Allelic imbalance of expression and epigenetic regulation within the alpha‐synuclein wild‐type and p.Ala53Thr alleles in Parkinson disease
Identifieur interne : 000822 ( Main/Exploration ); précédent : 000821; suivant : 000823Allelic imbalance of expression and epigenetic regulation within the alpha‐synuclein wild‐type and p.Ala53Thr alleles in Parkinson disease
Auteurs : Gerassimos E. Voutsinas [Grèce] ; Eleana F. Stavrou [Grèce] ; Gerassimos Karousos [Grèce] ; Aggeliki Dasoula [Grèce] ; Adamantia Papachatzopoulou [Grèce] ; Maria Syrrou [Grèce] ; Annemieke J. M. H. Verkerk [Pays-Bas] ; Peter Van Der Spek [Pays-Bas] ; George P. Patrinos [Pays-Bas, Grèce] ; Reinhard Stöger [États-Unis, Royaume-Uni] ; Aglaia Athanassiadou [Grèce]Source :
- Human Mutation [ 1059-7794 ] ; 2010-06.
English descriptors
- KwdEn :
Abstract
Genetic alterations in the alpha‐synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady‐state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild‐type‐allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis. Hum Mutat 31:1–7, 2010. © 2010 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/humu.21248
Affiliations:
- Grèce, Pays-Bas, Royaume-Uni, États-Unis
- Angleterre, Hollande-Méridionale, Nottinghamshire, Washington (État)
- Nottingham, Rotterdam
- Université de Nottingham
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Allelic imbalance of expression and epigenetic regulation within the alpha‐synuclein wild‐type and p.Ala53Thr alleles in Parkinson disease</title><author><name sortKey="Voutsinas, Gerassimos E" sort="Voutsinas, Gerassimos E" uniqKey="Voutsinas G" first="Gerassimos E." last="Voutsinas">Gerassimos E. Voutsinas</name></author><author><name sortKey="Stavrou, Eleana F" sort="Stavrou, Eleana F" uniqKey="Stavrou E" first="Eleana F." last="Stavrou">Eleana F. Stavrou</name></author><author><name sortKey="Karousos, Gerassimos" sort="Karousos, Gerassimos" uniqKey="Karousos G" first="Gerassimos" last="Karousos">Gerassimos Karousos</name></author><author><name sortKey="Dasoula, Aggeliki" sort="Dasoula, Aggeliki" uniqKey="Dasoula A" first="Aggeliki" last="Dasoula">Aggeliki Dasoula</name></author><author><name sortKey="Papachatzopoulou, Adamantia" sort="Papachatzopoulou, Adamantia" uniqKey="Papachatzopoulou A" first="Adamantia" last="Papachatzopoulou">Adamantia Papachatzopoulou</name></author><author><name sortKey="Syrrou, Maria" sort="Syrrou, Maria" uniqKey="Syrrou M" first="Maria" last="Syrrou">Maria Syrrou</name></author><author><name sortKey="Verkerk, Annemieke J M H" sort="Verkerk, Annemieke J M H" uniqKey="Verkerk A" first="Annemieke J. M. H." last="Verkerk">Annemieke J. M. H. Verkerk</name></author><author><name sortKey="Van Der Spek, Peter" sort="Van Der Spek, Peter" uniqKey="Van Der Spek P" first="Peter" last="Van Der Spek">Peter Van Der Spek</name></author><author><name sortKey="Patrinos, George P" sort="Patrinos, George P" uniqKey="Patrinos G" first="George P." last="Patrinos">George P. Patrinos</name></author><author><name sortKey="Stoger, Reinhard" sort="Stoger, Reinhard" uniqKey="Stoger R" first="Reinhard" last="Stöger">Reinhard Stöger</name></author><author><name sortKey="Athanassiadou, Aglaia" sort="Athanassiadou, Aglaia" uniqKey="Athanassiadou A" first="Aglaia" last="Athanassiadou">Aglaia Athanassiadou</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0780772AEDD857BDB4A67C3DC98CFF472926E7B0</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/humu.21248</idno><idno type="url">https://api.istex.fr/document/0780772AEDD857BDB4A67C3DC98CFF472926E7B0/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000617</idno><idno type="wicri:Area/Main/Curation">000535</idno><idno type="wicri:Area/Main/Exploration">000822</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Allelic imbalance of expression and epigenetic regulation within the alpha‐synuclein wild‐type and p.Ala53Thr alleles in Parkinson disease</title><author><name sortKey="Voutsinas, Gerassimos E" sort="Voutsinas, Gerassimos E" uniqKey="Voutsinas G" first="Gerassimos E." last="Voutsinas">Gerassimos