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

Step 1 : Understanding the Question:
This question focuses on the molecular basis of Sickle Cell Anemia. We must identify the specific {mutated} mRNA codon at the sixth position of the beta-globin chain that leads to the disease.
Step 2 : Key Formulas and Approach:
1. Normal DNA: CTC/GAG $\rightarrow$ Normal mRNA: GAG (Glutamic acid).
2. Mutated DNA: CAC/GTG $\rightarrow$ Mutated mRNA: GUG (Valine).
3. We are looking specifically for the mutant mRNA codon.
Step 3 : Detailed Explanation:

Healthy State: In a normal individual, the sixth codon of the mRNA for the beta-globin chain is GAG. This codon specifies the amino acid Glutamic Acid, which is hydrophilic and keeps the hemoglobin molecules soluble.

Point Mutation: Sickle cell anemia is caused by a single base substitution (transversion) in the DNA. The base Adenine is replaced by Thymine at the middle position of the codon ($A \rightarrow T$).

Consequence on mRNA: This DNA mutation results in the transcription of a GUG codon in the mRNA instead of the original GAG.

Structural Outcome: The GUG codon codes for Valine, which is hydrophobic. Under low oxygen tension, these hydrophobic mutant hemoglobin molecules polymerize into long fibers, forcing the RBC to take a rigid, sickle shape.

Step 4 : Final Answer:
The mutant codon responsible for the polymerization of hemoglobin is GUG. This corresponds to option (B).