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| Status |
Public on Jan 29, 2014 |
| Title |
Restless Legs Syndrome-associated variant in MEIS1 confers altered gene expression in embryonic ganglionic eminences |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Genome-wide association studies (GWASs) identified the MEIS1 locus for Restless Legs Syndrome (RLS), but causal single nucleotide polymorphisms (SNPs) and the functional relevance have remained to be elucidated. The MEIS1 locus contains an exceptionally large number of highly conserved non-coding regions (HCNRs), which potentially function as cis-regulatory modules. We analyzed the HCNRs in the RLS-associated linkage disequilibrium (LD) block for allele-dependent enhancer activity in both zebrafish and mouse, comparing the protective and risk alleles of RLS-associated common variants. We found one enhancer, harboring the lead SNP rs12469063, which showed an allele-dependent reduction of reporter gene expression exclusively in the embryonic ganglionic eminences at developmental stage E12.5. Notably, the reporter activity overlapped with the endogenous telencephalic Meis1 expression domain, which co-localized with transcripts of all four validated RLS loci. Thus, the developing telencephalon represents the first neuroanatomic region implicated for RLS based on GWAS findings.
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| Overall design |
Total RNA obtained from 2-3 male and female mice E12.5 (wildtype, heterzygote, homozygote) and 3-4 male heterozygote and wildtype mice (adult)
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| Contributor(s) |
Beckers J, Horsch M |
| Citation(s) |
24642863 |
| |
| Submission date |
Feb 22, 2013 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Martin Irmler |
| Organization name |
Helmholtz Zentrum München GmbH
|
| Department |
Institute of Experimental Genetics
|
| Lab |
Gene Regulation & Epigenetics
|
| Street address |
Ingolstaedter Landstrasse 1
|
| City |
Neuherberg |
| State/province |
Bayern |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA190599 |
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