Presenter Bruno Lopes
Authors Bruno Lopes1,2, Ellen Schofield1, Katherine Stanbury1, Louise Pettitt1, Paul Freeman3, Cathryn Mellersh1
Affiliations 1 The Canine Genetics Centre, University of Cambridge, Cambridge, United Kingdom. 2 Southfields Veterinary Specialists, Basildon, United Kingdom. 3 Queens Veterinary School Hospital, University of Cambridge, Cambridge, United Kingdom.
Presentation Type Talk
Abstract
Congenital peripheral vestibular disorder is rare in dogs, and has only previously been described in Dobermann Pinscher, English Cocker Spaniel, and German Shepherd breeds. Genetic mutations in the MYO7A and PTPRQ genes have been previously reported as associated.
Two puppies in a litter of nine Welsh Springer Spaniels (WSS) showed circling and rolling from one week of age. Examination of both puppies revealed peripheral vestibular signs, and investigations with magnetic resonance imaging at two months old did not reveal any structural abnormality. Additionally, one other puppy from a litter of five, which was two years old and closely related to the affected puppies, was reported to have had similar signs which stabilised over time. An autosomal recessive genetic causal variant was hypothesised.
DNA Samples were obtained from both affected families (parents and affected and unaffected progeny) and whole genome sequencing (WGS) was undertaken. Pipeline variant filtering, profiling and parentage analysis, analysis for runs of homozygosity, genome-wide association studies, and structural variant detection were performed.
Following thorough analysis, including filtering for correct segregation, an intronic, single nucleotide variant (SNV) in the MYO7A gene was identified. Splice site analysis (SpliceAI) was suggestive of a possible new donor splice site gain.
A novel intronic SNP mutation associated with canine congenital vestibular disease has been identified. Further in-silico and RNA analysis is necessary to confirm the RNA expression of the MYO7A gene in affected and non-affected dogs as well as possible protein stability.