Genetic and genomic investigations of hereditary, viral, and parasitic wildlife diseases in non-model organisms

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The objectives of this proposal are to elucidate genetic/genomic factors associated with wildlife diseases in wild canid models. Infectious and inherited wildlife diseases cause economic and cultural losses and pose potential health threats to humans. The red fox is a non-model organism ideally suited for molecular genetic and genomic investigations into causes and consequences of wildlife diseases. Foxes are "genomically enabled" by the available domestic dog genome assembly, providing access to genomic resources such as microarrays and candidate gene sequences. Newfoundland red foxes harbour at least three significant wildlife diseases, including hereditary, viral, and parasitic. Farmed silver foxes in Newfoundland and parts of Europe experience hereditary hyperplastic gingivitis (HHG), a gum disease that hinders breeding programs. Using canine microarrays, we (HQP and I) have identified a set of functional candidate genes in developmental genetic cell signalling pathways which we intend to characterize via candidate gene sequencing and quantitative PCR, with the objective of discovering the gene and causative mutation of this condition. Additional candidate genes will be identified and tested using linkage analyses. The only endemic focus in North America of the global endoparasitic nematode French heartworm is in Newfoundland. This infectious disease is of concern due to transmission from foxes to domestic dogs, and increasingly to coyotes, foreshadowing its possible spread to other parts of Canada. Functional genomic approaches will be used to identify correlates of successful heartworm transmission and host infection. The red fox strain of rabies virus persists in northern Canada and threatens to invade a wider geographic area, as exemplified by a mid-1950s spread throughout eastern Canada, with obvious concerns for public health. I propose to eludicate fox phylogeographic structure in northeastern Canada, using genome-wide single nucleotide polymorphisms (SNPs) to identify geographic or other barriers to viral transmission and genetic correlates of disease resistance. This research forges collaborations among Memorial University, the Fur Breeder’s Association, and Animal Health Division, and will be important to fur farmers in Canada and Europe, wildlife management officials and dog owners throughout Canada, researchers of human disease, and basic researchers of mammalian growth and development. For example, the gum overgrowth causes dental abscess and compromises feeding ability of foxes, affecting their quality of life and economic value. The Fur Breeder's Association is therefore unable to propagate foxes while the genetic cause and inheritance pattern of the gum condition, and related fur quality, are unknown. An anticipated outcome of our research is a diagnostic test of this disease. The discovery of the gene and causative mutation of HHG will also provide an entry point into the genetics of a similar human disease, especially the form characterized by hypertrichosis; 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 associated with the cell cycle will also be informative to cancer research. Understanding the nature of the hyperplasia contributes to basic knowledge about growth and development. The canine pulmonary angiostrongylus work will help develop a spatio-temporal model of parasite spread and maintenance in wild canids and contributes to understanding and prevention of further spread of this severe infection in dogs. Rabies is also a serious wildlife concern and potentially harmful to humans as well, and understanding its transmission is vital to monitoring and preventing spread of this virus.