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Multicapillary gel electrophoresis based analysis of genetic variants in the WFS1 gene
Author(s) -
Elek Zsuzsanna,
Dénes Réka,
Prokop Susanne,
Somogyi Anikó,
Yowanto Handy,
Luo Jane,
Souquet Manfred,
Guttman András,
Rónai Zsolt
Publication year - 2016
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201600251
Subject(s) - genetics , linkage disequilibrium , biology , genotyping , multiplex , allele , genetic association , snp , genotype , snp genotyping , gene , single nucleotide polymorphism
The WFS1 gene is one of the thoroughly investigated targets in diabetes research, variants of the gene were suggested to be the genetic components of the common forms (type 1 and type 2) of diabetes. Our project focused on the analysis of polymorphisms (rs4689388, rs148797429, rs4273545) localized in the WFS1 promoter region. Although submarine gel electrophoresis based approaches were also employed in the genetic tests, it was demonstrated that multicapillary electrophoresis offers a state of the art approach for reliable high‐throughput SNP and VNTR analysis. Association studies were carried out in a case–control setup. Luciferase reporter assay was employed to test the effect of the investigated loci on the activity of gene expression in vitro. Significant association could be demonstrated between all three polymorphisms and type 2 diabetes in both allele‐ and genotype‐wise settings even using Bonferroni correction. It is notable; however, that the three loci were in strong linkage disequilibrium, thus the observed associations cannot be considered as separate effects. Molecular analyses showed that the rs4273545 GT SNP played a role in the regulation of transcription in vitro. However, this effect took place only in the presence of the region including the rs148797429 site, although this latter locus did not have its own impact on the regulation of gene expression. The paper provides genotyping protocols readily applicable in any multiplex SNP and VNTR analyses, moreover confirms and extends previous results about the role of WFS1 polymorphisms in the genetic risk of diabetes mellitus.