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Papers In Press, published online ahead of print July 1, 2008
J. Lipid Res., doi:10.1194/jlr.M800053-JLR200

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Journal of Lipid Research, Vol. 49, 1500-1510, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Candidate genes for plasma triglyceride, FFA, and glucose revealed from an intercross between inbred mouse strains NZB/B1NJ and NZW/LacJ^*,

Zhiguang Su, Shirng-wern Tsaih, Jin Szatkiewicz, Yuan Shen and Beverly Paigen¹

The Jackson Laboratory, Bar Harbor, ME 04609

^* This work was funded by National Institutes of Health Grants HL-81162, HL-74086, HL-77796, and GM-764668), American Heart Association Grant 0725905T (to S.Z.), and National Cancer Institute Cancer Core Grant CA-034196 to The Jackson Laboratory.

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

Published, JLR Papers in Press, March 24, 2008.

¹ To whom correspondence should be addressed. e-mail: bev.paigen{at}jax.org

To identify the genes controlling plasma concentrations of triglycerides (TGs), FFAs, and glucose, we carried out a quantitative trait loci (QTL) analysis of the closely related mouse strains New Zealand Black (NZB/B1NJ) and New Zealand White (NZW/LacJ), which share 63% of their genomes. The NZB x NZW F₂ progeny were genotyped and phenotyped to detect QTL, and then comparative genomics, bioinformatics, and sequencing were used to narrow the QTL and reduce the number of candidate genes. Triglyceride concentrations were linked to loci on chromosomes (Chr) 4, 7, 8, 10, and 18. FFA concentrations were affected by a significant locus on Chr 4, a suggestive locus on Chr 16, and two interacting loci on Chr 2 and 15. Plasma glucose concentrations were affected by QTL on Chr 2, 4, 7, 8, 10, 15, 17, and 18. Comparative genomics narrowed the QTL by 31% to 86%; haplotype analysis was usually able to further narrow it by 80%. We suggest several candidate genes: Gba2 on Chr 4, Irs2 on Chr 8, and Ppargc1b on Chr 18 for TG; A2bp1 on Chr 16 for FFA; and G6pc2 on Chr 2 and Timp3 on Chr 10 for glucose.

Supplementary key words quantitative trait loci gene • comparative genomics • haplotype

Abbreviations: Chr, chromosome; Ct, cycle threshold; FFA, free fatty acid; IBD, identical by descent; LOD, logarithm of the odds ratio; PPA, phosphatase A; SNP, single-nucleotide polymorphism; TG, triglyceride; QTL, quantitative trait loci

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