Journal of Lipid Research
Volume 50, Issue 10, October 2009, Pages 2083-2094
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Research Article
Four additional mouse crosses improve the lipid QTL landscape and identify Lipg as a QTL gene[S]

https://doi.org/10.1194/jlr.M900076-JLR200Get rights and content
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To identify genes controlling plasma HDL and triglyceride levels, quantitative trait locus (QTL) analysis was performed in one backcross, (NZO/H1Lt × NON/LtJ) × NON/LtJ, and three intercrosses, C57BL/6J × DBA/2J, C57BL/6J × C3H/HeJ, and NZB/B1NJ × NZW/LacJ. HDL concentrations were affected by 25 QTL distributed on most chromosomes (Chrs); those on Chrs 1, 8, 12, and 16 were newly identified, and the remainder were replications of previously identified QTL. Triglyceride concentrations were controlled by nine loci; those on Chrs 1, 2, 3, 7, 16, and 18 were newly identified QTL, and the remainder were replications. Combining mouse crosses with haplotype analysis for the HDL QTL on Chr 18 reduced the list of candidates to six genes. Further expression analysis, sequencing, and quantitative complementation testing of these six genes identified Lipg as the HDL QTL gene on distal Chr 18. The data from these crosses further increase the ability to perform haplotype analyses that can lead to the identification of causal lipid genes.

high density lipoprotein
triglyceride
quantitative trait locus

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This work was funded by US National Institutes of Health grants to B.P. (HL-81162, HL-74086, and HL-77796) and GM-070683 to G.A.C., by American Heart Association Grant 0725905T to Z.S., and by the Novartis Institutes for Biomedical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

    Abbreviations:

    Chr

    chromosome

    cM

    centimorgan

    QTL

    quantitative trait locus

    SNP

    single nucleotide polymorphism

    TC

    total cholesterol

    TG

    triglyceride

[S]

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of two figures and five tables.