Systems genetics of liver fibrosis

Identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population

Rabea A. Hall, Roman Liebe, Katrin Hochrath, Andrey Kazakov, Rudi Alberts, Ulrich Laufs, Michael Böhm, Hans Peter Fischer, Robert Williams, Klaus Schughart, Susanne N. Weber, Frank Lammert

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL) analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs) with genomewide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cisregulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury.

Original languageEnglish (US)
Article numbere89279
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 28 2014

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liver cirrhosis
Quantitative Trait Loci
Liver Cirrhosis
Liver
quantitative trait loci
Genes
mice
Population
fibrosis
genes
Fibrosis
toxicogenomics
Toxicogenetics
Phenotype
phenotype
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 4
carbon tetrachloride
gene interaction
Carbon Tetrachloride

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Systems genetics of liver fibrosis : Identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population. / Hall, Rabea A.; Liebe, Roman; Hochrath, Katrin; Kazakov, Andrey; Alberts, Rudi; Laufs, Ulrich; Böhm, Michael; Fischer, Hans Peter; Williams, Robert; Schughart, Klaus; Weber, Susanne N.; Lammert, Frank.

In: PloS one, Vol. 9, No. 2, e89279, 28.02.2014.

Research output: Contribution to journalArticle

Hall, RA, Liebe, R, Hochrath, K, Kazakov, A, Alberts, R, Laufs, U, Böhm, M, Fischer, HP, Williams, R, Schughart, K, Weber, SN & Lammert, F 2014, 'Systems genetics of liver fibrosis: Identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population', PloS one, vol. 9, no. 2, e89279. https://doi.org/10.1371/journal.pone.0089279
Hall, Rabea A. ; Liebe, Roman ; Hochrath, Katrin ; Kazakov, Andrey ; Alberts, Rudi ; Laufs, Ulrich ; Böhm, Michael ; Fischer, Hans Peter ; Williams, Robert ; Schughart, Klaus ; Weber, Susanne N. ; Lammert, Frank. / Systems genetics of liver fibrosis : Identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population. In: PloS one. 2014 ; Vol. 9, No. 2.
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