Genetics of Hereditary Ataxia in Scottish Terriers.

Abstract

BackgroundScottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction.ObjectiveTo identify chromosomal regions associated with hereditary ataxia in Scottish Terriers.AnimalsOne hundred and fifty‐three Scottish Terriers were recruited through the Scottish Terrier Club of America.Materials and MethodsProspective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome‐wide mapping was performed using both linkage‐ and association‐based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively.ResultsLinkage and genome‐wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information.Conclusion and Clinical ImportanceThis finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed.