Regulation of fetal hemoglobin production

Recent data bearing on the regulation of γ chain synthesis in man indicate the following. Two or more γ chain loci are genetically linked to the δ and β chain loci. A qualitative switch in hemoglobin type occurs not once but twice prior to a conceptual age of 40 wk, and after 5 wk of fetal age, the production of both adult and fetal type chains takes place in a fraction of erythroid precursors throughout life. Genetic heterogeneity in the etiology of diseases of hemoglobin chain regulation, including the thalassemia syndromes and hereditary persistence of fetal hemoglobin (HPFH), is great; e.g., at least 7 different genes produce the HPFH state. On the other hand, present knowledge of the mechanisms by which γ chain synthesis is regulated, is weak, and even information on the normal process of γ chain assembly is lacking. At this time, there is no general theory which explains the normal hemoglobin changes in development, and the various Hb F levels and γ chain types in the HPFH, thalassemia, and abnormal hemoglobin states.