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  Assessment of microRNA-related SNP effects in the 3' untranslated region of the IL22RA2 risk locus in multiple sclerosis

Lill, C., Schilling, M., Ansaloni, S., Schröder, J., Jaedicke, M., Luessi, F., et al. (2014). Assessment of microRNA-related SNP effects in the 3' untranslated region of the IL22RA2 risk locus in multiple sclerosis. Neurogenetics, 15(2), 129-134. doi:10.1007/s10048-014-0396-y.

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art_10.1007_s10048-014-0396-y.pdf (Verlagsversion), 438KB
 
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2014-01-01
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Springer-Verlag Berlin Heidelberg 201
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 Urheber:
Lill, Christina1, Autor           
Schilling, Marcel1, Autor           
Ansaloni, Sara1, Autor           
Schröder, Julia, Autor
Jaedicke, Marian, Autor
Luessi, Felix, Autor
Schjeide, Brit-Maren1, Autor           
Mashychev, Andriy, Autor
Graetz, Christiane, Autor
Akkad, Denis, Autor
Gerdes, Lisa-Ann, Autor
Kroner, Antje, Autor
Blaschke, Paul, Autor
Hoffjan, Sabine, Autor
Winkelmann, Alexander, Autor
Dörner, Thomas, Autor
Rieckmann, Peter, Autor
Steinhagen-Thiessen, Elisabeth, Autor
Lindenberger, Ulman2, Autor           
Chan, Andrew, Autor
Hartung, Hans-Peter, AutorAktas, Orhan, AutorLohse, Peter, AutorButtmann, Mathias, AutorKümpfel, Tania3, Autor           Kubisch, Christian, AutorZettl, Uwe, AutorEpplen, Jörg T.3, Autor           Zipp, Frauke3, Autor           Bertram, Lars1, Autor            mehr..
Affiliations:
1Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479655              
2Center for Lifespan Psychology, Max Planck Institute for Human Development, Max Planck Society, ou_2074288              
3Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

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 Zusammenfassung: Recent large-scale association studies have identified over 100 MS risk loci. One of these MS risk variants is single-nucleotide polymorphism (SNP) rs17066096, located ~14 kb downstream of IL22RA2. IL22RA2 represents a compelling MS candidate gene due to the role of IL-22 in autoimmunity; however, rs17066096 does not map into any known functional element. We assessed whether rs17066096 or a nearby proxy SNP may exert pathogenic effects by affecting microRNA-to-mRNA binding and thus IL22RA2 expression using comprehensive in silico predictions, in vitro reporter assays, and genotyping experiments in 6,722 individuals. In silico screening identified two predicted microRNA binding sites in the 3'UTR of IL22RA2 (for hsa-miR-2278 and hsa-miR-411-5p) encompassing a SNP (rs28366) in moderate linkage disequilibrium with rs17066096 (r (2) = 0.4). The binding of both microRNAs to the IL22RA2 3'UTR was confirmed in vitro, but their binding affinities were not significantly affected by rs28366. Association analyses revealed significant association of rs17066096 and MS risk in our independent German dataset (odds ratio  = 1.15, P = 3.48 × 10(-4)), but did not indicate rs28366 to be the cause of this signal. While our study provides independent validation of the association between rs17066096 and MS risk, this signal does not appear to be caused by sequence variants affecting microRNA function.

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Sprache(n): eng - English
 Datum: 2014-02-112014-02-272014-03-18
 Publikationsstatus: Online veröffentlicht
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 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: DOI: 10.1007/s10048-014-0396-y
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Titel: Neurogenetics
  Andere : Neurogenetics
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Oxford, UK : Oxford University Press
Seiten: - Band / Heft: 15 (2) Artikelnummer: - Start- / Endseite: 129 - 134 Identifikator: ISSN: 1364-6745
CoNE: https://pure.mpg.de/cone/journals/resource/954927741865