A non-stop S-antigen gene mutation is associated with late onset hereditary retinal degeneration in dogs.

Abstract

PURPOSE:

To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog.

METHODS:

Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated.

RESULTS:

The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on three chromosomes. Homozygosity and linkage disequilibrium analyses favored one chromosome, CFA25, and screening of the S-antigen (SAG) gene identified a non-stop mutation (c.1216T>C), which would result in the addition of 25 amino acids (p.*405Rext*25).

CONCLUSIONS:

Identification of this non-stop SAG mutation in dogs affected with retinal degeneration establishes this canine disease as orthologous to Oguchi disease and SAG-associated retinitis pigmentosa in humans, and offers opportunities for genetic therapeutic intervention.

• Authors: Orly Goldstein, Julie Ann Jordan, Gustavo D Aguirre, Gregory M Acland
• Journal: Molecular vision (Mol Vis) Vol. 19 Pg. 1871-84 ( 2013) ISSN: 1090-0535 [Electronic] United States
• PMID: 24019744 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Arrestin
• Codon, Nonsense
• RNA, Messenger

Topics

• Amino Acid Sequence
• Animals
• Arrestin (chemistry, genetics)
• Base Sequence
• Case-Control Studies
• Codon, Nonsense (genetics)
• Dogs
• Female
• Fundus Oculi
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Homozygote
• Male
• Molecular Sequence Data
• Mutation (genetics)
• Pedigree
• Phenotype
• Polymorphism, Single Nucleotide (genetics)
• RNA, Messenger (genetics, metabolism)
• Retinal Degeneration (genetics, veterinary)