Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
Vet Comp Oncol. 2011 Dec;9(4):241-50. doi: 10.1111/j.1476-5829.2010.00250.x. Epub 2011 Jan 17.
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.
犬乳腺肿瘤（CMTs）的发病率在不同品种之间存在显著差异，强烈支持遗传风险因素的影响。我们旨在鉴定与犬乳腺肿瘤相关基因的种系遗传变异，并调查这些变异是否可能改变编码蛋白。我们对 11 个基因（BRCA1、BRCA2、BRIP1、CDH1、CHEK2、EGFR、ESR1、HER2、PTEN、STK11 和 TP53）进行了测序和遗传变异筛选。共发现 64 个单核苷酸多态性（SNP）。其中 9 个编码 SNP 是非同义的，其中 4 个位于跨越四个物种的基因区域中保守。根据 PolyPhen 预测，其中 3 个非同义 SNP 可能具有破坏性。鉴定出的一个插入缺失先前与 CMTs 有关。由于许多犬种的奠基者效应、遗传漂变和近亲繁殖，所研究基因的等位基因频率在不同品种之间可能存在显著差异，并导致与癌症相关的遗传风险存在显著差异。
