Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed
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 Austra...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
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Genetics Society of America
2019
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| _version_ | 1797087023108980736 |
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| author | Pugh, C Farrell, L Carlisle, A Bush, S Trejo-Reveles, V Matika, O De Kloet, A Walsh, C Bishop, S Prendergast, J Schoenebeck, J Rainger, J Summers, K |
| author_facet | Pugh, C Farrell, L Carlisle, A Bush, S Trejo-Reveles, V Matika, O De Kloet, A Walsh, C Bishop, S Prendergast, J Schoenebeck, J Rainger, J Summers, K |
| author_sort | Pugh, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:30:14Z |
| format | Journal article |
| id | oxford-uuid:a6fcc958-9807-4c88-a97f-42c6edb24be4 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:30:14Z |
| publishDate | 2019 |
| publisher | Genetics Society of America |
| record_format | dspace |
| spelling | oxford-uuid:a6fcc958-9807-4c88-a97f-42c6edb24be42022-03-27T02:51:23ZArginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breedJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a6fcc958-9807-4c88-a97f-42c6edb24be4Symplectic Elements at OxfordGenetics Society of America2019Pugh, CFarrell, LCarlisle, ABush, STrejo-Reveles, VMatika, ODe Kloet, AWalsh, CBishop, SPrendergast, JSchoenebeck, JRainger, JSummers, KGoniodysgenesis 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. |
| spellingShingle | Pugh, C Farrell, L Carlisle, A Bush, S Trejo-Reveles, V Matika, O De Kloet, A Walsh, C Bishop, S Prendergast, J Schoenebeck, J Rainger, J Summers, K Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed |
| title | Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed |
| title_full | Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed |
| title_fullStr | Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed |
| title_full_unstemmed | Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed |
| title_short | Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed |
| title_sort | arginine to glutamine mutation in olfactomedin like 3 olfml3 is a candidate for severe goniodysgenesis and glaucoma in the border collie dog breed |
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