225: Establishing a Genetic Linkage Between Addison's Disease and DNA Markers

Project Summary

Addison's disease is a late onset disorder caused by deterioration of the adrenal gland cortex. Although Addison's disease occurs in the general canine population, the existence of Addisonian dogs repeatedly appearing in pedigrees of certain dogs led breeders to speculate that Addison's disease is inherited. Although Addison's disease occurs in the dog population as a whole, within certain breeds there has been a higher than expected incidence noted. We have determined the heritability and mode of inheritance if feasible in the Standard Poodle, Great Dane, West Highland White Terrier, Bearded Collie, Portuguese Water Dog, and Leonberger. In all breeds except the Great Dane (which currently lacks the necessary numbers of dogs enrolled in the study) the heritability for Addison's disease is greater than 0.7 indicating a very large degree of genetic regulation. Complex segregation analyses confirm the genetic component and suggest that the best fit mode of inheritance is autosomal recessive with modifying genes. In other words, Addison's appears to be polygenic but with a major controlling gene. The lesser genes likely regulate the age of onset and the progression of the disorder. Of note, is that there is no sex affect in any of the breeds reflecting an equal number of males and females diagnosed with Addison's disease. Based upon these findings, the investigators have approached the genetic linkage study in several ways using candidate loci chosen for their involvement in normal immune function and cell recognition and microsatellite markers. The causative genetic association for Addison's disease continues to be explored.

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