00981-A: Collecting DNA for Identifying Modifiers of COMMD1 in Bedlington Copper Toxicosis

Grant Amount: $12,160

Diane W. Cox, PhD; University of Alberta

September 1, 2007 - August 30, 2008

Sponsor(s): American Cavalier King Charles Spaniel Club Charitable Trust, American Miniature Schnauzer Club, Inc., Greater Daytona Dog Fancier's Association

Breed(s): Bedlington Terrier

Research Program Area: Hepatic Disease

Project Summary

Bedlington Terriers, and other breeds such as the Skye Terrier, the West Highland White Terrier and the Doberman Pinscher, develop copper storage that can lead to early death from liver disease (copper toxicosis (CT). Recently, the gene COMMD1 was reported to be the cause of the liver disease in Bedlingtons, as a deletion of the mid part of the gene was identified in some affected dogs. We also identified this deletion in our pedigrees, but proposed that this could not be the sole cause of the disease, as the deletion results did not always predict the disease status of the dogs. Our pedigrees suggest that another gene is important, or may even be the primary cause of the disease. We have collected several large pedigrees of Bedlingtons that include both sick and healthy dogs that do not fit the expectations according to deletion results. We have identified sick dogs that do not have the deletion and normal dogs that have the deletion. In this study, we continued to collect blood samples from sick and healthy dogs. This will allow us to perform a total genome scan in a future study to identify an additional gene involved in producing CT. We collected a total of 17 new dog samples and a second sample for one dog with the assistance of Bedlington owners and/or breeders. Six control and eight affected dogs are suitable for the whole genome scan based on pedigree and liver copper biopsy reports provided by the breeder/owner. We are currently in contact with additional breeders/owners about four more control dogs and 3 more affected dogs which would allow us to reach our goal of 10 control dogs with a low liver copper level and 10 affected dogs with a high liver copper level. The dogs collected over the course of this grant combined with our previously collected dogs result in a total of 24 affected dogs and 18 control dogs for the whole genome scan. We have genotyped all dogs collected for the COMMD1 deletion and nearby markers. We are prepared to enter phase 2 of our study where we plan to identify the gene critical for a high liver copper, using the total genome scan. Our present and future studies will lead to the identification of a new gene involved in CT in Bedlington Terriers and lead to reliable testing, avoiding the misclassification that can result from current tests and can possibly eliminate the occurrence of CT.

Publication(s)

None at this time.