LUPA · Unravelling the molecular basis of common complex human disorders using the dog as a model system

Despite major efforts, identifying susceptibility genes for common human diseases - cancer, cardiovascular, inflammatory and neurological disorders - is difficult due to the complexity of the underlying causes. The dog population is composed of ~ 400 purebred breeds; each one is a genetic isolate with unique characteristics resulting from persistent selection for desired attributes or from genetic drift / inbreeding. Dogs tend to suffer from the same range of diseases than human but the genetic complexity of these diseases within a breed is reduced as a consequence of the genetic drift and – due to long-range linkage disequilibrium – the number of SNP markers needed to perform whole genome scans is divided by at least ten. Here, we propose a European effort gathering experts in genomics to take advantage of this extraordinary genetic model. Veterinary clinics from 12 European countries will collect DNA samples from large cohorts of dogs suffering from a range of thoroughly defined diseases of relevance to human health. Once these different cohorts will be built, DNA samples will be sent to a centralized, high-throughput SNP genotyping facility. The SNP genotypes will be stored in central database and made available to participating collaborating centres, who will analyze the data with the support of dedicated statistical genetics platforms. Following genome wide association and fine-mapping candidate genes will be followed up at the molecular level by expert animal and human genomics centers. This innovative approach using the dog model will ultimately provide insights into the pathogenesis of common human diseases – its primary goal.