Because of the frequency with which Irish wolfhounds were observed to have intrahepatic portosystemic shunts, the concentration of ammonia was measured in samples of venous blood taken at seven to eight weeks old from the 1066 Irish wolfhounds born in the Netherlands between 1984 and 1992. The average rate of incidence of the condition (defined as an ammonia concentration exceeding 150 microM) over this period was 2.1 per cent and it increased (P < 0.03) at an average annual rate of 0.34 per cent. The genetic similarity between the individual dogs with portosystemic shunts, defined by their degree of relationship (Rpq), was significantly higher (P < 0.00001) than either the Rpq among the control dogs which had an ammonia concentration below 46 microM or the Rpq between the affected dogs and the controls. Furthermore, the mean ammonia concentration in clinically normal Irish wolfhounds was higher than that in the healthy control dogs of various breeds (73.8 v 33.4 microM). The overrepresentation of portosystemic shunts in Irish wolfhounds, the increasing rate of incidence of the shunts, and the familial distribution of the animals with the condition are evidence for a hereditary basis for the disorder in this population.
Purebred dog populations have been subject to strong selection which has resulted in extreme differences between breeds and decreased heterogeneity within breeds. As a result, breed-specific inherited diseases have accumulated in many populations. The aim of this study was to analyse genetic heterogeneity in relation to the distribution of elbow dysplasia in labrador retrievers, portosystemic shunts in Irish wolfhounds, and hepatic copper toxicosis, in Bedlington terriers. Decreased heterogeneity was demonstrated in the multiple genetic interrelations in the three populations. In pedigrees containing seven generations of ancestors, the average number of common ancestors in all pair-wise combinations of dogs was five to six (range 0 to 18). These complex interrelationships were resolved by a cluster analysis on matrices of relatedness. This analysis gave clusters of highly related animals, the average relatedness of these clusters, and the average relatedness of the entire population, as expressions of its genetic variability. The mean relatedness was 0.032 for Irish wolfhounds and Bedlington terriers, and 0.002 for labrador retrievers. The labrador retriever cohort was resolved into 31 clusters, and all cases of elbow dysplasia were concentrated in five highly related clusters with an overall incidence of 17 per cent. The Bedlington terrier cohort consisted of 12 clusters which all contained cases of copper toxicosis, with an overall incidence of 46 per cent. The Irish wolfhounds were divided into 14 clusters with a disease incidence of 4 per cent. Dogs with portosystemic shunts were found in four averagely related clusters. A genetic distribution became obvious only when relatedness due to common ancestors of the cases was used as a criterion, and the cases were then concentrated in five highly related clusters.
Since purebred dog populations represent closed gene pools, a relatively high level of consanguinity between individuals, and hence of inbreeding, is common. This case control study was conducted to establish the possible connection between the actual level of homozygosity due to inbreeding and specific diseases (flea allergy, osteochondrosis, laryngeal paralysis, neoplasm, autoimmune disease, hypoplastic trachea, and food allergy) occurring in the Bouvier Belge des Flandres breed. One hundred and sixty-eight animals referred to the Utrecht University Clinic formed the patient group. Each of the seven diseases was chosen because of the demonstrability of the diagnosis. Each animal was chosen because one of the selected diseases was established in that individual, and because its pedigree was complete. All dogs of the patient group were born between 1 January 1980 and 31 December 1985. A control group (n = 123) was randomly chosen from the total population of registered Bouviers born in the Netherlands in the same period. pedigree data were obtained from the Dutch Kennel Club. The extent of inbreeding was determined for all animals using Wright's inbreeding coefficient. The distribution of inbreeding coefficients in each patient group was compared with the distribution in controls. Inbreeding coefficients in the control group ranged from 0.0 to 0.406. Animals in which osteochondrosis, food allergy, autoimmune disease, neoplasm, or hypoplastic trachea was diagnosed had higher inbreeding coefficients than controls. It was concluded that in the Bouvier Belge des Flandres dog population examined, the level of homozygosity was positively correlated with occurrence of these diseases.
As a result of strong selection in closed gene pools, dog breeds represent 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 purebred 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 combined breeding stock. This approach is independent of assumptions about modes of inheritance or thresholds. In a cohort study, all the common ancestors of the cases are selected and their degree of relatedness to both cases and controls is estimated. The ancestors which are positively 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 analysis is applied. Finally a logistic model, based on the principal components and the case control definitions, describes the most likely pattern of the passage of genetic risk factors down the generations. Estimates of relatedness to seven highly related ancestors were sufficient to describe the distribution of disease in a population of Dutch labrador retrievers. This approach may be used for genetic counselling for any clinical phenotypically dichotomous trait in such a highly related population of companion animals, and may also help to identify suitable dogs for molecular studies of the underlying defect.
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