The first step which is genetic mapping is currently underway. Due to the complex inbreeding in the CKCS, a preliminary genetic analysis
was necessary to evaluate the informativeness of the genetic markers
and hence the feasibility of a whole genome scan in such breed.
Consequently, 10 dogs were selected for genotyping with 122 markers
distributed among the 38 autosomes and X chromosome. The markers were found to be sufficiently polymorphic and informative. Next, 200 dogs were selected for a whole genome scan, primarily for Chiari
malformation. However with additional phenotypic information on
mitral valve disease, it is possible to use the same data to map the
gene(s) defective in this disease. The whole genome scan was
conducted at the Mammalian genotyping Center at the Marshfield Clinic in Wisconsin, USA. The genotyping data will now be analyzed using both linkage-based and association studies. In the latter, we will be taking advantage of the founder effect demonstrated for both these disorders in the CKCS breed.
This strategy involves: 1) genetic mapping of the underlying gene(s),
2) identification of these defective gene(s) using the positional
candidate gene approach and characterization of the mutation(s) and
3) initial functional characterization of the protein(s) encoded by
the gene(s). This will help better understand the underlying
pathogenic mechanisms for better diagnosis, prognosis and clinical
management of these devastating conditions. These studies will also
help unravel some of the complexity involved in this malformation in
humans and in the embryonic development of the affected structures."