Abstract：
Dog leukocyte antigen (DLA) polymorphisms have been found to be associated with inter-individual variations in the risk, susceptibility, and severity of immune-related phenomena. While DLA class II genes have been extensively studied, less research has been performed on the polymorphisms of DLA class I genes, especially in beagle dogs commonly used as laboratory animals for safety evaluations in drug development. We genotyped four DLA class I genes and four DLA class II genes by locus-specific Sanger sequencing using 93 laboratory beagle dogs derived from two different strains: TOYO and Marshall. The results showed that, for DLA class I genes, 11, 4, 1, and 2 alleles, including a novel allele, were detected in DLA-88, DLA-12/88L, DLA-64, and DLA-79, while, for DLA class II genes, 1, 10, 6, and 7 alleles were detected in DLA-DRA, DLA-DRB1, DLA-DQA1, and DLA-DQB1, respectively. It was estimated that there were 14 DLA haplotypes, six of which had a frequency of ≥ 5%. Furthermore, when comparing the DLA diversity between TOYO and Marshall strains, the most common alleles and haplotypes differed between them. This is the first study to genotype all DLA loci and determine DLA haplotypes including all DLA class I and class II genes in dogs. Integrating information on the DLA diversity of laboratory beagle dogs should reinforce their benefit as an animal model for understanding various diseases associated with a specific DLA type.
摘要：
已发现狗白细胞抗原（DLA）多态性与风险的个体间差异有关，易感性，以及免疫相关现象的严重性。虽然DLAII类基因已被广泛研究，对DLAI类基因多态性的研究较少，特别是在比格犬中，通常用作实验动物，用于药物开发中的安全性评估。我们使用来自两种不同菌株：TOYO和Marshall的93只实验室比格犬，通过基因座特异性Sanger测序对四个DLAI类基因和四个DLAII类基因进行了基因分型。结果表明,对于DLAI类基因，11、4、1和2个等位基因，包括一个新的等位基因,在DLA-88、DLA-12/88L、DLA-64和DLA-79,对于DLAII类基因，在DLA-DRA中检测到1、10、6和7个等位基因，分别为DLA-DRB1、DLA-DQA1和DLA-DQB1。据估计，有14个DLA单倍型，其中6例的频率≥5%。此外，当比较TOYO和Marshall菌株之间的DLA多样性时，最常见的等位基因和单倍型之间存在差异。这是第一项对狗中所有DLA基因座进行基因分型并确定包括所有DLAI类和II类基因的DLA单倍型的研究。整合实验室比格犬DLA多样性的信息应加强其作为动物模型的益处，以了解与特定DLA类型相关的各种疾病。
