These authors contributed equally to this work.
Genome-level analysis of genetic regulation of liver gene expression networks†
Article first published online: 31 MAY 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 2, pages 548–557, August 2007
How to Cite
Gatti, D., Maki, A., Chesler, E. J., Kirova, R., Kosyk, O., Lu, L., Manly, K. F., Williams, R. W., Perkins, A., Langston, M. A., Threadgill, D. W. and Rusyn, I. (2007), Genome-level analysis of genetic regulation of liver gene expression networks. Hepatology, 46: 548–557. doi: 10.1002/hep.21682
Potential conflict of interest: Nothing to report.
- Issue published online: 27 JUL 2007
- Article first published online: 31 MAY 2007
- Manuscript Accepted: 31 JAN 2007
- Manuscript Received: 8 DEC 2006
- National Institutes of Health. Grant Numbers: ES011391, ES010126, AA016258, AA013499, AA013513, AA014425
- Environmental Protection Agency. Grant Number: STAR-RD832720
- Bioinformatics and Computational Biology Training Program at the University of North Carolina at Chapel Hill
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. Conclusion: 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. (HEPATOLOGY 2007.)