title: Genetic screening for PRA-associated mutations in multiple dog breeds shows that PRA is heterogeneous within and between breeds.
abstract: OBJECTIVE
  To assess the extent of progressive retinal atrophy (PRA) genetic heterogeneity within and between domestic dog breeds.
  
  
  METHODS
  DNA from 231 dogs with PRA, representing 36 breeds, was screened for 17 mutations previously associated with PRA in at least one breed of dog. Screening methods included amplified fragment size discrimination using gel electrophoresis or detection of fluorescence, (TaqMan(®) ; Life Technologies, Carlsbad, CA, USA) allelic discrimination, and Sanger sequencing.
  
  
  RESULTS
  Of the 231 dogs screened, 129 were homozygous for a PRA-associated mutation, 29 dogs were carriers, and 73 were homozygous for the wild-type allele at all loci tested. In two of the 129 dogs, homozygous mutations were identified that had not previously been observed in the respective breeds: one Chinese Crested dog was homozygous for the RCD3-associated mutation usually found in the Cardigan Welsh Corgi, and one Standard Poodle was homozygous for the RCD4-associated mutation previously reported to segregate in Gordon and Irish Setters. In the majority of the breeds (15/21) in which a PRA-associated mutation is known to segregate, cases were identified that did not carry any of the known PRA-associated mutations.
  
  
  CONCLUSIONS
  Progressive retinal atrophy in the dog displays significant genetic heterogeneity within as well as between breeds. There are also several instances where PRA-associated mutations segregate among breeds with no known close ancestry.
authors.affiliation: Kennel Club Genetics Centre, Animal Health Trust, Lanwades Park, Newmarket, CB8 7UU, UK.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Downs
authors.forename: Rebekkah
authors.initials: R
authors.lastname: Hitti
authors.forename: Silvia
authors.initials: S
authors.lastname: Pregnolato
authors.forename: Cathryn S
authors.initials: CS
authors.lastname: Mellersh
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005136:Eye Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D009154:Mutation; D012162:Retinal Degeneration / Q000235:genetics / Q000662:veterinary*
chemical_list: D005136:Eye Proteins; D004247:DNA
keywords: PRA; progressive retinal atrophy