CHARACTERIZATION OF THE HUMAN CLASS MU-GLUTATHIONE-S-TRANSFERASE GENE-CLUSTER AND THE GSTM1 DELETION

A partial physical map has been constructed of the human class Mu glut athione S-transferase genes on chromosome 1p13.3. The glutathione S-tr ansferase genes in this cluster are spaced about 20 kilobase pairs (kb ) apart, and arranged as 5'-GSTM4-GSTM2-GSTM1-GSTM5-3'. This map has b een used to localize the end points of the polymorphic GSTM1 deletion, The left repeated region is 5 kb downstream from the 3'-end of the GS TM2 gene and 5 kb upstream from the beginning of the GSTM1 gene; the r ight repeated region is 5 kb downstream from the 5'-end of the GSTM1 a nd 10 kb upstream from the 5'-end of the GSTM5 gene. The GSTM1-0 delet ion produces a novel 7.4-kb HindIII fragment with the loss of 10.3- an d 11.4-kb HindIII fragments. The same novel fragment was seen in 13 un related individuals (20 null alleles), suggesting that most GSTM1-0 de letions involve recombinations between the same two regions. We have c loned and sequenced the deletion junction that is produced at the GSTM 1-null locus; the 5'- and 5'-flanking regions are more than 99% identi cal to each other and to the deletion junction sequence over 2.3 kb. B ecause of the high sequence identity between the left repeat, right re peat, and deletion junction regions, the crossing over cannot be local ized within the 2.3-kb region, The 2.3-kb repeated region contains a r everse class IV Alu repetitive element near one end of the repeat.