**Core Concept**
Sickle cell anemia is a genetic disorder caused by a mutation in the HBB gene, leading to the production of abnormal hemoglobin called hemoglobin S (HbS). This mutation affects the structure of hemoglobin, changing its function and leading to the characteristic sickling of red blood cells.

**Why the Correct Answer is Right**
The mutation in the HBB gene results in a substitution of glutamic acid with valine at position 6 of the beta-globin chain. This substitution causes the hemoglobin to polymerize under low oxygen conditions, leading to the formation of fibers within the red blood cell. These fibers cause the cell to change shape, becoming sickle-shaped and leading to vaso-occlusive crises and other complications. The polymerization of hemoglobin is a result of the altered hydrophobic interaction between the valine residue and other hemoglobin molecules.

**Why Each Wrong Option is Incorrect**
**Option A:** Oxygen affinity - Incorrect because sickle cell anemia does not affect the oxygen affinity of hemoglobin, which is determined by the Bohr effect and 2,3-bisphosphoglycerate levels.

**Option B:** Thalassemia - Incorrect because thalassemia is a separate genetic disorder affecting hemoglobin production, characterized by reduced beta-globin chain synthesis.

**Option C:** Methemoglobinemia - Incorrect because methemoglobinemia is a disorder caused by abnormal hemoglobin that cannot bind oxygen, which is not the case in sickle cell anemia.

**Clinical Pearl / High-Yield Fact**
Sickle cell anemia is a classic example of a genetic disorder that affects hemoglobin function, leading to a cascade of downstream effects on red blood cell morphology and function.

**Correct Answer:** C. Polymerization of hemoglobin.