Unleashing the Canine Genome
- Elaine A. Ostrander1,2 and
- Leonid Kruglyak1,3
- 1Division of Human Biology, 2Division of Clinical Research, and 3Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109–1024, USA
This extract was created in the absence of an abstract.
In humans, common diseases show complex modes of inheritance and, as a result, have been largely refractory to genetic analysis. Rodent systems are more tractable genetically, but the mutations typically represent induced rather than naturally arising alleles, and results are often of limited direct relevance to human disease because of profound differences in physiology. By comparison, the physiology, disease presentation, and clinical response of dogs often mimic human diseases closely. In addition, the modern dog offers key advantages over other animal systems for mapping genes relevant to human disease. In the following discussion, we highlight some of these advantages and provide specific examples where canine genetics is best suited to solve difficult problems in human genetics. In particular, we focus on the strong promise of linkage-disequilibrium (LD) mapping in dogs.
LD Mapping
LD mapping relies on population-level associations among alleles at disease loci and those at nearby markers. Such associations typically arise when all or most of the disease alleles in a population share a common ancestral origin. LD mapping has been applied with success in isolated human populations. For instance, LD methods have been used to fine-map a number of disease genes in Finnish populations, for which LD frequently extends over distances of several cM around the disease mutation (de la Chapelle and Wright 1998). Examples of de novo mapping of human disease genes by the LD approach include the mapping of Hirchsprung's disease in a large, inbred Mennonite kindred (Puffenberger et al. 1994). The gene was mapped to chromosome 13q following analysis of a microsatellite screen of 10-cM density in only six affected individuals. Importantly, all six were related through multiple lines of descent to a single ancestral couple eight to 12 generations earlier. In addition, a gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by …
