Which of the following is caused due to substitution of glutamic acid to valine on 6th position of $β$-globin chain of Haemoglobin molecule?

Sickle cell anaemia

The correct answer is Option (3) → Sickle cell anaemia

Sickle-cell anaemia: This is an autosome-linked recessive trait that can be transmitted from parents to the offspring when both the partners are carrier for the gene (or heterozygous). The disease is controlled by a single pair of allele, Hb^A and Hb^S. Out of the three possible genotypes, only homozygous individuals for Hb^S (Hb^SHb^S) show the diseased phenotype. Heterozygous (Hb^AHb^S) individuals appear apparently unaffected but they are carrier of the disease as there is 50 per cent probability of transmission of the mutant gene to the progeny, thus exhibiting sickle-cell trait .

The defect 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 substitution of amino acid in the globin protein results due to the single base substitution at the sixth codon of the beta-globin gene from GAG to GUG. The mutant haemoglobin molecule undergoes polymerisation under low oxygen tension causing the change in the shape of the RBC from a biconcave disc to an elongated sickle-like structure.