Alpha‐synuclein and familial Parkinson's disease
Identifieur interne : 002D19 ( Main/Merge ); précédent : 002D18; suivant : 002D20Alpha‐synuclein and familial Parkinson's disease
Auteurs : Nathan Pankratz [États-Unis] ; William C. Nichols [États-Unis] ; Veronika E. Elsaesser [États-Unis] ; Michael W. Pauciulo [États-Unis] ; Diane K. Marek [États-Unis] ; Cheryl A. Halter [États-Unis] ; Joanne Wojcieszek [États-Unis] ; Alice Rudolph [États-Unis] ; Ronald F. Pfeiffer [États-Unis] ; Tatiana Foroud [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2009-06-15.
English descriptors
- KwdEn :
- Aged, DNA Mutational Analysis, Family Health, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Logistic Models, Male, Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson's disease, Polymorphism, Single Nucleotide (genetics), Promoter Regions, Genetic (genetics), Rep1, alpha-Synuclein (genetics), alpha‐synuclein, association, dosage.
- MESH :
- chemical , genetics : alpha-Synuclein.
- genetics : Parkinson Disease, Polymorphism, Single Nucleotide, Promoter Regions, Genetic.
- metabolism : Parkinson Disease.
- Aged, DNA Mutational Analysis, Family Health, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Logistic Models, Male.
Abstract
Whole gene duplications and triplications of alpha‐synuclein (SNCA) can cause Parkinson's disease (PD), and variation in the promoter region (Rep1) and 3' region of SNCA has been reported to increase disease susceptibility. Within our cohort, one affected individual from each of 92 multiplex PD families showing the greatest evidence of linkage to the region around SNCA was screened for dosage alterations and sequence changes; no dosage or non‐synonymous sequence changes were found. In addition, 737 individuals (from 450 multiplex PD families) that met strict diagnostic criteria for PD and did not harbor a known causative mutation, as well as 359 neurologically normal controls, were genotyped for the Rep1 polymorphism and four SNPs in the 3′ region of SNCA. The four SNPs were in high LD (r2 > 0.95) and were analyzed as a haplotype. The effects of the Rep1 genotype and the 3′ haplotype were evaluated using regression models employing only one individual per family. Cases had a 3% higher frequency of the Rep1 263 bp allele compared with controls (OR = 1.54; empirical P‐value = 0.02). There was an inverse linear relationship between the number of 263 bp alleles and age of onset (empirical P‐value = 0.0004). The 3′ haplotype was also associated with disease (OR = 1.29; empirical P‐value = 0.01), but not age of onset (P = 0.40). These data suggest that dosage and sequence changes are a rare cause of PD, but variation in the promoter and 3′ region of SNCA convey an increased risk for PD. © 2009 Movement Disorder Society
Url:
- https://api.istex.fr/document/FB662CF728D4EE694BFEF300A6AC579A23982984/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397145
DOI: 10.1002/mds.22524
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ISTEX:FB662CF728D4EE694BFEF300A6AC579A23982984Le document en format XML
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Pfeiffer</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</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="2009-06-15">2009-06-15</date><biblScope unit="vol">24</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1125">1125</biblScope><biblScope unit="page" to="1131">1131</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">FB662CF728D4EE694BFEF300A6AC579A23982984</idno><idno type="DOI">10.1002/mds.22524</idno><idno type="ArticleID">MDS22524</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>DNA Mutational Analysis</term><term>Family Health</term><term>Female</term><term>Gene Frequency</term><term>Genetic Predisposition to Disease</term><term>Genotype</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Logistic Models</term><term>Male</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson's disease</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Promoter Regions, Genetic (genetics)</term><term>Rep1</term><term>alpha-Synuclein (genetics)</term><term>alpha‐synuclein</term><term>association</term><term>dosage</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term><term>Polymorphism, Single Nucleotide</term><term>Promoter Regions, Genetic</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>DNA Mutational Analysis</term><term>Family Health</term><term>Female</term><term>Gene Frequency</term><term>Genetic Predisposition to Disease</term><term>Genotype</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Logistic Models</term><term>Male</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Whole gene duplications and triplications of alpha‐synuclein (SNCA) can cause Parkinson's disease (PD), and variation in the promoter region (Rep1) and 3' region of SNCA has been reported to increase disease susceptibility. Within our cohort, one affected individual from each of 92 multiplex PD families showing the greatest evidence of linkage to the region around SNCA was screened for dosage alterations and sequence changes; no dosage or non‐synonymous sequence changes were found. In addition, 737 individuals (from 450 multiplex PD families) that met strict diagnostic criteria for PD and did not harbor a known causative mutation, as well as 359 neurologically normal controls, were genotyped for the