Faculty of Science, Sydney School of Veterinary Science, University of Sydney, Sydney, NSW, Australia.
School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.
Sci Rep. 2020 Nov 5;10(1):19194. doi: 10.1038/s41598-020-76166-3.
Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case-control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes, ANK1, EPHX2 and LOX2, implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.
糖尿病是一种常见的内分泌疾病，影响家猫，与人类 2 型糖尿病有许多临床和病理特征。在澳大利亚和欧洲，糖尿病在缅甸猫中的发病率比其他品种高近 4 倍。作为一个遗传隔离的群体，患有糖尿病的澳大利亚缅甸猫为研究人类糖尿病提供了一个自发的遗传模型。在纯种犬中研究复杂疾病可以更严格地控制混杂因素，包括人口分层、等位基因频率和环境异质性。我们使用了猫的 SNV 阵列和全基因组序列数据，对澳大利亚和欧洲缅甸猫的病例对照队列进行了全基因组关联研究和纯合子运行分析。我们的结果在染色体 A3、B1 和 E1 上确定了与糖尿病相关的单倍型，在染色体 B1、B3、D1 和 D4 上对缅甸品种进行了选择清扫。这两个分析共同的染色体 B1 上的基因座揭示了候选基因 ANK1、EPHX2 和 LOX2 中的编码和剪接区域变异，这些基因与糖尿病和脂质失调有关。在缅甸猫中定位这种疾病揭示了一个多基因谱，暗示与胰腺β细胞功能障碍、脂质失调和胰岛素抵抗相关的基因座在缅甸猫糖尿病的发病机制中起作用。
