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Originally published In Press as doi:10.1194/jlr.M800244-JLR200 on May 23, 2008

Papers In Press, published online ahead of print November 1, 2008
J. Lipid Res., doi:10.1194/jlr.M800244-JLR200
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Journal of Lipid Research, Vol. 49, 2402-2413, November 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Differences in DBA/1J and DBA/2J reveal lipid QTL genesboxs

Ioannis M. Stylianou1,*, Sarah R. Langley*, Kenneth Walsh*, Yuan Chen*, Céline Revenu{dagger} and Beverly Paigen2,*

* The Jackson Laboratory, Bar Harbor, ME
{dagger} Laboratoire de Morphogenèse et Signalisation Cellulaires, Unité Mixte de Recherche 144, Centre National de la Recherche Scientifique/Institut Curie, Paris, France
1 Present address of I. M. Stylianou: University of Pennsylvania, School of Medicine, Institute for Translational Medicine and Therapeutics, Philadelphia, PA 19104, USA.

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

Published, JLR Papers in Press, May 23, 2008.

This work was supported by The American Heart Association, Grant 0525816T (I.M.S.), The National Institutes of Health, Grants HL-77796, HL-81162, and HL-74086 (B.P), and by CA34196, a Cancer Center Core grant to The Jackson Laboratory.

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

Recent advances in mouse genomics have revealed considerable variation in the form of single-nucleotide polymorphisms (SNPs) among common inbred strains. This has made it possible to characterize closely related strains and to identify genes that differ; such genes may be causal for quantitative phenotypes. The mouse strains DBA/1J and DBA/2J differ by just 5.6% at the SNP level. These strains exhibit differences in a number of metabolic and lipid phenotypes, such as plasma levels of triglycerides (TGs) and HDL. A cross between these strains revealed multiple quantitative trait loci (QTLs) in 294 progeny. We identified significant TG QTLs on chromosomes (Chrs) 1, 2, 3, 4, 8, 9, 10, 11, 12, 13, 14, 16, and 19, and significant HDL QTLs on Chrs 3, 9, and 16. Some QTLs mapped to chromosomes with limited variability between the two strains, thus facilitating the identification of candidate genes. We suggest that Tshr is the QTL gene for Chr 12 TG and HDL levels and that Ihh may account for the TG QTL on Chr 1. This cross highlights the advantage of crossing closely related strains for subsequent identification of QTL genes.

Supplementary key words quantitative trait loci • triglycerides • body weight • Tshr • Villin • Cyp27a1 • Ihh


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