Genomic analysis of gum disease and hypertrichosis in foxes.
Since the 1940s, a proliferative gingival disease called hereditary hyperplastic gingivitis (HHG) has been described in the farmed silver fox, Vulpes vulpes (Dyrendahl and Henricson 1960). HHG displays an autosomal recessive transmission and has a pleiotropic relationship with superior fur quality in terms of length and thickness of guard hairs. An analogous human disease, hereditary gingival fibromatosis (HGF), is characterized by a predominantly autosomal dominant transmission and a complex etiology, occurring either as an isolated condition or as a part of a syndrome. Similar to HHG, the symptom most commonly associated with syndromic HGF is hypertrichosis. Here we explore potential mechanisms involved in HHG by comparison to known genetic information about hypertrichosis co-occurring with HGF, using an Affymetrix canine genome microarray platform, quantitative PCR, and candidate gene sequencing. We conclude that the mitogen-activated protein kinase pathway is involved in HHG, however despite involvement of the mitogen-activated protein kinase kinase 6 gene in congenital hypertrichosis with gingival fibromatosis in humans, this gene did not contain any fixed mutations in exons or exon-intron boundaries in HHG-affected foxes, suggesting that it is not causative of HHG in the farmed silver fox population. Differential up-regulation of MAP2K6 gene in HHG-affected foxes does implicate this gene in the HHG phenotype.
Department of Biology, Memorial University of Newfoundland, St. John's NL, Canada.
J-A B J
JA
Clark
Department of Biology, Memorial University of Newfoundland, St. John's NL, Canada.
D
D
Whalen
Department of Biology, Memorial University of Newfoundland, St. John's NL, Canada.
H D
HD
Marshall
D000818:Animals; D004285:Dogs; D005351:Fibromatosis, Gingival / Q000235:genetics* / Q000473:pathology; D005589:Foxes / Q000235:genetics*; D056726:Genetic Association Studies; D016678:Genome; D023281:Genomics; D005882:Gingival Diseases / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006983:Hypertrichosis / Q000235:genetics* / Q000473:pathology; D048669:MAP Kinase Kinase 6 / Q000235:genetics
D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human