Journal
GENOMICS
Volume 88, Issue 5, Pages 541-550Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2006.05.013
Keywords
disease models, animal; genetic diversity; genetic linkage; genetic markers; genetic predisposition to disease; genetic variation; retinal degeneration
Funding
- NEI NIH HHS [R01 EY013132, R01 EY006855, EY13132, EY06855] Funding Source: Medline
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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 similar to 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 SEC 14-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. (c) 2006 Elsevier Inc. All rights reserved.
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