title: Identification of genetic variation in 11 candidate genes of canine mammary tumour.
abstract: The incidence of canine mammary tumours (CMTs) differs significantly between breeds, strongly supporting an influence of genetic risk factors. We aimed at identifying germline genetic variations in mammary tumour-associated genes in dogs and survey whether these might alter the encoded proteins. We sequenced 11 genes (BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EGFR, ESR1, HER2, PTEN, STK11 and TP53) and screened for genetic variations. Sixty-four single nucleotide polymorphisms (SNPs) were identified. Nine of the coding SNPs were non-synonymous, of which four were located in gene regions conserved across four species. Three of the non-synonymous SNPs might be damaging according to PolyPhen predictions. One of the indels identified has previously been associated with CMTs. Because of the founder effects, genetic drift and inbreeding in many dog breeds the allele frequencies of the genes studied are likely to vary significantly between breeds and contribute to the considerable difference in genetic risk associated with cancer.
authors.affiliation: Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway. KajaSverdrup.Borge@nvh.no
authors.forename: K S
authors.initials: KS
authors.lastname: Borge
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: F
authors.initials: F
authors.lastname: Lingaas
mesh_terms: D000818:Animals; D030561:Databases, Nucleic Acid; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018773:Genes, erbB-1 / Q000235:genetics; D018734:Genes, erbB-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D014644:Genetic Variation; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D009664:Norway; D051059:PTEN Phosphohydrolase / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000662:veterinary; D020641:Polymorphism, Single Nucleotide; D017421:Sequence Analysis / Q000662:veterinary
chemical_list: D051059:PTEN Phosphohydrolase