Genomewide SNP assay reveals mutations underlying Parkinson disease
Identifieur interne : 002514 ( Main/Corpus ); précédent : 002513; suivant : 002515Genomewide SNP assay reveals mutations underlying Parkinson disease
Auteurs : Javier Simon-Sanchez ; Sonja Scholz ; Maria Del Mar Matarin ; Hon-Chung Fung ; Dena Hernandez ; J Raphael Gibbs ; Angela Britton ; John Hardy ; Andrew SingletonSource :
- Human Mutation [ 1059-7794 ] ; 2008-02.
English descriptors
- KwdEn :
- CNV, PARK2, Parkinson, SNP, deletion, duplication, genomewide.
Abstract
Technologies that allow genotyping of more than 100,000 polymorphisms in a single assay enable the execution of genomewide SNP (GWSNP) association studies to identify common genetic variants underlying traits. Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the PARK2 locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within PARK2 were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease. Hum Mutat 29(2), 315–322, 2008. Published 2007 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/humu.20626
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ISTEX:9462D0CC5554EE859366158DF54E7AE2E171CD30Le document en format XML
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Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the PARK2 locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within PARK2 were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease. Hum Mutat 29(2), 315–322, 2008. Published 2007 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Javier Simon‐Sanchez</name><affiliations><json:string>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</json:string><json:string>Unidad de Genética Molecular, Departamento de Genómica y Proteómica, Instituto de Biomedicina de Valencia‐Consejo Superior de Investigaciones Sientificas (CSIC), Valencia, Spain</json:string></affiliations></json:item><json:item><name>Sonja Scholz</name><affiliations><json:string>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</json:string><json:string>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Maria del Mar Matarin</name><affiliations><json:string>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Hon‐Chung Fung</name><affiliations><json:string>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</json:string><json:string>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Dena Hernandez</name><affiliations><json:string>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>J Raphael Gibbs</name><affiliations><json:string>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</json:string><json:string>Computational Biology Core, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Angela Britton</name><affiliations><json:string>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>John Hardy</name><affiliations><json:string>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Andrew Singleton</name><affiliations><json:string>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>PARK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genomewide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>duplication</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>deletion</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNP</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CNV</value></json:item></subject><articleId><json:string>HUMU20626</json:string></articleId><language><json:string>eng</json:string></language><abstract>Technologies that allow genotyping of more than 100,000 polymorphisms in a single assay enable the execution of genomewide SNP (GWSNP) association studies to identify common genetic variants underlying traits. Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the PARK2 locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within PARK2 were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease. Hum Mutat 29(2), 315–322, 2008. 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work.</affiliation><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><affiliation>Unidad de Genética Molecular, Departamento de Genómica y Proteómica, Instituto de Biomedicina de Valencia‐Consejo Superior de Investigaciones Sientificas (CSIC), Valencia, Spain</affiliation></author><author><persName><forename type="first">Sonja</forename><surname>Scholz</surname></persName><note type="biography">Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</note><affiliation>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</affiliation><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><affiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</affiliation></author><author><persName><forename type="first">Maria</forename><surname>del Mar Matarin</surname></persName><note type="biography">Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</note><affiliation>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</affiliation><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation></author><author><persName><forename type="first">Hon‐Chung</forename><surname>Fung</surname></persName><note type="biography">Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</note><affiliation>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</affiliation><affiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative 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Published in 2007 by Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2007-06-04"></event><event type="manuscriptAccepted" date="2007-07-11"></event><event type="publishedOnlineEarlyUnpaginated" date="2007-11-09"></event><event type="firstOnline" date="2007-11-09"></event><event type="publishedOnlineFinalForm" date="2008-01-14"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-27"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-24"></event></eventGroup><numberingGroup><numbering type="pageFirst">315</numbering><numbering type="pageLast">322</numbering></numberingGroup><correspondenceTo>Molecular Genetics Unit, National Institutes of Health, Bethesda, MD 20892</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:HUMU.HUMU20626.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="19"></count></countGroup><titleGroup><title type="main" xml:lang="en">Genomewide SNP assay reveals mutations underlying Parkinson disease<link href="#fn1"></link><link href="#fn2"></link></title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2" noteRef="#fn3"><personName><givenNames>Javier</givenNames><familyName>Simon‐Sanchez</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af3" noteRef="#fn4"><personName><givenNames>Sonja</givenNames><familyName>Scholz</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1" noteRef="#fn5"><personName><givenNames>Maria</givenNames><familyName>del Mar Matarin</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3 #af4" noteRef="#fn6"><personName><givenNames>Hon‐Chung</givenNames><familyName>Fung</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Dena</givenNames><familyName>Hernandez</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af3 #af5"><personName><givenNames>J