Genetic mapping in the dog towards localising the genes responsible for progressive retinal atrophy in miniature long-haired dachshunds and Labrador retrievers

Ryder, Edward James (2000). Genetic mapping in the dog towards localising the genes responsible for progressive retinal atrophy in miniature long-haired dachshunds and Labrador retrievers. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000ff96

Abstract

The current linkage map of the domestic dog Canis familiaris is poorly defined with few linkage groups and few markers physically assigned to chromosomes. To expand the canine linkage map, 33 microsatellite markers were typed on to the DogMap reference families. Ten new linkage groups were established (designated L8, L13, L16, L20, L21, L22, L23, L24, L25 and L26), and one marker was added to linkage group L5. The new linkage groups cover a potential 332cM; approximately 11% of the canine genome. Progressive retinal atrophies are hereditary retinal degenerations which lead to loss of vision, and are a major problem in pedigree dogs. The disease was studied in two breeds; miniature long-haired dachshunds and Labrador retrievers.
Due to the lack of a complete canine genetic linkage map, the approach taken was to type random markers on to resource pedigrees segregating the disease allele. Markers were provisionally screened on three affected individuals and ranked for the number of homozygotes present. Three carriers were also typed to evaluate marker polymorphism. Selected markers were then typed on to the whole family and linkage analysis performed. Although no markers were found linked to the PRA locus in Labrador retrievers, marker CPH4 was found linked to the disease locus in miniature long-haired dachshunds at a distance of 4cM. Further studies using published data produced four more linked markers and one linked gene. A subset of markers was used to probe a canine BAG library and the subsequent clones were assigned to chromosomes by FISH, locating the disease locus to CFA 15q23 - q24.1. Radiation hybrid mapping of the region allowed ordering of the markers relative to each other. The interval mapped contains an evolutionary breakpoint between HSA12 and HSA1, although the disease locus could not be unambiguously mapped to a particular human chromosome.