Chldq12^NZB/BlNJ
QTL Variant Detail

Summary

• QTL variant: Chldq12^NZB/BlNJ
• Name: cholesterol and HDL QTL 12; NZB/BlNJ
• MGI ID: MGI:3720128
• QTL: Chldq12 Location: Chr5:104386871-104387065 bp Genetic Position: Chr5, Syntenic

Variant origin

• Strain of Specimen: NZB/BlNJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased serum total cholesterol and HDL in females compared to RF/J. (J:123776)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Chldq12 exhibits additive inheritance.

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

J:123776

Linkage analysis was performed on 542 female (NZB/BlNJ x RF/J)F2 intercross animals to identify QTLs associated with serum lipid levels. F2 female animals were fed a CHOW diet and sacrificed at 10 weeks of age for phenotype analysis. A panel of 94 polymorphic markers was used for linkage analysis. Parental strain NZB/BlNJ displays 48% increased plasma cholesterol and 57% increased plasma HDL compared to RF/J, and parental strain RF/J has 58% increased triglycerides and 10% higher body weight compared to NZB/BlNJ. Data from a previously studied population of 621 (MRL/MpJ x SJL/J)F2 females was also used for a combined analysis. A set of 231 microsatellite markers was used to genotype the combined data set.

In the initial (NZB/BlNJ x RF/J)F2 intercross significant QTL for cholesterol and HDL concentrations were identified on mouse Chromosomes 5, 12 and 19, as well as two novel triglyceride QTL on Chromosomes 12 and 15.

On mouse Chromosome 5 linkage to serum cholesterol (LOD=17.63) and HDL (LOD=16.95) mapped between 58 cM-60 cM with a peak LOD=16.7 at D5Mit10. This QTL has been named Chldq12.

The 95% confidence interval spans approximately 53 cM - 66 cM. It explains 17% of the cholesterol variance and 18% of the HDL variance. Homozygotes for the NZB/BlNJ-derived alleles at Chldq12 had 23% higher HDL compared with the homozygotes for the RF allele. The phenotypic effects of the NZB allele best fit an additive model of inheritance. Potential candidate genes for Chdlq12 include Abcg3 (59 cM), Lrrc8c, Dgkq (57 cM), Hps4 (59 cM), Mvk (64 cM), and Gk2 (53 cM).

On Chromosome 12 significant linkage to serum cholesterol (LOD=4.85) and HDL (LOD=3.57) peaked at 14 cM with D12Mit182. This locus was designated Chldq7 (cholesterol and HDL QTL 7). The 95% confidenceinterval spanned 0 cM - 30 cM. F2 females homozygous for NZB/BlNJ-derived alleles at Chldq7 display 9% increased serum HDL compared to RF/J-homozygous females, with the high allele dominant.

A novel triglyceride QTL was also identified on Chr 12 in the (NZB/BlNJ x RF/J)F2 intercross; LOD=8.66 at 8.0 cM with a 95% confidence interval spanning 0-30.0 cM. It is suggested that this QTL isthe previoulsy mapped QTL Tglq2.

03.10.2015 Curators Note: Because Tglq2 was originally mapped in J:106033 in 2006 using an

(MRL/MpJ x SJL/J)F2 intercross, which differs from the cross used here, we have named this trigylceride QTL, Tglq4.

Triglyceride levels for homozygotes with the NZB derived alleles at Tglq4 were 28% higher then those for the homozygotes with RF alleles at the same locus; NZB alleles were inherited in an additive manner. It was confirmed in the combined data, also mapping to 8.0 cM LOD=9.99

On Chromosome 19 another novel QTL, named Chldq9 (cholesterol and HDL QTL 9), linked to serum cholesterol (LOD=6.29) and HDL (LOD=5.56) mapped with peak maker D19Mit1 at 48-49 cM.The 95% confidence interval spans approximately 40 cM - 52 cM. Homozygosity for RF/J-derived alleles at Chldq9 confers 12%lower plasma HDL levels than the homozygotes for the NZB allele. Phenotypic effect for the NZB allele appears to be inherited recessively. Potential candidate genes for Chldq9 having known SNP differences between NZB/BlNJ and RF/J include Scd1, Scd2 (43cM), Pi4k2a (47 cM), Cpn1 (47 cM), Elovl3 (47 cM), and Gpam(52cM).

A triglyceride QTL, Tglq3, was also detected in the (NZB/BlNJ x RF/J)F2 cross mapping to mouse Chromosme 15 at 02.0 cM with D15Mit13, LOD=3.46, with a 95% conficence interval spanning 0-25.0 cM. Homozygotes with the RF alleles had 14% higher trigylceride levels compared with the NZB homozygotes at this locus and appeared to be inherited recessively.

References

• Original: J:123776 Wergedal JE, et al., Mapping genetic loci that regulate lipid levels in a NZB/B1NJxRF/J intercross and a combined intercross involving NZB/B1NJ, RF/J, MRL/MpJ, and SJL/J mouse strains. J Lipid Res. 2007 Aug;48(8):1724-34
• All: 1 reference(s)