Cluster analysis of the genetic heterogeneity and disease distributions in purebred dog populations

Abstract

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.

Lifespan and disease predispositions in the Irish Wolfhound: A review

“…In Irish Wolfhounds, this condition has been reported to occur in 2.1% to 3.4% of all puppies and 18% of all litters (39,46,62). Furthermore, its prevalence in the offspring of certain individual Wolfhounds has been reported to be as high as 15% (61).…”

“…Wolfhounds is hereditary (46), and a method for predicting its occurrence through pedigree analysis was discussed in 1998 (61,62). Intrahepatic PSS was later described to follow a simple autosomal recessive mode of inheritance (57).…”

Population Dynamics of Inherited Copper Toxicosis in Dutch Bedlington Terriers (1977–1997)

“…Such populations have been reported to be in fact complex familial webs of highly interrelated dogs. 9 Resolution of the population into clusters of related animals reduces the complexity to a surveyable structure. In the Dutch Bedlington Terriers of the 1st cohort the different clusters seemed to be highly related and the population had little heterogeneity.…”

“…These methods have been reported in detail. 9 The population was resolved into a number of clusters of highly related dogs. This analysis gives the number of clusters, the relatedness between the clusters, and the average relatedness of the entire population as expression of its genetic heterogeneity.…”

“…Ubbink and others 9 have reported epidemiologic techniques to resolve a population into clusters of closely related dogs and to analyze the distribution of an inherited disease over the clusters. This provides a measure of the potential genetic heterogeneity of the population, and an indication of the possibilities of selecting between related clusters against the disease.…”