OMIA 001876-9615 : Progressive retinal atrophy, Basenji in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 258100

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

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".

Breed: Basenji.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SAG S-antigen; retina and pineal gland (arrestin) Canis lupus familiaris 25 NC_006607.3 (44800141..44843580) SAG Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Basenji Progressive retinal atrophy, Basenji SAG extension (stop-lost) 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

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.
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.

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