Grant 01771: Defining the Unique Genetic Markers in Dogs That Define Immune Function, Disease Resistance and Tissue Transplantation

The MHC genes are highly
polymorphic and each gene has many different forms or alleles. Matching of MHC alleles
between the donor and recipient is important for the success of stem cell and tissue
transplants. Specific assortments of MHC alleles or haplotypes have been associated with an
increased risk for the development of diabetes and auto immune diseases in humans.
Knowledge of these associations has been valuable in understanding disease mechanisms.
Recently we have developed improved methods for identifying the different forms of the DLA
genes, in a large number of dogs of diverse breeds. In this application, we propose to
characterize haplotypes, in over 1200 dogs from at least 50 breeds using a high throughput
sequencing strategy. The distribution and frequency of different forms of each of these genes
and their specific clustering among different breeds will greatly enhance our knowledge of the
genetic diversity among breeds. The methodology and data gained from this study will
enhance the power of association studies between MHC types and canine diseases. Such a
database will also enable tissue transplantation from unrelated but matched donors as a
treatment for advanced malignancies and other diseases, among dogs of most breeds.