RISK ESTIMATES FOR DICHOTOMOUS GENETIC-DISEASE TRAITS BASED ON A COHORT STUDY OF RELATEDNESS IN PUREBRED DOG-POPULATIONS

As a result of strong selection in closed gene pools, dog breeds repre sent populations of highly related animals. Prominent founder-effects are responsible for inherited diseases occurring in particular breeds, and each breed may have several breed-related diseases, often with a high incidence, Such inherited diseases are a major problem in purebre d dog populations, and probably threaten their survival. On the basis of pedigree information held by the National Kennel Clubs and reliable medical data of a representative longitudinal cohort, estimates have been made of the relative risks of dichotomous disease traits in all c ombined breeding stock. This approach is independent of assumptions ab out modes of inheritance or thresholds. In a cohort study, all the com mon ancestors of the cases are selected and their degree of relatednes s to both cases and controls is estimated. The ancestors which are pos itively associated with the dichotomous disease trait are selected on the basis of scores of relatedness. To reduce the number of parameters , while maintaining maximal informativeness, a principal component ana lysis is applied. Finally a logistic model, based on the principal com ponents and the case control definitions, describes the most likely pa ttern of the passage of genetic risk factors down the generations. Est imates of relatedness to seven highly related ancestors were sufficien t to describe the distribution of disease in a population of Dutch lab rador retrievers. This approach may be used for genetic counselling fo r any clinical phenotypically dichotomous trait in such a highly relat ed population of companion animals, and may also help to identify suit able dogs for molecular studies of the underlying defect.