Hb switching at the human α- and β-globin loci. Green, embryonic globins; blue, fetal globins; red, adult globins. Primitive erythropoiesis, derived from the yolk sac, is characterized by the expression of ζ-globin (from the α-globin locus) and ɛ-globin (from the β-globin locus). These are silenced at approximately 8 weeks' gestation. α-Globin then accounts for the entirety of the transcriptional output from the α-globin locus. At the β-globin locus, there is a switch to fetal globin (γ-globin) during fetal life and then a second switch to the adult β-globin. The predominant type of Hb corresponding to each developmental stage is shown below. Adapted with permission from King and Higgs 2018.⁴