A Missense Variant in the Bardet-Biedl Syndrome 2 Gene ( BBS2 ) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog

Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized by photoreceptor cell death in the retina, leading to visual impairment. Despite the identification of multiple PRA-causing variants, extensive heterogeneity of PRA is observed across and within dog breed...

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Bibliographic Details
Published in:Genes 2021-11, Vol.12 (11), p.1771
Main Authors: Hitti-Malin, Rebekkah J, Burmeister, Louise M, Lingaas, Frode, Kaukonen, Maria, Pettinen, Inka, Lohi, Hannes, Sargan, David, Mellersh, Cathryn S
Format: Article
Language:English
Subjects:
Animals
Atrophy
Bardet-Biedl syndrome
Breeding of animals
Cell death
Disease
Dog Diseases - genetics
Dogs
Female
Genes
Genetic disorders
Genomes
Genomics
Genotyping
Hereditary diseases
Homozygotes
Hybridization, Genetic
Life sciences
Male
Mutation, Missense
Phenotype
Phenotypes
Proteins - genetics
Retina
Retinal degeneration
Retinal Degeneration - genetics
Retinal Degeneration - veterinary
Whole Genome Sequencing
Wolves
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Summary:Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized by photoreceptor cell death in the retina, leading to visual impairment. Despite the identification of multiple PRA-causing variants, extensive heterogeneity of PRA is observed across and within dog breeds, with many still genetically unsolved. This study sought to elucidate the causal variant for a distinct form of PRA in the Shetland sheepdog, using a whole-genome sequencing approach. Filtering variants from a single PRA-affected Shetland sheepdog genome compared to 176 genomes of other breeds identified a single nucleotide variant in exon 11 of the Bardet-Biedl syndrome-2 gene ( ) (c.1222G>C; p.Ala408Pro). Genotyping 1386 canids of 155 dog breeds, 15 cross breeds and 8 wolves indicated the c.1222G>C variant was only segregated within Shetland sheepdogs. Out of 505 Shetland sheepdogs, seven were homozygous for the variant. Clinical history and photographs for three homozygotes indicated the presence of a novel phenotype. In addition to PRA, additional clinical features in homozygous dogs support the discovery of a novel syndromic PRA in the breed. The development and utilization of a diagnostic DNA test aim to prevent the mutation from becoming more prevalent in the breed.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes12111771