Question

In sickle cell anaemia:

• A. Substitution of glutamic acid by valine at the sixth position of the α-chain of haemoglobin.
• B. The mutant haemoglobin molecule undergoes polymerization under low oxygen tension, causing the change in the shape of RBC.
• C. The mutant haemoglobin molecule undergoes high oxygen tension, causing the change in the shape of RBC.
• D. α-globin chain is modified.

Answer 1

Answer: (B)

Sickle Cell Anemia:
Cause: As it is autosomal recessive disease, therefore it can be transmitted from parents to the offspring when both male and female individuals are carriers (heterozygous) for the gene. The disease is controlled by a single pair of alleles, Hb^A and Hb^S. Thus three genotypes are possible in population.
(a) Hb^AHb^A (Normal, homozygous)
(b) Hb^AHb^S (Normal, carrier)
(c) Hb^SHb^S (Diseased, die before attaining maturity)
The genes are located on chromosome number 11. Heterozygous (Hb^AHb^S) individuals are carriers of the disease and there is a 50% probability of transmission of the mutant gene to the offsprings.
The disease/defect is caused by a mutation (transversion) of the gene controlling β-chain of haemoglobin. The mutated gene is called Hb^S. Hb^S cause one change in the amino acid sequence of β-chain. It replaces glutamic acid (Glu) present at the 6th position of the β-chain by amino acid valine (Val).

Symptoms: The mutant haemoglobin molecule undergoes polymerization under low O2 tension causing the change in the shape of the RBC from biconcave disc to the elongated sickle-like structure. Such sickle cells are not able to pass through the blood capillaries, causing the deposition of sickle cell RBC near small capillaries. The reason for the deposition is lost of elasticity due to the replacement of negative aa- by neutral aa-. The breakdown of RBCs leads to hemolytic anemia.
Treatment: Repeated blood transfusion.