Genetic Test for a Mutation Causing Canine Hyperuricosuria Facilitates Selective Breeding to Produce Healthier Dogs
Hyperuricosuria, elevated levels of uric acid in urine, predisposes dogs to urate bladder stone formation which can lead to urinary blockage in male dogs. Hyperuricosuria has been a recognized health problem in the Dalmatian breed for almost 100 years. Hyperuricosuria is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, a multigenerational Dalmatian x Pointer backcross was used. A single Pointer ancestor contributed the normal allele that segregates in subsequent backcrosses to purebred Dalmatians. The interbreed backcross allowed linkage mapping of hyperuricosuria that was localized to CFA03 and positional cloning techniques defined a critical interval of 333 kb containing only four genes. Sequence analysis of SLC2A9, one of the four candidates, indicated a missense mutation (G616T;C188F) in exon 5 of the gene. The missense mutation is fully associated with hyperuricosuria in the Dalmatian breed since it is homozygous in all full blooded Dalmatians. The mutation segregates and is concordant with the urinary uric acid phenotype in the Bulldog and Black Russian Terrier breeds. Breeders can now DNA test their dogs in order to prevent the occurrence of urate stone disease by selecting against the hyperuricosuria mutation. Dalmatian breeders are encouraged to use the progeny of the backcross which are normal uric acid Dalmatians in their breeding programs.