Cq6^RR
QTL Variant Detail

Summary

• QTL variant: Cq6^RR
• Name: cholesterol QTL 6; RR
• MGI ID: MGI:3522042
• QTL: Cq6 Location: unknown Genetic Position: Chr1, cM position of peak correlated region/allele: 80.33 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: RR

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased plasma total cholesterol compared to C57BL/6J. (J:94251)
• Inheritance: Dominant

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Candidate Genes

J:99474

Linkage analysis was performed on 3 separate F2 crosses in 3 previous studies: J: 54322, J:87328 and J:94251 to map QTLs associated with plasma cholesterol levels. Cq1, Cq2, and Cq6 mapped to mouse Chromosome 1, Cq3 mapped to mouse Chromosome 3, and Cq4 and Cq5 mapped to mouse Chromosome 9.

Cq2 and Cq6 map to the same location on distal mouse Chromosome 1 at approximately 100 cM. Cq2 was identified in a (C57BL/6J x KK-A^y)F2 intercross and Cq6 was identified in a (C57BL/6J x RR)F2 intercross. Apoa2 wasinvestigated as a possible candidate gene. The Apoa2^b allele is found in KK and RR strains and is associated with increased cholesterol levels while inbred strain C57BL/6J carries the Apoa2^a allele. It is thought that the Apoa2^b allele may be responsible for the QTL effects of Cq2 and Cq6.

Inbred strains A/J and SM/J carry the Apoa2^c allele. It was previously unknown whether the Apoa2^a and Apoa2^c alleles had the same or different influences on plasma cholesterol level. An F2 intercross between congenic strains C57BL/6J-Apoa2^a and C57BL/6J-Apoa2^c revealed no physiological differences between the Apoa2^a and Apoa2^c alleles. Therefore, the Apoa2^b allele confers increased plasma cholesterol compared to the Apoa2^a and Apoa2^c alleles.

Cq4 and Cq5 map to the same location on mouse Chromosome 9 at approximately 27 cM and Apoa1 and Apoa4 were investigated as possible candidate genes. Cq4 was identified in a (C57BL/6J x KK-A^y)F2 intercross and Cq5 was identified in a (KK x RR)F2 intercross. Sequence analysis of Apoa1 revealed that polymorphic differences between the involved strains did not correlate to cholesterol phenotype. Analysis of Apoa4 revealed a silent polymorphism (C771T) that exhibits complete correlation to cholesterol phenotype. Inbred strain KK carries the T allele whereas inbred strain C57BL/6J and RR carry the C allele. Another polymorphism in Apoa4 was detected involving a 12 nucleotide insertion encoding Glu-Gln-Ala/Val-Gln. Inbred strain KK carries 3 repeats, inbred strain C57BL/6J carries 4 repeats, and inbred strain RR carries 5 repeats. However, it could not be determined if this particular polymorphism explains the QTL effect of Cq4 and Cq5 on cholesterol levels.

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

J:94251

Linkage analysis was performed on 187 female (C57BL/6J x RR)F2 intercross animals to identify QTLs associated with plasma lipid traits. Parental strain RR exhibits increased body weight, plasma cholesterol and triglycerides compared to parental strain C57BL/6J. 80 microsatellite markers at an average spacing of 20 cM were used for the genome scan.

A locus associated with total plasma cholesterol, Cq6, mapped to distal mouse Chromosome 1 near D1Mit206 (LOD=16.3). This locus explains 33.1% of the phenotypic variance. The 95% confidence interval of Cq6 spans 87.2 cM - 97.8 cM. RR-derived alleles at Cq6 confer increased plasma cholesterol with dominant inheritance. Cq6 coincides with Cq2 but authors have chosen to keep the QTLs separate at present. A strongcandidate gene mapping near Cq6 is Apoa2 (92.6 cM). D1Mit206 also shows linkage to plasma triglycerides. The authors have designated a separate symbol, Trglyd, for this linkage. RR-derived alleles confer increased plasma triglycerides at Trglyd.

Suggestive linkage to plasma cholesterol mapped to 45 cM on mouse Chromosome 5 near D5Mit259 (LOD=2.6). Suggestive linkage to body weight mapped to 80 cM on mouse Chromosome 4 near D4Mit225 (LOD=3.8). RR-derived alleles confer decreased body weight at the chromosome 4 locus.

References

• Original: J:94251 Suto J, et al., Quantitative trait locus analysis of plasma cholesterol and triglyceride levels in C57BL/6J x RR F2 mice. Biochem Genet. 2004 Oct;42(9-10):347-63
• All: 1 reference(s)