title: Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect.
abstract: OBJECTIVE
  To clone and characterize the canine RPE65 cDNA from normal dog, examine for mutations, and establish if the mutation identified in Swedish briard dogs with retinal dystrophy is present in dogs of the same breed that originated from the United States and other countries, and are affected with congenital stationary night blindness.
  
  
  METHODS
  Fifteen briard dogs were studied, of which 10 were affected with csnb, and five were clinically normal. In addition, we tested samples from four Swedish dogs, and samples from a briard affected with progressive retinal atrophy. RPE65 cDNA was cloned a from retinal cDNA library by PCR, and from canine retina by RT-PCR. ERG and morphology were used to characterize csnb.
  
  
  RESULTS
  The normal RPE65 cDNA spans 1724 nucleotides (GenBank accession number AF084537), and includes 1602 nucleotides of coding sequence; the deduced amino acid sequence shares 98%, 97%, and 93% identity with homologous human, bovine, and rat sequences, respectively. A homozygous four nucleotide (AAGA) deletion, representing nucleotides 487-490 of wildtype RPE65 sequence, was found only in csnb and retinal dystrophy affected dogs; heterozygous animals had normal and mutant alleles. The mutation produces a frameshift, causing a deduced mistranslation with a premature stop codon. The mutation causes retinal dysfunction and RPE accumulation of lipid vacuoles.
  
  
  CONCLUSIONS
  Identification of the same mutation in csnb and retinal dystrophy confirms the molecular identity of the two disorders. A common mutation in dogs derived from different countries suggests a founder effect causing the propagation of a common mutant allele in the population at risk.
authors.affiliation: James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA. gda1@cornell.edu
authors.forename: G D
authors.initials: GD
authors.lastname: Aguirre
authors.forename: V
authors.initials: V
authors.lastname: Baldwin
authors.forename: S
authors.initials: S
authors.lastname: Pearce-Kelling
authors.forename: K
authors.initials: K
authors.lastname: Narfström
authors.forename: K
authors.initials: K
authors.lastname: Ray
authors.forename: G M
authors.initials: GM
authors.lastname: Acland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D003001:Cloning, Molecular; D004285:Dogs; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D018703:Founder Effect; D008969:Molecular Sequence Data; D009154:Mutation; D009755:Night Blindness / Q000235:genetics*; D010375:Pedigree; D010857:Pigment Epithelium of Eye / Q000503:physiopathology; D011506:Proteins; D012160:Retina / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013548:Sweden; D014481:United States; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase