Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families
Identifieur interne : 000277 ( Main/Corpus ); précédent : 000276; suivant : 000278Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families
Auteurs : Nathan Pankratz ; William C. Nichols ; Sean K. Uniacke ; Cheryl Halter ; Jill Murrell ; Alice Rudolph ; Clifford W. Shults ; P. Michael Conneally ; Tatiana ForoudSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2003-10-15.
Abstract
Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the parkin gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the parkin gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD=4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD=2.4) and X (LOD=3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.
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DOI: 10.1093/hmg/ddg270
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Shults</name><affiliation><mods:affiliation>Department of Neurosciences, University of California, La Jolla, CA and the VA San Diego Healthcare System, San Diego, CA, USA</mods:affiliation></affiliation></author><author><name sortKey="Conneally, P Michael" sort="Conneally, P Michael" uniqKey="Conneally P" first="P. Michael" last="Conneally">P. Michael Conneally</name><affiliation><mods:affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</mods:affiliation></affiliation></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><affiliation><mods:affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. 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We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the parkin gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the parkin gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD=4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD=2.4) and X (LOD=3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Nathan Pankratz</name><affiliations><json:string>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</json:string></affiliations></json:item><json:item><name>William C. Nichols</name><affiliations><json:string>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</json:string></affiliations></json:item><json:item><name>Sean K. Uniacke</name><affiliations><json:string>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</json:string></affiliations></json:item><json:item><name>Cheryl Halter</name><affiliations><json:string>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</json:string></affiliations></json:item><json:item><name>Jill Murrell</name><affiliations><json:string>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</json:string></affiliations></json:item><json:item><name>Alice Rudolph</name><affiliations><json:string>Department of Neurology, University of Rochester, Rochester, NY, USA and</json:string></affiliations></json:item><json:item><name>Clifford W. Shults</name><affiliations><json:string>Department of Neurosciences, University of California, La Jolla, CA and the VA San Diego Healthcare System, San Diego, CA, USA</json:string></affiliations></json:item><json:item><name>P. Michael Conneally</name><affiliations><json:string>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</json:string></affiliations></json:item><json:item><name>Tatiana Foroud</name><affiliations><json:string>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Article</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the parkin gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the parkin gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD=4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD=2.4) and X (LOD=3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.</abstract><qualityIndicators><score>8</score><pdfVersion>1.2</pdfVersion><pdfPageSize>609.675 x 795.005 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>1</keywordCount><abstractCharCount>1566</abstractCharCount><pdfWordCount>7158</pdfWordCount><pdfCharCount>44461</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>251</abstractWordCount></qualityIndicators><title>Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families</title><corporate><json:item><name>the Parkinson Study Group</name></json:item></corporate><genre><json:string>research-article</json:string></genre><host><volume>12</volume><pages><last>2608</last><first>2599</first></pages><issn><json:string>0964-6906</json:string></issn><issue>20</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2083</json:string></eissn><title>Human Molecular Genetics</title></host><categories><wos><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string><json:string>GENETICS & HEREDITY</json:string></wos></categories><publicationDate>2003</publicationDate><copyrightDate>2003</copyrightDate><doi><json:string>10.1093/hmg/ddg270</json:string></doi><id>8424CA86B345DA165E99E467B3A47696CD4D7E04</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2003</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families</title><author><orgName>the Parkinson Study Group</orgName></author><author><persName><forename type="first">Nathan</forename><surname>Pankratz</surname></persName><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation></author><author><persName><forename type="first">William C.</forename><surname>Nichols</surname></persName><affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</affiliation></author><author><persName><forename type="first">Sean K.</forename><surname>Uniacke</surname></persName><affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</affiliation></author><author><persName><forename type="first">Cheryl</forename><surname>Halter</surname></persName><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation></author><author><persName><forename type="first">Jill</forename><surname>Murrell</surname></persName><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation></author><author><persName><forename type="first">Alice</forename><surname>Rudolph</surname></persName><affiliation>Department of Neurology, University of Rochester, Rochester, NY, USA and</affiliation></author><author><persName><forename type="first">Clifford W.</forename><surname>Shults</surname></persName><affiliation>Department of Neurosciences, University of California, La Jolla, CA and the VA San Diego Healthcare System, San Diego, CA, USA</affiliation></author><author><persName><forename type="first">P. Michael</forename><surname>Conneally</surname></persName><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation></author><author><persName><forename type="first">Tatiana</forename><surname>Foroud</surname></persName><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation></author></analytic><monogr><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. Genet.