What Mutation Causes Sickle Cell Anemia?

Concept of Sickle cell anemia Surrounded Around the Earth

Sickle cell anemia is caused by a specific genetic mutation in the HBB gene (hemoglobin beta gene) located on chromosome 11. This mutation results in the production of abnormal hemoglobin, known as hemoglobin S (HbS), instead of the normal adult hemoglobin (HbA). The mutation responsible for sickle cell anemia is known as a point mutation, where a single nucleotide base in the DNA sequence is altered.

In sickle cell anemia, a single DNA base change in the HBB gene replaces adenine (A) with thymine (T) in the sixth codon of the gene. This mutation leads to the substitution of a glutamic acid amino acid with a valine amino acid in the beta-globin chain of hemoglobin. This change results in the formation of hemoglobin S (HbS), which is less soluble and more prone to polymerization in low-oxygen conditions.

The polymerization of HbS causes red blood cells to change from their normal, flexible, and biconcave disc shape into a characteristic sickle or crescent shape. These deformed red blood cells can lead to blockages in blood vessels, causing pain, organ damage, and a range of health problems associated with sickle cell disease.

Sickle cell anemia is an inherited condition, which means that an individual must inherit two copies of the HbS mutation (one from each parent) to develop the disease. Those who inherit one normal HBB gene and one HbS gene are considered carriers and have a condition known as sickle cell trait. Carriers of the trait are typically asymptomatic and do not have the severe symptoms associated with sickle cell anemia.