The Roslin Institute and Royal (Dick) School of Veterinary Studies, Easter Bush, EH25 9RG, United Kingdom
The Roslin Institute and Royal (Dick) School of Veterinary Studies, Easter Bush, EH25 9RG, United Kingdom.
G3 (Bethesda). 2019 Mar 7;9(3):943-954. doi: 10.1534/g3.118.200944.
Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (), 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 have subsequently been found in this breed 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 single nucleotide variant genotyping chip was used to identify a candidate genetic region. There was a highly significant peak of association over chromosome 17, with a -value of 2 × 10 Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Whole genome sequences of three dogs with glaucoma, three severely affected by goniodysgenesis and three unaffected dogs identified a missense variant in the olfactomedin like 3 () gene in all six affected animals. This was homozygous for the risk allele in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one was homozygous for this variant (offspring of parents both with goniodysgenesis who were also homozygous for the variant). Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. The identification of a candidate genetic region and putative causative variant will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.
原发性房角发育不全是一种眼部前房的发育异常。它通常被认为是犬类的先天性疾病（），并与青光眼和失明有关。原发性房角发育不全和早发性青光眼最初出现在 20 世纪 90 年代末的澳大利亚边境牧羊犬中，随后在欧洲和美国的这一品种中也发现了这种疾病。本研究的目的是确定边境牧羊犬原发性房角发育不全的遗传基础。临床诊断基于兽医眼科医生对来自 11 个不同国家的受影响和未受影响的犬只的检查结果。使用 Illumina 高密度犬单核苷酸变异基因分型芯片进行基因分型，以确定候选遗传区域。在第 17 号染色体上有一个高度显著的关联峰，-值为 2 × 10-8。使用公共数据库评估候选基因的表达谱和进化保守性。对 3 只患有青光眼、3 只严重受原发性房角发育不全影响和 3 只未受影响的犬只的全基因组序列进行分析，在所有 6 只受影响的动物中发现了嗅觉素样 3 （）基因的错义变异。在所有 9 例青光眼和 12 例其他严重受影响动物中，该基因均为纯合风险等位基因。在 67 只据报道未受影响的动物中，只有 1 只为该变异的纯合子（父母双方均患有原发性房角发育不全且均为该变异的纯合子的后代）。系谱信息分析与这种品种的严重原发性房角发育不全（可能导致青光眼）的常染色体隐性遗传模式一致。候选遗传区域和潜在的致病变异的确定将有助于饲养者减少边境牧羊犬群体中原发性房角发育不全的频率和青光眼的风险。
