Human genetics — Sickle cell disease: Which change underlies this disorder at the level of hemoglobin chains?

Introduction / Context:Sickle cell disease is a classic example of a single-gene disorder with a well-defined molecular lesion that alters protein structure and causes profound clinical consequences including hemolytic anemia and vaso-occlusive crises.

Given Data / Assumptions:

• The disease affects hemoglobin structure and red blood cell deformability.
• Question asks which globin chain is mutated.
• Focus is on the genetic cause, not environmental infection.

Concept / Approach:The disease is caused by a point mutation in the HBB gene encoding the beta globin chain: a single nucleotide change substitutes valine for glutamic acid at position 6 (Glu6Val). This hydrophobic residue promotes polymerization of deoxygenated hemoglobin S, distorting red cells into a sickle shape.

Step-by-Step Solution:

Verification / Alternative check:Electrophoretic mobility (HbS differs from HbA) and DNA diagnostics (PCR/RFLP or sequencing) confirm the beta chain mutation.

Why Other Options Are Wrong:

• Alpha chain mutations cause alpha-thalassemia, not sickle cell disease.
• Parasitic infection (e.g., Plasmodium) causes malaria, not SCD; however, HbS heterozygosity confers partial malaria protection.
• “None of the above” conflicts with established genetics.

Common Pitfalls:Confusing sickle cell trait (heterozygous, typically asymptomatic) with disease (homozygous HbSS). Also mixing up thalassemias (reduced chain synthesis) with structural hemoglobinopathies.

Final Answer:A mutation in the beta chain of hemoglobin (HBB gene)