</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-10-15"></date><biblScope unit="volume">12</biblScope><biblScope unit="issue">20</biblScope><biblScope unit="page" from="2599">2599</biblScope><biblScope unit="page" to="2608">2608</biblScope></imprint></monogr><idno type="istex">8424CA86B345DA165E99E467B3A47696CD4D7E04</idno><idno type="DOI">10.1093/hmg/ddg270</idno><idno type="local">ddg270</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2003</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the parkin gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the parkin gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD=4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD=2.4) and X (LOD=3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.</p></abstract></profileDesc><revisionDesc><change when="2003-10-15">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-15">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">hmg</journal-id><journal-id journal-id-type="nlm-ta">Hum Mol Genet</journal-id><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><abbrev-journal-title abbrev-type="publisher">Hum. Mol. Genet.</abbrev-journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="other">ddg270</article-id><article-id pub-id-type="doi">10.1093/hmg/ddg270</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Pankratz</surname><given-names>Nathan</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Nichols</surname><given-names>William C.</given-names></name><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Uniacke</surname><given-names>Sean K.</given-names></name><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Halter</surname><given-names>Cheryl</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Murrell</surname><given-names>Jill</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rudolph</surname><given-names>Alice</given-names></name><xref rid="AF3">3</xref></contrib><contrib contrib-type="author"><name><surname>Shults</surname><given-names>Clifford W.</given-names></name><xref rid="AF4">4</xref></contrib><contrib contrib-type="author"><name><surname>Conneally</surname><given-names>P. Michael</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Foroud</surname><given-names>Tatiana</given-names></name><xref rid="AF1">1</xref><xref rid="FN1">*</xref></contrib><contrib contrib-type="author"><collab collab-type="author">the Parkinson Study Group</collab></contrib><aff id="AF1"><sup>1</sup>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</aff><aff id="AF2"><sup>2</sup>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</aff><aff id="AF3"><sup>3</sup>Department of Neurology, University of Rochester, Rochester, NY, USA and</aff><aff id="AF4"><sup>4</sup>Department of Neurosciences, University of California, La Jolla, CA and the VA San Diego Healthcare System, San Diego, CA, USA</aff></contrib-group><pub-date pub-type="ppub"><day>15</day><month>10</month><year>2003</year></pub-date><volume>12</volume><issue>20</issue><fpage>2599</fpage><lpage>2608</lpage><history><date date-type="accepted"><day>1</day><month>08</month><year>2003</year></date><date date-type="received"><day>30</day><month>05</month><year>2003</year></date><date date-type="rev-recd"><day>29</day><month>07</month><year>2003</year></date></history><permissions><copyright-year>2003</copyright-year></permissions><abstract xml:lang="en"><p>Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the <italic>parkin</italic> gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the <italic>parkin</italic> gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the <italic>parkin</italic> gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD=4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD=2.4) and X (LOD=3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.</p></abstract><custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name><meta-value>2599</meta-value></custom-meta><custom-meta><meta-name>hwp-legacy-dochead</meta-name><meta-value>Article</meta-value></custom-meta></custom-meta-wrap></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families</title></titleInfo><name type="corporate"><namePart>the Parkinson Study Group</namePart></name><name type="personal"><namePart type="given">Nathan</namePart><namePart type="family">Pankratz</namePart><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William C.</namePart><namePart type="family">Nichols</namePart><affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sean K.</namePart><namePart type="family">Uniacke</namePart><affiliation>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cheryl</namePart><namePart type="family">Halter</namePart><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jill</namePart><namePart type="family">Murrell</namePart><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alice</namePart><namePart type="family">Rudolph</namePart><affiliation>Department of Neurology, University of Rochester, Rochester, NY, USA and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Clifford W.</namePart><namePart type="family">Shults</namePart><affiliation>Department of Neurosciences, University of California, La Jolla, CA and the VA San Diego Healthcare System, San Diego, CA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P. Michael</namePart><namePart type="family">Conneally</namePart><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tatiana</namePart><namePart type="family">Foroud</namePart><affiliation>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2003-10-15</dateIssued><copyrightDate encoding="w3cdtf">2003</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the parkin gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the parkin gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD=4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD=2.4) and X (LOD=3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mol. Genet.</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><identifier type="PublisherID-nlm-ta">Hum Mol Genet</identifier><part><date>2003</date><detail type="volume"><caption>vol.</caption><number>12</number></detail><detail type="issue"><caption>no.</caption><number>20</number></detail><extent unit="pages"><start>2599</start><end>2608</end></extent></part></relatedItem><identifier type="istex">8424CA86B345DA165E99E467B3A47696CD4D7E04</identifier><identifier type="DOI">10.1093/hmg/ddg270</identifier><identifier type="local">ddg270</identifier><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/8424CA86B345DA165E99E467B3A47696CD4D7E04/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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