Experiment
Loci associated with ENU-induced cancer susceptibility were identified by whole genome scan analysis using 20 inbred strains. A total of 240 experimental animals were administered ENU at 9-10 weeks of age. 13,278 single nucleotide polymorphisms (SNPs) with an average spacing of 160 kb were used for the genome scan.
Two loci associated with ENU-induced lung adenoma susceptibility mapped to mouse Chromosome 3 with SNP rs13477230 at 82 Mb and with SNP rs13477242 at 86 Mb. [Table 3.] These loci are named Elads1 (ENU induced lung adenoma susceptibility 1) and Elads2 (ENU induced lung adenoma susceptibility 2), respectively. The log probability ratio (LPR) for Elads1 and Elads2 both reached 3.62. Potential candidate genes mapping near Elads1 include Ctso, Tdo2, Accn5, Gucy1b3, Gucy1a3, Lrat, Fgg (41.3 cM), Fga (44.8 cM), Fgb (48.2 cM), Plrg1, and Npy2r (36 cM). Potential candidate genes mapping near Elads2 include Sh3d19, Rps3a, Mab21l2, Cd1d1 (48 cM), Dcamkl2, Hig1, Lrba, and Cd1d2 (48 cM).
Susceptibility to ENU-induced lung adenomas mapped to mouse Chromosome 9 at approximately 58.7 Mb with SNP rs13480220. [Table 3.] This locus is named Elads3 (ENU induced lung adenoma susceptibility 3). The LPR for Elads3 reached 3.86. Potential candidate genes mapping near Elads3 include Stoml1, Pml (32 cM), Islr, Stra6, Tbc1d21, Cd276, Nptn (formerly Sdfr1), Hcn4, Loxl1 (33 cM), and Neo1.
Susceptibility to ENU-induced lung adenomas mapped to mouse Chromosome 6 between 27.5 Mb and 28.7 Mb with SNP rs13478675. [Table 3]. This locus is named Elads4 (ENU induced lung adenoma susceptibility 4) and maps near previously identified lung cancer QTL Sluc7 (6 cM). The LPR for Elads4 reached 4.44. Potential candidate genes mapping near Elads4 include Grm8, Pax4 (9 cM), Fscn3, Arf5, and Gcc1.
ENU-induced lung carcinoma susceptibility was greatest in A/J, PERA/EiJ, and SWR/J inbred strains with an incidence of 50% or more. Susceptibility to ENU-induced lung carcinomas mapped to 10 Mb on mouse Chromosome 15. This locus is named Elcs1 (ENU induced lung carcinoma susceptibility 1) and maps near previously identified lung cancer QTL Sluc25 (32 cM). The LPR for Elcs1 reached 5.28. Prlr at 4.6 cM is a potential candidate gene for Elcs1. A second lung carcinoma susceptibility locus may reside at 37.5 Mb on chromosome 15. This locus is named Elcs2 (LPR=4.15). Ncald at 11 cM is a potential candidate genefor Elcs2.
ENU-induced lymphoma susceptibility was greatest in AKR/J, C58/J, C57BL/6J, and NOD/LtJ inbred strains with an incidence of 50% or more. Susceptibility to ENU-induced lymphomas mapped to 23 Mb with SNP rs3671702 on mouse Chromosome 15. [Table 3]. This locus is named Elyms1 (ENU induced lymphoma susceptibility 1). The LPR for Elyms1 reached 3.77. Cdh18 is a potential candidate gene for Elyms1. A second lymphoma susceptibility locus was detected at 37 Mb with SNP rs3705939 on mouse Chromosome 3. [Table 3.] This locus is named Elyms2 (LPR=3.68). Potential candidate genes mapping near Elyms2 include Spry1 and Spata5.
Analysis Tools