Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  2
• Reference
  J:248531 Makhanova N, et al., Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds. PLoS One. 2017;12(8):e0182882
• ID
  MGI:6107218

Genes

Gene	Assay Type
Aalq1	visible phenotype

Notes

• Experiment
  Atherosclerosis is the major cause of morbidity and mortality in North America. It is an inflammatory disease of arteries, characterized by the development of lipid-laden plaques affecting multiple vascular beds. Apoe-null mice on different strain backgrounds show differences in susceptibility to atherosclerosis in a vascular location-specific manner.
  
  The aim of the current study was to ascertain and narrow the candidate intervals of QTLs influencing atherosclerosis susceptibility in a vascular location dependent manner. An F2 population between B6.129P2-Apoe^tm1Unc (B6-Apoe) and D2.129P2-Apoe^tm1Unc (DBA-ApoE) was generated, phenotyped, and genotyped. 136 female and 96 males, aged 4.5 months were used for analysis.
  
  Sizes of atherosclerotic plaques in the aortic root and the aortic arch were measured. The plaque areas in the defined locations of the aortic arch were measured using images captured with Image J software. The plaques at the inner curve of the aortic arch were used to represent arch plaque size. Mice were fasted for 4 h in the morning. Plasma levels of total cholesterol were measured. HDL cholesterol levels were measured after removing with magnesium/dextran sulfate apoB containing lipoproteins. Measurements of plasma triglycerides were made using a kit from Stanbio Laboratory.
  
  Genomic DNA was isolated from livers of F2 mice. Genome-wide SNP genotyping was performed with a Mouse Universal Genotyping Array (MUGA). QTL analysis was carried out using R/qtl software. The significance thresholds for LOD scores were determined by 1000 permutations. QTL were considered significant if LOD scores exceeded 95% (p<0.05) of the permutation distribution. They were considered suggestive if the scores exceed 37% (p<0.63) distribution as recommended by the Complex Trait Consortium. The physical (Mb) positions (GRCm38) were calculated using Mouse Map Converter tool of the Jackson Laboratory.
  
  A genome-wide QTL scan using a sex-additive model identified a highly significant QTL for aortic arch lesion on Chromosome 2:
  
  QTL Aalq1 (aortic arch lesion QTL 1) mapped the Chr 2 peaking at 66 cM with a LOD score of 13.6 in a confidence interval spanning 60-71 cM. Aalq1 accounted for 21.1% of trait variance. At the QTL peak, the DBA allele was associated with bigger arch lesion size than the B6 allele, and had an additive effect. The QTL influenced plaque sizes at all locations of the aortic arch.
  
  The sex-additive scan also detected a suggestive QTL on Chr 10 (peak 35 cM, CI = 2869 cM, LOD = 3.4), which accounted for 4.0% of the variance. The B6 allele at the Chr10 QTL was associated with an increased plaque size at the aortic arch and was recessive with respect to the DBA allele. The QTL at Chr10 was also suggestive for plaque size at the branching point of the innominate artery but not other branches.
  
  The features of these QTL were consistent with the assignment of overlapping QTL on Chr2 and Chr10 as Aath4 and Aath5 respectively, that were previously identified in an F2 population from D2.129P2(B6)-Apoe^tm1Unc (DBA-ApoE) x 1296/SvEvTAc-Apoe^tm4Mae ( 129-Apoe)/J [J:229127].
  
  A single locus scan for QTLs for atherosclerotic lesions at the aortic root using sex as an additive covariate detected suggestive QTLs on Chr2 (peak 74 cM, CI = 58103 cM, LOD = 2.9,), Chr7 (peak 37 cM, CI = 2348 cM, LOD = 3.0)) and Chr14 (peak 22 cM, CI = 732 cM, LOD = 2.6), contributing 6.8, 5.0 and 4.9% to the variance, respectively. Single-QTL genome scan for root plaque size with sex as an interactive covariate determined suggestive QTL on Chr7.
  
  Consistent with earlier observations in the B6-apoE x 129-apoE [J:170863] and DBA-apoE x 129-apoE [J:229127] crosses, the QTLs for the aortic atherosclerosis and root atherosclerosis in the F2 from B6-apoE x DBA-apoE were largely independent.