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Journal of Heredity Advance Access published online on March 25, 2009
Journal of Heredity, doi:10.1093/jhered/esp011
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© The American Genetic Association. 2009. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Genetic Mapping of Fixed Phenotypes: Disease Frequency as a Breed Characteristic

Kevin Chase, Paul Jones, Alan Martin, Elaine A. Ostrander, and Karl G. Lark

From the Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112 (Chase and Lark); the WALTHAM Centre for Pet Nutrition, Waltham on the Wolds, Leicsestershire, UK (Jones and Martin); and Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (Ostrander)

Address correspondence to Kevin Chase at the address above, or e-mail: kchase99{at}gmail.com.

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pacreatitis.

Key Words: association • canine • disease • longevity • morphology • QTL

Corresponding Editor: Francis Galibert

Received November 20, 2008
Revised February 10, 2009
Accepted February 25, 2009


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