Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome.
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 approximately 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.
Goldstein
Orly
O
James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Zangerl
Barbara
B
Pearce-Kelling
Sue
S
Sidjanin
Duska J
DJ
Kijas
James W
JW
Felix
Jeanette
J
Acland
Gregory M
GM
Aguirre
Gustavo D
GD
D000818:Animals; D001483:Base Sequence; D001947:Breeding; D002874:Chromosome Mapping / Q000662:veterinary*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D023281:Genomics; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008297:Male; D010802:Phylogeny; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D013045:Species Specificity
D018076:DNA, Complementary