Border Collie array data for 58 dogs from Illumina 170k CanineHD BeadChip

Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (Canis lupus familiaris), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and has subsequently been found in Europe and the USA. The objective of the present study was to determine the genetic basis of goniodysgenesis in Border Collies. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Genotyping using the Illumina high density canine SNP chip and whole genome sequencing were used to identify candidate genetic regions. Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. There was a highly significant peak of association over chromosome 17, with a p-value of 2 x 10-13. Whole genome sequences of three dogs with glaucoma, three severely affected and three unaffected dogs identified a missense variant in the olfactomedin like 3 (OLFML3) gene in all six affected animals. This was homozygous in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one (offspring of two homozygous affected parents) was homozygous for this variant. The identification of a candidate genetic region and putative causative mutation will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.

房角发育异常（Goniodysgenesis）是眼前房的一种发育异常性疾病。该病通常被认为在犬（家犬，Canis lupus familiaris）中为先天性疾病，且与青光眼及失明密切相关。房角发育异常与早发性青光眼最初于20世纪90年代末在澳大利亚的边境牧羊犬中被发现，随后在欧洲与美国也有相关病例报道。本研究旨在明确边境牧羊犬房角发育异常的遗传基础。临床诊断基于来自11个不同国家的患病与健康犬只的兽医眼科检查结果。研究采用Illumina高密度犬类单核苷酸多态性（SNP）芯片基因分型技术与全基因组测序，以鉴定候选遗传区域。通过公共数据库对候选基因的表达谱与进化保守性进行了评估。系谱信息分析显示，该品种中严重房角发育异常（可进展为青光眼）的遗传方式符合常染色体隐性遗传模式。17号染色体上存在一个高度显著的关联信号峰，其P值为2×10^-13。对3只青光眼患犬、3只严重患病犬与3只健康犬的全基因组测序结果显示，6只患病犬均在嗅素样3（OLFML3）基因中存在一个错义变异。该变异在所有9只青光眼患犬以及14只其他严重患病犬中的12只均呈纯合状态。在67只据报道为健康的犬只中，仅1只（来自两个纯合患病亲本的后代）携带该变异的纯合基因型。候选遗传区域与潜在致病突变的鉴定，将有助于育种者降低边境牧羊犬种群中房角发育异常的发生率与青光眼发病风险。