Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  2
• Reference
  J:84842 Ewart-Toland A, et al., Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nat Genet. 2003 Aug;34(4):403-12
• ID
  MGI:3055775

Genes

Gene	Assay Type
Skts13	resistance/susceptibility
D2Mit229	PCR amplified length variant
Aurka	reported elsewhere
Cyp24a1	reported elsewhere
Zfp217	reported elsewhere
D2Mit198	PCR amplified length variant

Notes

• Experiment
  Linkage analysis to skin tumor resistance was performed on a previously constructed backcross between M. spretus and NIH/Ola. Parental strain M. spretus is resistant to skin tumor development whereas parental strain NIH/Ola is susceptible. High resolution mapping was performed on 326 (NIH/Ola x M. spretus)F1 x NIH/Ola backcross animals. A papilloma resistance locus named Skts13 was identified on distal mouse Chromosome 2. This region is syntenic to human Chromosome 20q13.2.
  
  Linkage analysis was performed on two additional backcross populations: 106 animals from a (NIH/Ola x SEG/Pas)F1 x NIH/Ola backcross and 163 animals from a (NIH/Ola x SPRET/EiJ)F1 x NIH/Ola backcross. Strong linkage to papilloma resistance was observed at Stks13 in the SPRET/EiJ x NIH/Ola backross (P= 3.7 x 10-5, LOD=4.8). No linkage to papilloma resistance was observed in the NIH/Ola x SEG/Pas backcross.
  
  Haplotype analysis refined the Skts13 resistance interval to a 1 cM region between D2Mit229 (99 cM) and D2Jau1 (100 cM). D2Jau1 refers to a CA3 repeat sequence located 8.1 kb distal of the 5' end of Stk6 and is shown in the same location as D2Mit198. The peakLOD score at this interval is 6.1. Potential candidate genes identified in the Stks13 interval are Cyp24a1 (99 cM), Stk6 (100 cM), and Zfp217 (99 cM). Gene expression analysis of mouse skin tumor mRNA revealed differential expression of Stk6 and Zfp217 but not Cyp24a1. Gene expression analysis of normal mouse skin mRNA revealed increased Stk6 expression in NIH/Ola compared to M. spretus. Zpf217 did not show differential expression in normal mouse skin mRNA between NIH/Ola and M. spretus. Sequence analysisof Stk6 failed to identify polymorphisms between the 2 parental strains. The human ortholog STK6 at 20q13.2 contains a polymorphism at amino acid 31 that may be associated with human cancers.