E. Voutsinas</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of General Biology, School of Medicine, University of Patras, Patras</wicri:regionArea><wicri:noRegion>Patras</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Laboratory of Environmental Mutagenesis and Carcinogenesis, Institute of Biology, NCSR “Demokritos,” GR‐15310 Athens</wicri:regionArea><wicri:noRegion>” GR‐15310 Athens</wicri:noRegion></affiliation></author><author><name sortKey="Stavrou, Eleana F" sort="Stavrou, Eleana F" uniqKey="Stavrou E" first="Eleana F." last="Stavrou">Eleana F. Stavrou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of General Biology, School of Medicine, University of Patras, Patras</wicri:regionArea><wicri:noRegion>Patras</wicri:noRegion></affiliation></author><author><name sortKey="Karousos, Gerassimos" sort="Karousos, Gerassimos" uniqKey="Karousos G" first="Gerassimos" last="Karousos">Gerassimos Karousos</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of General Biology, School of Medicine, University of Patras, Patras</wicri:regionArea><wicri:noRegion>Patras</wicri:noRegion></affiliation></author><author><name sortKey="Dasoula, Aggeliki" sort="Dasoula, Aggeliki" uniqKey="Dasoula A" first="Aggeliki" last="Dasoula">Aggeliki Dasoula</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Laboratory of General Biology, School of Medicine, University of Ioannina, Ioannina</wicri:regionArea><wicri:noRegion>Ioannina</wicri:noRegion></affiliation></author><author><name sortKey="Papachatzopoulou, Adamantia" sort="Papachatzopoulou, Adamantia" uniqKey="Papachatzopoulou A" first="Adamantia" last="Papachatzopoulou">Adamantia Papachatzopoulou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of General Biology, School of Medicine, University of Patras, Patras</wicri:regionArea><wicri:noRegion>Patras</wicri:noRegion></affiliation></author><author><name sortKey="Syrrou, Maria" sort="Syrrou, Maria" uniqKey="Syrrou M" first="Maria" last="Syrrou">Maria Syrrou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Laboratory of General Biology, School of Medicine, University of Ioannina, Ioannina</wicri:regionArea><wicri:noRegion>Ioannina</wicri:noRegion></affiliation></author><author><name sortKey="Verkerk, Annemieke J M H" sort="Verkerk, Annemieke J M H" uniqKey="Verkerk A" first="Annemieke J. M. H." last="Verkerk">Annemieke J. M. H. Verkerk</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Erasmus University Medical Center, Faculty of Medicine and Health Sciences, Department of Bioinformatics, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Der Spek, Peter" sort="Van Der Spek, Peter" uniqKey="Van Der Spek P" first="Peter" last="Van Der Spek">Peter Van Der Spek</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Erasmus University Medical Center, Faculty of Medicine and Health Sciences, Department of Bioinformatics, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Patrinos, George P" sort="Patrinos, George P" uniqKey="Patrinos G" first="George P." last="Patrinos">George P. Patrinos</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Erasmus University Medical Center, Faculty of Medicine and Health Sciences, Department of Bioinformatics, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>University of Patras, School of Health Sciences, Department of Pharmacy, Patras</wicri:regionArea><wicri:noRegion>Patras</wicri:noRegion></affiliation></author><author><name sortKey="Stoger, Reinhard" sort="Stoger, Reinhard" uniqKey="Stoger R" first="Reinhard" last="Stöger">Reinhard Stöger</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Biology, University of Washington, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Current Address: School of Biosciences, University of Nottingham</wicri:regionArea><placeName><settlement type="city">Nottingham</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Nottinghamshire</region></placeName><orgName type="university">Université de Nottingham</orgName></affiliation></author><author><name sortKey="Athanassiadou, Aglaia" sort="Athanassiadou, Aglaia" uniqKey="Athanassiadou