The genetic architecture of murine glutathione transferases

Lu Lu, Ashutosh K. Pandey, M. Trevor Houseal, Megan Mulligan

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Glutathione S-transferase (GST) genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6) and DBA2/J (D2)-the BXD family-was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs) in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01) with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

Original languageEnglish (US)
Article numbere0148230
JournalPLoS ONE
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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Glutathione Transferase
glutathione transferase
Brain
Genes
Alleles
mice
alleles
brain
Liver
inheritance (genetics)
liver
Oxidative stress
Pharmacokinetics
genes
Bioinformatics
Computational Biology
bioinformatics
pharmacokinetics
linkage (genetics)
quantitative trait loci

All Science Journal Classification (ASJC) codes

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

Cite this

The genetic architecture of murine glutathione transferases. / Lu, Lu; Pandey, Ashutosh K.; Houseal, M. Trevor; Mulligan, Megan.

In: PLoS ONE, Vol. 11, No. 2, e0148230, 01.02.2016.

Research output: Contribution to journalArticle

Lu, Lu ; Pandey, Ashutosh K. ; Houseal, M. Trevor ; Mulligan, Megan. / The genetic architecture of murine glutathione transferases. In: PLoS ONE. 2016 ; Vol. 11, No. 2.
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