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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ftpubmed:oai:pubmedcentral.nih.gov:6404605 2023-05-15T15:50:57+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 Pugh, Carys A. Farrell, Lindsay L. Carlisle, Ailsa J. Bush, Stephen J. Ewing, Adam Trejo-Reveles, Violeta Matika, Oswald de Kloet, Arne Walsh, Caitlin Bishop, Stephen C. Prendergast, James G. D. Rainger, Joe Schoenebeck, Jeffrey J. Summers, Kim M. 2019-02-01 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404605/ http://www.ncbi.nlm.nih.gov/pubmed/30696701 https://doi.org/10.1534/g3.118.200944 en eng Genetics Society of America http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404605/ http://www.ncbi.nlm.nih.gov/pubmed/30696701 http://dx.doi.org/10.1534/g3.118.200944 Copyright © 2019 Pugh et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. CC-BY Investigations Text 2019 ftpubmed https://doi.org/10.1534/g3.118.200944 2019-03-17T01:18:33Z 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. Text Canis lupus PubMed Central (PMC) G3 Genes|Genomes|Genetics 9 3 943 954 |
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Investigations Pugh, Carys A. Farrell, Lindsay L. Carlisle, Ailsa J. Bush, Stephen J. Ewing, Adam Trejo-Reveles, Violeta Matika, Oswald de Kloet, Arne Walsh, Caitlin Bishop, Stephen C. Prendergast, James G. D. Rainger, Joe Schoenebeck, Jeffrey J. Summers, Kim M. Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed |
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Investigations |
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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. |
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Text |
author |
Pugh, Carys A. Farrell, Lindsay L. Carlisle, Ailsa J. Bush, Stephen J. Ewing, Adam Trejo-Reveles, Violeta Matika, Oswald de Kloet, Arne Walsh, Caitlin Bishop, Stephen C. Prendergast, James G. D. Rainger, Joe Schoenebeck, Jeffrey J. Summers, Kim M. |
author_facet |
Pugh, Carys A. Farrell, Lindsay L. Carlisle, Ailsa J. Bush, Stephen J. Ewing, Adam Trejo-Reveles, Violeta Matika, Oswald de Kloet, Arne Walsh, Caitlin Bishop, Stephen C. Prendergast, James G. D. Rainger, Joe Schoenebeck, Jeffrey J. Summers, Kim M. |
author_sort |
Pugh, Carys A. |
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 |
Genetics Society of America |
publishDate |
2019 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404605/ http://www.ncbi.nlm.nih.gov/pubmed/30696701 https://doi.org/10.1534/g3.118.200944 |
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Canis lupus |
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Canis lupus |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404605/ http://www.ncbi.nlm.nih.gov/pubmed/30696701 http://dx.doi.org/10.1534/g3.118.200944 |
op_rights |
Copyright © 2019 Pugh et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
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CC-BY |
op_doi |
https://doi.org/10.1534/g3.118.200944 |
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