Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra
Identifieur interne : 003906 ( Main/Curation ); précédent : 003905; suivant : 003907Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra
Auteurs : Maher A. Noureddine [États-Unis] ; Yi-Ju Li [États-Unis] ; Joelle M. Van Der Walt [États-Unis] ; Robert Walters [États-Unis] ; Rita M. Jewett [États-Unis] ; Hong Xu [États-Unis] ; Tianyuan Wang [États-Unis] ; Jeffrey W. Walter [États-Unis] ; Burton L. Scott [États-Unis] ; Christine Hulette [États-Unis] ; Don Schmechel [États-Unis] ; Judith E. Stenger [États-Unis] ; Fred Dietrich [États-Unis] ; Jeffery M. Vance [États-Unis] ; Michael A. Hauser [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2005-10.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Convergence, DNA, Mitochondrial (genetics), Expressed Sequence Tags (metabolism), Female, Gene Expression, Gene Library, Genetic Linkage (genetics), Genetic Predisposition to Disease, Genetic Techniques, Genetic linkage, Humans, Locus niger, Male, Nervous system diseases, Oligonucleotide Array Sequence Analysis (methods), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology), Parkinson disease, Parkinson's disease, Proteomics (methods), RNA, Messenger (genetics), RNA, Messenger (metabolism), Risk Factors, Substantia Nigra (metabolism), Substantia Nigra (pathology), genomic convergence, linkage.
- MESH :
- chemical , genetics : DNA, Mitochondrial, RNA, Messenger.
- genetics : Genetic Linkage, Parkinson Disease.
- metabolism : Expressed Sequence Tags, Parkinson Disease, RNA, Messenger, Substantia Nigra.
- methods : Oligonucleotide Array Sequence Analysis, Proteomics.
- pathology : Parkinson Disease, Substantia Nigra.
- Aged, Aged, 80 and over, Female, Gene Expression, Gene Library, Genetic Predisposition to Disease, Genetic Techniques, Humans, Male, Risk Factors.
Abstract
Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671–677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239–2242] to analyze substantia nigra tissue from three PD patients and two age‐matched controls. We find 933 differentially expressed genes (P < 0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5‐fold higher in PD patients versus controls, without an increase in the corresponding nuclear‐encoded mitochondrial components, suggesting an increase in mtDNA genomes in PD or a disjunction with nuclear expression. The next step in the genomic convergence process will be to screen these 50 high‐quality candidate genes for association with PD risk susceptibility and genetic effects on AAO. © 2005 Movement Disorder Society
Url:
DOI: 10.1002/mds.20573
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<term>Aged, 80 and over</term>
<term>Convergence</term>
<term>DNA, Mitochondrial (genetics)</term>
<term>Expressed Sequence Tags (metabolism)</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Gene Library</term>
<term>Genetic Linkage (genetics)</term>
<term>Genetic Predisposition to Disease</term>
<term>Genetic Techniques</term>
<term>Genetic linkage</term>
<term>Humans</term>
<term>Locus niger</term>
<term>Male</term>
<term>Nervous system diseases</term>
<term>Oligonucleotide Array Sequence Analysis (methods)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinson Disease (pathology)</term>
<term>Parkinson disease</term>
<term>Parkinson's disease</term>
<term>Proteomics (methods)</term>
<term>RNA, Messenger (genetics)</term>
<term>RNA, Messenger (metabolism)</term>
<term>Risk Factors</term>
<term>Substantia Nigra (metabolism)</term>
<term>Substantia Nigra (pathology)</term>
<term>genomic convergence</term>
<term>linkage</term>
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<term>Aged, 80 and over</term>
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<term>Gene Library</term>
<term>Genetic Predisposition to Disease</term>
<term>Genetic Techniques</term>
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<front><div type="abstract" xml:lang="fr">Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671–677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239–2242] to analyze substantia nigra tissue from three PD patients and two age‐matched controls. We find 933 differentially expressed genes (P < 0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5‐fold higher in PD patients versus controls, without an increase in the corresponding nuclear‐encoded mitochondrial components, suggesting an increase in mtDNA genomes in PD or a disjunction with nuclear expression. The next step in the genomic convergence process will be to screen these 50 high‐quality candidate genes for association with PD risk susceptibility and genetic effects on AAO. © 2005 Movement Disorder Society</div>
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<double idat="0885-3185:2005:Noureddine M:genomic:convergence:to"><INIST><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Genomic convergence to identify candidate genes for parkinson disease : SAGE analysis of the substantia Nigra</title>