Rep1 polymorphism and four SNPs in the 3′ region of SNCA. The four SNPs were in high LD (r2 > 0.95) and were analyzed as a haplotype. The effects of the Rep1 genotype and the 3′ haplotype were evaluated using regression models employing only one individual per family. Cases had a 3% higher frequency of the Rep1 263 bp allele compared with controls (OR = 1.54; empirical P‐value = 0.02). There was an inverse linear relationship between the number of 263 bp alleles and age of onset (empirical P‐value = 0.0004). The 3′ haplotype was also associated with disease (OR = 1.29; empirical P‐value = 0.01), but not age of onset (P = 0.40). These data suggest that dosage and sequence changes are a rare cause of PD, but variation in the promoter and 3′ region of SNCA convey an increased risk for PD. © 2009 Movement Disorder Society</div></front></TEI><double doi="10.1002/mds.22524"><ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alpha‐synuclein and familial Parkinson's disease</title><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name></author><author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name></author><author><name sortKey="Elsaesser, Veronika E" sort="Elsaesser, Veronika E" uniqKey="Elsaesser V" first="Veronika E." last="Elsaesser">Veronika E. Elsaesser</name></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K." last="Marek">Diane K. Marek</name></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A." last="Halter">Cheryl A. Halter</name></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name></author><author><name sortKey="Pfeiffer, Ronald F" sort="Pfeiffer, Ronald F" uniqKey="Pfeiffer R" first="Ronald F." last="Pfeiffer">Ronald F. Pfeiffer</name></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:FB662CF728D4EE694BFEF300A6AC579A23982984</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1002/mds.22524</idno><idno type="url">https://api.istex.fr/document/FB662CF728D4EE694BFEF300A6AC579A23982984/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000903</idno><idno type="wicri:Area/Istex/Curation">000903</idno><idno type="wicri:Area/Istex/Checkpoint">001060</idno><idno type="wicri:doubleKey">0885-3185:2009:Pankratz N:alpha:synuclein:and</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Alpha‐synuclein and familial Parkinson's disease</title><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Elsaesser, Veronika E" sort="Elsaesser, Veronika E" uniqKey="Elsaesser V" first="Veronika E." last="Elsaesser">Veronika E. Elsaesser</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K." last="Marek">Diane K. Marek</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A." last="Halter">Cheryl A. Halter</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Rochester, Rochester, Rochester, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Pfeiffer, Ronald F" sort="Pfeiffer, Ronald F" uniqKey="Pfeiffer R" first="Ronald F." last="Pfeiffer">Ronald F. Pfeiffer</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</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="2009-06-15">2009-06-15</date><biblScope unit="vol">24</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1125">1125</biblScope><biblScope unit="page" to="1131">1131</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">FB662CF728D4EE694BFEF300A6AC579A23982984</idno><idno type="DOI">10.1002/mds.22524</idno><idno type="ArticleID">MDS22524</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>Rep1</term><term>alpha‐synuclein</term><term>association</term><term>dosage</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Whole gene duplications and triplications of alpha‐synuclein (SNCA) can cause Parkinson's disease (PD), and variation in the promoter region (Rep1) and 3' region of SNCA has been reported to increase disease susceptibility. Within our cohort, one affected individual from each of 92 multiplex PD families showing the greatest evidence of linkage to the region around SNCA was screened for dosage alterations and sequence changes; no dosage or non‐synonymous sequence changes were found. In addition, 737 individuals (from 450 multiplex PD families) that met strict diagnostic criteria for PD and did not harbor a known causative mutation, as well as 359 neurologically normal controls, were genotyped for the Rep1 polymorphism and four SNPs in the 3′ region of SNCA. The four SNPs were in high LD (r2 > 0.95) and were analyzed as a haplotype. The effects of the Rep1 genotype and the 3′ haplotype were evaluated using regression models employing only one individual per family. Cases had a 3% higher frequency of the Rep1 263 bp allele compared with controls (OR = 1.54; empirical P‐value = 0.02). There was an inverse linear relationship between the number of 263 bp alleles and age of onset (empirical P‐value = 0.0004). The 3′ haplotype was also associated with disease (OR = 1.29; empirical P‐value = 0.01), but not age of onset (P = 0.40). These data suggest that dosage and sequence changes are a rare cause of PD, but variation in the promoter and 3′ region of SNCA convey an increased risk for PD. © 2009 Movement Disorder Society</div></front></TEI></ISTEX><PMC><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alpha-Synuclein and Familial Parkinson’s Disease</title><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Elsaesser, Veronika E" sort="Elsaesser, Veronika E" uniqKey="Elsaesser