Question

A relevant portion of β-chain of haemoglobin of a normal human is given below:

The codon for the sixth amino acid is GAG. The sixth codon GAG mutates to CAA as a result of mutation ‘A’ and into GUG as a result of mutation ‘B’. Haemoglobin structure did not change as a result of mutation ‘A’ whereas haemoglobin structure changed because of mutation ‘B’ leading to sickle-shaped RBCs. Explain giving reasons how could mutation ‘B’ change the haemoglobin structure and not mutation ‘A’.

Answer 1

The alteration in haemoglobin structure caused by mutation 'B' results from the substitution of glutamic acid with valine at the sixth position of the β-globin chain. This amino acid change originates from a single nucleotide substitution in the β-globin gene, where the codon GAG is replaced by GUG. Under conditions of low oxygen, the mutated haemoglobin molecules polymerize, leading to a deformation in red blood cells. Consequently, the red blood cells change their shape from the normal biconcave discs into elongated, sickle-like forms characteristic of sickle-cell anaemia.