Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  10
• Reference
  J:76127 Dansky HM, et al., A phenotype-sensitizing apoe-deficient genetic background reveals novel atherosclerosis predisposition Loci in the mouse. Genetics. 2002 Apr;160(4):1599-608
• ID
  MGI:2386537

Genes

Gene	Assay Type
Ath11	resistance/susceptibility
D10Mit213
D10Mit214
Ifngr1	reported elsewhere
Ccn2	reported elsewhere
Esr1	reported elsewhere
Tnfaip3	reported elsewhere

Notes

• Experiment
  Two independent strain intercosses that carry atherosclerosis phenotype-sensitizing Apoe deficiency were performed to reveal artherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels.
  
  Animals from a C57BL/6J-derived background are susceptible to atherosclerosis and yield several-fold higher aortic lesion scores compared to animals from an FVB/NCr-derived background.
  
  In the first cross, referred to as cross 1, B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 197 (B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres) F2 mice for the QTL analysis. Interval mapping was done with 194 markers at a distance of no more than 10cM.
  
  In the second, confirmatory cross, B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 186 (B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres)F2 mice for QTL analysis. This cross was referred to as cross 2; these mice were genotyped using 127 markers at no more than 10cM intervals.
  
  A highly significant locus on chromosome 10 was identified in both crosses with a LOD score of 7.8 at D10Mit213 in cross 1 and 11.9 at D10Mit214 in cross 2. The locus accounted for 19% of log lesion variance in cross 1 and 25% in cross 2. Interval mapping of chromosome 10 in cross 1 revealed a peak that included both D10Mit13 and D10Mit14. The locus was labeled Ath11.
  
  Highly significant LOD scores were obtained using either a dominant or additive model.
  Unexpectedly, in cross one, homozygosity for FVB/NCr-derived alleles conferred increased lesion size when compared to mice heterozygous or homozygous for the C57BL/J allele.
  
  The strongest candidate gene for Ath11 is Ifngr, which is located at 15cM on mouse chromosome 10. Ath11 maps to an interval (0-19cM) that is evolutionarily conserved with human chromosome 6q22-24.