The sixth mutant codon of beta globin gene causing polymerization of Haemoglobin and change in RBC shape is ________

The beta‑globin gene encodes the β chain of hemoglobin. Each amino‑acid is specified by a three‑nucleotide codon.

In the normal adult hemoglobin (Hb A) the sixth codon of the β‑globin mRNA is $GAG$, which codes for the amino‑acid glutamic acid (Glu). This residue is located on the surface of the hemoglobin molecule.

A single‑base substitution at this position can change the codon. If the second nucleotide “A” is replaced by “U”, the codon becomes $GUG$. The new codon $GUG$ encodes valine (Val) instead of glutamic acid.

The replacement of a polar, negatively charged glutamic acid with a non‑polar valine creates a hydrophobic patch on the hemoglobin surface. This altered β‑chain (Hemoglobin S) tends to stick to other hemoglobin molecules, leading to polymerization when deoxygenated.

Polymerized hemoglobin distorts the red blood cells into the characteristic sickle shape, which impairs their passage through capillaries and causes the clinical manifestations of sickle‑cell disease.

Therefore, the sixth mutant codon of the β‑globin gene that causes hemoglobin polymerization and a change in red blood‑cell shape is GUG.