A mutation in Olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in Border Collies

Presenter pawprints
Authors Carys A Pugh, Lindsay L Farrell, Ailsa J Carlisle, Stephen J Bush, Violeta Trejo-Reveles, Oswald Matika, Stephen C Bishop, Jeffrey J Schoenebeck, Joe Rainger, Kim M Summers
Presentation Type Talk


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 emerged in the Border Collie breed in Australia in the late 1990s and has since been found in Europe and the USA. Increasing concern regarding the condition led to its inclusion in the Schedule B list of ‘Conditions Under Investigation’ for Border Collies in the British Veterinary Association Eye Scheme and the objective of this study was to determine its genetic basis in the breed. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Reports were gleaned from a publicly available database, managed by breeders, and from test results submitted directly by owners. 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 5 x 10-13. Whole genome sequences of three dogs with glaucoma, three dogs with severe goniodysgenesis and three unaffected dogs identified a missense variant in the olfactomedin-like 3 (OLFML3) gene in all six affected animals and this was homozygous in all nine cases with glaucoma and nine of 11 other animals with severe goniodysgenesis. None of 56 unaffected animals was homozygous for this variant. The identification of a candidate genetic region and putative causative mutation will inform breeding programs to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.