Genome-level analysis of genetic regulation of liver gene expression networks

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Hepatology

DOI:https://doi.org/10.1002/hep.21682· OSTI ID:930884

Gatti, Daniel ^[1]; Maki, Akira ^[1]; Chesler, Elissa J ^[2]; Kirova, Roumyana ^[3]; Kosyk, Oksana ^[1]; Lu, Lu ^[4]; Manly, Kenneth ^[4]; Matthews, Douglas B. ^[5]; Qu, Yanhua ^[4]; Williams, Robert ^[4]; Perkins, Andy ^[6]; Langston, Michael A ^[6]; Threadgill, David ^[1]; Rusyn, Ivan ^[1]

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1. University of North Carolina, Chapel Hill
2. ORNL
3. Oak Ridge National Laboratory (ORNL)
4. University of Tennessee Health Science Center, Memphis
5. University of Memphis
6. University of Tennessee, Knoxville (UTK)

Liver is the primary site for metabolism of nutrients, drugs and chemical agents. While metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variation in gene expression levels, introduces complexity into research on liver disease. This study aimed to dissect genetic networks that control liver gene expression by combining largescale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive SNP, haplotype and phenotypic data is 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. This data was used to map quantitative trait loci (QTLs) responsible for variation in expression of about 19,000 transcripts. We identified polymorphic cis- and trans-acting loci, including several loci that control expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL. The data is available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of co-regulated transcripts and correlated phenotypes, cross-tissue and -species comparisons, as well as testing of a broad array of hypotheses.

• Research Organization: Oak Ridge National Laboratory (ORNL)
• Sponsoring Organization: SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 930884
• Journal Information: Hepatology, Journal Name: Hepatology Journal Issue: 2 Vol. 46
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL PATHWAYS
GENES
GENETIC MAPPING
GENETICS
LIVER
METABOLISM
MICE
MINING
NUTRIENTS
OLIGONUCLEOTIDES
REGULATIONS
STRAINS
TESTING
eQTL
genetical genomics
liver
microarray
mouse