Linkage analysis and comparative mapping of canine progressive rod-cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans

Gregory M. Acland, Kunal Ray, Cathryn S. Mellersh, Weikuan Gu, Amelia A. Langston, Jasper Rine, Elaine A. Ostrander, Gustavo D. Aguirre

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Abstract

Progressive rod-cone degeneration (prcd) is the most widespread hereditary retinal disease leading to blindness in dogs and phenotypically is the canine counterpart of retinitis pigmentosa (RP) in humans. In previous efforts to identify the genetic locus for prcd, the canine homologs for many of the genes causally associated with RP in humans, such as RHO, PDE6B, and RDS/peripherin, have been excluded. In parallel with a recent undertaking to establish a framework map of the canine genome, multiple prcd-informative pedigrees have been typed with a panel of more than 100 anchor loci and microsatellite-based markers. Identification of a linkage group flanking prcd ([TK1, GALK1, prcd]-[MYL4, C09.173, C09.2263]-RARA-C09.250-C09.474- NF1) localizes prcd close to the centromeric end of canine chromosome 9 (CFA9), and excludes RARA as a candidate gene. The conserved synteny of this region of CFA9 and distal human chromosome 17q establishes the potential locus homology of prcd in the dog with RP17, a human retinitis pigmentosa locus for which no gene has yet been identified. Assignment of the prcd disease locus to an identified canine autosome represents a powerful application of the developing canine linkage map in medical genetics. The usefulness of this approach is further demonstrated by identification of the correspondence of the prcd interval to homologous human and mouse chromosomal regions. The rapid progress that is now occurring in the field of canine genetics will expedite the identification of the genes underlying many of the inherited traits and diseases that make the dog a unique asset for the study of mammalian traits.

Original languageEnglish (US)
Pages (from-to)3048-3053
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number6
DOIs
StatePublished - Mar 17 1998

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Retinitis Pigmentosa
Canidae
Genes
Peripherins
Dogs
Dog Diseases
Synteny
Cone-Rod Dystrophies
Retinal Diseases
Chromosomes, Human, Pair 9
Inborn Genetic Diseases
Genetic Loci
Medical Genetics
Human Chromosomes
Blindness
Pedigree
Microsatellite Repeats
Genome

All Science Journal Classification (ASJC) codes

  • General

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Linkage analysis and comparative mapping of canine progressive rod-cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans. / Acland, Gregory M.; Ray, Kunal; Mellersh, Cathryn S.; Gu, Weikuan; Langston, Amelia A.; Rine, Jasper; Ostrander, Elaine A.; Aguirre, Gustavo D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 6, 17.03.1998, p. 3048-3053.

Research output: Contribution to journalArticle

Acland, Gregory M. ; Ray, Kunal ; Mellersh, Cathryn S. ; Gu, Weikuan ; Langston, Amelia A. ; Rine, Jasper ; Ostrander, Elaine A. ; Aguirre, Gustavo D. / Linkage analysis and comparative mapping of canine progressive rod-cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 6. pp. 3048-3053.
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abstract = "Progressive rod-cone degeneration (prcd) is the most widespread hereditary retinal disease leading to blindness in dogs and phenotypically is the canine counterpart of retinitis pigmentosa (RP) in humans. In previous efforts to identify the genetic locus for prcd, the canine homologs for many of the genes causally associated with RP in humans, such as RHO, PDE6B, and RDS/peripherin, have been excluded. In parallel with a recent undertaking to establish a framework map of the canine genome, multiple prcd-informative pedigrees have been typed with a panel of more than 100 anchor loci and microsatellite-based markers. Identification of a linkage group flanking prcd ([TK1, GALK1, prcd]-[MYL4, C09.173, C09.2263]-RARA-C09.250-C09.474- NF1) localizes prcd close to the centromeric end of canine chromosome 9 (CFA9), and excludes RARA as a candidate gene. The conserved synteny of this region of CFA9 and distal human chromosome 17q establishes the potential locus homology of prcd in the dog with RP17, a human retinitis pigmentosa locus for which no gene has yet been identified. Assignment of the prcd disease locus to an identified canine autosome represents a powerful application of the developing canine linkage map in medical genetics. The usefulness of this approach is further demonstrated by identification of the correspondence of the prcd interval to homologous human and mouse chromosomal regions. The rapid progress that is now occurring in the field of canine genetics will expedite the identification of the genes underlying many of the inherited traits and diseases that make the dog a unique asset for the study of mammalian traits.",
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