Current Information on the Development of DNA Markers for Familial Shar-Pei Fever
One of the first research projects funded by the Chinese Shar-Pei Club of America, Inc. and the CSPCA Charitable Trust was begun in 1997 by Dr. Gary Johnson at the University of Missouri, Columbia. The main objective of the project was to test the theory that FSF is a canine version of Familial Mediterranean Fever in humans. It was felt that a mutation occurring in the canine equivalent of the human FMF gene was responsible for FSF in the Shar-Pei breed. Initially this was to be accomplished by several molecular genetic techniques including linkage analysis and the use of genetic markers.
In the Fall of 1997, two human FMF research groups independently cloned the human FMF gene and the DNA sequence was reported. Using this information Dr. Johnson and his group was able to sequence the canine FMF gene. Unfortunately, further studies revealed that the canine FMF gene is not the site of the mutation responsible for Familial Shar-Pei Fever in the Shar-Pei breed. One of the major problems encountered in this study was the difficulty in evaluating the phenotype of many members of Shar-Pei families in which FSF exists. Phenotype refers to the physical manifestations of the underlying genotype or genetic makeup of the individual. The primary symptom of FSF is the significant fever which occurs during an episode. Obviously there can be other causes of fever in dogs and fever is not specific for FSF. Other symptoms such as lameness, Swollen Hock Syndrome (SHS), pain, amyloidosis, and kidney failure occur sporadically and unless the constellation of signs occurs together, a diagnosis of FSF is always tentative. In addition, there are no specific blood tests or laboratory findings which allow a diagnosis of FSF. Likewise, the age of onset of FSF is extremely variable makes it difficult to determine “normal” individuals.
Future research on FSF will have to focus on using genetic information from other episodic fever disorders in humans and find the equivalent gene locations and DNA sequences on the canine genome to search for mutations which are responsible for FSF. This was recently done with two human FMF-like diseases and the mutations in these genes are being looked at as possible sources of the FSF mutation.
Dr. Johnson’s research has helped to fill out the canine genome and this information will be invaluable in the future. As an aside, there is still considerable confusion among the Shar-Pei fancy concerning FSF and amyloidosis. Familial Shar-Pei Fever is not synonymous with amyloidosis. My opinion, and others may agree, is that FSF is one genetic problem and amyloidosis is another. I believe FSF is a significant risk factor to those Shar-Pei with a genetic tendency to develop amyloidosis and I still strongly feel we need to pursue research to give breeders the tools to breed away from FSF.