title: Canine RD3 mutation establishes rod-cone dysplasia type 2 (rcd2) as ortholog of human and murine rd3.
abstract: Rod-cone dysplasia type 2 (rcd2) is an autosomal recessive disorder that segregates in collie dogs. Linkage disequilibrium and meiotic linkage mapping were combined to take advantage of population structure within this breed and to fine map rcd2 to a 230-kb candidate region that included the gene C1orf36 responsible for human and murine rd3, and within which all affected dogs were homozygous for one haplotype. In one of three identified canine retinal RD3 splice variants, an insertion was found that cosegregates with rcd2 and is predicted to alter the last 61 codons of the normal open reading frame and further extend the open reading frame. Thus, combined meiotic linkage and LD mapping within a single canine breed can yield critical reduction of the disease interval when appropriate advantage is taken of within-breed population structure. This should permit a similar approach to tackle other hereditary traits that segregate in single closed populations.
authors.affiliation: James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Hungerford Hill Road, Ithaca, New York 14853, USA.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Kukekova
authors.forename: Orly
authors.initials: O
authors.lastname: Goldstein
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Richardson
authors.forename: Susan E
authors.initials: SE
authors.lastname: Pearce-Kelling
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: James S
authors.initials: JS
authors.lastname: Friedman
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Aguirre
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Acland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005136:Eye Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D015792:Retinal Dysplasia / Q000235:genetics / Q000662:veterinary*
chemical_list: D005136:Eye Proteins; D009687:Nuclear Proteins; C477438:RD3 protein, human; C516799:retinal degeneration 3 protein, mouse