Genetic polymorphism in the 3' untranslated region of human phosphoglucomutase-1

A 317-bp segment of DNA from the 3' region of the human phosphoglucomutase-1 (PGM1) gene has been examined by a non-radioactive technique for the occurrence of single-strand conformation polymorphism (SSCP). Eight phenotypes were detected and attributed to the presence of four alleles. Genetic analysis of 75 unrelated individuals and six CEPH families whose PGM1 protein phenotypes were known revealed strong association between the PGM1 '+' and '-' isozyme phenotypes and the variation detected in this region, but no association with the PGM1 1 and PGM1 2 isozyme phenotypes. DNA sequence analysis demonstrated the presence of three nucleotide substitutions underlying the alleles, which were located in the untranslated region of the PGM1 gene. There was complete correlation between the nucleotide sequence and the phenotype detected by SSCP analysis. This study provides support for the model that the PGM1 isozyme polymorphism is determined at two distinct sites in the coding sequence, one coding for the '1' and '2' alleles and the other coding for the '+' and '-' alleles, separated by a region where intragenic recombination occurs.