AKC Canine Health Foundation Grant 801-A
Title: Characterization of the Mutation Responsible for Fanconi Syndrome in Basenjis
Researcher: Gary S. Johnson, DVM, PhD
Sponsors: The Basenji Club of America, Inc. & The Basenji Health Endowment, Inc.
Abstract: We have been working to characterize the mutation responsible for Fanconi Syndrome, a serious disease of the kidney, which has been fairly common in Basenjis for many years. The disease is recessive with symptoms seldom showing up until dogs are over 4.5 years old. It is, therefore, very hard for Basenji breeders to avoid the disease by conventional breeding strategies. A DNA test that could identify affected and carrier Basenjis as puppies would provide Basenji breeders with a means of eradicating Fanconi Syndrome by selective breeding. Step one in creating a DNA test is to determine the chromosomal location of the mutation. We have completed the first step and localized to a segment of a specific chromosome that represents less than 2 percent of a dog’s DNA. Because this segment of chromosome still contains over 200 genes, our next step is to further narrow the target region as much as possible. We will then examine selected genes within the narrowed region to find the mutation causing the disease. We will create a DNA assay that detects the mutant allele and validate the assay by testing the over 600 Basenji DNA samples in or collection.
Current Status: in progress.
The first generation linked marker DNA test for Fanconi Syndrome in Basenjis is now ready for production and Dr. Johnson’s lab will begin accepting testing requests Tuesday July 17th. The test is $60.00 US (Payable to the University of Missouri) and includes the recording of results in the OFA public DNA database.
To request a test, you must first enroll the dog in the Canine Phenome Project (CPP) at www.CaninePhenome.org and complete the questionnaires. Print the DNA Sample Submission Form (if you are submitting a blood sample for the first time) and a Linked Marker Test Form for each dog being tested.
Dr. Johnson’s lab can process approximately 150 samples per week, barring problems. If at all possible, please limit test requests to dogs you are planning to breed this year until the initial rush of testing requests has ebbed. Watch this site for updates on the backlog.
Dr. Johnson continues to work on locating the exact mutation responsible for Fanconi Syndrome with the goal of creating a direct test.
Go to the BHE’s Fanconi Test FAQ for answers any questions you may have.
Dr. Johnson is considering PRA research in basenjis employing S.N.P. (Single Nucleotide Polymorphism) chips donated to his facility. These chips are used to rapidly identify single nucleotide differences in the same fragment of DNA from different sources which, when applied to a full genome scan, usually produces excellent results if the data set is sound and the mode of inheritance is reasonably straightforward.
Dr. Johnson will apply his PRA findings in other breeds using these snip chips to basenjis as time becomes available.
What Makes a Good Research Pedigree?
To start research on any disorder, we need good research pedigrees. Pedigrees refers to a family cluster of dogs. Good research pedigrees include families of 30 or more dogs, meeting the criteria listed below, with at least 1/3 not affected. Each dog submitted helps build up that good pedigree – you don’t need to submit multiple dogs to help get us there. The unaffecteds are as important as the affecteds, as one of the ways this information is analyzed is to compare the DNA of related dogs that have the disorder with those that do not.
Researchers look for:
1. Dogs with a condition that is believed to be inherited (Fanconi, PRA, Hip Dysplasia, IPSID, etc.)
2. First degree relatives of the affected (parents, offspring, full siblings).
3. Any mating partner of the affected whether or not affected themselves to complete the family unit.