Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs Dóra Koller1,2, Melinda Bence1,2, Enikő Kubinyi1 Anna Kis3,4, Zsuzsanna Elek2, Gabriella Lakatos1, Zsolt Rónai2, Ádám Miklósi1,3 koller.dora@med.semmelweis-univ.hu 1 MTA-ELTE Comparative Ethology Research Group, Hungary 2 Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary 3 Department of Ethology, Eötvös University, Budapest, Hungary 4 Research Centre for Natural Sciences, Institute of Cognitive Neuroscience and Psychology, Hungarian Academy of Sciences Introduction The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor (OXTR) gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are suitable models for behavioral genetic research. The aim of our study was to identify SNPs in the OXTR gene in different dog breeds, which could have associations with social behavior. Methods OXTR SNPs determined by direct sequencing Buccal DNA samples were collected from 792 dogs (Border Collies, German Shepherds, Siberian Huskies). 5’UTR 3’UTR Four SNPs (rs8679682, −212AG, −73CG and −49CG) were genotyped by PCR-RFLP method. Two polymorphisms (19131AG, rs8679684) were genotyped by real time PCR using sequence specific probes. Two SNPs (−93TC, rs22927829) were investigated by allelespecific amplification (ASA). rs8679682 -93TC 100bp ladder 100bp ladder CT CC TT CC TT CC −212AG Results Proximity seeking scores mean differences between the different −212AG genotypes in German Shepherds (a) and Border Collies (b). We found that OXTR SNPs are associated with human directed social behavior in dogs. We have constructed a test series containing five different sub-tests (greeting by a stranger, separation from the owner, problem solving, threatening approach, hiding), for characterizing the behavioral phenotype. These tests revealed dogs’ socio-cognitive skills when interacting with humans. Behavioral variables were grouped by Principal Component Analysis into four scales (friendliness, attachment, trust, referential looking). We used ANOVA for analyzing the genotype-phenotype association. F = 4.030, p = 0.021 t = 2.282, p = 0.025 As a result of linkage disequilibrium the 19131AG polymorphism, similarly to the rs8679684 SNP, was associated with Friendliness both in case of German Shepherds and Border Collies. 19131AG t = 2.800, p = 0.013 t = 2.724, p = 0.008 Conclusion This work was supported by the Hungarian Scientific Research Fund K 84036 and by the Hungarian Academy of Sciences (MTA 01 031). Our results suggest that the single nucleotide polymorphisms in the OXTR gene might contribute to the genetic backround of dog social behavior. These SNPs probably influence the regulation of mRNA expression level. Our results indicate that the identified SNPs are polymorphic among the different dog breeds.The differences of these genetic variations between dog and wolf populations might be related to the domestication process of dogs.