Mapping and identification of the mutation causing Progressive Retinal Atrophy (PRA) in Shetland sheepdog

Prosjektet har hatt en god framdrift. Etter at vi tidligere i prosjektet identifiserte en genomisk region der det finnes risikogener for sykdommen har vi i 2014 og 2015 fortsatt arbeidet med å beskrive den genomiske regionen. Totalt har det vært samlet inn blodprøver fra ca 220 hunder, 31 hunder med typisk PRA, 23 hunder med den lignende øyesykdommen retinopati og 165 friske controller. Gjennom mutasjonsanalyse har vi identifisert et gen og en mutasjon som kan ha sammenheng med denne øyesykdommen hos shelties samt formell dokumentasjon av mutasjonen. Prosjektgruppen oppdaget at at det antagelig finnes to ulike typer PRA hos shelties, i tillegg til øyesykdommen retinopati. Det er nå utarbeidet en gentlest som kan tilbys eiere av shelties for den ene varianten av PRA hos shelties som vi har identifisert, som var hovedmålet for prosjektet.

The dog population harbour a number of inherited diseases, both diseases with a simple Mendelian inheritance and disorders with a quantitative genetic background. As a result of the sequencing of the canine genome, the development of state-of-the-art gene tic tools, including genomic SNP-arrays, expression arrays etc., it has become relatively easy to identify genes associated with canine diseases. The structure of the canine dog populations, with a number of breeds, often with a limited genetic variation, long regions of evolutionary concerved haplotypes (long LD) and often with a high frequency of specific inherited diseases, provide an optimal model for the identification of inherited disorders. Progressive retinal atrophy is among the most frequently occurring inherited diseases in dogs, and yearly reduce the life quality of a high number of dogs in a high number of breeds. In many breeds the breeding programs, based on clinical tests to identify diseased dogs, are higly inefficient and very costly f or the owner. Similar inherited diseases is also frequently occurring in human. Blood samples have been collected from approximately 20 cases and 40 controls. We plan to perform a genome wide association study using genomic SNP-microarrays in an effort to identify haplotypes linked to the disease. The number of samples needed for identification of linked haplotypes to autosomal recessive diseases is 20 cases and 20 controls. We recently identiied the causual mutation of a similar eye disease using 14 case s and 14 controls. A close collaboration is established between Norwegian School of Veterinary Science (Dep of Basic Science & Aquatic Medicine and Dep of Companion Animal Clinical Sciences) and "Broad Institute" in Boston, US. ". The high competence in t he "consortium", the available samples and the excellent laboratory facilities should make a high likelihood of success in the project.