title: Genome-wide expression analysis of hereditary hyperplastic gingivitis in silver foxes (Vulpes vulpes) using canine microarrays.
abstract: Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive condition found predominantly in farmed silver foxes, first documented in Europe in the 1940s. Hereditary gingival fibromatosis (HGF) is an analogous condition occurring in humans. HGF has a heterogeneous aetiology with emphasis placed on the autosomal dominant forms of inheritance for which there are three known loci: HGF1, HGF2, and HGF3. Among these, only one causative mutation has been determined, in the Son of sevenless homolog 1 (SOS1) gene. The goal of this study was to explore potential molecular or cellular mechanisms underlying HHG by analysis of global gene expression patterns from Affymetrix Canine 2.0 microarrays cross-referenced against candidate genes within the human loci. We conclude that the SOS1 gene involved in HGF1 is not significantly up-regulated in HHG. However, the structurally and functionally similar SOS2 gene is up-regulated in affected foxes, and we propose this as a candidate gene for HHG. At HGF2 we identify RASA1 (rat sarcoma viral p21 protein activator 1) as a candidate gene for HHG, as it is up-regulated in affected foxes and is involved in MAPK signalling. From comparison to the genes within the HGF3 locus, we find evidence for a role of androgens in HHG phenotype severity by differential up-regulation of SRD5A2 in HHG-affected foxes. We hypothesize that the putative mutation occurs upstream of RAS in the extracellular signal-regulated kinase component of MAPK signalling.
authors.affiliation: a Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
authors.forename: Jo-Anna B J
authors.initials: JA
authors.lastname: Clark
authors.forename: Marije
authors.initials: M
authors.lastname: Booman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hudson
authors.forename: H Dawn
authors.initials: HD
authors.lastname: Marshall
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000818:Animals; D005589:Foxes / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005885:Gingival Hyperplasia / Q000235:genetics* / Q000662:veterinary*; D046228:Microarray Analysis / Q000662:veterinary; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020664:Son of Sevenless Proteins / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D020729:p120 GTPase Activating Protein / Q000235:genetics
chemical_list: D020664:Son of Sevenless Proteins; D020729:p120 GTPase Activating Protein; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase
keywords: Son of sevenless homolog; Son of sevenless homolog 1; canine microarray; fibromatose gingivale congénitale; hereditary gingival fibromatosis; hereditary hyperplastic gingivitis; hyperplasie gingivale congénitale; mitogen-activated protein kinase pathway; puce à ADN canine; voie de signalisation des protéines kinases activées par un mitogène