Which one of the following disorders is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth position of the beta globin chain of the haemoglobin molecule ?

The question asks which disorder is caused by the substitution of glutamic acid (Glu) by valine (Val) at the sixth position of the β‑globin chain of the hemoglobin molecule.

Hemoglobin is a protein composed of two α‑chains and two β‑chains. Each chain is a sequence of amino acids. In normal adult hemoglobin (HbA), the sixth amino acid in the β‑chain is glutamic acid, which is negatively charged and interacts well with water, keeping the molecule soluble.

When a point mutation occurs in the β‑globin gene (HBB), the codon for glutamic acid (GAG) is changed to a codon for valine (GTG). This replaces a polar, charged residue with a non‑polar, hydrophobic one at position 6.

This single‑letter change (Glu → Val) alters the physical properties of the hemoglobin molecule. Under low‑oxygen conditions, the mutated hemoglobin (HbS) tends to polymerize, causing red blood cells to become rigid and assume a sickle shape.

The clinical condition associated with this specific mutation is sickle‑cell anaemia. It is characterized by hemolytic anemia, pain crises, and various complications due to the distorted red cells.

Therefore, among the listed options, the disorder caused by the Glu→Val substitution at position 6 of the β‑globin chain is Sickle‑cell anaemia.