Document Detail


Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster.
MedLine Citation:
PMID:  19913078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glutathione S-transferases (GSTs: EC2.5.1.18) are a superfamily of multifunctional dimeric enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic chemicals. In most animals and in humans, GSTs are the principal enzymes responsible for detoxifying the mycotoxin aflatoxin B(1) (AFB(1)) and GST dysfunction is a known risk factor for susceptibility towards AFB(1). Turkeys are one of the most susceptible animals known to AFB(1), which is a common contaminant of poultry feeds. The extreme susceptibility of turkeys is associated with hepatic GSTs unable to detoxify the highly reactive and electrophilic metabolite exo-AFB(1)-8,9-epoxide (AFBO). In this study, comparative genomic approaches were used to amplify and identify the alpha-class tGST genes (tGSTA1.1, tGSTA1.2, tGSTA1.3, tGSTA2, tGSTA3 and tGSTA4) from turkey liver. The conserved GST domains and four alpha-class signature motifs in turkey GSTs (with the exception of tGSTA1.1 which lacked one motif) confirm the presence of hepatic alpha-class GSTs in the turkey. Four signature motifs and conserved residues found in alpha-class tGSTs are (1) xMExxxWLLAAAGVE, (2) YGKDxKERAxIDMYVxG, (3) PVxEKVLKxHGxxxL and (4) PxIKKFLXPGSxxKPxxx. A BAC clone containing the alpha-class GST gene cluster was isolated and sequenced. The turkey alpha-class GTS genes genetically map to chromosome MGA2 with synteny between turkey and human alpha-class GSTs and flanking genes. This study identifies the alpha-class tGST gene cluster and genetic markers (SNPs, single nucleotide polymorphisms) that can be used to further examine AFB(1) susceptibility and resistance in turkeys. Functional characterization of heterologously expressed proteins from these genes is currently underway.
Authors:
Ji Eun Kim; Miranda M Bauer; Kristelle M Mendoza; Kent M Reed; Roger A Coulombe
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-11-10
Journal Detail:
Title:  Gene     Volume:  452     ISSN:  1879-0038     ISO Abbreviation:  Gene     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-03-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  45-53     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier B.V. All rights reserved.
Affiliation:
Department of Veterinary Sciences and Graduate Toxicology Program, Utah State University, Logan, UT 84322, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Conserved Sequence
Genomics
Glutathione Transferase / chemistry,  genetics*
Humans
Male
Molecular Sequence Data
Multigene Family
Sequence Alignment
Turkeys / genetics*
Chemical
Reg. No./Substance:
EC 2.5.1.18/Glutathione Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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