Genetic and genomic investigations of hereditary and infectious wildlife diseases in non-model organisms

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The objectives of this research are to elucidate genetic/genomic factors associated with two wildlife diseases in canid models. Infectious and inherited wildlife diseases cause economic and cultural losses and pose potential health threats to humans. The indigenous canids of the island of Newfoundland, red foxes and coyotes, present an ideal model system in which to investigate genetic correlates of wildlife disease, including host and disease genome interactions. Foxes and coyotes are "genomically enabled" by canid genome resources like gene expression and single nucleotide polymorphism (SNP) microarrays. These two canids also provide distinct time windows into wildlife disease genetics as foxes colonized the island post-glacially whereas coyotes are recent migrants. First, Newfoundland is the only endemic focus in North America of the canid endoparasitic nematode French heartworm. This parasite is of significant concern due to intraguild transmission from foxes to coyotes and domestic canines. Here I propose to use target-enriched sequence capture, candidate gene sequencing, and genomewide SNPs to investigate genetic correlates of host susceptibility/resistance, and SNP panels to map host and parasite co-phylogeographies to determine demographic, spatial and historical correlates of disease transmission and prevalence, and identify parasite markers related to host interactions. Second, farmed silver foxes in Newfoundland and Europe experience hereditary hyperplastic gingivitis (HHG), a gum disease that hinders breeding programs. Using canine gene expression microarrays, my laboratory has identified the cell signalling pathway involved in this inherited disease, which I intend to further explore via target-enriched genome sequencing. The goal is to discover the gene and causative mutation of this condition, determine occurrence and frequency in the wild, and develop a diagnostic test. My proposed research forges collaborations among Memorial University and Newfoundland’s Animal Health Division, and will be important to Fur Breeder’s Associations, wildlife management officials and dog owners throughout Canada and abroad, and basic researchers of human disease and mammalian growth and development. The discovery of the causative mutation of HHG will provide an entry point into a similar human disease; by using a furbearing carnivore disease to model a human one, both human and animal health issues are addressed. The identification of pathogenic mutations of genes in the cell cycle will also be informative to cancer research. The French heartworm work will help develop a spatio-temporal model of parasite spread and maintenance in wild canids, contribute to prevention of further spread of this infectious disease, and serve as a model for understanding the basis of host/parasite genetic diversity and the largely unexplained scope of mammalian genetic variation.