Bioinformatic analysis of a potential hereditary disease in New Zealand police dogs : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Animal Science, Massey University, Palmerston North, New Zealand

Abstract

Dogs have been used as working animals for centuries, one more recent example being the German Shepherd Dog (GSD) being trained and utilised as police dogs. Problems can arise from diseases associated to specific breeds, as well as the increased risks of inbreeding within already limited populations. This study aimed to investigate the genetic cause of an unknown illness seen in four dogs from a litter of seven GSD puppies bred for the New Zealand police dog section. Four nine-month-old GSDs presented with clinical symptoms of severe exercise intolerance, and extremely elevated muscle enzymes (creatine kinase, alanine aminotransferase and aspartate transferase) post-exercise. A muscle biopsy of an affected dog gave insufficient evidence for conclusive diagnosis, leading to subsequent whole genome sequencing. Various bioinformatic filters were applied to the sequence data from all seven puppies, and the dam and sire, to determine the mode of inheritance for the affected phenotype. Sex-linked, autosomal dominant and mitochondrial inheritance were ruled out due to a lack of evidence, which suggests that autosomal recessive inheritance was likely. The recessive filtering marked variants where the affected animals had a homozygous affected haplotype, and the parents were both heterozygous. Unaffected animals could be either heterozygous or homozygous unaffected. There were 94 variants across 30 different genes estimated to have either moderate or high impact. Further filters reduced this to four candidate variants, in the genes BOP1, IQANK1, THEMIS2, and ZNF517. None of the genes identified were directly associated with exercise tolerance in the affected phenotype, therefore it remains unclear whether one or a combination of these may be the cause of the phenomenon presented in affected animals. Variants were almost exclusively found across a 21 million base pair region on chromosome 2 and a 10 million base pair region on chromosome 13. This is a possible indication of a larger structural issue within the affected animals; however, it was not within the scope of this study to investigate this further. With inconclusive evidence, no single variant can be nominated as the likely causal variant, but considering the welfare implications of the affected condition, alongside their inability to continue their training as police dogs, all nine animals should be removed from further breeding to prevent the spread of the deleterious alleles.