School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia.
J Hered. 2011 Sep-Oct;102 Suppl 1:S74-80. doi: 10.1093/jhered/esr054.
Immunoglobulin E (IgE)-mediated hypersensitivity against environmental allergens, commonly including Dermatophagoides farinae, is associated with atopic diseases in both humans and dogs. We have recently identified a family of clinically healthy West Highland white terriers (WHWTs) with high-serum D. farinae-IgE levels. In this study, we investigated the genetic mechanism controlling IgE responsiveness in dogs by performing a genome-wide association study (GWAS) using the Affymetrix V2 Dog SNP array in 31 high-IgE and 24 low-IgE responder WHWTs. A gene-dropping simulation method, using SIB-PAIR software, showed significant allelic association between serum D. farinae-specific IgE levels and a 2.3-Mb area on CFA35 (best empirical P = 1 × 10(-5)). A nearby candidate gene, CD83, encodes a protein which has important immunological functions in antigen presentation and regulation of humoral immune responses. We sequenced this gene in 2 high-IgE responders and 2 low-IgE responders and identified an intronic polymorphic repeat sequence with a predicted functional effect, but the association was insufficient to explain the GWAS association signal in this population (P = 1 × 10(-3)). Further studies are necessary to investigate the significance of these findings for IgE responsiveness and atopic disease in the dog.
免疫球蛋白 E(IgE)介导的对环境过敏原的过敏反应,通常包括屋尘螨,与人类和犬的特应性疾病有关。我们最近鉴定了一个临床健康的西部高地白梗(WHWT)家族,其血清中含有高浓度的屋尘螨-IgE。在这项研究中,我们通过在 31 只高 IgE 和 24 只低 IgE 反应的 WHWT 中使用 Affymetrix V2 犬 SNP 阵列进行全基因组关联研究(GWAS),研究了控制犬 IgE 反应的遗传机制。使用 SIB-PAIR 软件进行的基因剔除模拟方法表明,血清屋尘螨特异性 IgE 水平与 CFA35 上的 2.3-Mb 区域之间存在显著的等位基因关联(最佳经验 P = 1×10(-5))。一个附近的候选基因 CD83 编码一种在抗原呈递和体液免疫反应调节中具有重要免疫功能的蛋白质。我们在 2 只高 IgE 反应者和 2 只低 IgE 反应者中对该基因进行了测序,发现了一个具有预测功能效应的内含子多态性重复序列,但这种关联不足以解释该人群中 GWAS 关联信号(P = 1×10(-3))。需要进一步的研究来探讨这些发现对犬 IgE 反应性和特应性疾病的意义。