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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.
NOTICE: This is the author’s version of a work that was accepted for publication in Genomics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Genomics, 88, 5, 10.1016/j.ygeno.2006.05.013.
disease models, animal, genetic diversity, genetic linkage, genetic markers, genetic predisposition to disease, genetic variation, retinal degeneration
Goldstein, O., Zangerl, B., Pearce-Kelling, S., Sidjanin, D. J., Kijas, J. W., Felix, J., Acland, G. M., & Aguirre, G. D. (2006). Linkage Disequilibrium Mapping in Domestic Dog Breeds Narrows the Progressive Rod-Cone Degeneration Interval and Identifies Ancestral Disease-Transmitting Chromosome. Genomics, 88 (5), 541-550. http://dx.doi.org/10.1016/j.ygeno.2006.05.013
Date Posted: 06 May 2015
This document has been peer reviewed.