Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  1
• Reference
  J:84430 Wang X, et al., Using advanced intercross lines for high-resolution mapping of HDL cholesterol quantitative trait loci. Genome Res. 2003 Jul;13(7):1654-64
• ID
  MGI:3038127

Genes

Gene	Assay Type
Hdlq5	visible phenotype
D1Mit206	PCR amplified length variant
Nr1i3	reported elsewhere
Apoa2	reported elsewhere
Apcs	reported elsewhere
Hdlq6	visible phenotype
D1Mit291	PCR amplified length variant
Tgfb2	reported elsewhere

Notes

• Experiment
  Genome scan was performed on 104 female (C57BL/6J x NZB/BlNJ)F1 x C57BL/6J backcross animals to identify QTLs associated with CHOW- and atherogenic-fed HDL cholesterol levels. 97 polymorphic markers were typed and statistically significant loci were confirmed and resolved using (C57BL/6J x NZB/BlNJ)F11 advanced intercross lines (AIL). Parental strain C57BL/6J exhibits decreased HDL cholesterol levels and susceptibility to atherosclerosis compared to parental strain NZB/BlNJ. 6 weeks on an atherogenic diet results in increased HDL levels in NZB/BlNJ but not in C57BL/6J.
  
  Significant linkage was detected at 96 cM on mouse Chromosome 1 near D1Mit206 (LOD=5.5) in the backcross population. This locus, named Hdlq5, is associated with CHOW- and atherogenic-fed HDL levels. Using AILs, the Hdlq5 locus was resolved to a 6 cM interval (87 cM - 93 cM) and a second QTL is named Hdlq6 was discovered. Hdlq6 maps to 102 cM near D1Mit291 (LOD=5.8) and is associated with atherogenic-fed HDL levels. The confidence intervalof Hdlq6 spans 87 cM - 110 cM. Homozygosity for C57BL/6J-derived alleles at Hdlq5 and Hdlq6 confers decreased HDL level whereas homozygosity for NZB/BlNJ-derived alleles confers increased HDL levels. Heterozygous animals exhibit an intermediate phenotype.Three candidate genes for Hdlq5 show differential expression between C57BL/6J and NZB/BlNJ: Nr1i3, Apoa2, and Apcs (Sap). Tgfb2 is a candidate gene for Hdlq6 exhibiting differential expression between the two parental strains.
  
  Significant linkage was also detected at 38 cM on mouse Chromosome 5 near D5Mit200 (LOD=4.7 on the atherogenic diet). Using AILs this locus was resolved into 3 separate QTLs: Hdlq7, Hdlq8, and Hdlq1. Hdlq7 maps to 29 cM and is associated with HDL levels on both CHOW and atherogenic diets (LOD=12 at D5Mit233). The confidence interval of Hdlq7 spans 25 cM - 32 cM. Hdlq8 maps to 60 cM and is associated with HDL levels on an atherogenic diet (LOD=3.6 at D5Mit155). The confidence interval of Hdlq8 spans 58 cM - 63 cM. Hdlq1 (identifiedin a previous study) maps to 69 cM and is associated with HDL levels on both CHOW and atherogenic diets (LOD=7.1 at D5Mit242.) The confidence interval of Hdlq1 spans 66 cM - 77 cM. Homozygosity for C57BL/6J-derived alleles at Hdlq7, Hdlq8, and Hdlq1 confers decreased HDL level whereas homozygosity for NZB/BlNJ-derived alleles confers increased HDL levels. Heterozygous animals exhibit an intermediate phenotype. Several candidate genes exhibiting differential expression between C57BL/6J and NZB/BlNJ map tothe region containing Hdlq7, Hdlq8, and Hdlq1: Fgfbp1, Prom1, Ppargc1a, Tcf1, Ncor2, Scarb1 (Srb1).
  
  Hdlq9 mapped to 59 cM on mouse Chromosome 16 near D16Mit227 (LOD=1.3 on CHOW diet). The confidence interval of Hdlq9 spans 50 cM - 60 cM. This locus wasfound to interact with Hdlq7 on mouse Chromosome 5. Animals homozygous for C57BL/6J-derived alleles at both Hdlq7 and Hdlq9 exhibit the lowest HDL cholesterol levels on a CHOW diet. Candidate genes for Hdlq9 showing differential expression between the parental strains are App and Ifnar1.