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<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name>
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<author><name sortKey="Van Der Walt, Joelle M" sort="Van Der Walt, Joelle M" uniqKey="Van Der Walt J" first="Joelle M." last="Van Der Walt">Joelle M. Van Der Walt</name>
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<author><name sortKey="Walters, Robert" sort="Walters, Robert" uniqKey="Walters R" first="Robert" last="Walters">Robert Walters</name>
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<author><name sortKey="Jewett, Rita M" sort="Jewett, Rita M" uniqKey="Jewett R" first="Rita M." last="Jewett">Rita M. Jewett</name>
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<author><name sortKey="Hong Xu" sort="Hong Xu" uniqKey="Hong Xu" last="Hong Xu">HONG XU</name>
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<author><name sortKey="Tianyuan Wang" sort="Tianyuan Wang" uniqKey="Tianyuan Wang" last="Tianyuan Wang">TIANYUAN WANG</name>
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<author><name sortKey="Waiter, Jeffrey W" sort="Waiter, Jeffrey W" uniqKey="Waiter J" first="Jeffrey W." last="Waiter">Jeffrey W. Waiter</name>
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<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton L." last="Scott">Burton L. Scott</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Genomic convergence to identify candidate genes for parkinson disease : SAGE analysis of the substantia Nigra</title>
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<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
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<s3>USA</s3>
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<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
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<author><name sortKey="Van Der Walt, Joelle M" sort="Van Der Walt, Joelle M" uniqKey="Van Der Walt J" first="Joelle M." last="Van Der Walt">Joelle M. Van Der Walt</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
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<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
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<author><name sortKey="Walters, Robert" sort="Walters, Robert" uniqKey="Walters R" first="Robert" last="Walters">Robert Walters</name>
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<author><name sortKey="Jewett, Rita M" sort="Jewett, Rita M" uniqKey="Jewett R" first="Rita M." last="Jewett">Rita M. Jewett</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
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<placeName><region type="state">Caroline du Nord</region>
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</author>
<author><name sortKey="Hong Xu" sort="Hong Xu" uniqKey="Hong Xu" last="Hong Xu">HONG XU</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
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</affiliation>
</author>
<author><name sortKey="Tianyuan Wang" sort="Tianyuan Wang" uniqKey="Tianyuan Wang" last="Tianyuan Wang">TIANYUAN WANG</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
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<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<author><name sortKey="Waiter, Jeffrey W" sort="Waiter, Jeffrey W" uniqKey="Waiter J" first="Jeffrey W." last="Waiter">Jeffrey W. Waiter</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton L." last="Scott">Burton L. Scott</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<placeName><region type="state">Caroline du Nord</region>
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<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Medicine, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
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<author><name sortKey="Hulette, Christine" sort="Hulette, Christine" uniqKey="Hulette C" first="Christine" last="Hulette">Christine Hulette</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<placeName><region type="state">Caroline du Nord</region>
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<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Pathology, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
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<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
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</author>
<author><name sortKey="Schmechel, Don" sort="Schmechel, Don" uniqKey="Schmechel D" first="Don" last="Schmechel">Don Schmechel</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Medicine, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<sZ>11 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
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<author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith E." last="Stenger">Judith E. Stenger</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
