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Abstract：
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 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 p-value of 2 × 10-13 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 (OLFML3) 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.
摘要：
性腺发育是眼前房的发育异常。它通常被认为是先天性的狗（犬狼疮），并与青光眼和失明有关。性腺发育和早发性青光眼最初于1990年代后期在澳大利亚的BorderCollies中出现，随后在欧洲和美国的该品种中发现。本研究的目的是确定边境牧羊犬性腺发育的遗传基础。临床诊断基于来自11个不同国家的受影响和未受影响的狗的兽医眼科医生的检查结果。使用Illumina高密度犬单核苷酸变体基因分型芯片的基因分型用于鉴定候选遗传区域。在17号染色体上存在高度显著的关联峰,p值为2×10-13。使用公共数据库评估候选基因的表达谱和进化保守性。三只患有青光眼的狗的全基因组序列，在所有六只受影响的动物中，三只受性腺发育严重影响的狗和三只未受影响的狗在olfactomedinlike3（OLFML3）基因中发现了错义变异。在所有9例青光眼病例和14个其他严重受影响的动物中的12个中，这对于风险等位基因是纯合的。据报道，在67只未受影响的动物中，该变体只有一个是纯合的（父母的后代都具有性腺发育，他们也是该变体的纯合的）。对谱系信息的分析与该品种严重的性腺发育（可能导致青光眼）的常染色体隐性遗传方式一致。识别候选遗传区域和推定的致病变异将有助于育种者降低边境牧羊犬种群的性腺发生频率和青光眼风险。
