HbS (sickle haemoglobin) polymerises in the deoxygenated state. The single amino acid substitution responsible is:

• A Glu→Val at position 6 of the beta-globin chain ✓
• B Glu→Lys at position 6 of the beta-globin chain
• C His→Tyr at position 92 of the alpha-globin chain
• D Val→Glu at position 1 of the beta-globin chain

Explanation

Sickle cell disease results from a GAG→GTG mutation in codon 6 of the HbB gene, substituting glutamate (charged, hydrophilic) with valine (nonpolar, hydrophobic) in the beta-globin chain; in the deoxy conformation, the valine at position 6 fits into a complementary hydrophobic pocket on an adjacent HbS molecule (involving Val F9 and Leu G16), driving polymer formation and sickling. Glu→Lys at the same position is HbC. His92 mutations affect oxygen affinity but are not sickle cell.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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