Veterinary Genetics Laboratory, Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, 95616, CA, USA.
Appaloosa Project, Davis, 95616, CA, USA.
Anim Genet. 2020 Feb;51(1):111-116. doi: 10.1111/age.12883. Epub 2019 Dec 2.
Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low-grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome-wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10 , P = 5.91 × 10 , P = 4.91 × 10 , P = 6.46 × 10 ). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10 ). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU.
马属复发性眼色素层炎（ERU）的特征是眼内炎症，常导致马匹失明。与任何其他品种相比，阿帕卢萨马更有可能患上隐匿性 ERU，其特点是低度慢性眼内炎症，表明存在遗传易感性。阿帕卢萨马以其由豹斑复合斑等位基因（LP）和修饰基因 PATN1 引起的白色斑点图案而闻名。先前的研究表明，位于 ECA1 上与 LP 相关的标记物和位于 ECA20 上 MHC 附近的标记物与增加的 ERU 风险相关。本研究旨在进一步研究这些基因座并确定其他遗传风险因素。使用 Illumina Equine SNP70 BeadChip 在 91 匹马中进行了 GWAS。采用加性混合模型方法来校正相关性。虽然它们没有达到严格的 Bonferroni 全基因组显著性阈值，但 ECA1 上的两个 SNP、ECA12 上的一个 SNP 和 ECA29 上的一个 SNP 是排名最高的 SNP 之一，因此值得进一步分析（P = 1.20 × 10 -8 ，P = 5.91 × 10 -8 ，P = 4.91 × 10 -8 ，P = 6.46 × 10 -8 ）。在第二个队列（n = 98）中，仅在 ECA1 上的 LP 等位基因与疾病的相关性得到了复制（P = 5.33 × 10 -8 ）。使用 LP、年龄和其他去色素化因素（PATN1 基因型和斑驳程度）对疾病风险进行建模，支持 LP 的加性作用，并表明 PATN1 的加性作用。对 LP 和 PATN1 的基因分型可能有助于预测 ERU 风险（AUC = 0.83）。LP 和 PATN1 在 ERU 发展中的功能作用需要进一步研究。需要对具有豹斑复合斑图案的不同品种的样本进行基因分型，并使用更密集的标记物，以进一步完善 ERU 的遗传成分。
