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K Ray, V J Baldwin, G M Acland, S H Blanton, G D Aguirre; Cosegregation of codon 807 mutation of the canine rod cGMP phosphodiesterase beta gene and rcd1.. Invest. Ophthalmol. Vis. Sci. 1994;35(13):4291-4299.
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PURPOSE: To determine if a previously reported nonsense mutation (G to A transition at nucleotide position 2420) in the canine rod cyclic GMP (cGMP) phosphodiesterase beta (PDEB) subunit gene cosegregates with the rod-cone dysplasia 1 disease allele (rcd1) in the rcd1-dog reference colony; to establish the prevalence of this mutation among rcd1-affected Irish setters in the United States; and to screen for this mutation in other forms of canine hereditary progressive retinal atrophy (PRA). METHODS: Exon 21 of canine PDEB, previously reported to contain a nonsense mutation in rcd1-affected dogs, was amplified by polymerase chain reaction from genomic DNA isolated from peripheral blood samples. The mutation was detected in amplified DNA by restriction enzyme digestion and double-stranded conformational polymorphism. Linkage between rcd1 and the PDEB mutation was tested using the computer program LIPED: RESULTS: Three different rcd1-informative canine pedigrees were tested for the PDEB nonsense mutation. The first was a multigenerational pedigree representing the rcd1 reference colony. The other two pedigrees represented purebred Irish setter breeding lines in which rcd1 was known to be segregating. In all three pedigrees, the same point mutation was present and segregated with no discordance with the rcd1 allele. Linkage analysis established a maximum logarithm of odds (LOD) score of 12.05 at a linkage distance (theta) of 0.0. In a representative sampling of Irish setters in the United States diagnosed clinically as affected with typical rcd1 phenotype, all dogs were demonstrated to have the same (codon 807) PDEB mutation. Three of four Irish setters affected with atypical, relatively slower disease also had this mutation, but one dog did not. This point mutation in the canine PDEB gene was absent in other forms of canine hereditary retinal degeneration. CONCLUSIONS: In three informative pedigrees, the codon 807 mutation in canine PDEB cosegregates with the rcd1 disease allele with zero discordance. A linkage distance (theta) of zero, with an LOD score of 12.05, indicates identity of this mutation and rcd1. This appears to be the only mutation causing rcd1 in the United States. In all other forms of canine hereditary retinal degeneration tested (cd, erd, prcd, rcd2, X-linked PRA, and in one Iris degeneration tested (cd, erd, prcd, rcd2, X-linked PRA, and in one Irish setter with late onset PRA), this PDEB point mutation was absent.
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