A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations
Causative genetic variants for more than 30 heritable eye disorders in dogs have been reported. For other clinically described eye disorders, the genetic cause is still unclear. We investigated four Golden Retriever litters segregating for highly variable congenital eye malformations. Several affect...
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ftmdpi:oai:mdpi.com:/2073-4425/10/6/454/ 2023-08-20T04:05:49+02:00 A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations Petra Hug Linda Anderegg Nicole Dürig Vincent Lepori Vidhya Jagannathan Bernhard Spiess Marianne Richter Tosso Leeb agris 2019-06-14 application/pdf https://doi.org/10.3390/genes10060454 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes10060454 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 10; Issue 6; Pages: 454 Canis lupus familiaris dog whole genome sequence animal model homeobox ophthalmology development optic nerve retinal dysplasia nystagmus Text 2019 ftmdpi https://doi.org/10.3390/genes10060454 2023-07-31T22:21:30Z Causative genetic variants for more than 30 heritable eye disorders in dogs have been reported. For other clinically described eye disorders, the genetic cause is still unclear. We investigated four Golden Retriever litters segregating for highly variable congenital eye malformations. Several affected puppies had unilateral or bilateral retina dysplasia and/or optic nerve hypoplasia. The four litters shared the same father or grandfather suggesting a heritable condition with an autosomal dominant mode of inheritance. The genome of one affected dog was sequenced and compared to 601 control genomes. A heterozygous private nonsense variant, c.487C>T, was found in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*). We genotyped all available family members and 464 unrelated Golden Retrievers. All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases. The SIX6 protein is a homeobox transcription factor with a known role in eye development. In humans and other species, SIX6 loss of function variants were reported to cause congenital eye malformations. This strongly suggests that the c.487C>T variant detected contributed to the observed eye malformations. We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs. Text Canis lupus MDPI Open Access Publishing Genes 10 6 454 |
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MDPI Open Access Publishing |
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ftmdpi |
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English |
topic |
Canis lupus familiaris dog whole genome sequence animal model homeobox ophthalmology development optic nerve retinal dysplasia nystagmus |
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Canis lupus familiaris dog whole genome sequence animal model homeobox ophthalmology development optic nerve retinal dysplasia nystagmus Petra Hug Linda Anderegg Nicole Dürig Vincent Lepori Vidhya Jagannathan Bernhard Spiess Marianne Richter Tosso Leeb A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations |
topic_facet |
Canis lupus familiaris dog whole genome sequence animal model homeobox ophthalmology development optic nerve retinal dysplasia nystagmus |
description |
Causative genetic variants for more than 30 heritable eye disorders in dogs have been reported. For other clinically described eye disorders, the genetic cause is still unclear. We investigated four Golden Retriever litters segregating for highly variable congenital eye malformations. Several affected puppies had unilateral or bilateral retina dysplasia and/or optic nerve hypoplasia. The four litters shared the same father or grandfather suggesting a heritable condition with an autosomal dominant mode of inheritance. The genome of one affected dog was sequenced and compared to 601 control genomes. A heterozygous private nonsense variant, c.487C>T, was found in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*). We genotyped all available family members and 464 unrelated Golden Retrievers. All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases. The SIX6 protein is a homeobox transcription factor with a known role in eye development. In humans and other species, SIX6 loss of function variants were reported to cause congenital eye malformations. This strongly suggests that the c.487C>T variant detected contributed to the observed eye malformations. We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs. |
format |
Text |
author |
Petra Hug Linda Anderegg Nicole Dürig Vincent Lepori Vidhya Jagannathan Bernhard Spiess Marianne Richter Tosso Leeb |
author_facet |
Petra Hug Linda Anderegg Nicole Dürig Vincent Lepori Vidhya Jagannathan Bernhard Spiess Marianne Richter Tosso Leeb |
author_sort |
Petra Hug |
title |
A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations |
title_short |
A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations |
title_full |
A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations |
title_fullStr |
A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations |
title_full_unstemmed |
A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations |
title_sort |
six6 nonsense variant in golden retrievers with congenital eye malformations |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2019 |
url |
https://doi.org/10.3390/genes10060454 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 10; Issue 6; Pages: 454 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes10060454 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes10060454 |
container_title |
Genes |
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10 |
container_issue |
6 |
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454 |
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1774716571550220288 |