Identification of a new susceptibility variant for multiple sclerosis in OAS1 by population genetics analysis
Identifieur interne : 002276 ( Main/Exploration ); précédent : 002275; suivant : 002277Identification of a new susceptibility variant for multiple sclerosis in OAS1 by population genetics analysis
Auteurs : Rachele Cagliani [Italie] ; Matteo Fumagalli [Italie] ; Franca R. Guerini [Italie] ; Stefania Riva [Italie] ; Daniela Galimberti [Italie] ; Giacomo P. Comi [Italie] ; Cristina Agliardi [Italie] ; Elio Scarpini [Italie] ; Uberto Pozzoli [Italie] ; Diego Forni [Italie] ; Domenico Caputo [Italie] ; Rosanna Asselta [Italie] ; Mara Biasin [Italie] ; Elvezia M. Paraboschi [Italie] ; Nereo Bresolin [Italie] ; Mario Clerici [Italie] ; Manuela Sironi [Italie]Source :
- Human Genetics [ 0340-6717 ] ; 2012-01-01.
Abstract
Abstract: Contrasting results have been reported concerning the association of a splice-site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed two OAS1 regions encompassing alternatively spliced exons. While the region carrying the splice-site variant is neutrally evolving, a signature of long-standing balancing selection was observed across an alternative exon 7. Analysis of variants in this exon identified an insertion/deletion polymorphism (rs11352835, A/−) that originates predicted products with distinct C termini. This variant is located along the major branch of the haplotype genealogy, suggesting that it may represent the selection target. A case/control study for MS indicated that rs11352835 is associated with disease susceptibility (for an allelic model with the deleted allele predisposing to MS, OR 1.27, 95% CI 1.072–1.513, p = 0.010). No association was found between rs10774671 and MS. As the two SNPs are in linkage disequilibrium in Europeans, the previously reported association between rs10774671 and MS susceptibility might be driven by rs11352835, possibly explaining the contrasting results previously observed for the splice-site polymorphism. Thus, we describe a novel susceptibility variant for MS in OAS1 and show that population genetic analyses can be instrumental to the identification of selection targets and, consequently, of functional polymorphisms with an effect on phenotypic traits.
Url:
DOI: 10.1007/s00439-011-1053-2
Affiliations:
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Medea, Via don L. Monza 20, 23842, Bosisio Parini, LC</wicri:regionArea><wicri:noRegion>LC</wicri:noRegion></affiliation></author><author><name sortKey="Fumagalli, Matteo" sort="Fumagalli, Matteo" uniqKey="Fumagalli M" first="Matteo" last="Fumagalli">Matteo Fumagalli</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Bioinformatic Lab, Scientific Institute IRCCS E. Medea, Via don L. Monza 20, 23842, Bosisio Parini, LC</wicri:regionArea><wicri:noRegion>LC</wicri:noRegion></affiliation></author><author><name sortKey="Guerini, Franca R" sort="Guerini, Franca R" uniqKey="Guerini F" first="Franca R." last="Guerini">Franca R. Guerini</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Laboratory of Molecular Medicine and Biotechnologies, Don C. 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Comi</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurological Sciences, Dino Ferrari Centre, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, 20122, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Agliardi, Cristina" sort="Agliardi, Cristina" uniqKey="Agliardi C" first="Cristina" last="Agliardi">Cristina Agliardi</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Laboratory of Molecular Medicine and Biotechnologies, Don C. 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Monza 20, 23842, Bosisio Parini, LC</wicri:regionArea><wicri:noRegion>LC</wicri:noRegion></affiliation></author><author><name sortKey="Forni, Diego" sort="Forni, Diego" uniqKey="Forni D" first="Diego" last="Forni">Diego Forni</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Bioinformatic Lab, Scientific Institute IRCCS E. Medea, Via don L. Monza 20, 23842, Bosisio Parini, LC</wicri:regionArea><wicri:noRegion>LC</wicri:noRegion></affiliation></author><author><name sortKey="Caputo, Domenico" sort="Caputo, Domenico" uniqKey="Caputo D" first="Domenico" last="Caputo">Domenico Caputo</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Multiple Sclerosis Unit, Don C. Gnocchi Foundation ONLUS, IRCCS, S. Maria Nascente, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Asselta, Rosanna" sort="Asselta, Rosanna" uniqKey="Asselta R" first="Rosanna" last="Asselta">Rosanna Asselta</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Biasin, Mara" sort="Biasin, Mara" uniqKey="Biasin M" first="Mara" last="Biasin">Mara Biasin</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>DISC LITA Vialba, University of Milano, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Paraboschi, Elvezia M" sort="Paraboschi, Elvezia M" uniqKey="Paraboschi E" first="Elvezia M." last="Paraboschi">Elvezia M. Paraboschi</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Bresolin, Nereo" sort="Bresolin, Nereo" uniqKey="Bresolin N" first="Nereo" last="Bresolin">Nereo Bresolin</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Bioinformatic Lab, Scientific Institute IRCCS E. Medea, Via don L. Monza 20, 23842, Bosisio Parini, LC</wicri:regionArea><wicri:noRegion>LC</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurological Sciences, Dino Ferrari Centre, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, 20122, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Clerici, Mario" sort="Clerici, Mario" uniqKey="Clerici