Genetic control of haemoglobin production

Hb comprises 4 protein subunits (e.g. adult Hb = 2 xa + 2 x|3 chains, a2^2) each linked to a haem group. Production of different globin chains 70 varies from embryo—»adult to meet the particular environment at each stage. Globin genes are located on chromosomes 11 and 16. All globins related to a globin are located on chromosome 16; all those related to |3 globin are on chromosome 11. The sequence in which they are produced during development reflects their physical order on chromosomes such that Z is the first a-like globin to be produced in life. After Z expression stops, a production occurs (Z—>a switch). On chromosome 11 the arrangement of |3-like globin genes follows the order (from left—►right) e—►y—►§—mirroring the |3-like globin chains produced during development. As embryo develops into fetus, Z production stops and a is produced. The a globin combines with y chains and produces a2g2 (fetal Hb, HbF). After birth y production 5 and § and |3 chains are produced. Adults have predominantly HbA (a2^2) although small amounts of HbA2 (a2§2) and HbF are produced.

Hb switching is physiological but the mechanism is unclear. HbF (a2g2) binds O2 more tightly than adult haemoglobin, ensuring adequate O2 delivery to the fetus which must extract its O2 from mother's circulation. After birth the lungs expand and the O2 is derived from the air, with |3 production replacing that of y, leading to an increase in adult haemoglobin

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