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(Investigative Ophthalmology and Visual Science. 2001;42:2466-2471.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Fine Mapping of Canine XLPRA Establishes Homology of the Human and Canine RP3 Intervals

Qi Zhang1, Gregory M. Acland1, Barbara Zangerl1, Jennifer L. Johnson1, Zuohua Mao1,2, Caroline J. Zeiss1,3, Elaine A. Ostrander4 and Gustavo D. Aguirre1

1 From the James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York; the 2 Department of Microbiology and Parasitology, Medical College of Fudan University, Shanghai, China; the 3 Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut; and the 4 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

PURPOSE. Canine X-linked progressive retinal atrophy (XLPRA) is a hereditary, 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 1 (TIMP1) genes, and is tightly linked to the gene RPGR. The comparable region of the human X chromosome includes the disease locus for RP3, an X-linked form of retinitis pigmentosa, although the current canine disease interval is much larger.

METHODS. To refine the map of the canine XLPRA disease interval, 11 X-linked markers were mapped, both meiotically, in two extensive canine pedigrees informative for XLPRA, and on a 3000-rad canine-hamster radiation hybrid (RH) panel. A 12th marker 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 strong conservation of synteny between humans and dogs. Genes defining the human RP3 zero-recombination interval (human homologue of mouse t complex [TCTE1L], sushi repeat-containing protein, X chromosome [SRPX], and retinitis pigmentosa guanosine triphosphatase [GTPase] regulator [RPGR]) are tightly linked to each other, to the XLPRA locus, and to the gene ornithine transcarbamylase (OTC) in dogs.

CONCLUSIONS. Strong conservation of gene order was demonstrated in the short arm of the X chromosome between dogs and humans as was homology of the canine XLPRA and human RP3 intervals. These results create a valuable tool for investigating canine XLPRA and other X-linked eye diseases in dogs.




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