Sickle cell anemia is caused by a specific type of mutation known as a point mutation. This occurs in the HBB gene, which provides instructions for making a component of hemoglobin, the protein in red blood cells that carries oxygen.
In sickle cell anemia, the mutation is a substitution of a single nucleotide in the DNA sequence: an adenine (A) is replaced by thymine (T) at the sixth codon of the β-globin gene. This change alters the corresponding amino acid in the hemoglobin protein, substituting valine for glutamic acid. The resulting abnormal hemoglobin, called hemoglobin S (HbS), can cause red blood cells to become rigid and sickle-shaped, leading to various complications related to blood flow and oxygen delivery in the body.