Pnhdlc1^CASA/RkJ
QTL Variant Detail

Summary

• QTL variant: Pnhdlc1^CASA/RkJ
• Name: plasma non-HDL cholesterol 1; CASA/RkJ
• MGI ID: MGI:3525309
• QTL: Pnhdlc1 Location: Chr6:105541783-114345810 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: CASA/RkJ

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

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

J:94547

Linkage analysis was performed on 185 male and 184 female F2 intercross to identify QTLs associated with HDL and non-HDL cholesterol levels on a CHOW diet. Parental strain CASA/RkJ exhibits 87% non-HDL cholesterol in males and 25% increased non-HDL cholesterol in females compared to parental C57BL/6J males and females. F1 hybrids exhibit decreased HDL and non-HDL cholesterol similar to the C57BL/6J parental. 255 polymorphic markers at an average spacing of 5.9 cM were used in the genome scan.

Linkage to non-HDL cholesterol mapped to 49 cM on mouse Chromosome 6 (Pnhdlc1, plasma non-HDL cholesterol 1). Pnhdlc1 gave a peak LOD score of 5.17 between D6Mit37 (46 cM) and D6Mit63 (50 cM). Homozygosity for C57BL/6J-derived alleles at Pnhdlc1 confers increased plasma non-HDL cholesterol levels. The CASA/RkJ allele exhibits dominant inheritance at Pnhdlc1. This locus explains 5% of the variance in males and 12% of the variance in females. Potential candidate genes mapping near the Pnhdlc1 interval are Pparg (52.7 cM) and Apobec1 (54.5 cM).

Linkage to non-HDL cholesterol mapped to 55 cM on mouse Chromosome 4 (Pnhdlc2). Pnhdlc2 gave a peak LOD score of 4.22 between D4Mit46 (51 cM) and D4Mit204 (62 cM). Homozygosity for C57BL/6J-derived alleles at Pnhdlc2 confers increased plasma non-HDL cholesterol levels. The CASA/RkJ allele exhibits dominant inheritance in males and codominant inheritance in females. Pnhdlc2 explains 4% of the variance in males and 10% of the variance in females. Potential candidate genes mappingnear the Pnhdlc2 interval are Lepr (46.7 cM), Cpt2 (54.4 cM), Scp2 (52 cM), and Cda.

Linkage to non-HDL cholesterol mapped to 7 cM on mouse Chromosome 8 (Pnhdlc3). Pnhdlc3 gave a peak LOD score of 3.68 between D8Mit58 (1 cM) and D8Mit171 (8 cM). Homozygosity for CASA/RkJ-derived alleles confers increased plasma non-HDL cholesterol at Pnhdlc3 with a codominant mode of inheritance. This locus explains 5% of the variance in males and 3% of the variance in females. A potential candidate gene mapping near the Pnhdlc3 interval is Irs2 (5 cM).

Linkage to plasma HDL cholesterol mapped to 14 cM on mouse Chromosome 9 (Phdlc1). Phdlc1 gives a peak LOD score of 7.53 between D9Mit325 (14 cM) and D9Mit140 (25 cM). Homozygosity for CASA/RkJ-derived alleles confers increase plasma HDL cholesterol with codominant inheritance. This locus explains 8% of the variance in males and 10% of the variance in females. Potential candidate genes mapping near the Phdlc1 interval are Apoa1 (27 cM), Apoc3 (27. cM), Apoa4 (27 cM), andApoa5.

Linkage to plasma HDL cholesterol mapped to 76 cM on mouse Chromosome 8 (Phdlc2). Phdlc2 gives a peak LOD score of 4.69 between D8Mit91 (67 cM) and D8Mit56 (73 cM). Homozygosity for C57BL/6J-derived alleles confers increased plasma HDL cholesterol at Phdlc2. The CASA/RkJ allele exhibits dominant inheritance in males and codominant inheritance in females. This locus explains 8% of the variance in males and 4% of the variance in females. Phdlc1 and Phdlc2 coincide with suggestive HDL QTLs mapped byMehrabian et al, 2000 at D9Mit2 (17 cM) and D8Mit14 (67 cM). No candidate genes were identified for this QTL interval.

An epistatic interacting locus pair was identified on mouse Chromosome 2 at 26 cM and mouse Chromosome 5 at 64 cM. The joint LOD scorefor the interacting locus pair is 8.68 and the epistasis LOD score is 7.47.This locus pair affects plasma non-HDL cholesterol so they are named Pnhdlc4 and Pnhdlc5, respectively.

References

• Original: J:94547 Sehayek E, et al., Loci controlling plasma non-HDL and HDL cholesterol levels in a C57BL /6J x CASA /Rk intercross. J Lipid Res. 2003 Sep;44(9):1744-50
• All: 1 reference(s)