Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci

Car-R and Car-S outbred mouse lines, phenotypically selected for resistance and susceptibility to skin carcinogenesis respectively, show significant l inkage disequilibrium (LD) at genetic markers mapping on chromosomal region s where skin cancer modifier loci (Skts3, Skts1, and Psl1 on Chrs 5, 7, and 9 respectively) have been mapped in standard crosses. Analysis of these re gions for genetic linkage with skin cancer phenotypes in 245 (Car-R X Car-S )F-2 intercross mice, by using single nucleotide polymorphisms (SNPs), reve aled significant linkage at a possible allelic form of the Skts1 locus, who se mapping region was shortened to a <5.5-cM interval near the Tyr locus. T he Car-derived Skts1 locus was linked with papilloma multiplicity and laten cy by a recessive inheritance of the susceptibility allele. Putative loci o n Chr 5 (Skts3) and 9 (Psl1) showed no significant linkage. These results p oint to the important role of the Stks1 locus in mouse skin tumorigenesis i n independent crosses. The shortened Skts1 mapping region should facilitate the identification of candidate genes.