Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.
Small Animal Specialist Hospital, North Ryde, Australia.
Am J Vet Res. 2022 Oct 3;83(11):1-8. doi: 10.2460/ajvr.22.07.0106.
To identify genetic associations with primary glaucoma (PG) in American Cocker Spaniels using a genome-wide association study (GWAS).
A nationwide ambidirectional case-control cohort study was performed in American Cocker Spaniels that had an ophthalmic examination performed by a veterinarian. Ninety-four dogs with PG (cases) and 111 dogs without glaucoma (controls) met phenotypic criteria and had a blood sample collected after receiving informed owner consent.
Genomic DNA was extracted from whole blood samples and genotyped (CanineHD BeadChip, Illumina Inc). A case-control GWAS using a linear mixed model was performed, and 3 significance thresholds were calculated (1) using a Bonferroni correction on all single nucleotide polymorphisms (SNPs) included in the GWAS, (2) using a Bonferroni correction on only the unlinked SNPs from a pruned data set, and (3) using 10,000 random phenotype permutations.
Following genotype data quality control, 89 cases and 93 controls were included in the GWAS. We identified an association on canine chromosome (CFA10); however, it did not reach statistical significance. Potential candidate genes within the surrounding linkage disequilibrium interval include coiled-coil domain containing 85A (CCDC85A) and extracellular growth factor containing fibulin extracellular matrix protein 1 (EFEMP1).
Primary glaucoma in the American Cocker Spaniel is a complex heterogeneous disease that may be influenced by a locus on CFA10. The candidate genes CCDC85A and EFEMP1 within the identified linkage disequilibrium interval have been shown to be involved in human open-angle glaucoma.
通过全基因组关联研究（GWAS）鉴定美国可卡犬原发性青光眼（PG）的遗传关联。
在美国可卡犬中进行了一项全国性的双向病例对照队列研究，该犬种接受了兽医进行的眼科检查。94 只患有 PG（病例）的犬和 111 只无青光眼（对照）的犬符合表型标准，并在获得知情主人同意后采集了血液样本。
从全血样本中提取基因组 DNA，并进行基因分型（CanineHD BeadChip，Illumina Inc.）。使用线性混合模型进行病例对照 GWAS，并计算了 3 个显著性阈值（1）使用全基因组关联研究中包含的所有单核苷酸多态性（SNP）的 Bonferroni 校正，（2）仅使用修剪数据集的非连锁 SNP 的 Bonferroni 校正，（3）使用 10,000 个随机表型置换。
在基因型数据质量控制后，GWAS 中纳入了 89 例病例和 93 例对照。我们在犬染色体 CFA10 上发现了一个关联；然而，它没有达到统计学意义。周围连锁不平衡区间内的潜在候选基因包括卷曲螺旋域包含 85A（CCDC85A）和细胞外生长因子包含纤维调蛋白细胞外基质蛋白 1（EFEMP1）。
美国可卡犬原发性青光眼是一种复杂的异质性疾病，可能受 CFA10 上的一个基因座影响。在所确定的连锁不平衡区间内的候选基因 CCDC85A 和 EFEMP1 已被证明参与了人类开角型青光眼。
