Forman Oliver P, Freyer Jamie, Kerr Abigail, Labadie Julia D, Denyer Michael, Gow Debbie J, Alexander Janet, Daya Michelle, Olivera Yaindrys Rodriguez, Lozoya Cecilia, Leutenegger Christian, Savard Christian, Huff Jason T, Foran Rebecca Chodroff
Wisdom Panel, Science and Diagnostics, Mars Petcare, Los Angeles, CA, United States.
Veterinary Specialists Scotland, Linnaeus Veterinary Limited, Mars Veterinary Health, Livingston, United Kingdom.
Front Vet Sci. 2025 Jun 19;12:1550617. doi: 10.3389/fvets.2025.1550617. eCollection 2025.
Canine atopic dermatitis (CAD) is a common inflammatory skin condition in dogs. It is a lifelong issue that poses a significant welfare concern due to the chronic skin discomfort and pruritus (itching) experienced by affected animals. Excessive scratching, licking, and chewing cause self-inflicted injuries to the skin and increase the risk of secondary infections. Several dog breeds, including Labrador Retriever, Boxer, and French Bulldog, are known to be predisposed to these issues, suggesting a genetic link to the condition.
Access to a large population of dogs genotyped on a medium-density single-nucleotide polymorphism (SNP) array through commercial Wisdom Panel testing, along with their linked clinical records, allowed a large-scale, highly powered genome-wide association study (GWAS) to be performed. In this study, over 28,000 dogs were examined to identify genetic changes associated with CAD.
A statistically significant signal on canine chromosome 38 was identified, with a particularly strong signal in French Bulldogs. Whole-genome resequencing revealed a compelling splice donor variant in the signaling lymphocytic activation molecule 1 (), a transmembrane receptor with important functions in immune cells. Further analysis of additional genome sequences and RNA samples from the MARS PETCARE BIOBANK confirmed that the splice variant is a strong potential contributor to an increased risk of atopic dermatitis.
The discovery represents the first compelling genetic variant associated with CAD to be validated in more than one breed of dog. The study identifies as a potential pharmaceutical target and the associated variant as a biomarker to enable dog breeders to make informed breeding decisions to reduce risk of CAD in future generations. The presence of the variant in many dog breeds and free-roaming dogs worldwide, indicates its potential role in contributing to the global risk of CAD.
犬特应性皮炎（CAD）是犬类常见的炎症性皮肤病。这是一个终身问题，由于患病动物会经历慢性皮肤不适和瘙痒，因此引发了对动物福利的重大关注。过度抓挠、舔舐和啃咬会导致皮肤出现自我损伤，并增加继发感染的风险。已知包括拉布拉多寻回犬、拳师犬和法国斗牛犬在内的几个犬种易患这些问题，这表明该病存在遗传联系。
通过商业智慧基因检测，获取了大量在中密度单核苷酸多态性（SNP）阵列上进行基因分型的犬只及其相关临床记录，从而能够进行大规模、高功效的全基因组关联研究（GWAS）。在这项研究中，对超过28000只犬进行了检查，以确定与CAD相关的基因变化。
在犬38号染色体上发现了一个具有统计学意义的信号，在法国斗牛犬中信号尤为强烈。全基因组重测序揭示了信号淋巴细胞激活分子1（ ）中有一个引人注目的剪接供体变体，该分子是一种在免疫细胞中具有重要功能的跨膜受体。对来自MARS宠物护理生物样本库的其他基因组序列和RNA样本的进一步分析证实，该剪接变体是特应性皮炎风险增加的一个强有力的潜在因素。
这一发现代表了首个在多个犬种中得到验证的与CAD相关的令人信服的基因变体。该研究确定 为潜在的药物靶点，相关变体为生物标志物，使犬类育种者能够做出明智的育种决策，以降低后代患CAD的风险。该变体在全球许多犬种和流浪犬中的存在，表明其在导致全球CAD风险方面可能发挥的作用。