A" first="Aglaia" last="Athanassiadou">Aglaia Athanassiadou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of General Biology, School of Medicine, University of Patras, Patras</wicri:regionArea><wicri:noRegion>Patras</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-06">2010-06</date><biblScope unit="volume">31</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="685">685</biblScope><biblScope unit="page" to="691">691</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">0780772AEDD857BDB4A67C3DC98CFF472926E7B0</idno><idno type="DOI">10.1002/humu.21248</idno><idno type="ArticleID">HUMU21248</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson</term><term>SNCA</term><term>alpha‐synuclein</term><term>epigenetic</term><term>monoallelic</term><term>overexpression</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Genetic alterations in the alpha‐synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady‐state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild‐type‐allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis. Hum Mutat 31:1–7, 2010. © 2010 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Grèce</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Hollande-Méridionale</li><li>Nottinghamshire</li><li>Washington (État)</li></region><settlement><li>Nottingham</li><li>Rotterdam</li></settlement><orgName><li>Université de Nottingham</li></orgName></list><tree><country name="Grèce"><noRegion><name sortKey="Voutsinas, Gerassimos E" sort="Voutsinas, Gerassimos E" uniqKey="Voutsinas G" first="Gerassimos E." last="Voutsinas">Gerassimos E. Voutsinas</name></noRegion><name sortKey="Athanassiadou, Aglaia" sort="Athanassiadou, Aglaia" uniqKey="Athanassiadou A" first="Aglaia" last="Athanassiadou">Aglaia Athanassiadou</name><name sortKey="Dasoula, Aggeliki" sort="Dasoula, Aggeliki" uniqKey="Dasoula A" first="Aggeliki" last="Dasoula">Aggeliki Dasoula</name><name sortKey="Karousos, Gerassimos" sort="Karousos, Gerassimos" uniqKey="Karousos G" first="Gerassimos" last="Karousos">Gerassimos Karousos</name><name sortKey="Papachatzopoulou, Adamantia" sort="Papachatzopoulou, Adamantia" uniqKey="Papachatzopoulou A" first="Adamantia" last="Papachatzopoulou">Adamantia Papachatzopoulou</name><name sortKey="Patrinos, George P" sort="Patrinos, George P" uniqKey="Patrinos G" first="George P." last="Patrinos">George P. Patrinos</name><name sortKey="Stavrou, Eleana F" sort="Stavrou, Eleana F" uniqKey="Stavrou E" first="Eleana F." last="Stavrou">Eleana F. Stavrou</name><name sortKey="Syrrou, Maria" sort="Syrrou, Maria" uniqKey="Syrrou M" first="Maria" last="Syrrou">Maria Syrrou</name><name sortKey="Voutsinas, Gerassimos E" sort="Voutsinas, Gerassimos E" uniqKey="Voutsinas G" first="Gerassimos E." last="Voutsinas">Gerassimos E. Voutsinas</name></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Verkerk, Annemieke J M H" sort="Verkerk, Annemieke J M H" uniqKey="Verkerk A" first="Annemieke J. M. H." last="Verkerk">Annemieke J. M. H. Verkerk</name></region><name sortKey="Patrinos, George P" sort="Patrinos, George P" uniqKey="Patrinos G" first="George P." last="Patrinos">George P. Patrinos</name><name sortKey="Van Der Spek, Peter" sort="Van Der Spek, Peter" uniqKey="Van Der Spek P" first="Peter" last="Van Der Spek">Peter Van Der Spek</name></country><country name="États-Unis"><region name="Washington (État)"><name sortKey="Stoger, Reinhard" sort="Stoger, Reinhard" uniqKey="Stoger R" first="Reinhard" last="Stöger">Reinhard Stöger</name></region></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Stoger, Reinhard" sort="Stoger, Reinhard" uniqKey="Stoger R" first="Reinhard" last="Stöger">Reinhard Stöger</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000822 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000822 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:0780772AEDD857BDB4A67C3DC98CFF472926E7B0
|texte= Allelic imbalance of expression and epigenetic regulation within the alpha‐synuclein wild‐type and p.Ala53Thr alleles in Parkinson disease
}}
| This area was generated with Dilib version V0.6.23. |  |