Identification of common variant alleles of the human guanosine monophosphate reductase gene.

Examination of nucleotide sequences of genomic DNA samples obtained from several unrelated Caucasians and orientals revealed the existence of four variant alleles in the chromosome 6-linked quanosine monophosphate reductase locus. The wild-type gene has T at position 42 (counting from A of the chain initiation codon), C at 630, G at 700, and T at 766, i.e., its structure is T(42)-C(630)-G(700)-T(766). The variant gene, T-T-G-T, was found in about 10% of the loci examined. The C-to-T change at 630 was silent and did not induce any amino acid substitution (His at amino acid residue 210), but it created an additional NcoI cleavage site in the variant gene. The frequency of another variant, the T-C-G-A gene, was about 30%. The T-to-A change at 766 caused an amino acid substitution Phe----Ile at amino acid residue 256 in the variant protein. Frequencies of the C-C-G-T variant and the T-C-A-T variant were probably lower than 5% in Caucasians and orientals.