Data from: A genome-wide association study identifies a region strongly associated with symmetrical onychomadesis on chromosome 12 in dogs

Symmetrical onychomadesis causes periodic loss of claws in otherwise healthy dogs. Genome-wide association analysis in 225 Gordon Setters identified a single region associated with symmetrical onychomadesis on chromosome 12 (spanning about 3.3 mb). A meta-analysis including also English Setters indicated that this genomic region predisposes for symmetrical onychomadesis in English Setters as well. The associated region spans most of the major histocompatibility complex and nearly 1 Mb downstream. Like many other autoimmune diseases, associations of symmetrical onychomadesis with DLA class II alleles have been reported. In this study, no associated markers were revealed within any of the DLA-DRB1, -DQA1 or -DQB1 genes, and the odds for symmetrical onychomadesis in the Gordon Setters were much higher, carrying significant single nucleotide polymorphisms compared to the odds of any of the recorded DLA-DRB1/DQA1/DQB1 haplotypes. We noticed that some of the associated DLA haplotypes were different between the English Setters and the Gordon Setters. Interestingly, associated SNP chip markers showed a more consistent pattern of allelic variants related to cases or controls regardless of breed. In conclusion, the associated genetic markers identified in this study hold the potential to aid in selection of breeding animals to reduce the frequency of symmetrical onychomadesis in the dog.

对称性爪甲脱落症（symmetrical onychomadesis）可导致外观健康的犬只周期性脱落爪甲。研究人员对225只戈登雪达犬（Gordon Setter）开展全基因组关联分析（genome-wide association analysis），在12号染色体（chromosome 12）上定位到一个与对称性爪甲脱落症相关的基因组区域，该区域跨度约3.3兆碱基对（mb）。后续纳入英国雪达犬（English Setter）数据的荟萃分析（meta-analysis）结果显示，该基因组区域同样可使英国雪达犬易感对称性爪甲脱落症。该关联区域覆盖了大部分主要组织相容性复合体（major histocompatibility complex, MHC）以及其下游近1兆碱基对的序列。与诸多自身免疫性疾病（autoimmune diseases）类似，此前已有研究报道对称性爪甲脱落症与犬白细胞抗原（DLA）II类等位基因存在关联。本研究未在DLA-DRB1、-DQA1或-DQB1基因内部检测到关联标记；相较于任意已记录的DLA-DRB1/DQA1/DQB1单倍型（haplotypes），携带显著性单核苷酸多态性（single nucleotide polymorphisms, SNP）的戈登雪达犬患对称性爪甲脱落症的比值比显著更高。我们观察到，英国雪达犬与戈登雪达犬的关联DLA单倍型存在部分差异。值得注意的是，无论犬品种如何，与病例组或对照组相关的等位基因变异模式在SNP芯片（SNP chip）标记中均呈现出更高的一致性。综上，本研究鉴定出的关联遗传标记有望用于辅助选育种用犬只，以降低犬对称性爪甲脱落症的发病频率。