Abstract
Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that presents with progressive gingival proliferation in farmed silver foxes. Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that is genetically heterogeneous with several known autosomal dominant loci. For one locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene. For the remaining loci, the molecular mechanisms are unknown but Ras pathway involvement is suspected. Here we compare sequences for the SOS1 gene, and two adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and epidermal growth factor receptor (EGFR), between HHG-affected and unaffected foxes. We conclude that the known HGF causative mutation does not cause HHG in foxes, nor do the coding regions or intron–exon boundaries of these three genes contain any candidate mutations for fox gum disease. Patterns of molecular evolution among foxes and other mammals reflect high conservation and strong functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of variability in EGFR consistent with mutational rate differences, relaxed functional constraints, and possibly positive selection.
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Acknowledgments
We gratefully acknowledge Dr. Robert Hudson, from Animal Health Division, Department of Natural Resources, Government of Newfoundland and Labrador, for his time and dedication with caring for the animals and sample collection. We would also like to thank Dr. Laura Rogers, Animal Health Division, Department of Natural Resources, Government of Newfoundland and Labrador, for aiding with sample collection. Finally, we would like to acknowledge Merv Wiseman for bringing this issue to our attention and providing us samples of affected fox and for the many opportunities he gave us to observe and examine foxes on the farm as well as review his breeding records.
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Clark, JA.B.J., Tully, S.J. & Dawn Marshall, H. Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis. Genetica 142, 517–523 (2014). https://doi.org/10.1007/s10709-014-9798-x
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DOI: https://doi.org/10.1007/s10709-014-9798-x