An extensive search for RFLP in the human glucose-6-phosphate dehydrogenase locus has revealed a silent mutation in the coding sequence

The genetic polymorphism of an ~100-kb DNA region comprising and flanking the glucose 6-phosphate dehydrogenase (G6PD) gene on human chromosome Xq28 has been analyzed in detail. By using 14 unique sequence probes and 18 restriction enzymes, we have characterized 257 restriction fragments or 370 restriction sites. On testing 12-57 individual X chromosomes, all sites but one were nonpolymorphic. However, a PstI site that maps to exon 10 of the G6PD gene, which is still monomorphic in all British and Italian subjects testes, is polymorphic in west-African people. Specifically, it is absent from 22% of Nigerian X chromosomes. By sequence analysis we have shown that the absence of this PstI site results from a G->A replacement at position 1116, corresponding to the third base of a glutamine codon; no amino acid change is produced in the protein. Thus, a polymorphic silent mutation is demonstrated in a human gene.