Ecological and Evolutionary Functional Genomics
Gene Discovery in a Non-Model Organism, the Red Fox (Vulpes vulpes)
Understanding the functions of genes and
polymorphisms is the goal of functional
genomics. EEFG transfers the strategies and techinques
of typical functional genomics studies to wild organisms (or
their proxies) to evaluate naturally-occurring molecular
variation and Darwinian fitness of ecologically important
traits.
Foxes are a promising EEFG species because they are widely distributed, adaptable, and easily observed in the wild. Additionally, they demonstrate naturally occuring, putatively adaptive genetic variation, for example in coat colour. They have been the subjects of selective breeding regimes for the past century for both research and farming purposes. Furthermore, foxes are closely related to domestic dogs (Canis familiaris) which means that the resouces of the dog genome project can be used to find genes in foxes. Gene discovery is the first stage in any functional genomics study.
Since the 1940's, farmed foxes have been observed to exhibit an
inherited
gum condition called hereditary
hyperplastic gingivitis (HHG) which is associated with
long, thick fur. This condition is very similar to hereditary
gingival fibromatosis (HGF), a genetically heterogeneous human
disease sometimes accompanied by hypertrichosis or excess hair
growth. As a consequence, uncovering the cause of HHG in foxes
will not only address animal welfare and economic concerns, but
also serve as a model for human genetic diseases. HHG and HGF
cause a progressive, overgrowth of the gum tissue. Although they
are benign conditions, the relevant genes most likely control
growth and/or the cell cycle and could be proto-oncogenes.
Understanding the mechanism of gene action in HHG may therefore
also be informative in cancer research.
The first of the fox EEFG study
goals is to discover the gene and mutation that causes
HHG. This involves a three-pronged approach: 1) Sequencing and
mutational analysis of candidate genes determined from the human
studies and the literature 2) pedigree-based linkage analysis to
identify positional candidate genes 3) microarray-based gene
expression analysis. Other EEFG goals include assaying the
origin and frequency of the mutation in natural populations,
deciphering patterns of adaptive genetic variation at coat
colour loci (mc1r and agouti) in nature, and inference of the
phylgeographic structure of red foxes throughout their range
using neutral genetic variation.
Research positions are available for two B.Sc. Honours students and two M.Sc. students. Specific projects can be tailored to the student's interests.