boston University School of Medicine, Boston</wicri:cityArea></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Correspondence address: Department of Neurology, Boston University School of Medicine, 715 Albany St., Boston</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">American Journal of Medical Genetics Part A</title><title level="j" type="alt">AMERICAN JOURNAL OF MEDICAL GENETICS</title><idno type="ISSN">1552-4825</idno><idno type="eISSN">1552-4833</idno><imprint><biblScope unit="vol">119A</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="279">279</biblScope><biblScope unit="page" to="282">282</biblScope><biblScope unit="page-count">4</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2003-06-15">2003-06-15</date></imprint><idno type="ISSN">1552-4825</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4825</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allele</term><term>Boston university school</term><term>British columbia</term><term>Cellular toxicity</term><term>Chromosome</term><term>Cohort</term><term>Conneally</term><term>England huntington disease center</term><term>Expandeda unexpanded</term><term>Genet</term><term>Glur6 gene</term><term>Grant sponsor</term><term>Highest tertile</term><term>Huntingtin</term><term>Huntington</term><term>Huntington disease</term><term>Interaction term</term><term>Medical genetics</term><term>Mutant huntingtin</term><term>Myers</term><term>Neurodegenerative disorder</term><term>Neurology</term><term>Normal chromosome</term><term>Proc natl acad</term><term>Size unexpanded</term><term>Tertile</term><term>Third tertile</term><term>Trinucleotide</term><term>Unexpanded</term><term>Unique families</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Allele</term><term>Boston university school</term><term>British columbia</term><term>Cellular toxicity</term><term>Chromosome</term><term>Cohort</term><term>Conneally</term><term>England huntington disease center</term><term>Expandeda unexpanded</term><term>Genet</term><term>Glur6 gene</term><term>Grant sponsor</term><term>Highest tertile</term><term>Huntingtin</term><term>Huntington</term><term>Huntington disease</term><term>Interaction term</term><term>Medical genetics</term><term>Mutant huntingtin</term><term>Myers</term><term>Neurodegenerative disorder</term><term>Neurology</term><term>Normal chromosome</term><term>Proc natl acad</term><term>Size unexpanded</term><term>Tertile</term><term>Third tertile</term><term>Trinucleotide</term><term>Unexpanded</term><term>Unique families</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Neurologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD‐MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47–83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats. © 2003 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Espagne</li><li>France</li><li>Géorgie (pays)</li><li>Italie</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Californie</li><li>Caroline du Sud</li><li>Communauté de Madrid</li><li>Iowa</li><li>Latium</li><li>Maryland</li><li>Massachusetts</li><li>Minnesota</li><li>Nouvelle-Galles du Sud</li><li>Virginie</li><li>Île-de-France</li></region><settlement><li>Madrid</li><li>Paris</li><li>Rome</li><li>Sydney</li></settlement><orgName><li>Université de Sydney</li></orgName></list><tree><noCountry><name sortKey="Almqvist, E W" sort="Almqvist, E W" uniqKey="Almqvist E" first="E. W." last="Almqvist">E. W. Almqvist</name><name sortKey="Brinkman, R" sort="Brinkman, R" uniqKey="Brinkman R" first="R." last="Brinkman">R. Brinkman</name><name sortKey="Hayden, M" sort="Hayden, M" uniqKey="Hayden M" first="M." last="Hayden">M. Hayden</name><name sortKey="Suchowersky, O" sort="Suchowersky, O" uniqKey="Suchowersky O" first="O." last="Suchowersky">O. Suchowersky</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Djousse, L" sort="Djousse, L" uniqKey="Djousse L" first="L." last="Djoussé">L. Djoussé</name></region><name sortKey="Abramson, R" sort="Abramson, R" uniqKey="Abramson R" first="R." last="Abramson">R. Abramson</name><name sortKey="Cupples, L A" sort="Cupples, L A" uniqKey="Cupples L" first="L. A." last="Cupples">L. A. Cupples</name><name sortKey="Gusella, J F" sort="Gusella, J F" uniqKey="Gusella J" first="J. F." last="Gusella">J. F. Gusella</name><name sortKey="Harrison, M" sort="Harrison, M" uniqKey="Harrison M" first="M." last="Harrison">M. Harrison</name><name sortKey="Knowlton, B" sort="Knowlton, B" uniqKey="Knowlton B" first="B." last="Knowlton">B. Knowlton</name><name sortKey="Macdonald, M E" sort="Macdonald, M E" uniqKey="Macdonald M" first="M. E." last="Macdonald">M. E. Macdonald</name><name sortKey="Margolis, R" sort="Margolis, R" uniqKey="Margolis R" first="R." last="Margolis">R. Margolis</name><name sortKey="Myers, R H" sort="Myers, R H" uniqKey="Myers R" first="R. H." last="Myers">R. H. Myers</name><name sortKey="Myers, R H" sort="Myers, R H" uniqKey="Myers R" first="R. H." last="Myers">R. H. Myers</name><name sortKey="Myers, R H" sort="Myers, R H" uniqKey="Myers R" first="R. H." last="Myers">R. H. Myers</name><name sortKey="Nance, M" sort="Nance, M" uniqKey="Nance M" first="M." last="Nance">M. Nance</name><name sortKey="Paulsen, J" sort="Paulsen, J" uniqKey="Paulsen J" first="J." last="Paulsen">J. Paulsen</name><name sortKey="Rosenblatt, A" sort="Rosenblatt, A" uniqKey="Rosenblatt A" first="A." last="Rosenblatt">A. Rosenblatt</name><name sortKey="Ross, C" sort="Ross, C" uniqKey="Ross C" first="C." last="Ross">C. Ross</name><name sortKey="Yang, Q" sort="Yang, Q" uniqKey="Yang Q" first="Q." last="Yang">Q. Yang</name><name sortKey="Zanko, A" sort="Zanko, A" uniqKey="Zanko A" first="A." last="Zanko">A. Zanko</name></country><country name="France"><region name="Île-de-France"><name sortKey="Durr, A" sort="Durr, A" uniqKey="Durr A" first="A." last="Durr">A. Durr</name></region><name sortKey="Dode, C" sort="Dode, C" uniqKey="Dode C" first="C." last="Dode">C. Dode</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Morrison, P J" sort="Morrison, P J" uniqKey="Morrison P" first="P. J." last="Morrison">P. J. Morrison</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Novelletto, A" sort="Novelletto, A" uniqKey="Novelletto A" first="A." last="Novelletto">A. Novelletto</name></noRegion><name sortKey="Frontali, M" sort="Frontali, M" uniqKey="Frontali M" first="M." last="Frontali">M. Frontali</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Trent, R J A" sort="Trent, R J A" uniqKey="Trent R" first="R. J. A." last="Trent">R. J. A. Trent</name></region><name sortKey="Mccusker, E" sort="Mccusker, E" uniqKey="Mccusker E" first="E." last="Mccusker">E. Mccusker</name></country><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="G Mez Ortosa, E" sort="G Mez Ortosa, E" uniqKey="G Mez Ortosa E" first="E." last="G Mez-Tortosa">E. G Mez-Tortosa</name></region><name sortKey="Mayo, D" sort="Mayo, D" uniqKey="Mayo D" first="D." last="Mayo">D. Mayo</name></country><country name="Géorgie (pays)"><noRegion><name sortKey="Jones, R" sort="Jones, R" uniqKey="Jones R" first="R." last="Jones">R. Jones</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 00AF18 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 00AF18 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:4338708DF83B0821C39E2E5102457BA83D77375B
|texte= Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease
}}
| This area was generated with Dilib version V0.6.33. |  |