An exploratory association analysis of the insulin gene region with diabetes mellitus in two dog breeds

Samoyeds and Australian Terriers are the 2 dog breeds at highest risk (>10-fold) for diabetes mellitus in the United States. It is unknown if the insulin (INS) gene is involved in the pathophysiology of diabetes in Samoyeds and Australian Terriers. It was hypothesized that the INS gene region provides a common genetic causality for diabetes in Samoyeds and Australian Terriers. We conducted a 2-stage genetic association study involving both breeds. In the discovery stage (Stage 1), Samoyeds with and without diabetes were compared in the frequencies of 447 tagging single-nucleotide polymorphisms (SNPs) within 2.5 megabases (Mb) up- and downstream of the INS gene on the Illumina CanineHD BeadChip. SNPs yielding a P-value < 0.005 were selected for further follow-up. In the validation stage (Stage 2), Australian Terriers with and without diabetes were compared in the SNPs genotyped by the Affymetrix GeneChip Canine Genome 2.0 Array and within 1 Mb up- and downstream of the selected SNP...

在美国，萨摩耶犬与澳大利亚梗犬是罹患糖尿病（diabetes mellitus）风险最高的两个犬种，其发病风险较普通犬升高10倍以上。目前尚不明确胰岛素（Insulin, INS）基因是否参与萨摩耶犬与澳大利亚梗犬糖尿病的病理生理进程。本研究提出假说：胰岛素基因区域可为萨摩耶犬与澳大利亚梗犬的糖尿病提供共同的遗传致病基础。本研究针对这两个犬种开展了两阶段遗传关联研究。在发现阶段（第一阶段），本研究依托Illumina犬类高密度基因分型芯片（Illumina CanineHD BeadChip），对比了INS基因上下游2.5兆碱基（Mb）范围内447个标签单核苷酸多态性（tagging single-nucleotide polymorphisms, SNPs）的等位基因频率，在患糖尿病与未患糖尿病的萨摩耶犬中的分布差异。P值小于0.005的SNPs被筛选出来用于后续验证实验。在验证阶段（第二阶段），本研究采用Affymetrix犬类基因组2.0基因芯片（Affymetrix GeneChip Canine Genome 2.0 Array），对经该芯片分型的SNPs以及上述筛选出的SNP上下游1兆碱基（Mb）范围内的位点，在患糖尿病与未患糖尿病的澳大利亚梗犬中进行对比分析……