Linkage studies of the esterase D and retinoblastoma genes to canine copper toxicosis: a model for Wilson disease.

Canine copper toxicosis, an autosomal recessive disorder, is prevalent among certain dog breeds. It results in liver disease from copper accumulation and toxicity similar to the human autosomal recessive disorder, Wilson disease. The Wilson disease locus has been mapped to 13q and is closely linked to the esterase D and retinoblastoma genes. We developed informative polymorphic systems in the dog using the human cDNA clones of the esterase D and retinoblastoma loci as probes. We investigated the linkage relationship of these two loci to the copper toxicosis locus, and to each other in the dog. Our results indicate that none of the loci are closely linked in the dog. Linkage of copper toxicosis to the retinoblastoma locus can be excluded up to 13% recombination, and to esterase D up to 5% recombination. Furthermore, esterase D and retinoblastoma, tightly linked in the mouse and human genomes, are not found to be closely linked in the canine genome.