OMIA:001876-9615 : Retinal atrophy, progressive, SAG-related in Canis lupus familiaris (dog)

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 258100 (trait) , 613758 (trait) , 181031 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Disease was previously called 'Progressive retinal atrophy, Basenji'. Renamed 'Retinal atrophy, progressive, SAG-related' [13/06/2023]

History: This particular form of PRA was first mentioned by Goldstein et al. (2006), who, by judicious matings, showed that even though its clinical sings are very similar to Progressive rod-cone degeneration (prcd) (OMIA 001298-9615) in a wide range of breeds, the Basenji disorder is not allelic to prcd.

Inheritance: The mating results of Goldstein et al. (2006) suggested autosomal recessive inheritance.

Mapping: A GWAS conducted by Goldstein et al. (2013) on 6 affected and 3 control Basenjis, each genotyped with the Illumina HD Canine SNP Chip comprising 173,662 SNPs, implicated regions on chromosomes CFA4, CFA13 and CFA25. Haplotype analysis suggested the CFA25 region as the most likely candidate region. Homozygosity mapping analysis confirmed the CFA25 region as most likely.

Molecular basis: Sequencing of the two candidate genes in this region led Goldstein et al. (2013) to the discovery of the causal mutation as a stop-loss or extensionl base substitution in the SAG gene (encoding S-antigen): a "tyrosine to cysteine transition mutation at position CFA25:47,845,680 (c.1216T>C . . .) that changed the normal stop codon to code for the amino acid arginine, which would result in a deduced addition of 25 amino acids (p.*405Rext*25) to the normal 405 amino acid protein".

Clinical features: While there are multiple types of progressive retinal atrophy (PRA), Basenjis generally obtain late onset PRA (Goldstein et al., 2013). Initially, affected individuals lose their vision in dim light and lose their peripheral visual field, resulting in tunnel vision. Many individuals can maintain forward day vision for years as disease progresses (Goldstein et al., 2013). Retinal thinning (stage I) can typically be detected at five years old, and reduced blood flow through retinal vasculature (stage II) is normally detected around seven years of age (Goldstein et al., 2013). IT thanks DVM student Maya Yaffe, who provided the basis of this contribution in May 2023.

Breed: Basenji (Dog) (VBO_0200120).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SAG S-antigen; retina and pineal gland (arrestin) Canis lupus familiaris - no genomic information (-..-) SAG Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
359 Basenji (Dog) Progressive retinal atrophy, Basenji SAG extension (stop-lost) Naturally occurring variant CanFam3.1 25 g.44843440T>C c.1216T>C p.(*405Rext*25) 2013 24019744 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001876-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Ghilardi, S., Bagardi, M., Frattini, S., Barbariga, G.E., Brambilla, P.G., Minozzi, G., Polli, M. :
Genotypic and allelic frequencies of progressive rod-cone degeneration and other main variants associated with progressive retinal atrophy in Italian dogs. Vet Rec Open 10:e77, 2023. Pubmed reference: 38028226. DOI: 10.1002/vro2.77.
2021 Genetics Committee of the American College of Veterinary Opthalmologists :
The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf , 2021.
2013 Goldstein, O., Jordan, J.A., Aguirre, G.D., Acland, G.M. :
A non-stop S-antigen gene mutation is associated with late onset hereditary retinal degeneration in dogs. Mol Vis 19:1871-84, 2013. Pubmed reference: 24019744.
2006 Goldstein, O., Zangerl, B., Pearce-Kelling, S., Sidjanin, D.J., Kijas, J.W., Felix, J., Acland, G.M., Aguirre, G.D. :
Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome. Genomics 88:541-50, 2006. Pubmed reference: 16859891. DOI: 10.1016/j.ygeno.2006.05.013.
1974 Priester, W.A. :
Canine progressive retinal atrophy. Occurrence by age, breed and sex. Am J Vet Res 35:571-574, 1974.

Edit History


  • Created by Frank Nicholas on 03 Sep 2013
  • Changed by Frank Nicholas on 03 Sep 2013
  • Changed by Frank Nicholas on 28 Aug 2016
  • Changed by Imke Tammen2 on 13 Jun 2023