The molecular basis of α-thalassemia: a model for understanding human molecular genetics.

Down-regulation of α-globin synthesis causes α-thalassemia with underproduction of fetal (HbF, α(2)γ(2)) and adult (HbA, α(2)β(2)) hemoglobin. This article focuses on the human α-globin cluster, which has been characterized in great depth over the past 30 years. In particular the authors describe how the α genes are normally switched on during erythropoiesis and switched off as hematopoietic stem cells commit to nonerythroid lineages. In addition, the principles by which α-globin expression may be perturbed by natural mutations that cause α-thalassemia are reviewed.