Sickle Cell Anemia

Sickle cell anemia is, unfortunately, a perfect example of how dangerous a single base substitution can be.

In the population, the major form of hemoglobin is hemoglobin A, which contains two identical α chains and two identical β chains. However, patients suffering from sickle cell anemia have a different type of hemoglobin - hemoglobin S.

Hemoglobin S differs from hemoglobin A in the sixth codon of the β chain, which contains a base substitution GAG → GTG. The codon originally specified glutamic acid but because of the mutation, it specifies valine. This is a missense mutation, a base substitution that changes the codon in a way that a different amino acid is synthesized.

This change of a single nucleotide results in the synthesis of hemoglobin S. Patients with hemoglobin S have an abnormal shape of red blood cells, which resembles a sickle, hence the name sickle cell anemia. These sickle-shaped red blood cells do not transport oxygen efficiently and cause severe complications.

References:
Klug, W. S., Cummings, M. R., Spencer, C. A., Palladino, M. A., & Killian, D. (2019). Concepts of Genetics. Pearson.
Pierce, B. A. (2019). Genetics: A Conceptual Approach (Seventh ed.). W. H. Freeman.
Snustad, D. P., & Simmons, M. J. (2012). Principles of Genetics. Wiley