2026-06-14T03:28:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/73472024-10-31T11:40:55Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Spieler, Derek
author
Kaffe, Maria
author
Knauf, Franziska
author
Bessa, José
author
Tena, Juan J
author
Giesert, Florian
author
Schormair, Barbara
author
Tilch, Erik
author
Lee, Heekyoung
author
Horsch, Marion
author
Czamara, Darina
author
Karbalai, Nazanin
author
von Toerne, Christine
author
Waldenberger, Melanie
author
Gieger, Christian
author
Lichtner, Peter
author
Claussnitzer, Melina
author
Naumann, Ronald
author
Müller-Myhsok, Bertram
author
Torres, Miguel
author
Garrett, Lillian
author
Rozman, Jan
author
Klingenspor, Martin
author
Gailus-Durner, Valérie
author
Fuchs, Helmut
author
Hrabě de Angelis, Martin
author
Beckers, Johannes
author
Hölter, Sabine M
author
Meitinger, Thomas
author
Hauck, Stefanie M
author
Laumen, Helmut
author
Wurst, Wolfgang
author
Casares, Fernando
author
Gómez-Skarmeta, Jose Luis
author
Winkelmann, Juliane
funder
Fritz Thyssen Foundation
funder
German Academic Exchange Service
funder
Unión Europea. European Cooperation in Science and Technology (COST)
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
Helmholtz Zentrum München
funder
Federal Ministry of Education & Research (Alemania)
funder
Ludwig-Maximilians-Universität München (Alemania)
funder
Ministerio de Ciencia e Innovación (España)
funder
Regional Government of Andalusia (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2019-03-15T14:21:38Z
2019-03-15T14:21:38Z
2014-04
Genome Res. 2014; 24(4):592-603
10.1101/gr.166751.113
1549-5469
1088-9051
Genome research
24642863
http://hdl.handle.net/20.500.12105/7347
Genome-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.
eng
Restless legs syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon
journal article
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