Gene discovery and the genetic basis of inherited disease in non-model organisms

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The novel focus of the present study is to uncover the genetic component of inherited disease in non-model organisms - specifically large mammals that are of commercial and/or conservation interest regionally. The proposed research takes advantage of genomic resources and bioinformatics tools, with the immediate goal of discovering genes responsible for a devastating hereditary condition in silver foxes, and the more general one of illuminating the relationship between genotypic and phenotypic variation in species that, although depauperately represented in PubMed, share a comparatively recent evolutionary history with our own. The specific goals of the research are to determine candidate genes for hereditary hyperplastic gingivitis (gum overgrowth) in foxes, to evaluate the association between the DNA sequence of these genes and disease status of foxes, to compare affected and unaffected foxes at an unlinked putatively neutral genetic locus, and to assay the frequency and distribution of disease-associated genetic variation in natural populations. An additional goal is to investigate the evolutionary origin of the mutation that causes Kermodism in black bears (located on the same gene as red hair in humans) and its uniqueness and adaptive significance among mammals. This research is significant because it uses a human disease to model a furbearing carnivore disease at the molecular level. In addition to providing valuable information to the fur breeding industry, it therefore also contributes to our knowledge of a troublesome human condition. The identification of genes associated with aspects of the cell cycle provides potentially important new tools for cancer research. And studying variation in these genes in both bred and natural populations will contribute to the disentanglement of the complex relationship between genotype and phenotype and ultimately help explain the vast scope of mammalian genetic variation. It is in this latter context that elucidation of the molecular genetic mechanisms of melanism in Kermode bears is important. In addition to its scientific contributions, this research involves the development of new biotechnologies, such as microchip DNA re-sequencing, and forges regional institutional collaborations.