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The molecular effect of a polymorphic microRNA binding site of Wolfram syndrome 1 gene in dogs.
BMC Genetics ( IF 2.9 ) Pub Date : 2020-07-28 , DOI: 10.1186/s12863-020-00879-7
Dora Koller 1, 2, 3 , Eniko Kubinyi 1, 3 , Zsuzsanna Elek 2 , Helga Nemeth 2 , Adam Miklosi 1, 3 , Maria Sasvari-Szekely 2 , Zsolt Ronai 2
Affiliation  

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.

中文翻译:

Wolfram综合征1基因在狗中的多态性microRNA结合位点的分子效应。

尽管狼精蛋白的分子功能尚不清楚,但是已知缺乏这种蛋白会引起内质网的应激。Wolfram综合症1基因(WFS1)的某些变异与人类的各种神经精神疾病有关,例如攻击性,冲动性和焦虑性。在这里,我们进行了一项计算机模拟研究,预测犬WFS1基因中的单核苷酸多态性(rs852850348),该基因已通过直接测序验证并通过基于PCR的技术进行了基因分型。我们发现rs852850348多态性位于推定的microRNA(cfa-miR-8834a和cfa-miR-1838)结合位点。因此,在允许评估基因表达的荧光素酶报道系统中研究了等位基因变体的分子效应。我们证明了该变体以等位基因特异性的方式降低了报道蛋白表达的活性。此外,我们进行了一项行为实验,并研究了与该基因座与本次测试中不同表现的关联。发现食物的占有率与边境牧羊犬品种中研究的WFS1基因多态性之间存在关联。根据我们的发现,rs852850348基因座可能会导致至少一个品种的犬拥有性行为的遗传风险,并可能影响Wolframin表达的调节。
更新日期:2020-07-28
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