Experiment
Linkage analysis was performed on 208 (FVB/NTac x PWK/Rbrc)F1 x FVB/NTac backcross mice to identify new loci for skin tumor susceptibility. Animals were subjected to 2-step treatment with DMBA and TPA at 8-11 weeks of age. Skin tumor phenotype was assessed at regular intervals for 20 weeks after initiation of treatment. Parental strain FVB/NTac is susceptible to chemically-induced skin tumors whereas parental strain PWK/Rbrc is resistant, and males appear to have increased susceptibility compared to females. A panel of 204 polymorphic markers was used for the genome scan.
Significant linkage to skin tumor susceptibility mapped to a broad region on mouse Chromosome 4 between D4Mit111 (22.1 cM) and D4Mit308 (51.9 cM). This locus explains 18% of the traitvariance and is named Skts-fp1 (skin tumor susceptibility in FVB and PWK 1). Skts-fp1 may consist of multiple QTLs as evidenced by 2 linkage peaks near D4Mit26 (36.3 cM, LRS=38.5) and D4Mit146 (40 cM, LRS=40.5). Previously identified skin tumor QTL Skts7(56 cM) is located near Skts-fp1.
An interacting locus pair exhibiting statistical significance mapped to mouse Chromosome 11 between D11Mit155 and D11Mit178 with LRS=27.6 and mouse Chromosome 16 between D16Mit202 and D16Mit195 with LRS=15.3. The chromosome 11 locus peaks at D11Mit339 (33.8 cM) and is designated Skts-fp2 (skin tumor susceptibility in FVB and PWK 2) while the chromosome 16 locus peaks at D16Mit14 (34 cM) and is designated Skts-fp3 (skin tumor susceptibility in FVB and PWK 3). Homozygosity for FVB/NTac-derived alleles at both Skts-fp2 and Skts-fp3 confers skin tumor susceptibility. Skts-fp2 and Skts-fp3 explain 26% and 14% of the trait variance, respectively, in this interaction. Previously identified skin tumor loci Scc15 (34 cM) and Pas5 (formerly Sluc4, 40 cM) map near Skts-fp2. Skts9 (14 cM) and Sluc27 (54 cM) map to the same chromosome as Skts-fp3 but do not appear to overlap.
Suggestive linkage to skin tumor susceptibility mapped to 36.1 cM on mouse Chromosome 3 (LRS=7.6 near D3Mit40), 3.3 cM and 16.1 cM on mouse Chromosome 4 near D4Mit235 (LRS=7.4) and D4Mit93 (LRS=11), respectively, 33.8 cM on mouse Chromosome 11 (LRS=8.3 near D11Mit339), and 9.4 cM on mouse Chromosome 12 (LRS=7.8 near D12Mit283).
Suggestive linkage to skin tumorsusceptibility in females mapped to 21.4 cM on mouse Chromosome 1 (LRS=7.4 at D1Mit18) and 58.1 cM on mouse Chromosome 2 (LRS=5.2 at D2Mit401). Suggestive linkage to skin tumor susceptibility in males mapped to 48.3 cM on mouse Chromosome 14 (LRS=12.3 atD14Mit193) and 68.8 cM on mouse Chromosome 15 (LRS=4.8 at D15Mit161).
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