Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Genes (Basel). 2020 Nov 5;11(11):1313. doi: 10.3390/genes11111313.
Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. The genetic correlates of GDV have not previously been systematically explored. We undertook an inter-breed genome-wide association analysis (GWAS) of 253 dogs from ten breeds including 106 healthy dogs and 147 dogs with at least one GDV episode. SNP array genotyping followed by imputation was conducted on 241 samples to identify GDV-associated single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs). A subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds) was characterized by whole genome sequencing (WGS). After genome-wide Bonferroni correction, we identified a significant putatively protective intergenic SNP (rs851737064) across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 significant additional putatively protective or deleterious SNPs. Notable significant SNPs included those occurring in genes involved in gastric tone and motility including and . These data provide important new clues to canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.
犬胃扩张-扭转（GDV）是一种常见的危及生命的疾病，主要发生在大型和巨型犬种，其终生风险为 3.9%至 36.7%。GDV 的遗传相关性尚未被系统地探索过。我们对来自十个品种的 253 只狗进行了跨品种全基因组关联分析（GWAS），包括 106 只健康狗和 147 只至少有一次 GDV 发作的狗。对 241 个样本进行了 SNP 芯片基因分型和推断，以确定与 GDV 相关的单核苷酸多态性（SNP）和拷贝数变异（CNV）。对 33 只狗（15 只健康狗和 18 只来自三个代表品种的 GDV 患者）进行了全基因组测序（WGS）。在全基因组 Bonferroni 校正后，我们在所有品种中发现了一个显著的假定保护性基因间 SNP（rs851737064）。在牧羊犬、德国短毛指针犬和大丹犬中信号最显著。随后在这三个品种中进行的重点分析确定了 12 个具有显著保护作用或致病变异的附加 SNP。值得注意的显著 SNP 包括那些发生在与胃张力和运动有关的基因中的 SNP，包括 和 。这些数据为犬 GDV 的危险因素提供了重要的新线索，并有助于提出关于该综合征遗传和分子基础的假设。
