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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:107.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

Farp2 and Stk25 Are Candidate Genes for the HDL Cholesterol Locus on Mouse Chromosome 1

Zhiguang Su; Allison Cox; Yuan Shen; Ioannis M. Stylianou; Beverly Paigen

From the Jackson Laboratory, Bar Harbor, Me. Current address for I.M.S.: University of Pennsylvania, School of Medicine, Institute for Translational Research, Philadelphia.

Correspondence to Beverly Paigen, 600 Main St, The Jackson Laboratory, Bar Harbor, ME 04609. E-mail bev.paigen{at}jax.org

Objective— To identify the gene responsible for the quantitative trait locus (QTL) Hdlq14, a high-density lipoprotein cholesterol (HDL) QTL previously identified in a C57BL/6Jx129S1/SvImJ cross.

Methods and Results— Hdlq14 was first confirmed as an independent QTL by detecting it in an intercross between NZB/B1NJ and NZW/LacJ, 2 strains that had identical genotypes at nearby QTL genes on chromosome 1. Using the bioinformatics tools of combined cross data and haplotype analysis, we narrowed this QTL from a 45-Mb 225-gene region to 2 genes, Farp2 and Stk25. Sequencing and expression studies showed that Farp2 had an amino acid polymorphism in an important plekstrin domain and that Stk25 had a significant expression difference between the parental strains. These 2 genes are immediately adjacent to each other and share the same haplotype over 45 inbred strains. The haplotype was associated with a significant difference in HDL levels among these strains.

Conclusion— We confirmed Hdlq14 as a separate independent QTL for HDL and narrowed the region to 2 genes, Farp2 and Stk25, with considerable evidence for both. Additional studies are needed to choose between these 2 genes or to show that both are important in determining HDL levels.

Key Words: HDL • QTL • Farp2, Stk25, mouse

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