title: Haplotype-defined linkage region for gPRA in Schapendoes dogs.
abstract: OBJECTIVE
  In order to determine the molecular basis of canine generalized progressive retinal atrophy (gPRA), we initiated whole-genome scanning for linkage in gPRA-informative pedigrees of the Schapendoes breed.
  
  
  METHODS
  Detailed pedigree and ophthalmological data were assembled in selected Schapendoes pedigrees. A whole-genome scan was initiated by two-point linkage analysis using microsatellite markers in combination with haplotype analyses. Mutation screening was carried out in respective candidate genes by DNA sequencing of amplified products and quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Genotyping data of the microsatellite genome scan evidenced a peak two-point lod score of 4.78 for marker REN93E07 on CFA20. Haplotype analyses inferred the gPRA locus in a 5.6 megabase (Mb) region between markers FH3358 and TL336MS. Mutation screening in the genes CACNA2D3, HT017, and WNT5A revealed no causative sequence deviations. In addition, CACNA2D3 mRNA levels were equivalent in retinas of affected and healthy dogs.
  
  
  CONCLUSIONS
  By genome-wide linkage analysis a region for gPRA was identified and fine-localized in Schapendoes dogs. Although the mutation causing gPRA in Schapendoes dogs has not yet been identified, we established indirect DNA testing for gPRA in this breed based on linkage analysis data.
authors.affiliation: Human Genetics, Ruhr-University, Bochum, Germany. tanja.lippmann@t-online.de <tanja.lippmann@t-online.de>
authors.forename: Tanja
authors.initials: T
authors.lastname: Lippmann
authors.forename: Anna
authors.initials: A
authors.lastname: Jonkisz
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Dobosz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petrasch-Parwez
authors.forename: Jorg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
mesh_terms: D000818:Animals; D001284:Atrophy; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D005260:Female; D008040:Genetic Linkage; D016678:Genome; D005838:Genotype; D006239:Haplotypes; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000473:pathology / Q000662:veterinary*; D020133:Reverse Transcriptase Polymerase Chain Reaction