Farp2 and Stk25 Are Candidate Genes for the HDL Cholesterol Locus on Mouse Chromosome 1
Copyright policy )Farp2 and Stk25 Are Candidate Genes for the HDL Cholesterol Locus on Mouse Chromosome 1
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/6J×129S1/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.
- University of Pennsylvania United States
- Translational Genomics Research Institute United States
- Jackson Laboratory United States
Male, Genotype, Quantitative-Trait-Loci, Chromosomes-Mammalian, Intracellular-Signaling-Peptides-and-Proteins, Polymorphism-Genetic, Protein-Serine-Threonine-Kinases, 610, Cholesterol-HDL, Mice, Inbred Strains, 630, Mice, Animals, Guanine Nucleotide Exchange Factors, Crosses, Genetic, Adaptor Proteins, Signal Transducing, Polymorphism, Genetic, Mice-Inbred-C57BL, Cholesterol, HDL, Intracellular Signaling Peptides and Proteins, Chromosome Mapping, Crosses-Genetic, Atherosclerosis, Chromosomes, Mammalian, Mice, Inbred C57BL, Lipoproteins-HDL, Disease Models, Animal, Phenotype, Chromosome-Mapping, Mice-Inbred-Strains, Diet-Atherogenic, Diet, Atherogenic, Female, Disease-Models-Animal, Lipoproteins, HDL, Guanine-Nucleotide-Exchange-Factors
Male, Genotype, Quantitative-Trait-Loci, Chromosomes-Mammalian, Intracellular-Signaling-Peptides-and-Proteins, Polymorphism-Genetic, Protein-Serine-Threonine-Kinases, 610, Cholesterol-HDL, Mice, Inbred Strains, 630, Mice, Animals, Guanine Nucleotide Exchange Factors, Crosses, Genetic, Adaptor Proteins, Signal Transducing, Polymorphism, Genetic, Mice-Inbred-C57BL, Cholesterol, HDL, Intracellular Signaling Peptides and Proteins, Chromosome Mapping, Crosses-Genetic, Atherosclerosis, Chromosomes, Mammalian, Mice, Inbred C57BL, Lipoproteins-HDL, Disease Models, Animal, Phenotype, Chromosome-Mapping, Mice-Inbred-Strains, Diet-Atherogenic, Diet, Atherogenic, Female, Disease-Models-Animal, Lipoproteins, HDL, Guanine-Nucleotide-Exchange-Factors
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