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Canine copper toxicosis ("CT") is an autosomal recessive disorder of copper accumulation which results in severe liver disease in several dog breeds. Unless specific anti-copper treatment is instituted, most affected dogs die at three to seven years of age. CT is, in particular, a severe problem in Bedlington Terriers. The frequency of the CT gene in Bedlingtons is estimated to be as high as 50 percent in the U.S., with a similar frequency in England. This means that more than 25 percent of Bedlingtons are "CT-affected," and another 50 percent are "CT carriers." Until now, dogs have been tested for CT by taking liver biopsy samples after one year of age. The liver biopsy technique has the capacity to identify CT-affected dogs, but cannot identify CT carriers. Therefore, CT carriers continue to be bred, creating extreme difficulties for responsible Bedlington breeders and owners who wish to halt the perpetuation of the disease.
VetGen began by offering a genetic linkage test for Copper Toxicosis in Bedlington Terriers. This test used a linked marker, which we established that had two alleles, or marker types, called 1 and 2. Our first use of this test required submission of DNA samples from a pedigree (a set of related dogs) that included at least one affected dog, diagnosed by liver biopsy. It was therefore somewhat cumbersome. Not all clients had the right situation to even submit samples, and in over half the samples submitted, the marker was not sufficiently informative to provide useful information. However, the data collected was invaluable not only in helping many breeders, but in establishing the existence of strong genetic disequilibrium.
Genetic Disequilibrium Between Copper Toxicosis and the Linked Marker
What was found was that over 90% of dogs that were 1/1 marker type were homozygous normal (clear) and over 90% of dogs that were affected were 2/2 marker type. Obviously, most 1/2 dogs are carriers with the 2 allele usually associated with the CT (disease) allele.
New VetGen Test Procedure - Marker Typing
The finding of such a strong genetic disequilibrium allows VetGen to offer improved service for CT - marker typing. Bedlington breeder/owners can submit a DNA sample on a single dog, and VetGen will type it. This information can then be used as indicated above. If the dog is a 1/1, it is 90% + likely that the dog is homozygous normal (clear). If the dog is a 2/2 it is 72% likely that the dog is affected (90%+ of affected dogs are 2/2, but 72% of 2/2 dogs are affected - 24% are carriers). If the dog is a 1/2, VetGen data indicate the dog has a 95% chance of being a carrier.
Recommendations Regarding Breeding
VetGen recommends that 1/1 and 1/2 dogs be chosen primarily for breeding, eliminating the 2 gene in subsequent generations. Getting rid of the 2 gene should reduce the CT gene frequency by well over 90%. Breeders should continue liver biopsies in 1/1 dogs to be used for breeding for the near to intermediate future because it is currently the only way to reduce the small pocket of CT associated with the 1 allele. Eventually, VetGen hopes to have a second genetic marker which will be useful for this situation, but even in that event biopsy data will be necessary in the beginning to get linkage phase information.
By following the simple instructions provided in VetGen's DNA Sample Collection Kit, dog owners and breeders collect DNA samples using a soft cheek brush. By gently brushing the inside of the dog's cheek, cells containing DNA are removed. It is this DNA sample that VetGen analyzes to determine the genetic status of each dog. As soon as VetGen receives the completed DNA Sample Collection Kit, the DNA samples are processed and a diagnosis is formed. Within two to four weeks, this diagnosis is provided to the customer in a summary report.
Useful for dogs of any age, the DNA sample collection, analysis, and reporting activities can be completed before puppies are placed at 6 to 10 weeks. As a supplement to the summary report, VetGen can assist its customers with genetic counseling services to further help them make informed breeding decisions to eliminate the CT gene from their bloodlines while maintaining the integrity of their breed.
The results of the CT test can be formally registered with the Orthopedic Foundation for Animals (OFA). VetGen recommends registering your tested dog with the OFA, regardless of the test findings. When used for breeding, dogs proven "Clear" of the disease gene should afford the breeder a significant advantage in selling puppies. For further information about the OFA's Registry for Copper Toxicosis in Bedlington Terriers, contact: Orthopedic Foundation for Animals, 2300 E. Nifong Boulevard, Columbia, MO 65201-3856, or telephone (573) 442-0418.
VetGen can conduct a DNA profile, or DNA "fingerprint", on your dog. This service uses the same DNA you submit for your CT test. We highly recommend that you consider using VetGen's DNA Profiling service.
VetGen will store your dog's DNA sample for up to 10 years. We encourage you to consider DNA Storage as well.
Special thanks to the helpful Bedlington Terrier breeders from around the country who assisted CT research, and the American Kennel Club, Morris Animal Foundation, and Orthopedic Foundation for Animals for their financial support of canine genetic research at the University of Michigan and Michigan State University that led to the genetic test for copper toxicosis in Bedlington Terriers.
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