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</author>
<author><name sortKey="Dietrich, Fred" sort="Dietrich, Fred" uniqKey="Dietrich F" first="Fred" last="Dietrich">Fred Dietrich</name>
<affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Molecular Genetics and Microbiology, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Center for Human Genetics, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Duke Udall Center of Excellence, Duke University</s1>
<s2>Durham, North Carolina</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
<idno type="ISSN">0885-3185</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
<idno type="ISSN">0885-3185</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Convergence</term>
<term>Genetic linkage</term>
<term>Locus niger</term>
<term>Nervous system diseases</term>
<term>Parkinson disease</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term>
<term>Parkinson maladie</term>
<term>Convergence</term>
<term>Locus niger</term>
<term>Liaison génétique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671-677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239-2242] to analyze substantia nigra tissue from three PD patients and two age-matched controls. We find 933 differentially expressed genes (P < 0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5-fold higher in PD patients versus controls, without an increase in the corresponding nuclear-encoded mitochondrial components, suggesting an increase in intDNA genomes in PD or a disjunction with nuclear expression The next step in the genomic convergence process will be to screen these 50 high-quality candidate genes for association with PD risk susceptibility and genetic effects on AAO.</div>
</front>
</TEI>
</INIST>
<ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra</title>
<author><name sortKey="Noureddine, Maher A" sort="Noureddine, Maher A" uniqKey="Noureddine M" first="Maher A." last="Noureddine">Maher A. Noureddine</name>
</author>
<author><name sortKey="Li, Yi U" sort="Li, Yi U" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name>
</author>
<author><name sortKey="Van Der Walt, Joelle M" sort="Van Der Walt, Joelle M" uniqKey="Van Der Walt J" first="Joelle M." last="Van Der Walt">Joelle M. Van Der Walt</name>
</author>
<author><name sortKey="Walters, Robert" sort="Walters, Robert" uniqKey="Walters R" first="Robert" last="Walters">Robert Walters</name>
</author>
<author><name sortKey="Jewett, Rita M" sort="Jewett, Rita M" uniqKey="Jewett R" first="Rita M." last="Jewett">Rita M. Jewett</name>
</author>
<author><name sortKey="Xu, Hong" sort="Xu, Hong" uniqKey="Xu H" first="Hong" last="Xu">Hong Xu</name>
</author>
<author><name sortKey="Wang, Tianyuan" sort="Wang, Tianyuan" uniqKey="Wang T" first="Tianyuan" last="Wang">Tianyuan Wang</name>
</author>
<author><name sortKey="Walter, Jeffrey W" sort="Walter, Jeffrey W" uniqKey="Walter J" first="Jeffrey W." last="Walter">Jeffrey W. Walter</name>
</author>
<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton L." last="Scott">Burton L. Scott</name>
</author>
<author><name sortKey="Hulette, Christine" sort="Hulette, Christine" uniqKey="Hulette C" first="Christine" last="Hulette">Christine Hulette</name>
</author>
<author><name sortKey="Schmechel, Don" sort="Schmechel, Don" uniqKey="Schmechel D" first="Don" last="Schmechel">Don Schmechel</name>
</author>
<author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith E." last="Stenger">Judith E. Stenger</name>
</author>
<author><name sortKey="Dietrich, Fred" sort="Dietrich, Fred" uniqKey="Dietrich F" first="Fred" last="Dietrich">Fred Dietrich</name>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name>
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<author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name>
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<placeName><region type="state">Caroline du Nord</region>
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<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
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</author>
<author><name sortKey="Li, Yi U" sort="Li, Yi U" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Van Der Walt, Joelle M" sort="Van Der Walt, Joelle M" uniqKey="Van Der Walt J" first="Joelle M." last="Van Der Walt">Joelle M. Van Der Walt</name>
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<author><name sortKey="Walters, Robert" sort="Walters, Robert" uniqKey="Walters R" first="Robert" last="Walters">Robert Walters</name>
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<author><name sortKey="Jewett, Rita M" sort="Jewett, Rita M" uniqKey="Jewett R" first="Rita M." last="Jewett">Rita M. Jewett</name>
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<author><name sortKey="Xu, Hong" sort="Xu, Hong" uniqKey="Xu H" first="Hong" last="Xu">Hong Xu</name>
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<wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
