title: A large deletion in RPGR causes XLPRA in Weimaraner dogs.
abstract: BACKGROUND
  Progressive retinal atrophy (PRA) belongs to a group of inherited retinal disorders associated with gradual vision impairment due to degeneration of retinal photoreceptors in various dog breeds. PRA is highly heterogeneous, with autosomal dominant, recessive or X-linked modes of inheritance. In this study we used exome sequencing to investigate the molecular genetic basis of a new type of PRA, which occurred spontaneously in a litter of German short-hair Weimaraner dogs.
  
  
  RESULTS
  Whole exome sequencing in two PRA-affected Weimaraner dogs identified a large deletion comprising the first four exons of the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene known to be involved in human retinitis pigmentosa and canine PRA. Screening of 16 individuals in the corresponding pedigree of short-hair Weimaraners by qPCR, verified the deletion in hemizygous or heterozygous state in one male and six female dogs, respectively. The mutation was absent in 88 additional unrelated Weimaraners. The deletion was not detectable in the parents of one older female which transmitted the mutation to her offspring, indicating that the RPGR deletion represents a de novo mutation concerning only recent generations of the Weimaraner breed in Germany.
  
  
  CONCLUSIONS
  Our results demonstrate the value of an existing DNA biobank combined with exome sequencing to identify the underlying genetic cause of a spontaneously occurring inherited disease. Identification of the genetic cause has allowed the development of a diagnostic test, which should help to eradicate the PRA causing mutation from the respective canine line. Thus, planning of future pairings is facilitated and manifestation of this type of PRA can be prevented.
authors.affiliation: Department of Human Genetics, Ruhr-University, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Kropatsch
authors.affiliation: Department of Human Genetics, Ruhr-University, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Akkad
authors.affiliation: Kleintierklinik Frank, Mooswaldallee 10 i, 79108 Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Frank
authors.affiliation: Tierärztliche Überweisungspraxis, Lortzingstraße 12, 28209 Bremen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rosenhagen
authors.affiliation: Cologne Center for Genomics, University of Cologne, Weyertal 115 b, 50931 Cologne, Germany ; Institute of Human Genetics, University of Cologne, Kerpener Str. 34, 50931 Cologne, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.affiliation: Cologne Center for Genomics, University of Cologne, Weyertal 115 b, 50931 Cologne, Germany ; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch Str. 21, 50931 Cologne, Germany ; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Department of Human Genetics, Ruhr-University, Universitätsstraße 150, 44801 Bochum, Germany ; Faculty of Health, University Witten-Herdecke, Alfred-Herrhausen-Strasse 50, 58448 Witten, Germany.
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.affiliation: Department of Human Genetics, Ruhr-University, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
keywords: Exome sequencing; Progressive retinal atrophy; RPGR (retinitis pigmentosa GTPase regulator) gene; Weimaraner