Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  4
• Reference
  J:127711 Wang SS, et al., Mapping, genetic isolation, and characterization of genetic loci that determine resistance to atherosclerosis in C3H mice. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2671-6
• ID
  MGI:3765074

Genes

Gene	Assay Type
Ath4	resistance/susceptibility
D4Mit327	PCR amplified length variant
Angptl3	reported elsewhere

Notes

• Experiment
  Linkage analysis was performed on 135 CHOW-fed females from a (B6.129P2-Apoe^tm1Unc/J x C3.129P2-Apoe^tm1Unc/Lus)F2 intercross to identify QTLs associated with atherosclerosis resistance/susceptibility. This same cross was previously used to identify athersclerosis QTLs on a Western-fed diet. Inbred strain C3H/HeJ is resistant to atherosclerosis compared to C57BL/6J. Animals were sacrificed at 12 weeks of age and genome scan was performed using genetic markers at a 10 cM resolution.
  
  Significant linkage to HDL (LOD=7.1) and triglycerides (LOD=4.4) mapped to 92 cM on mouse Chromosome 1 near D1Mit540. This locus is likely identical to previously identified QTL Bodwt1. Potential candidate genes for Bodwt1 include Apoa2 (92.6 cM) and Soat1 (81.6 cM).
  
  Ath4 on mouse Chromosome 4 was identified in this study at 28 cM with suggestive significance near D4Mit327 (LOD=2.6). C57BL/6J-derived alleles at Ath4 confer atherosclerosis susceptibility. A potential candidate gene for Ath4 is Angptl3 (48 cM). Tlr4 was previously considered a candidate for Ath4 but authors excluded this gene based on congenic line analysis. Replacing the defective C3H/HeJ allele of Tlr4 with a functional allele from C3H/DNA did not result in increased atherosclerosis susceptibility.
  
  Significant linkage to atherosclerosis susceptibility mapped to 27 cM on mouse Chromosome 9 with LOD=5 near D9Mit25. This locus is believed to be identical to Ath29, which was previously identified in a BXH Western-fed population. C57BL/6J-derived alleles atAth29 confer atherosclerosis susceptibility in (B6.129P2-Apoe^tmiUnc/J x C3.129P2-Apoe^tm1Unc/Lus)F2 females. The Ath29 95% confidence interval spans 17 cM - 33 cM. Ath29 was confirmed in a congenic line carrying a C3H/HeJ-derived DNA segment from D9Mit297 (15 cM) to D9Mit16 (61 cM) on a B6.129P-Apoe^tm1Unc susceptible background. As expected congenic animals displayed decreased aortic lesion size compared to B6.129P2-Apoe^tm1Unc control animals. Potential candidate genes for Ath29 include Acat1 (30cM), Apoa1 (27 cM), Apoa4 (27 cM), Apoc3 (27 cM), Apoa5, Il10ra (26 cM), Il18 (29 cM), Nnmt (29 cM), Tirap (17 cM), Sorl1 (24 cM), Pafah1b2 (26 cM), Thsd4 (33 cM), and Loxl1 (33 cM).
  
  Suggestive linkage to HDL (LOD=3.8) and triglycerides (LOD=2.5) mapped to14 cM on mouse Chromosome 10. Suggestive linkage to atherosclerosis susceptibility mapped to 58 cM (LOD=2.5).