Raphael</givenNames><familyName>Gibbs</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Angela</givenNames><familyName>Britton</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af3"><personName><givenNames>John</givenNames><familyName>Hardy</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Andrew</givenNames><familyName>Singleton</familyName></personName><contactDetails><email>singleta@mail.nih.gov</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="ES" type="organization"><unparsedAffiliation>Unidad de Genética Molecular, Departamento de Genómica y Proteómica, Instituto de Biomedicina de Valencia‐Consejo Superior de Investigaciones Sientificas (CSIC), Valencia, Spain</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="GB" type="organization"><unparsedAffiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Computational Biology Core, National Institutes of Health, Bethesda, Maryland</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">PARK2</keyword><keyword xml:id="kwd2">genomewide</keyword><keyword xml:id="kwd3">Parkinson</keyword><keyword xml:id="kwd4">duplication</keyword><keyword xml:id="kwd5">deletion</keyword><keyword xml:id="kwd6">SNP</keyword><keyword xml:id="kwd7">CNV</keyword></keywordGroup><supportingInformation><p> The Supplementary material refered to in this article can be viewed at <url href="http://www.interscience.wiley.com/jpages/1059-7794/suppmat"> http://www.interscience.wiley.com/jpages/1059‐7794/suppmat </url> . </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:10597794:media:humu20626:humu20626-Supplementary_Table_S1"></mediaResource><caption>Supporting Information file humu20626‐Supplementary_Table_S1.xls</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:10597794:media:humu20626:humu20626-Supplementary_Table_S2"></mediaResource><caption>Supporting Information file humu20626‐Supplementary_Table_S2.xls</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Technologies that allow genotyping of more than 100,000 polymorphisms in a single assay enable the execution of genomewide SNP (GWSNP) association studies to identify common genetic variants underlying traits. Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the <i>PARK2</i> locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within <i>PARK2</i> were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease. Hum Mutat 29(2), 315–322, 2008. Published 2007 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Communicated by Ann‐Christine Syvänen</p></note><note xml:id="fn2"><p>This article is a US Government work and, as such, is in the public domain in the United States of America.</p></note><note xml:id="fn3"><p>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</p></note><note xml:id="fn4"><p>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</p></note><note xml:id="fn5"><p>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</p></note><note xml:id="fn6"><p>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Genomewide SNP assay reveals mutations underlying Parkinson disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Genomewide SNP assay reveals mutations underlying Parkinson disease</title></titleInfo><name type="personal"><namePart type="given">Javier</namePart><namePart type="family">Simon‐Sanchez</namePart><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><affiliation>Unidad de Genética Molecular, Departamento de Genómica y Proteómica, Instituto de Biomedicina de Valencia‐Consejo Superior de Investigaciones Sientificas (CSIC), Valencia, Spain</affiliation><description>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sonja</namePart><namePart type="family">Scholz</namePart><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><affiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</affiliation><description>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maria</namePart><namePart type="family">del Mar Matarin</namePart><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><description>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hon‐Chung</namePart><namePart type="family">Fung</namePart><affiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</affiliation><affiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland</affiliation><description>Javier Simon‐Sanchez, Sonja Scholz, Maria del Mar Matarin and Hon‐Chung Fung contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dena</namePart><namePart type="family">Hernandez</namePart><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J Raphael</namePart><namePart type="family">Gibbs</namePart><affiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</affiliation><affiliation>Computational Biology Core, National Institutes of Health, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Angela</namePart><namePart type="family">Britton</namePart><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Hardy</namePart><affiliation>Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andrew</namePart><namePart type="family">Singleton</namePart><affiliation>Molecular Genetics Unit, National Institutes of Health, Bethesda, Maryland</affiliation><description>Correspondence: Molecular Genetics Unit, National Institutes of Health, Bethesda, MD 20892</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2008-02</dateIssued><dateCaptured encoding="w3cdtf">2007-06-04</dateCaptured><dateValid encoding="w3cdtf">2007-07-11</dateValid><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="tables">3</extent><extent unit="references">19</extent></physicalDescription><abstract lang="en">Technologies that allow genotyping of more than 100,000 polymorphisms in a single assay enable the execution of genomewide SNP (GWSNP) association studies to identify common genetic variants underlying traits. Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the PARK2 locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within PARK2 were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease. Hum Mutat 29(2), 315–322, 2008. Published 2007 Wiley‐Liss, Inc.</abstract><note type="content">*Communicated by Ann‐Christine Syvänen</note><note type="content">*This article is a US Government work and, as such, is in the public domain in the United States of America.</note><subject lang="en"><genre>Keywords</genre><topic>PARK2</topic><topic>genomewide</topic><topic>Parkinson</topic><topic>duplication</topic><topic>deletion</topic><topic>SNP</topic><topic>CNV</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mutat.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> The Supplementary material refered to in this article can be viewed at http://www.interscience.wiley.com/jpages/1059‐7794/suppmat .Supporting Info Item: Supporting Information file humu20626‐Supplementary_Table_S1.xls - Supporting Information file humu20626‐Supplementary_Table_S2.xls - </note><subject><genre>article category</genre><topic>Methods</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>29</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>315</start><end>322</end><total>8</total></extent></part></relatedItem><identifier type="istex">9462D0CC5554EE859366158DF54E7AE2E171CD30</identifier><identifier type="DOI">10.1002/humu.20626</identifier><identifier type="ArticleID">HUMU20626</identifier><accessCondition type="use and reproduction" contentType="copyright">This article is a U.S. Government work and is in the public domain in the U.S.A. Published in 2007 by Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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