Fine mapping of canine XLPRA establishes homology of the human and canine RP3 intervals

PURPOSE. Canine X-linked progressive retinal atrophy (XLPRA) is a hereditar y, progressive retinal degeneration that has been mapped previously to the canine X chromosome in a region flanked by the dystrophin (DMD) and tissue inhibitor of metalloproteinase I (TIMP1) genes, and is tightly linked to th e gene RPGR. The comparable region of the human X chromosome includes the d isease locus for RP3, an X-linked form of retinitis pigmentosa, although th e current canine disease interval is much larger. METHODS. To refine the map of the canine XLPRA disease interval, 11 X-linke d markers were mapped, both meiotically, in two extensive canine pedigrees informative for XLPRA, and on a 3000-rad canine-hamster radiation hybrid (R H) panel. A 12th mark-er was mapped on the RH panel alone. RESULTS. The integrated map of this region of CFAX now covers approximately 47.3 centimorgans (cM) and 194 centirays (cR)(3000), and demonstrates stro ng conservation of synteny between humans and dogs. Genes defining the huma n RP3 zero-recombination interval (human homologue of mouse t complex [TCTE 1L], sushi repeat-containing protein, X chromosome [SRPX], and retinitis pi gmentosa guanosine triphosphatase [GTPase] regulator [PPGR]) are tightly li nked to each other, to the XLPRA locus, and to the gene ornithine transcarb amylase (OTC) in dogs. CONCLUSIONS. Strong conservation of gene order was demonstrated in the shor t arm of the X chromosome between dogs and humans as was homology of the ca nine XLPRA, and human RP3 intervals. These results create a valuable tool f or investigating canine XLPRA and other X-linked eye diseases in dogs.