Abstract
In a family with erythrocytosis, electrophoretic and chromatographic studies failed to demonstrate a hemoglobin variant. However, the oxygen dissociation curves of affected individuals were shifted to the left of normal and this shift persisted when oxygen equilibria were studied in 2.3-diphosphoglycerate-stripped hemolysates. A mutant hemoglobin was evidently present in the red blood cells of the affected persons and was responsible for the increased oxygen affinity and erythrocytosis. Specific staining of tryptic peptide maps of beta-chains from the propositus showed that peptide betaT(3) was positive for a sulfur-containing amino acid. Amino acid analysis yielded a composition identical to that of normal betaT(3), except that there were 2.6 residues of valine and 0.4 residues of methionine (normal composition: Val = 3.0, Met = 0). This suggested that the beta-chains of affected individuals consisted of a mixture of two kinds of chains, 40% of which had a methionyl residue in betaT(3). Structural studies of isolated cyanogen bromide fragments demonstrated unequivocally that, in the abnormal beta-chains, valine in position 20 is replaced by methionine. The new hemoglobin mutant is designated hemoglobin Olympia (beta20 (B2) valine --> methionine).