Unbalanced globin chain synthesis in reticulocytes of sickle cell trait individuals with low concentrations of hemoglobin S (original) (raw)

Reticulocytes were isolated from the blood of eight nonanemic individuals with sickle cell trait; five donors had relatively low hemoglobin S concentrations (26 to 327o) and three had high hemoglobin S concentrations (40 to 42%). The cells were incubated with [3HI leucine in a medium supporting protein synthesis. Total chain synthesis was equal to total ~ chain synthesis in cells from the high hemoglobin S donors. In cells from low. hemoglobin S donors the rate of ~ chain synthesis was about 65 to 80% that of total ~ chain synthesis. These data suggest that there was a deficit in ~ chain synthesis in the cells of sickle cell trait individuals with low hemoglobin S concentrations. The results are consistent with the presence of an ~-thalassemia or ~-thalassemia-like gene in the low hemoglobin S people. Individuals with sickle cell trait have both hemoglobin A (HbA) and hemoglobin S (HbS) in their peripheral blood. In most of these people the concent~tion of HbS is 35 to 45% of the total blood hemoglobin, the remainder being largely HbA (1-4). In a few individuals the blood concentration of HbS is as low as 25 to 30%. This laboratory has been investigating the molecular basis for the lower concentration of the variant hemoglobin. Several years ago Neel et al. (5) reported that the concentration of HbS in sickle cell trait people appeared to be under genetic control, because many, though not all, of the relatives of an individual with a given amount of HbS had similar amounts of the variant hemoglobin. These same investigators suggest ed that "modifying" genes, in addition to the sickle cell gene, might be responsible for the wide variation in HbS concentration among the sickle cell trait population. Subsequently, several investigators (6-9) reported, on the basis of genetic and *We are grateful to those individuals who volunteered blood samples, to the Re