QTL mapping for genetic determinants of lipoprotein cholesterol levels in combined crosses of inbred mouse strains

J Lipid Res. 2006 Aug;47(8):1780-90. doi: 10.1194/jlr.M500544-JLR200. Epub 2006 May 9.


To identify additional loci that influence lipoprotein cholesterol levels, we performed quantitative trait locus (QTL) mapping in offspring of PERA/EiJxI/LnJ and PERA/EiJxDBA/2J intercrosses and in a combined data set from both crosses after 8 weeks of consumption of a high fat-diet. Most QTLs identified were concordant with homologous chromosomal regions that were associated with lipoprotein levels in human studies. We detected significant new loci for HDL cholesterol levels on chromosome (Chr) 5 (Hdlq34) and for non-HDL cholesterol levels on Chrs 15 (Nhdlq9) and 16 (Nhdlq10). In addition, the analysis of combined data sets identified a QTL for HDL cholesterol on Chr 17 that was shared between both crosses; lower HDL cholesterol levels were conferred by strain PERA. This QTL colocalized with a shared QTL for cholesterol gallstone formation detected in the same crosses. Haplotype analysis narrowed this QTL, and sequencing of the candidate genes Abcg5 and Abcg8 confirmed shared alleles in strains I/LnJ and DBA/2J that differed from the alleles in strain PERA/EiJ. In conclusion, our analysis furthers the knowledge of genetic determinants of lipoprotein cholesterol levels in inbred mice and substantiates the hypothesis that polymorphisms of Abcg5/Abcg8 contribute to individual variation in both plasma HDL cholesterol levels and susceptibility to cholesterol gallstone formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cholesterol / blood*
  • Cholesterol / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / metabolism
  • Chromosome Mapping / methods
  • Chromosomes, Mammalian / genetics*
  • Crosses, Genetic
  • Female
  • Genetic Linkage / genetics
  • Genotype
  • Haplotypes / genetics
  • Lipoproteins / blood*
  • Lipoproteins / metabolism
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mice, Inbred Strains
  • Phenotype
  • Quantitative Trait Loci / genetics*
  • Regression Analysis
  • Sequence Analysis, DNA


  • Cholesterol, HDL
  • Lipoproteins
  • lipoprotein cholesterol
  • Cholesterol