The molecular effect of a polymorphic microRNA binding site of Wolfram syndrome 1 gene in dogs
Autor: | Ádám Miklósi, Zsolt Ronai, Dora Koller, Maria Sasvari-Szekely, Eniko Kubinyi, Zsuzsanna Elek, Helga Nemeth |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male lcsh:QH426-470 Genotype Wolfram syndrome In silico Single-nucleotide polymorphism Locus (genetics) Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Dogs microRNA Gene expression Genetics medicine Dog Animals Dog Diseases Allele Polymorphism Gene Genetics (clinical) Alleles miRNA Behavior Binding Sites Membrane Proteins Wolfram Syndrome medicine.disease WFS1 lcsh:Genetics MicroRNAs 030104 developmental biology Female 030217 neurology & neurosurgery Research Article |
Zdroj: | BMC Genetics BMC Genetics, Vol 21, Iss 1, Pp 1-10 (2020) |
ISSN: | 1471-2156 |
Popis: | Background Although the molecular function of wolframin remains unclear, the lack of this protein is known to cause stress in the endoplasmic reticulum. Some variants in the Wolfram Syndrome 1 gene (WFS1) were associated with various neuropsychiatric disorders in humans, such as aggressiveness, impulsivity and anxiety. Results Here we present an in silico study predicting a single nucleotide polymorphism (rs852850348) in the canine WFS1 gene which was verified by direct sequencing and was genotyped by a PCR-based technique. We found that the rs852850348 polymorphism is located in a putative microRNA (cfa-miR-8834a and cfa-miR-1838) binding site. Therefore, the molecular effect of allelic variants was studied in a luciferase reporter system that allowed assessing gene expression. We demonstrated that the variant reduced the activity of the reporter protein expression in an allele-specific manner. Additionally, we performed a behavioral experiment and investigated the association with this locus to different performance in this test. Association was found between food possessivity and the studied WFS1 gene polymorphism in the Border collie breed. Conclusions Based on our findings, the rs852850348 locus might contribute to the genetic risk of possessivity behavior of dogs in at least one breed and might influence the regulation of wolframin expression. |
Databáze: | OpenAIRE |
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