Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.
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Authors
Hall, Rabea ALiebe, Roman
Hochrath, Katrin
Kazakov, Andrey
Alberts, Rudi
Laufs, Ulrich
Böhm, Michael
Fischer, Hans-Peter
Williams, Robert W
Schughart, Klaus
Weber, Susanne N
Lammert, Frank
Issue Date
2014
Metadata
Show full item recordAbstract
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 genome-wide 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 cis-regulated 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.Citation
Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population. 2014, 9 (2):e89279 PLoS ONEJournal
PloS onePubMed ID
24586654Type
ArticleLanguage
enISSN
1932-6203ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0089279
Scopus Count
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