Abstract
The human expressed sequence tag (EST) database can be searched by different sequence alignment strategies to identify new members of gene families and allelic variants. To illustrate the value of database analysis for gene discovery, we have focused on the glutathioneS-transferase (GST) super family, an approach that has led to the identification of the Zeta class. The Zeta class GSTs catalyze the glutathione-dependent biotransformation of α-haloacids and the isomerization of maleylacetoacetic acid to fumarylacetoacetic acid, an essential step in the catabolism of tyrosine. Allelic variants of the GST Z1 and GST A2 genes have also been identified by EST database analysis. One GST Z1 variant (GST Z1A) has significantly higher activity with dichloroacetic acid as a substrate than other GST Z1 isoforms. This variant may be important in the clinical treatment of lactic acidosis where dichloroacetic acid is prescribed. Our experience with the application of EST database searching methods suggests that it may be productively applied to other gene families of pharmacogenetic interest.
Footnotes
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Send reprint requests to: P. G. Board, Molecular Genetics Group, John Curtin School of Medical Research, P.O. Box 334, Australian National University, Canberra ACT 2601, Australia. E-mail:Philip.Board{at}anu.edu.au
- Abbreviations used are::
- GST
- glutathione transferase
- EST
- expressed sequence tag
- MAAI
- maleylacetoacetate isomerase
- The American Society for Pharmacology and Experimental Therapeutics
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