Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra
Identifieur interne : 000806 ( Main/Curation ); précédent : 000805; suivant : 000807Genomic 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.
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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
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DOI: 10.1002/mds.20573
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Scott</name><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Medicine, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Hulette, Christine" sort="Hulette, Christine" uniqKey="Hulette C" first="Christine" last="Hulette">Christine Hulette</name><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Pathology, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Schmechel, Don" sort="Schmechel, Don" uniqKey="Schmechel D" first="Don" last="Schmechel">Don Schmechel</name><affiliation wicri:level="1"><mods:affiliation>Department of Medicine, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith E." last="Stenger">Judith E. 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Noureddine</name><affiliation wicri:level="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></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="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></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><affiliation wicri:level="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Walters, Robert" sort="Walters, Robert" uniqKey="Walters R" first="Robert" last="Walters">Robert Walters</name><affiliation wicri:level="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><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="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Hong" sort="Xu, Hong" uniqKey="Xu H" first="Hong" last="Xu">Hong Xu</name><affiliation wicri:level="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Tianyuan" sort="Wang, Tianyuan" uniqKey="Wang T" first="Tianyuan" last="Wang">Tianyuan Wang</name><affiliation wicri:level="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Walter, Jeffrey W" sort="Walter, Jeffrey W" uniqKey="Walter J" first="Jeffrey W." last="Walter">Jeffrey W. Walter</name><affiliation wicri:level="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><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="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Medicine, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Hulette, Christine" sort="Hulette, Christine" uniqKey="Hulette C" first="Christine" last="Hulette">Christine Hulette</name><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Pathology, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Schmechel, Don" sort="Schmechel, Don" uniqKey="Schmechel D" first="Don" last="Schmechel">Don Schmechel</name><affiliation wicri:level="1"><mods:affiliation>Department of Medicine, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><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="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Dietrich, Fred" sort="Dietrich, Fred" uniqKey="Dietrich F" first="Fred" last="Dietrich">Fred Dietrich</name><affiliation wicri:level="1"><mods:affiliation>Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina</wicri:regionArea></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="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></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="1"><mods:affiliation>Center for Human Genetics, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Human Genetics, Duke University, Durham, North Carolina</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Duke Udall Center of Excellence, Duke University, Durham, North Carolina, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Udall Center of Excellence, Duke University, Durham, North Carolina</wicri:regionArea></affiliation></author></analytic><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><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2005-10">2005-10</date><biblScope unit="volume">20</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1299">1299</biblScope><biblScope unit="page" to="1309">1309</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">5074B50F5F664B19062B337DCDC8A5C8366CC5B0</idno><idno type="DOI">10.1002/mds.20573</idno><idno type="ArticleID">MDS20573</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>genomic convergence</term><term>linkage</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><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></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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|flux= Main
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|type= RBID
|clé= ISTEX:5074B50F5F664B19062B337DCDC8A5C8366CC5B0
|texte= Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra
}}
| This area was generated with Dilib version V0.6.23. |  |