Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome

Genomics. 2006 Nov;88(5):541-50. doi: 10.1016/j.ygeno.2006.05.013. Epub 2006 Jul 20.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Breeding
  • Chromosome Mapping / veterinary*
  • Chromosomes, Artificial, Bacterial / genetics
  • DNA, Complementary / genetics
  • Dog Diseases / genetics*
  • Dog Diseases / pathology
  • Dogs / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genomics
  • Haplotypes
  • Linkage Disequilibrium
  • Male
  • Phylogeny
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Degeneration / veterinary*
  • Species Specificity

Substances

  • DNA, Complementary