Experiment
From a recombinant congenic (RC) panel generated from crossing the donor strain STS/A onto the background strain BALB/cHeA two highly susceptible RC strains (CcS19/Dem and CcS11/Dem) and the two most resistant RC (CcS10/Dem And CcS20/Dem) strains to colon tumors were tested for their susceptibility to lung tumors. It was observed that, concordant with colon tumor susceptibility or resistance, CcS19 was highly susceptibly to ENU-induced lung tumors compared to Ccs20; and CcS11 was highly susceptible to ENU-induced lung tumors compared to CcS10.
To elucidate the concorndant extreme susceptibility of CcS19 and resistance of CcS10 mice to both colon and lung tumors Sluc loci were mapped in an ENU-treated intercross of 226 (CcS10 x CcS19) F2 mice. The progeny were PCR-genotyped using 23 mircosatellite markers with a maximal distance less than 10 cM between any two markers. The chromosomal regions affecting tumor load, size and number were determined by analysis of variance (ANOVA) using the indiviual microsatellite markers used in the genotyping.
Fifteen Sluc loci were detected that affect tumor size, load and number. Eight of the loci had individual effects and seven were detected only in pair wise interactions in which the effect of one Sluc locus depended on the genotype of a second interacting Sluc locus.
Five of the 15 loci were reported as novel mapping to Chrs 2, 17, 5, 15 and 19.
The authors note that the remaining 10 significant Sluc linkages map very closely or relatively closely to previoulsy published Sluc or Pas loci, Table S2; they could not rule out whether they were duplicate or novel loci.
Curator Note: Because the previoulsy published loci that were noted in Table S2 were all originally mapped in mouse populations that differ from the RC panel used here, we consider the additional 10 loci, as well as the significant interactions identified, in the current study to be novel QTL and have assigned offical nomenclature to them.
Sluc39, a main effects QTL mapped to Chromosome 9 linked with D9Mit254 (25.0 cM) in the STS/A donor interval, between D9Mit253 (21.0 cM) and D9Mit154 (27.0 cM), inherited from CcS10; p=0.005, effecting the number of tumors in female mice.
Sluc39a was detected in an interaction between D9Mit254 (25.0 cM) and Sluc41c (D18Mit17, 20.0 cM), p=0.002, effecting tumor load in male mice.
Sluc39b was detected in an interaction between D9Mit254 (25.0 cM) and Sluc44c (D10Mit28, 4.0 cM), p=0.05, effecting the size of tumors in all mice.
Sluc39c was detected in an interaction between D9Mit254 (25.0 cM) and Sluc35 (D19Mit6, 55.0 cM), p=0.007, effecting the number of tumors in male mice.
Sluc39d was detected in an interaction between D9Mit254(25.0 cM) and Sluc43d (D4Mit15, p=0.00002, effecting tumor size in male mice.
[Table 3B, Table S2, QTL Sluc39 referred to in tables as previously mapped, overalpping QTL Sluc10].
Analysis of these loci strongly indicates that most susceptibility genes for lung and colon cancer are not genetically independent but are pairwise linked.
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