Chol6^CAST/Ei
QTL Variant Detail

Summary

• QTL variant: Chol6^CAST/Ei
• Name: cholesterol 6; CAST/Ei
• MGI ID: MGI:2663767
• QTL: Chol6 Location: Chr9:12902737-12902913 bp Genetic Position: Chr9, cM position of peak correlated region/allele: 2.93 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased total cholesterol and increased non-HDL cholesterol compared to DBA/2J. (J:83460)
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:83460

Genome scan was performed on 278 (CAST/Ei x DBA/2J)F2 animals to identify QTLs affecting cholesterol. Parental strain CAST/Ei exhibits lower HDL cholesterol but higher total cholesterol compared to parental strain DBA/2J.

A previously identified QTL for HDL cholesterol on mouse Chromosome 2, Hdl1, was confirmed in this cross. Hdl1 spans 44 cM - 56 cM with a LOD score of 5.4 at D2Mit94 (48.1 cM). DBA/2J-derived alleles confer increased HDL cholesterol with recessive inheritance at Hdl1.

1.21.2015 Curators' Note: Because Hdl1 was originally mapped in J:66421 in 2000 using a (CAST/Ei x C57BL/6J)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdl7.

Hdlq10, a novel QTL associated with HDL cholesterol spans 10 cM - 30 cM on mouse Chromosome 4 with a LOD score of 5.9 at D4Mit110 (21.9 cM). CAST/Ei-derived alleles confer increased HDL cholesterol with dominant or codominant inheritance at this locus. A potential candidate gene for Hdlq10 is Abca1. Abca1 shows a 2.4-fold higher expression in F2 animals homozygous for CAST/Ei-derived alleles.

Hdlq11 and Hdlq12 map to 46 cM and 71.2 cM on mouse Chromosome 6, respectively. Hdlq11 spans 40 cM - 60 cM and gives peak linkage at D6Mit36 with a LOD score of 4.2. Pparg is a promising candidate for Hdlq11 as gene expression is 12.5-fold higher in F2 animals homozygous for DBA/2J-derived alleles. Hdlq12 spans 64 cM - 80 cM and gives peak linkage at D4Mit14 with a LOD score of4.9. DBA/2J-derived alleles confer increased HDL cholesterol with codominant inheritance at both Hdlq11 and Hdlq12.

Chol6 spans 5 cM - 27 cM on mouse Chromosome 9 with a LOD score of 7.2 for total cholesterol and a LOD score of 4.6 for non-HDL cholesterol at D9Mit58 (5 cM). CAST/Ei-derived alleles confer increased total cholesterol and increased non-HDL cholesterol with recessive inheritance at this locus. A candidate gene for Chol6 is Ldlr. Ldlr shows 6.1-fold higher expression in F2 animals homozygousfor DBA/2J-derived alleles compared to F2 animals homozygous for CAST/Ei-derived alleles.

References

• Original: J:83460 Lyons MA, et al., Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice. J Lipid Res. 2003 May;44(5):953-67
• All: 1 reference(s)