V" first="Veronika E." last="Elsaesser">Veronika E. Elsaesser</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K." last="Marek">Diane K. Marek</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A." last="Halter">Cheryl A. Halter</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><affiliation wicri:level="2"><nlm:aff id="A4">Department of Neurology, University of Rochester, Rochester, Rochester, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Rochester, Rochester, Rochester, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Pfeiffer, Ronald F" sort="Pfeiffer, Ronald F" uniqKey="Pfeiffer R" first="Ronald F." last="Pfeiffer">Ronald F. Pfeiffer</name><affiliation wicri:level="2"><nlm:aff id="A5">Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19412953</idno><idno type="pmc">3397145</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397145</idno><idno type="RBID">PMC:3397145</idno><idno type="doi">10.1002/mds.22524</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000186</idno><idno type="wicri:Area/Pmc/Curation">000186</idno><idno type="wicri:Area/Pmc/Checkpoint">000421</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">001D27</idno><idno type="wicri:Area/PubMed/Curation">001D27</idno><idno type="wicri:Area/PubMed/Checkpoint">001F61</idno><idno type="wicri:Area/Ncbi/Merge">002650</idno><idno type="wicri:Area/Ncbi/Curation">002650</idno><idno type="wicri:Area/Ncbi/Checkpoint">002650</idno><idno type="wicri:doubleKey">0885-3185:2009:Pankratz N:alpha:synuclein:and</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alpha-Synuclein and Familial Parkinson’s Disease</title><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Elsaesser, Veronika E" sort="Elsaesser, Veronika E" uniqKey="Elsaesser V" first="Veronika E." last="Elsaesser">Veronika E. Elsaesser</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K." last="Marek">Diane K. Marek</name><affiliation wicri:level="2"><nlm:aff id="A2">Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A." last="Halter">Cheryl A. Halter</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><affiliation wicri:level="2"><nlm:aff id="A4">Department of Neurology, University of Rochester, Rochester, Rochester, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Rochester, Rochester, Rochester, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Pfeiffer, Ronald F" sort="Pfeiffer, Ronald F" uniqKey="Pfeiffer R" first="Ronald F." last="Pfeiffer">Ronald F. Pfeiffer</name><affiliation wicri:level="2"><nlm:aff id="A5">Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author></analytic><series><title level="j">Movement Disorders</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>DNA Mutational Analysis</term><term>Family Health</term><term>Female</term><term>Gene Frequency</term><term>Genetic Predisposition to Disease</term><term>Genotype</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Logistic Models</term><term>Male</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Promoter Regions, Genetic (genetics)</term><term>alpha-Synuclein (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term><term>Polymorphism, Single Nucleotide</term><term>Promoter Regions, Genetic</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>DNA Mutational Analysis</term><term>Family Health</term><term>Female</term><term>Gene Frequency</term><term>Genetic Predisposition to Disease</term><term>Genotype</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Logistic Models</term><term>Male</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Whole gene duplications and triplications of <italic>alpha-synuclein</italic> (<italic>SNCA</italic>) can cause Parkinson’s disease (PD), and variation in the promoter region (Rep1) and 3′ region of <italic>SNCA</italic> has been reported to increase disease susceptibility. Within our cohort, one affected individual from each of 92 multiplex PD families showing the greatest evidence of linkage to the region around <italic>SNCA</italic> was screened for dosage alterations and sequence changes; no dosage or non-synonymous sequence changes were found. In addition, 737 individuals (from 450 multiplex PD families) that met strict diagnostic criteria for PD and did not harbor a known causative mutation, as well as 359 neurologically normal controls, were genotyped for the Rep1 polymorphism and four SNPs in the 3′ region of <italic>SNCA</italic>. The four SNPs were in high LD (r<sup>2</sup> > 0.95) and were analyzed as a haplotype. The effects of the Rep1 genotype and the 3′ haplotype were evaluated using regression models employing only one individual per family. Cases had a 3% higher frequency of the Rep1 263 bp allele compared with controls (OR = 1.54; empirical <italic>P</italic>-value = 0.02). There was an inverse linear relationship between the number of 263 bp alleles and age of onset (empirical <italic>P</italic>-value = 0.0004). The 3′ haplotype was also associated with disease (OR = 1.29; empirical <italic>P</italic>-value = 0.01), but not age of onset (<italic>P</italic> = 0.40). These data suggest that dosage and sequence changes are a rare cause of PD, but variation in the promoter and 3′ region of <italic>SNCA</italic> convey an increased risk for PD.</p></div></front></TEI></PMC></double></record>Pour manipuler ce document sous Unix (Dilib)
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