Introduction

All human hemoglobin is composed of two α-globin-like chains and two non-α-globin chains that combine to form a tetramer. Normal adults have three hemoglobin types, HbA (α2β2; ∼ 96%), HbF (α2γ2; ∼ 1%), and HbA2 (α2δ2; ∼ 3%). The amino acid sequence, or primary structure of each globin chain differs; dissimilarities between α- and non-α-globin chains are greater than the variations among the globins of the β-like gene cluster, e.g. γ-, δ-, and β-globin. Despite these differences among globins their similarities are even greater as all have alike secondary and tertiary structure and function similarly. Human hemoglobin is ideally suited for its tasks – primarily oxygen uptake in lungs and delivery in tissues. A sigmoidal shaped curve, so critical for this oxygen transport, is a result of the interactions among the individual globin subunits of the tetramer. As for hemoglobin function, the sigmoidal shape of the oxygen dissociation curve of hemoglobin shows that totally deoxygenated hemoglobin is slow to become oxygenated, but as oxygenation proceeds, the reaction of heme with oxygen accelerates; the reverse is also true. Hemoglobin has other functions in CO2 exchange and control of vascular tone by nitric oxide (NO) and can modulate oxygen delivery by shifts in its oxygen-hemoglobin dissociation curve caused by temperature, pH, and organic phosphates.

Different classes of mutations can alter the structure, function, and synthesis of hemoglobin. More than 1,000 structurally abnormal hemoglobins have been characterized and the number of thalassemia-causing mutations exceeds 200.