Hdl4^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Hdl4^CAST/EiJ
• Name: high density lipoprotein (HDL) level 4; CAST/EiJ
• MGI ID: MGI:2429738
• QTL: Hdl4 Location: unknown Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased HDL cholsterol on an atherogenic diet compared to C57BL/6J. (J:66421)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Candidate Genes

J:99477

Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.

Potential candidate genes for Hdl4 (32.3 cM) on mouse Chromosome 17 as identified by ExQuest are Gnmt, Lrg1, and Sepx1 (10 cM). For QTL Insq5 (56.7 cM), potential candidate gene Abcg5 (54.5 cM) was identified. For QTL Obq4 (4 cM) and Wta4 (17 cM), potential candidate genes Plg (7.3 cM), Acat2 (7.55 cM), Acat3 (7.55 cM), Hagh (11 cM), Igfals, Decr2, Clps (17.1 cM), Tff1 (17 cM), Tff2 (17 cM), Tff3 (17 cM), and Apom were identified. Tff3 exhibits almost undetectable levels of transcription in the liver of Tally Ho animals compared C57BL/6J.

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

J:66421

A (CAST/Ei x C57BL/6J)F2 intercross was typed for polymorphic markers on all mouse chromosomes except the Y Chromosome at an average marker density of 10 cM to identify loci associated with plasma HDL levels in response to either chow or atherogenic diet. Inbred parental strain CAST/Ei exhibits lower plasma HDL levels compared to inbred parental strain C57BL/6J, with (CAST/Ei x C57BL/6J)F1 hybrids displaying an intermediate phenotype. HDL-associated QTLs with a LOD>4.3 threshold were detected and are as follows. Hdl1, a QTL associated with HDL levels on an atherogenic diet, mapped to mouse Chromosome 2 at approximately 37 cM with a peak LOD = 5.6 at D2Mit9. Hdl1 co-localizes with loci mapped for body fat and insulin levels. Pltp, a possible candidate gene for Hdl1, did not appear to segregate with this locus. Hdl2, a QTL associated with HLD levels on an atherogenic, diet mapped to mouse Chromosome 5 from 35 cM - 60 cM with a peak LOD = 6.1 near D5Mit10. Previously mapped HDL QTLs using different inbred strains are located near Hdl2. A possible candidate gene for Hdl2 is Srb1, but following investigation the authors conclude this QTL is unlikely due to the effect of Srb1. Hdl3, a QTL associate with HDL levels on a chow diet, mapped to mouse chromosome 16 from 9.61 cM - 38.0 cM with a peak LOD = 4.4 near D16Mit3. The LOD score peaks over the gene for ApoD but no difference in ApoD expression is apparent between CAST/Ei and C57BL/6J. Hdl4, a QTL associated with HDL levels on an atherogenic diet, mapped to mouse Chromosome 17 from 20 cM - 48 cM with a peak LOD = 6.5 near D17Mit7. Suggestive QTLs associated with HDL levels with LOD>2.8 (but less than 4.3) mapped to Chromosome 2 near D2Mit50, Chromosome 3 near D3Mit12, Chromosome 8 near D8Mit12 and D8Mit14, Chromosome 9 near D9Mit2, Chromosome 14 near D14Mit2, Chromosome 18 near D18Mit142, and Chromosome 19 near D19Mit5.

References

• Original: J:66421 Mehrabian M, et al., Genetic control of HDL levels and composition in an interspecific mouse cross (CAST/Ei x C57BL/6J). J Lipid Res. 2000 Dec;41(12):1936-46
• All: 1 reference(s)