Comparative Ethology Research Group, MTA-ELTE, Budapest, Hungary.
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
BMC Genet. 2020 Jul 28;21(1):82. doi: 10.1186/s12863-020-00879-7.
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.
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.
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.
虽然沃弗林蛋白的分子功能仍不清楚，但已知这种蛋白质的缺乏会导致内质网应激。沃夫勒姆综合征 1 基因（WFS1）的一些变体与人类的各种神经精神疾病有关，如攻击性、冲动性和焦虑症。
我们在此介绍了一项对犬 WFS1 基因中单个核苷酸多态性（rs852850348）的计算机研究，该多态性通过直接测序和基于 PCR 的技术进行了基因分型。我们发现 rs852850348 多态性位于一个假定的 microRNA（cfa-miR-8834a 和 cfa-miR-1838）结合位点。因此，我们在荧光素酶报告基因系统中研究了等位基因变异的分子效应，该系统允许评估基因表达。我们证明，该变体以等位基因特异性的方式降低了报告蛋白表达的活性。此外，我们进行了一项行为实验，并研究了该基因座与该测试中不同表现的关联。在边境牧羊犬品种中发现了食物占有欲与研究中的 WFS1 基因多态性之间的关联。
基于我们的发现，rs852850348 位点可能至少在一个品种中导致犬类占有欲行为的遗传风险，并可能影响沃弗林蛋白表达的调节。
