Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  15
• Reference
  J:244625 Grainger AT, et al., Polygenic Control of Carotid Atherosclerosis in a BALB/cJ x SM/J Intercross and a Combined Cross Involving Multiple Mouse Strains. G3 (Bethesda). 2017 Feb 09;7(2):731-739
• ID
  MGI:6107211

Genes

Gene	Assay Type
Cath5	visible phenotype

Notes

• Experiment
  Atherosclerosis in the carotid arteries is a major cause of ischemic stroke, which accounts for 85% of all stroke cases. The aim of the current study was to identify chromosomal regions harboring genes contributing to carotid atherosclerosis in mice. Apoe-/- mice with a SM/J (SM) genetic background develope significantly larger atherosclerotic lesions than those with a BALB background.
  
  From an intercross between C.129P2(B6)-Apoe^tm1Unc (BALB/cJ) and SM.129P2(B6)-Apoe^tm1Unc (SM/J) apolipoprotein E deficient (Apoe-/-) mice, 228 female F2 mice were generated and fed a Western diet for 12 wk. Atherosclerotic lesion sizes in the left carotid artery were quantified. Across the entire genome, 149 genetic markers were genotyped. LOD scores were obtained from genome-wide scans using J/qtl. LOD score threshold for suggestive QTL were >2.054; for significance >3.314 established by 1000 permutation tests.
  
  Table 1: Quantitative trait locus (QTL) analysis revealed eight suggestive loci for carotid lesion sizes, located on chromosomes 1, 5, 12, 13, 15, 16, and 18.
  
  The suggestive QTL on Chr 15 peaked at marker rs13482641 (46.74 cM) with a LOD score of 2.24 [Table 1 and 2]. The locus overlapped with a suggestive QTL for atherosclerosis in the innominate artery in a B6 x C3H Apoe-/- cross identified in J:232143. The authors have labeled the locus identified here in the current study as Cath5, carotid atherosclerosis 5. The SM/J allele was associated with increased lesion size at this locus when inherited recessively.
  
  The suggestive QTL on Chr 18 peaked at marker rs3683699 (16.27 cM) with a LOD score of 2.22 [Table 1 and 2]. The locus overlapped with a suggestive QTL for carotid atherosclerosis mapped in the B6 x BALB Apoe-/- cross in J:197549. The authors have labeled the locus identified here as Cath6, carotid atherosclerosis 6. The SM/J allele was associated with increased lesion size at this locus and inherited additively.
  
  Next, combined cross-linkage analysis was performed using data from the current cross, and two previous F2 crosses derived from C.129P2(B6)-Apoe^tm1Unc (BALB) x B6.129P2-Apoe^tm1Unc (C57BL/6J) [J:197549] and B6.129P2-Apoe^tm1Unc (C57BL/6J) x C3H/HeJ Apoe^tm1Unc [J:129301] strains. Phenotype data on carotid lesion sizes were switched from the total lesion area to the average of the top five lesion sizes for each F2 mouse in all crosses. Analysis identified five significant QTL on chromosomes 5, 9, 12, and 13, and nine suggestive QTL for carotid atherosclerosis from the combined data, Table 3:
  QTL Cath7 (carotid atherosclerosis 7) mapped to Chromosome 5 peaking at 39.05 cM (65.31 Mb) in the combined data with a combined LOD score of 3.84. The 95% confidence interval spanned from 61.51 to 69.16 Mb.
  
  QTL Cath9 (carotid atherosclerosis 9) mapped to Chromosome 5 peaking at 66.35 cM (127.32 Mb) in the combined data with a combined LOD score of 8.06. The 95% confidence interval spanned from 124.83-131.29 Mb.
  
  QTL Cath8 (carotid atherosclerosis 8) mapped to Chromosome 9 peaking at 75.33 cM (114.09 Mb) in the combined data with a combined LOD score of 3.92. The 95% confidence interval spanned from 103.61 to 114.09 Mb.
  
  QTL Cath10 (carotid atherosclerosis 10) mapped to Chromosome 12 peaking at 32.59 cM (70.23 Mb) in the combined data with a combined LOD score of 9.95. The 95% confidence interval spanned from 48.06 to 88.56 Mb. Bioinformatic analysis prioritized Arhgap5, Akap6, Mipol1, Clec14a, Fancm, Nin, Dact1, Rtn1, and Slc38a6 as probable candidate genes for this QTL.
  
  QTL Cath11 (carotid atherosclerosis 11) mapped to Chromosome 13 peaking at 53.35 cM (100.5 Mb) in the combined data with a combined LOD score of 9.49. The 95% confidence interval spanned from 68.40 to 103.48 Mb.
  
  Curator Note: Because the significant loci identified in the combined data were analyzed using multiple mapping populations that differ from the original mapping populations that Cath1, Cath2, Cath3 and Cath4 were originally identified in, we have assigned novel nomenclature to the loci identified here from the combined data analysis.
  
  Suggestive loci linked to carotid lesion size in the combined data mapped to Chr 2 at 80.22 cM, LOD=2.77; Chr 3 at 50.01 cM, LOD=2.31; Chr 6 at 66.21 cM, LOD=2.15; Chr 11 at 26.1 cM, LOD=3.02; Chr 11 at 51.0 cM, LOD=3.32; Chr 15 at 11.26 cM, LOD=2.35; Chr 16 at 41.66 cM, LOD=2.94; Chr 18 at 39.73 cM, LOD=3.01; Chr 19 at 2.43 cM, LOD=2.74.