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.

Defects in collagen proteins cause a variety of disorders in humans. It can be expected that collagen gene mutations are involved in collagenopathies in dogs. The collagen genes COL3A1, COL5A1, COL5A2, COL6A1, COL6A3, COL9A1, COL9A2, COL9A3, COL10A1 and COL11A1 were identified on the canine genome based on the homology with the human genes. Simple sequence repeats (microsatellites) were found in the chromosomal regions of these genes and investigated for polymorphism in Labrador Retrievers, Bernese Mountain dogs, Boxer dogs and German Shepherd dogs by PCR and subsequent detection of the DNA products. Nine informative microsatellite markers were identified. The markers closely situated to COL9A1, COL9A2 and COL9A3 were used to investigate the involvement of the genes in cranial cruciate ligament rupture in Boxer dogs. It was found that these genes are probably not involved in this abnormality. The markers described here will be useful for a candidate gene approach of suspected collagenopathies specific to dog breeds.