Farp2 and Stk25 are candidate genes for the HDL cholesterol locus on mouse chromosome 1.

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Animals, Atherosclerosis, Cholesterol-HDL, Chromosome-Mapping, Chromosomes-Mammalian, Crosses-Genetic, Diet-Atherogenic, Disease-Models-Animal, Genotype, Guanine-Nucleotide-Exchange-Factors, Intracellular-Signaling-Peptides-and-Proteins, Lipoproteins-HDL, Mice-Inbred-C57BL, Mice-Inbred-Strains, Phenotype, Polymorphism-Genetic, Protein-Serine-Threonine-Kinases, Quantitative-Trait-Loci

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JAX Source

Arterioscler Thromb Vasc Biol 2009 Jan; 29(1):107-13.


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. CONCLUSIONS: 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.

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