Arginine to Glutamine Variant 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...
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Oxford University Press
2019
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ftdoajarticles:oai:doaj.org/article:5f6ba9d23e0c4a9a99e17cea7ae5f8a3 2023-05-15T15:51:09+02:00 Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed Carys A. Pugh Lindsay L. Farrell Ailsa J. Carlisle Stephen J. Bush Adam Ewing Violeta Trejo-Reveles Oswald Matika Arne de Kloet Caitlin Walsh Stephen C. Bishop James G. D. Prendergast Joe Rainger Jeffrey J. Schoenebeck Kim M. Summers 2019-03-01T00:00:00Z https://doi.org/10.1534/g3.118.200944 https://doaj.org/article/5f6ba9d23e0c4a9a99e17cea7ae5f8a3 EN eng Oxford University Press http://g3journal.org/lookup/doi/10.1534/g3.118.200944 https://doaj.org/toc/2160-1836 2160-1836 doi:10.1534/g3.118.200944 https://doaj.org/article/5f6ba9d23e0c4a9a99e17cea7ae5f8a3 G3: Genes, Genomes, Genetics, Vol 9, Iss 3, Pp 943-954 (2019) glaucoma goniodysgenesis olfactomedin like 3 Border Collie eye development Genetics QH426-470 article 2019 ftdoajarticles https://doi.org/10.1534/g3.118.200944 2022-12-31T05:01:58Z 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. Article in Journal/Newspaper Canis lupus Directory of Open Access Journals: DOAJ Articles G3 Genes|Genomes|Genetics 9 3 943 954 |
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topic |
glaucoma goniodysgenesis olfactomedin like 3 Border Collie eye development Genetics QH426-470 |
spellingShingle |
glaucoma goniodysgenesis olfactomedin like 3 Border Collie eye development Genetics QH426-470 Carys A. Pugh Lindsay L. Farrell Ailsa J. Carlisle Stephen J. Bush Adam Ewing Violeta Trejo-Reveles Oswald Matika Arne de Kloet Caitlin Walsh Stephen C. Bishop James G. D. Prendergast Joe Rainger Jeffrey J. Schoenebeck Kim M. Summers Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed |
topic_facet |
glaucoma goniodysgenesis olfactomedin like 3 Border Collie eye development Genetics QH426-470 |
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 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. |
format |
Article in Journal/Newspaper |
author |
Carys A. Pugh Lindsay L. Farrell Ailsa J. Carlisle Stephen J. Bush Adam Ewing Violeta Trejo-Reveles Oswald Matika Arne de Kloet Caitlin Walsh Stephen C. Bishop James G. D. Prendergast Joe Rainger Jeffrey J. Schoenebeck Kim M. Summers |
author_facet |
Carys A. Pugh Lindsay L. Farrell Ailsa J. Carlisle Stephen J. Bush Adam Ewing Violeta Trejo-Reveles Oswald Matika Arne de Kloet Caitlin Walsh Stephen C. Bishop James G. D. Prendergast Joe Rainger Jeffrey J. Schoenebeck Kim M. Summers |
author_sort |
Carys A. Pugh |
title |
Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed |
title_short |
Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed |
title_full |
Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed |
title_fullStr |
Arginine to Glutamine Variant 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 Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed |
title_sort |
arginine to glutamine variant in olfactomedin like 3 (olfml3) is a candidate for severe goniodysgenesis and glaucoma in the border collie dog breed |
publisher |
Oxford University Press |
publishDate |
2019 |
url |
https://doi.org/10.1534/g3.118.200944 https://doaj.org/article/5f6ba9d23e0c4a9a99e17cea7ae5f8a3 |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
G3: Genes, Genomes, Genetics, Vol 9, Iss 3, Pp 943-954 (2019) |
op_relation |
http://g3journal.org/lookup/doi/10.1534/g3.118.200944 https://doaj.org/toc/2160-1836 2160-1836 doi:10.1534/g3.118.200944 https://doaj.org/article/5f6ba9d23e0c4a9a99e17cea7ae5f8a3 |
op_doi |
https://doi.org/10.1534/g3.118.200944 |
container_title |
G3 Genes|Genomes|Genetics |
container_volume |
9 |
container_issue |
3 |
container_start_page |
943 |
op_container_end_page |
954 |
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1766386219980161024 |