Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.

2.50
Hdl Handle:
http://hdl.handle.net/10033/322230
Title:
Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.
Authors:
Hall, Rabea A; Liebe, Roman; Hochrath, Katrin; Kazakov, Andrey; Alberts, Rudi; Laufs, Ulrich; Böhm, Michael; Fischer, Hans-Peter; Williams, Robert W; Schughart, Klaus ( 0000-0002-6824-7523 ) ; Weber, Susanne N; Lammert, Frank
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 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 ONE
Journal:
PloS one
Issue Date:
2014
URI:
http://hdl.handle.net/10033/322230
DOI:
10.1371/journal.pone.0089279
PubMed ID:
24586654
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authorHall, Rabea Aen
dc.contributor.authorLiebe, Romanen
dc.contributor.authorHochrath, Katrinen
dc.contributor.authorKazakov, Andreyen
dc.contributor.authorAlberts, Rudien
dc.contributor.authorLaufs, Ulrichen
dc.contributor.authorBöhm, Michaelen
dc.contributor.authorFischer, Hans-Peteren
dc.contributor.authorWilliams, Robert Wen
dc.contributor.authorSchughart, Klausen
dc.contributor.authorWeber, Susanne Nen
dc.contributor.authorLammert, Franken
dc.date.accessioned2014-06-24T12:58:19Zen
dc.date.available2014-06-24T12:58:19Zen
dc.date.issued2014en
dc.identifier.citationSystems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population. 2014, 9 (2):e89279 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid24586654en
dc.identifier.doi10.1371/journal.pone.0089279en
dc.identifier.urihttp://hdl.handle.net/10033/322230en
dc.description.abstractThe 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.en
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen
dc.titleSystems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.en
dc.typeArticleen
dc.identifier.journalPloS oneen

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