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/6Jx129S1/SvImJ cross.


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.
Su
Zhiguang
Z
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Cox
Allison
A
Shen
Yuan
Y
Stylianou
Ioannis M
IM
Paigen
Beverly
B
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics; D008076:Cholesterol, HDL / Q000235:genetics*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010641:Phenotype; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D040641:Quantitative Trait Loci; D000099317:Hippo Kinases
D048868:Adaptor Proteins, Signal Transducing; D008076:Cholesterol, HDL; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; D017346:Protein Serine-Threonine Kinases; C507259:FARP2 protein, mouse; C530661:Stk25 protein, mouse; D000099317:Hippo Kinases