M" first="Mario" last="Clerici">Mario Clerici</name><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical Sciences and Technologies LITA Segrate, University of Milan, 20090, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Fondazione Don C. Gnocchi, IRCCS, 20148, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Sironi, Manuela" sort="Sironi, Manuela" uniqKey="Sironi M" first="Manuela" last="Sironi">Manuela Sironi</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Bioinformatic Lab, Scientific Institute IRCCS E. Medea, Via don L. Monza 20, 23842, Bosisio Parini, LC</wicri:regionArea><wicri:noRegion>LC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Italie</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Genetics</title><title level="j" type="abbrev">Hum Genet</title><idno type="ISSN">0340-6717</idno><idno type="eISSN">1432-1203</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2012-01-01">2012-01-01</date><biblScope unit="volume">131</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="87">87</biblScope><biblScope unit="page" to="97">97</biblScope></imprint><idno type="ISSN">0340-6717</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-6717</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Contrasting results have been reported concerning the association of a splice-site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed two OAS1 regions encompassing alternatively spliced exons. While the region carrying the splice-site variant is neutrally evolving, a signature of long-standing balancing selection was observed across an alternative exon 7. Analysis of variants in this exon identified an insertion/deletion polymorphism (rs11352835, A/−) that originates predicted products with distinct C termini. This variant is located along the major branch of the haplotype genealogy, suggesting that it may represent the selection target. A case/control study for MS indicated that rs11352835 is associated with disease susceptibility (for an allelic model with the deleted allele predisposing to MS, OR 1.27, 95% CI 1.072–1.513, p = 0.010). No association was found between rs10774671 and MS. As the two SNPs are in linkage disequilibrium in Europeans, the previously reported association between rs10774671 and MS susceptibility might be driven by rs11352835, possibly explaining the contrasting results previously observed for the splice-site polymorphism. Thus, we describe a novel susceptibility variant for MS in OAS1 and show that population genetic analyses can be instrumental to the identification of selection targets and, consequently, of functional polymorphisms with an effect on phenotypic traits.</div></front></TEI><affiliations><list><country><li>Italie</li></country><region><li>Lombardie</li></region><settlement><li>Milan</li></settlement></list><tree><country name="Italie"><noRegion><name sortKey="Cagliani, Rachele" sort="Cagliani, Rachele" uniqKey="Cagliani R" first="Rachele" last="Cagliani">Rachele Cagliani</name></noRegion><name sortKey="Agliardi, Cristina" sort="Agliardi, Cristina" uniqKey="Agliardi C" first="Cristina" last="Agliardi">Cristina Agliardi</name><name sortKey="Asselta, Rosanna" sort="Asselta, Rosanna" uniqKey="Asselta R" first="Rosanna" last="Asselta">Rosanna Asselta</name><name sortKey="Biasin, Mara" sort="Biasin, Mara" uniqKey="Biasin M" first="Mara" last="Biasin">Mara Biasin</name><name sortKey="Bresolin, Nereo" sort="Bresolin, Nereo" uniqKey="Bresolin N" first="Nereo" last="Bresolin">Nereo Bresolin</name><name sortKey="Bresolin, Nereo" sort="Bresolin, Nereo" uniqKey="Bresolin N" first="Nereo" last="Bresolin">Nereo Bresolin</name><name sortKey="Caputo, Domenico" sort="Caputo, Domenico" uniqKey="Caputo D" first="Domenico" last="Caputo">Domenico Caputo</name><name sortKey="Clerici, Mario" sort="Clerici, Mario" uniqKey="Clerici M" first="Mario" last="Clerici">Mario Clerici</name><name sortKey="Clerici, Mario" sort="Clerici, Mario" uniqKey="Clerici M" first="Mario" last="Clerici">Mario Clerici</name><name sortKey="Comi, Giacomo P" sort="Comi, Giacomo P" uniqKey="Comi G" first="Giacomo P." last="Comi">Giacomo P. Comi</name><name sortKey="Forni, Diego" sort="Forni, Diego" uniqKey="Forni D" first="Diego" last="Forni">Diego Forni</name><name sortKey="Fumagalli, Matteo" sort="Fumagalli, Matteo" uniqKey="Fumagalli M" first="Matteo" last="Fumagalli">Matteo Fumagalli</name><name sortKey="Galimberti, Daniela" sort="Galimberti, Daniela" uniqKey="Galimberti D" first="Daniela" last="Galimberti">Daniela Galimberti</name><name sortKey="Guerini, Franca R" sort="Guerini, Franca R" uniqKey="Guerini F" first="Franca R." last="Guerini">Franca R. Guerini</name><name sortKey="Paraboschi, Elvezia M" sort="Paraboschi, Elvezia M" uniqKey="Paraboschi E" first="Elvezia M." last="Paraboschi">Elvezia M. Paraboschi</name><name sortKey="Pozzoli, Uberto" sort="Pozzoli, Uberto" uniqKey="Pozzoli U" first="Uberto" last="Pozzoli">Uberto Pozzoli</name><name sortKey="Riva, Stefania" sort="Riva, Stefania" uniqKey="Riva S" first="Stefania" last="Riva">Stefania Riva</name><name sortKey="Scarpini, Elio" sort="Scarpini, Elio" uniqKey="Scarpini E" first="Elio" last="Scarpini">Elio Scarpini</name><name sortKey="Sironi, Manuela" sort="Sironi, Manuela" uniqKey="Sironi M" first="Manuela" last="Sironi">Manuela Sironi</name><name sortKey="Sironi, Manuela" sort="Sironi, Manuela" uniqKey="Sironi M" first="Manuela" last="Sironi">Manuela Sironi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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