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<author><name sortKey="Wang, Tianyuan" sort="Wang, Tianyuan" uniqKey="Wang T" first="Tianyuan" last="Wang">Tianyuan Wang</name>
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<wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
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<author><name sortKey="Walter, Jeffrey W" sort="Walter, Jeffrey W" uniqKey="Walter J" first="Jeffrey W." last="Walter">Jeffrey W. Walter</name>
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<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton L." last="Scott">Burton L. Scott</name>
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<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Duke University, Durham, North Carolina</wicri:regionArea>
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<author><name sortKey="Hulette, Christine" sort="Hulette, Christine" uniqKey="Hulette C" first="Christine" last="Hulette">Christine Hulette</name>
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<author><name sortKey="Schmechel, Don" sort="Schmechel, Don" uniqKey="Schmechel D" first="Don" last="Schmechel">Don Schmechel</name>
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<wicri:regionArea>Department of Medicine, Duke University, Durham, North Carolina</wicri:regionArea>
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<author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith E." last="Stenger">Judith E. Stenger</name>
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<author><name sortKey="Dietrich, Fred" sort="Dietrich, Fred" uniqKey="Dietrich F" first="Fred" last="Dietrich">Fred Dietrich</name>
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<wicri:regionArea>Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina</wicri:regionArea>
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<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name>
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<author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name>
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<wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea>
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<monogr></monogr>
<series><title level="j">Movement Disorders</title>
<title level="j" type="sub">Official Journal of the Movement Disorder Society</title>
<title level="j" type="abbrev">Mov. Disord.</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
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<date type="published" when="2005-10">2005-10</date>
<biblScope unit="vol">20</biblScope>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>DNA, Mitochondrial (genetics)</term>
<term>Expressed Sequence Tags (metabolism)</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Gene Library</term>
<term>Genetic Linkage (genetics)</term>
<term>Genetic Predisposition to Disease</term>
<term>Genetic Techniques</term>
<term>Humans</term>
<term>Male</term>
<term>Oligonucleotide Array Sequence Analysis (methods)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinson Disease (pathology)</term>
<term>Parkinson's disease</term>
<term>Proteomics (methods)</term>
<term>RNA, Messenger (genetics)</term>
<term>RNA, Messenger (metabolism)</term>
<term>Risk Factors</term>
<term>Substantia Nigra (metabolism)</term>
<term>Substantia Nigra (pathology)</term>
<term>genomic convergence</term>
<term>linkage</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Mitochondrial</term>
<term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Linkage</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Expressed Sequence Tags</term>
<term>Parkinson Disease</term>
<term>RNA, Messenger</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Oligonucleotide Array Sequence Analysis</term>
<term>Proteomics</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Gene Library</term>
<term>Genetic Predisposition to Disease</term>
<term>Genetic Techniques</term>
<term>Humans</term>
<term>Male</term>
<term>Risk Factors</term>
</keywords>
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<front><div type="abstract" xml:lang="fr">Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671–677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239–2242] to analyze substantia nigra tissue from three PD patients and two age‐matched controls. We find 933 differentially expressed genes (P < 0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5‐fold higher in PD patients versus controls, without an increase in the corresponding nuclear‐encoded mitochondrial components, suggesting an increase in mtDNA genomes in PD or a disjunction with nuclear expression. The next step in the genomic convergence process will be to screen these 50 high‐quality candidate genes for association with PD risk susceptibility and genetic effects on AAO. © 2005 Movement Disorder Society</div>
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