The Genetic Architecture of Murine Glutathione Transferases
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 f...
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| Tác giả chính: | , , , |
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| Ngôn ngữ: | English |
| Năm xuất bản: |
Public Library of Science (PLoS)
2018
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| Chủ đề: | |
| Truy cập Trực tuyến: | http://lrc.quangbinhuni.edu.vn:8181/dspace/handle/DHQB_123456789/3841 |
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| Tóm tắt: | 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. |
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