Canine separation-related distress: investigating phenotype and genetic basis

Abstract

Canine separation-related distress (SRD) is a debilitating and common disorder in companion dogs. Affected dogs show physiological and behavioural signs of distress when left alone or separated from certain family members. Commonly reported signs are vocalisation, destruction and house-soiling. The disorder can reduce the quality of life of affected dogs and compromise the bond between dogs and owners. Canine SRD is likely to have a significant inherited component. The aims of this thesis were to review current knowledge of SRD, investigate the use of a questionnaire to phenotype SRD, and to identify associated genomic regions of interest. Populations of Labrador retrievers and golden retrievers from across Australia were phenotyped using an owner-based behaviour questionnaire that was validated by comparing the owner’s questionnaire responses to video footage of the dogs when left alone. To explore the genes that may influence the disorder, both a quantitative genome-wide association study and case/control candidate studies were performed. Four candidate genes associated with attachment were examined: oprm1, drd2, avpr1a and oxtr. One haplotype flanking drd2 demonstrated a significant association with SRD in a cohort of 55 golden retrievers. Genome-wide association analysis of our cohort of 90 Labrador retrievers identified a novel locus on chromosome 1 to be the most strongly associated with SRD. These findings of this work are preliminary. Future steps include validating our findings in a larger naïve phenotyped population, and sequencing the region of interest to identify mutations. Identifying the genetic basis of the disorder enables us to capture that elusive biology linking inheritance and behaviour. This can potentially lead to the development of more targeted pharmacological treatments or early identification of at-risk dogs, allowing for early therapeutic interventions