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Journal of Heredity Advance Access first published online on June 4, 2007
This version published online on August 3, 2007
Journal of Heredity, doi:10.1093/jhered/esm022
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© The American Genetic Association. 2007. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Localization of White Spotting Locus in Boxer Dogs on CFA20 by Genome-Wide Linkage Analysis with 1500 SNPs

Peter A. Leegwater, Marjan A. van Hagen, and Bernard A. van Oost

From the Department of Veterinary Medicine of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80154, 3508 TD Utrecht, The Netherlands. Marjan A. van Hagen is now at the Dutch Kennel Club, Amsterdam, The Netherlands. Bernard A. van Oost is now at the Department of Molecular Cell Biology, American University of the Caribbean, Sint Maarten, Netherlands Antilles

Address correspondence to P. Leegwater at the address above, or e-mail: p.a.j.leegwater{at}vet.uu.nl.

New techniques allow fast genotyping of large numbers of single-nucleotide polymorphisms (SNPs) of the genome. These techniques are used to map disorders with complex inheritance patterns and require large study groups. Linkage analysis of monogenetic traits exploits close family relationships between relatively small numbers of cases and controls. Linkage studies are typically performed with a set of microsatellite markers spaced at 10 cM. We were interested to test whether SNP typing could be applied in genome-wide linkage analysis because of the speed of the procedure. White spotting in Boxer dogs was chosen as a model because it is a semidominant trait, allowing the assignment of locus genotypes to each phenotyped dog. A set of just more than 1500 SNPs were typed in 5 families with heterozygous parents and offspring that included 11 white, 6 brown, and 19 spotted dogs. Multipoint linkage analysis was performed and a LOD score of 12.1 was obtained on canine chromosome 20. The CFA20 region was the only region with a positive LOD score. The gene MITF, coding for a transcription factor implicated in Waardenburg syndrome in humans, is located in the region close to a SNP that is in apparent linkage disequilibrium with the white spotting locus. Thus, MITF is a likely candidate for involvement in white spotting in boxers. We conclude that SNPs, spaced at an average distance of 1.6 Mb, are highly informative in linkage analysis of monogenic traits and are a powerful alternative to microsatellite markers.

Corresponding Editor: Steven Hannah

The symposium line has been added.

This paper was delivered at the 3rd International Conference on the Advances in Canine and Feline Genomics, School of Veterinary Medicine, University of California, Davis, CA, August 3–5, 2006.


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