Q.1 Sickle cell anemia is a disease characterised by the patient’s erythrocyte, having a characteristic sickle or crescent shape.
Select the correct statement hut the disease –
l. Deletion of glutamic acid from the 6th position of ß-chain.
2 Substitution of hydrophobic residue by a polar one.
3. Substitlon of polar residue by a hydrophobic one
4 Substitution of valine residue by a glutamic acid one.

Sickle cell anemia results from a specific point mutation in the β-globin gene, where glutamic acid (polar) at position 6 is replaced by valine (hydrophobic), causing red blood cells to sickle under low oxygen. The correct option is 3: Substitution of polar residue by a hydrophobic one.

Question Breakdown

This multiple-choice question tests knowledge of the molecular basis of sickle cell anemia, a common topic in exams like GATE Life Sciences.

• Option 1: Deletion of glutamic acid from the 6th position of β-chain. Incorrect—it’s a substitution (point mutation), not a deletion, which would shorten the protein chain.​

• Option 2: Substitution of hydrophobic residue by a polar one. Incorrect—this reverses the actual change; the mutation replaces polar glutamic acid with hydrophobic valine.

• Option 3: Substitution of polar residue by a hydrophobic one. Correct—glutamic acid (polar, charged) at β6 becomes valine (hydrophobic, nonpolar), altering hemoglobin’s surface and promoting polymerization in low oxygen.

• Option 4: Substitution of valine residue by a glutamic acid one. Incorrect—this describes the reverse mutation restoring normal hemoglobin, not causing the disease.​

Introduction to Sickle Cell Anemia Mutation

Sickle cell anemia mutation transforms normal round erythrocytes into sickle-shaped ones due to a single nucleotide change in the HBB gene. This sickle cell anemia mutation—specifically, substitution of polar glutamic acid by hydrophobic valine at the 6th position of the β-globin chain—leads to hemoglobin S (HbS) polymerization under deoxygenated conditions. Common in competitive exams like GATE Life Sciences, grasping this sickle cell anemia mutation helps explain the disease’s pathology.

Molecular Cause of the Mutation

The sickle cell anemia mutation is a point mutation (GAG to GTG) in codon 6 of the β-globin gene, replacing glutamic acid (Glu, polar and hydrophilic) with valine (Val, hydrophobic and nonpolar). This alters hemoglobin’s surface hydrophobicity, causing HbS molecules to stick together in low-oxygen states, distorting red blood cells into crescents. Homozygous individuals (HbSS) suffer severe symptoms like hemolytic anemia and vaso-occlusion.

Why Option 3 is Correct

In exam contexts, option 3 precisely describes the sickle cell anemia mutation: substitution of polar residue (glutamic acid) by a hydrophobic one (valine). Other options fail—option 1 suggests deletion (wrong type), option 2 reverses polarity, and option 4 inverts the change. This distinction is key for GATE Life Sciences PYQs on hemoglobinopathies.

Symptoms and Inheritance

Sickled cells block vessels, causing pain crises, fatigue, infections, and organ damage. Autosomal recessive inheritance means carriers (HbAS) are asymptomatic but pass the trait; two mutated alleles cause full disease. Hydroxyurea therapy boosts fetal hemoglobin to mitigate effects.