Linkage Disequilibrium Mapping in Domestic Dog Breeds Narrows the Progressive Rod-Cone Degeneration Interval and Identifies Ancestral Disease-Transmitting Chromosome

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Departmental Papers (Vet)
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disease models
animal
genetic diversity
genetic linkage
genetic markers
genetic predisposition to disease
genetic variation
retinal degeneration
Disease Modeling
Eye Diseases
Medical Genetics
Ophthalmology
Veterinary Medicine
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Goldstein, Orly
Pearce-Kelling, Sue
Sidjanin, Duska J
Kijas, James W
Felix, Jeanette
Acland, Gregory M
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Abstract

Canine progressive rod–cone degeneration (prcd) is a retinal disease previously mapped to a broad, gene-rich centromeric region of canine chromosome 9. As allelic disorders are present in multiple breeds, we used linkage disequilibrium (LD) to narrow the ∼6.4-Mb interval candidate region. Multiple dog breeds, each representing genetically isolated populations, were typed for SNPs and other polymorphisms identified from BACs. The candidate region was initially localized to a 1.5-Mb zero recombination interval between growth factor receptor-bound protein 2 (GRB2) and SEC14-like 1 (SEC14L). A fine-scale haplotype of the region was developed, which reduced the LD interval to 106 kb and identified a conserved haplotype of 98 polymorphisms present in all prcd-affected chromosomes from 14 different dog breeds. The findings strongly suggest that a common ancestor transmitted the prcd disease allele to many of the modern dog breeds and demonstrate the power of the LD approach in the canine model.

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2006-11-01
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Genomics
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