GENETIC AND RADIATION-REDUCED SOMATIC-CELL HYBRID SUBLOCALIZATION OF THE HUMAN GSTP1 GENE

A number of related enzymes like glutathione S-transferases (GSTs) and fatty acid ethyl ester synthases (FAEESs) have been implicated in det oxification and drug resistance. The anionic class of GSTs, pi, and cl osely related FAEES-III exhibit tissue-specific and developmentally re gulated expression, and the former has been shown to be overexpressed or amplified in a variety of tumors. The GSTP1 gene has previously bee n cloned and cytogenetically localized to human 11q13 by in situ hybri dization. Using a series of previously described radiation-reduced som atic cell hybrids, we have sublocalized GSTP1 to 11q13. We isolated a genomic clone containing the entire GSTP1 gene and sequenced it. Analy sis of the 5' region revealed 23 (TAAAA) tandem repeats interrupted by a single TA and TAA insertion. This repeat number differs among indiv iduals. Eleven alleles in a mostly Caucasian sample were observed. Thi s repeat has a polymorphism information content of 0.74. Linkage analy sis of the Venezuelan reference pedigree places GSTP1 5 cM distal to P YGM and 4 cM proximal to FGF3 thereby providing a genetic marker half- way between these two loci. The sublocalization and genetic characteri zation of GSTP1 facilitates linkage analyis of several disease genes m apped to this chromosome band as well as the correlation of genetic an d physical markers in the region.