title: Genome-level analysis of genetic regulation of liver gene expression networks.
abstract: The liver is the primary site for the metabolism of nutrients, drugs, and chemical agents. Although metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variations in gene expression levels, introduces complexity into research on liver disease. This study dissected genetic networks that control liver gene expression through the combination of large-scale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive single-nucleotide polymorphism, haplotype, and phenotypic data are publicly available. We profiled gene expression in livers of naive mice of both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent oligonucleotide microarrays. These data were used to map quantitative trait loci (QTLs) responsible for variations in the expression of about 19,000 transcripts. We identified polymorphic local and distant QTLs, including several loci that control the expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL.
  
  
  CONCLUSIONS
  The data are available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of coregulated transcripts and correlated phenotypes, cross-tissue, and cross-species comparisons, as well as testing of a broad array of hypotheses.
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gatti
authors.forename: Akira
authors.initials: A
authors.lastname: Maki
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: Roumyana
authors.initials: R
authors.lastname: Kirova
authors.forename: Oksana
authors.initials: O
authors.lastname: Kosyk
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Manly
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Andy
authors.initials: A
authors.lastname: Perkins
authors.forename: Michael A
authors.initials: MA
authors.lastname: Langston
authors.forename: David W
authors.initials: DW
authors.lastname: Threadgill
authors.forename: Ivan
authors.initials: I
authors.lastname: Rusyn
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005838:Genotype; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D016133:Polymerase Chain Reaction; D040641:Quantitative Trait Loci