The human globin loci and their role in β-thalassemia. (A) The β-LCR and structural genes (ε, Gγ, Aγ, δ, and β) within the β-globin locus on chromosome 11 are shown. The Corfu deletion, which includes part of the structural δ-globin gene and γ_δ intergenic sequences, is also shown. (B) The α-globin locus is shown with the ζ- and 2 α-globin genes on chromosome 16. (C) In early fetal life, the α- and γ-globin chains combine to form HbF (α₂γ₂), the main β-globin_like globin during the remainder of fetal life and early postnatal life. In late postnatal and adult life, normal hemoglobin (HbA, α₂β₂) predominates. In homozygous β-thalassemia, decreased or absent β-globin production leads to decreased or absent HbA levels, respectively. The synthesis of γ-globin does not increase enough to compensate for the reduced or absent β-globin level. As a result, excess α-globin accumulates and precipitates in erythroid cells and causes damage due to the action of ROS and apoptosis of the damaged cells. Severe anemia results.