Cook Shawna R, Hugen Sanne, Hayward Jessica J, Famula Thomas R, Belanger Janelle M, McNiel Elizabeth, Fieten Hille, Oberbauer Anita M, Leegwater Peter A J, Ostrander Elaine A, Mandigers Paul J J, Evans Jacquelyn M
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
bioRxiv. 2024 Aug 16:2024.08.14.604426. doi: 10.1101/2024.08.14.604426.
Gastric cancer (GC) is the fifth most common human cancer worldwide, but the genetic etiology is largely unknown. We performed a Bayesian genome-wide association study and selection analyses in a naturally-occurring canine model of GC, the Belgian Tervuren and Sheepdog breeds, to elucidate underlying genetic risk factors. We identified 15 loci with over 90% predictive accuracy for the GC phenotype. Variant filtering revealed germline putative regulatory variants for the () and genes and a coding variant in . Although closely related to Tervuren and Sheepdogs, Belgian Malinois rarely develop GC. Across-breed analyses uncovered protective haplotypes under selection in Malinois at and . Among Tervuren and Sheepdogs, putative regulatory variants were present at comparatively high frequency and were associated with GC. Here, we describe a complex genetic architecture governing GC in a dog model, including genes such as , that have not been associated with human GC.
胃癌（GC）是全球第五大常见人类癌症，但其遗传病因在很大程度上尚不清楚。我们在一种自然发生的犬类胃癌模型——比利时坦比连犬和牧羊犬品种中进行了贝叶斯全基因组关联研究和选择分析，以阐明潜在的遗传风险因素。我们确定了15个对GC表型具有超过90%预测准确性的基因座。变异筛选揭示了（）和基因的种系推定调控变异以及中的一个编码变异。尽管比利时玛利诺犬与坦比连犬和牧羊犬密切相关，但它们很少患GC。跨品种分析发现玛利诺犬在和处存在处于选择中的保护性单倍型。在坦比连犬和牧羊犬中，推定的调控变异以相对较高的频率出现，并与GC相关。在这里，我们描述了一种控制犬类模型中GC的复杂遗传结构，包括诸如等尚未与人类GC相关联的基因。
