**Core Concept**
The mutation in the beta (β) chain of hemoglobin in sickle cell anemia is a classic example of a point mutation, leading to the substitution of glutamic acid with valine at position 6 of the β-globin chain. This substitution causes the hemoglobin to undergo a conformational change under deoxygenated conditions, resulting in the characteristic sickle-shaped erythrocytes.

**Why the Correct Answer is Right**
The mutation is due to a single nucleotide change from GAG (glutamic acid codon) to GTG (valine codon) at the sixth position of the β-globin gene. This point mutation is a result of a G-to-A transition at the nucleotide level, which is a common type of mutation that can occur during DNA replication. The substitution of valine for glutamic acid disrupts the normal hemoglobin structure and function, leading to the formation of sickle-shaped erythrocytes.

**Why Each Wrong Option is Incorrect**
**Option A:** Deletion of a nucleotide base is not the primary mechanism responsible for the sickle cell mutation.
**Option B:** A frameshift mutation would result in a completely different amino acid sequence, which is not the case in sickle cell anemia.
**Option C:** A point mutation involving a different amino acid substitution would not result in the characteristic sickling of erythrocytes.

**Clinical Pearl / High-Yield Fact**
The sickle cell mutation is a classic example of a hemoglobinopathy, which is a group of disorders caused by mutations in the genes encoding hemoglobin. Sickle cell anemia is a significant public health concern in regions where it is endemic, such as parts of Africa, the Middle East, and the Caribbean.

**Correct Answer:** C.