Fritz K L, Kaese H J, Valberg S J, Hendrickson J A, Rendahl A K, Bellone R R, Dynes K M, Wagner M L, Lucio M A, Cuomo F M, Brinkmeyer-Langford C L, Skow L C, Mickelson J R, Rutherford M S, McCue M E
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55108, USA.
Anim Genet. 2014 Jun;45(3):392-9. doi: 10.1111/age.12129. Epub 2014 Jan 28.
Appaloosa horses are predisposed to equine recurrent uveitis (ERU), an immune-mediated disease characterized by recurring inflammation of the uveal tract in the eye, which is the leading cause of blindness in horses. Nine genetic markers from the ECA1 region responsible for the spotted coat color of Appaloosa horses, and 13 microsatellites spanning the equine major histocompatibility complex (ELA) on ECA20, were evaluated for association with ERU in a group of 53 Appaloosa ERU cases and 43 healthy Appaloosa controls. Three markers were significantly associated (corrected P-value <0.05): a SNP within intron 11 of the TRPM1 gene on ECA1, an ELA class I microsatellite located near the boundary of the ELA class III and class II regions and an ELA class II microsatellite located in intron 1 of the DRA gene. Association between these three genetic markers and the ERU phenotype was confirmed in a second population of 24 insidious ERU Appaloosa cases and 16 Appaloosa controls. The relative odds of being an ERU case for each allele of these three markers were estimated by fitting a logistic mixed model with each of the associated markers independently and with all three markers simultaneously. The risk model using these markers classified ~80% of ERU cases and 75% of controls in the second population as moderate or high risk, and low risk respectively. Future studies to refine the associations at ECA1 and ELA loci and identify functional variants could uncover alleles conferring susceptibility to ERU in Appaloosa horses.
阿帕卢萨马易患马复发性葡萄膜炎（ERU），这是一种免疫介导的疾病，其特征是眼部葡萄膜反复发炎，是马匹失明的主要原因。对来自负责阿帕卢萨马斑点毛色的ECA1区域的9个遗传标记，以及跨越ECA20上的马主要组织相容性复合体（ELA）的13个微卫星进行了评估，以确定它们与一组53例阿帕卢萨马ERU病例和43例健康阿帕卢萨马对照中ERU的关联。有三个标记显著相关（校正P值<0.05）：ECA1上TRPM1基因第11内含子内的一个单核苷酸多态性（SNP）、位于ELA III类和II类区域边界附近的一个ELA I类微卫星，以及位于DRA基因第1内含子中的一个ELA II类微卫星。在另一组24例隐匿性ERU阿帕卢萨病例和16例阿帕卢萨马对照中，证实了这三个遗传标记与ERU表型之间的关联。通过分别对每个相关标记以及同时对所有三个标记拟合逻辑混合模型，估计了这三个标记每个等位基因成为ERU病例的相对几率。使用这些标记的风险模型将第二组中的约80%的ERU病例和75%的对照分别分类为中度或高风险以及低风险。未来旨在细化ECA1和ELA基因座关联并鉴定功能变异的研究，可能会发现赋予阿帕卢萨马ERU易感性的等位基因。
