June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Rare Variant in a GTP-binding protein associated with a novel canine retinal degeneration
Author Affiliations & Notes
  • Leonardo Murgiano
    Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Sylvia M. Van Sloun Laboratory for Canine Genomic Analysis, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Jessica Niggel
    Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Sylvia M. Van Sloun Laboratory for Canine Genomic Analysis, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Gustavo D Aguirre
    Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Sylvia M. Van Sloun Laboratory for Canine Genomic Analysis, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Leonardo Murgiano None; Jessica Niggel None; Gustavo Aguirre None
  • Footnotes
    Support  NIH grants: EY 06855, 017549, the Guide Dog Foundation, Van Sloun Fund for Canine Genetic Research
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4498. doi:
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    • Get Citation

      Leonardo Murgiano, Jessica Niggel, Gustavo D Aguirre; Rare Variant in a GTP-binding protein associated with a novel canine retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4498.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Progressive retinal atrophy (PRA) is a heterogeneous grouping of canine inherited blindness. More than 250 genes are associated with retinal degenerations in mammals, included dogs, which and are suitable animal model for human pathologies. In dogs, different types of photoreceptor defects with different age of onset and severity have been reported, even in the same breed, and new ones are constantly being identified.

Methods : We collected samples from 3 affected dogs and 3 unaffected Labrador retriever siblings, along with the unaffected parents of the same litter. All retinal phenotypes of the dogs were assessed by board certified veterinary ophthalmologists and were characterized by early onset of visual impairment and retinal degeneration. The dogs were genotyped on Illumina 220k markers SNP chip and the parents and one case were whole genome sequenced (WGS) with a 30x coverage. Additional samples were gathered from a control population composed of dogs from the same kennel and a larger number of animals belonging to the general Labrador population.

Results : Homozygosity mapping detected ten potential candidate regions consistent with a recessive mode of inheritance. Exploration of all the variants falling within the candidate regions detected a rare in-frame deletion in a GTP-binding protein. The variant was absent from the online EVA, the Dog Biomedical Variants, and the Dog10k variants databases. Testing 20 non-affected dogs from the same kennel detected wild type and carrier individuals. More than 400 Labradors from the general population were genotyped for the variant.

Conclusions : A Combined approach of whole genome sequencing, mapping, and access to three large canine genomic variants databases allowed us to characterize a possible deleterious causative variant for PRA in Labrador different from the alleles previously reported, which appears to be extremely rare and circumscribed to a single family. Ongoing studies will characterize retinal expression of this gene/variant, and explore effects that mutation causes of protein function and localization to establish that the putative in-frame deletion is causally associated with the disease.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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