0HbS forms as a result of a single amino acid substitution in the β-chain of Hb. Replacement of the glutamate residue at position 6 in the β-chain by a valine residue is the only chemical difference between HbA and sickle-cell haemoglobin. The residue is present on the outer surface of the molecule. The change produces a sticky hydrophobic spot on the surface that results in the abnormal quaternary association of haemoglobin. This makes the deoxyHbS less soluble than deoxyHbA. Insoluble deoxyHbS forms polymers that aggregate into tubular fibres. The formation of insoluble deoxyHbS fibres distorts the RBC into the elongated sickle-shaped structure which is characteristic of the disease, sickle-cell anaemia. Sickle-cell anaemia and sickle-cell trait are different. Sickle-cell describes a condition in which an individual has one abnormal allele of the β-globin gene(heterozygous). A person with sickle-cell anaemia has two copies of the abnormal β-globin gene(homozygous).
