Genome-wide Genetic Association of Complex Traits in Heterogeneous Stock Mice

Nat Genet. 2006 Aug;38(8):879-87. doi: 10.1038/ng1840. Epub 2006 Jul 9.

Abstract

Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breeding
  • Chromosome Mapping
  • Female
  • Genomics
  • Genotype
  • Humans
  • Male
  • Mice / genetics*
  • Models, Genetic
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*