(A) The genes of the β-globin gene cluster (ε, Gγ, Aγ, δ, and β) are present on chromosome 11 in the same order in which they are expressed during development. The β–locus control region (β–LCR) is a major regulatory element located far upstream of the genes of the cluster that is necessary for the high level of expression of those genes. (B) The genes of the α-globin gene cluster (ζ, α₁, and α₂) are present on chromosome 16, also in the same order in which they are expressed during development. HS-40 is a major regulatory element located far upstream of the genes of the cluster that is necessary for their high level of expression. (C) During fetal life, Hb F (α₂γ₂) is the predominant type of hemoglobin. Hemoglobin switching refers to the developmental process that leads to the silencing of γ-globin gene expression and the reciprocal activation of adult β-globin gene expression. This results in the replacement of Hb F by Hb A (α₂β₂) as the predominant type of hemoglobin in adult life. Figure modified from ref. 128.