Gene Mutation Identified as Culprit in Familial Nephropathy
After 60 years of grappling with Familial Nephropathy, a hereditary disease that kills English cocker spaniels, veterinary researchers at Texas A&M University have pinpointed a recessive gene that causes it. George Lees, DVM, MS, DACVIM, and a team of veterinary professionals are talking to genetic test providers to produce a mutation-based DNA test to identify carriers.
The test, which may be available within the next six months, could sell for $75 to $100, said Lees, who introduced his findings earlier this month at the ACVIM meeting.
“We will now be able to eradicate the mutated gene from the breed within one generation,” he said. “This is a brand new discovery.”
Research began in the spring of 1993 with characterization of the clinical and pathological features of the disease. Immunostaining methods (the use of a coloring agent to show proteins within an antibody) showed that structural proteins were missing from basement membranes in the kidneys of affected dogs, Lees said. To find the causative mutation, a veterinary genetics team led by Keith Murphy, PhD, director of the canine genetics laboratory at Texas A&M University, used molecular genetic techniques to search genes that encode those proteins.
The group discovered that an IV collagen gene (COL4A4) had a premature stop code that caused Familial Nephropathy, which was originally called renal cortical hypoplasia. There is no cure for the disease, which is carried by one in four English cocker spaniels. The only treatments are dialysis or transplantation, which are not practical solutions for dogs with this disease, Lees said. Dogs affected by the disease develop kidney failure and die at about one year of age, he told reporters.
Once produced, the test can be used by veterinarians to analyze a dog’s DNA sample (from the cheek or blood) to determine the nucleotide sequence. The sequence will include the location of the mutated allele, if it is present, Lees explained.
“Every dog has two copies of this gene, one on each of the two chromosomes. A dog with two copies of the mutated allele is affected while dogs with one copy of the mutated allele and one copy of the normal allele are carriers.”
This hereditary nephropathy is a kidney disease that causes juvenile onset renal failure in English cocker spaniels. Dogs that are closely related to an affected dog or its parents have a 50-50 chance of being carriers, Lees explained. “We will now be able to clean up the breed after 60 years of fighting with it,” he added.