Hdlq7^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Hdlq7^C57BL/6J
• Name: HDL QTL 7; C57BL/6J
• MGI ID: MGI:3038138
• QTL: Hdlq7 Location: Chr5:52854568-52854714 bp Genetic Position: Chr5, cM position of peak correlated region/allele: 28.55 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased HDL cholesterol compared to NZB/BlNJ. (J:84430)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

This allele is associted with HDL cholesterol levels on both CHOW and atherogenic diets.

Animals homozygous for C57BL/6J-derived alleles at both Hdlq7 and Hdlq9 exhibit the lowest HDL cholesterol levels on a CHOW diet.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:84430

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 (identified in 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 to the 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 was found 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.

References

• Original: 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
• All: 1 reference(s)