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dc.contributor.authorSpieler, Derek
dc.contributor.authorKaffe, Maria
dc.contributor.authorKnauf, Franziska
dc.contributor.authorBessa, José
dc.contributor.authorTena, Juan J
dc.contributor.authorGiesert, Florian
dc.contributor.authorSchormair, Barbara
dc.contributor.authorTilch, Erik
dc.contributor.authorLee, Heekyoung
dc.contributor.authorHorsch, Marion
dc.contributor.authorCzamara, Darina
dc.contributor.authorKarbalai, Nazanin
dc.contributor.authorvon Toerne, Christine
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorGieger, Christian
dc.contributor.authorLichtner, Peter
dc.contributor.authorClaussnitzer, Melina
dc.contributor.authorNaumann, Ronald
dc.contributor.authorMüller-Myhsok, Bertram
dc.contributor.authorTorres, Miguel 
dc.contributor.authorGarrett, Lillian
dc.contributor.authorRozman, Jan
dc.contributor.authorKlingenspor, Martin
dc.contributor.authorGailus-Durner, Valérie
dc.contributor.authorFuchs, Helmut
dc.contributor.authorHrabě de Angelis, Martin
dc.contributor.authorBeckers, Johannes
dc.contributor.authorHölter, Sabine M
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorHauck, Stefanie M
dc.contributor.authorLaumen, Helmut
dc.contributor.authorWurst, Wolfgang
dc.contributor.authorCasares, Fernando
dc.contributor.authorGómez-Skarmeta, Jose Luis
dc.contributor.authorWinkelmann, Juliane
dc.identifier.citationGenome Res. 2014; 24(4):592-603es_ES
dc.description.abstractGenome-wide association studies (GWAS) identified the MEIS1 locus for Restless Legs Syndrome (RLS), but causal single nucleotide polymorphisms (SNPs) and their functional relevance remain unknown. This locus contains a large number of highly conserved noncoding regions (HCNRs) potentially functioning as cis-regulatory modules. We analyzed these HCNRs for allele-dependent enhancer activity in zebrafish and mice and found that the risk allele of the lead SNP rs12469063 reduces enhancer activity in the Meis1 expression domain of the murine embryonic ganglionic eminences (GE). CREB1 binds this enhancer and rs12469063 affects its binding in vitro. In addition, MEIS1 target genes suggest a role in the specification of neuronal progenitors in the GE, and heterozygous Meis1-deficient mice exhibit hyperactivity, resembling the RLS phenotype. Thus, in vivo and in vitro analysis of a common SNP with small effect size showed allele-dependent function in the prospective basal ganglia representing the first neurodevelopmental region implicated in RLS.es_ES
dc.description.sponsorshipThe project was supported by Fritz-Thyssen-Stiftung, Cologne, Germany (;, KKF-TUM (8766156), DAAD (0811963), and COST (‘‘HOX and TALE homeoproteins in Development and Disease’’). B.S. was partially supported by DFG grants (WI 1820/4-1; WI 1820/5-1) and a TUM-Excellence stipend. The KORA study was financed by the Helmholtz ZentrumMunchen, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. KORA research was supported within the Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-Universita¨t, as part of LMUinnovativ. J.L.G.-S. and F.C. acknowledge funding of the Spanish and the Andalusian Governments and the Feder program for grants (BFU2010-14839, BFU2009-07044, CSD2007-00008, and Proyectos de Excelencia CVI-3488 and CVI 2658). This work was funded in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD), to the German Mouse Clinic (Infrafrontier: 01KX1012), to the German Center for Neurodegenerative Diseases (DZNE), Germany; by the Initiative and Networking Fund of the Helmholtz Association in the framework of the Helmholtz Alliance for Mental Research in an Ageing Society (HA-215); and the Munich Cluster for Systems Neurology (EXC 1010 SyNergy) and its Collaborative Research Center (CRC) 870/2 ‘‘Assembly and Function ofNeuronal Circuits.’’es_ES
dc.publisherCold Spring Harbor Laboratory Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAlleles es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBasal Ganglia es_ES
dc.subject.meshDisease Models, Animales_ES
dc.subject.meshGenome-Wide Association Study es_ES
dc.subject.meshHomeodomain Proteins es_ES
dc.subject.meshIntrons es_ES
dc.subject.meshMice es_ES
dc.subject.meshMyeloid Ecotropic Viral Integration Site 1 Protein es_ES
dc.subject.meshNeoplasm Proteins es_ES
dc.subject.meshPolymorphism, Single Nucleotidees_ES
dc.subject.meshRestless Legs Syndrome es_ES
dc.subject.meshTelencephalon es_ES
dc.subject.meshEnhancer Elements, Genetices_ES
dc.titleRestless legs syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalones_ES
dc.rights.licenseAtribución-NoComercial 4.0 Internacional*
dc.contributor.funderFritz Thyssen Foundationes_ES
dc.contributor.funderDAAD (Germany)es_ES
dc.contributor.funderEuropean Cooperation in Science and Technology. COSTes_ES
dc.contributor.funderDeutsche Forschungsgemeinschaftes_ES
dc.contributor.funderHelmholtz-Zentrum Munchenes_ES
dc.contributor.funderBundesministerium für Bildung und Forschung (Germany)es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderJunta de Andaluciaes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.identifier.journalGenome researches_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Control Genético del Desarrollo y Regeneración de Órganoses_ES

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Atribución-NoComercial 4.0 Internacional
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