Question

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

• A. CAG
• B. GUG
• C. AUG
• D. GAG

Hint:

Logic Tip: Remember the sequence of the disaster: A changes to T (in DNA) $\rightarrow$ A changes to U (in mRNA) $\rightarrow$ GAG becomes GUG $\rightarrow$ Glutamic acid becomes Valine $\rightarrow$ RBC sickles.

Answer 1

The Correct Option is B

Concept:
Sickle-cell anaemia is a classic example of a genetic disorder caused by a point mutation. It is an autosome-linked recessive trait where a single base substitution alters the structure and function of the haemoglobin molecule, ultimately distorting the shape of the red blood cell (RBC).
Step 1:
Normal adult haemoglobin (HbA) consists of two alpha and two beta polypeptide chains. The sixth amino acid position of the normal beta-globin chain is occupied by Glutamic acid (Glu).
Step 2:
In a healthy individual, the mRNA codon that specifies Glutamic acid at this crucial sixth position is GAG.
Step 3:
Sickle-cell anaemia is caused by a transversion mutation. A single nitrogenous base in the DNA sequence is substituted: Adenine (A) is replaced by Thymine (T) in the coding strand.
Step 4:
Because of this DNA substitution, the resulting mRNA transcribed from the mutant gene will have a Uracil (U) instead of an Adenine (A). Therefore, the normal GAG codon is mutated into the GUG codon.
Step 5:
The mutant codon GUG codes for a completely different amino acid: Valine (Val). Valine is hydrophobic, unlike the hydrophilic Glutamic acid. Under low oxygen tension, these hydrophobic valine residues stick together, causing the haemoglobin molecules to polymerize and forcing the RBC into a rigid, sickle-like shape.
Step 6:
The mutant codon responsible for this cascade of events is GUG, making Option (2) the correct answer.