Heterozygous individuals are usually healthy, but they may suffer some symptoms of sickle cell anemia under conditions of low blood oxygen, such as high elevation. Because both forms of hemoglobin are made in heterozygotes, the A and S alleles are codominant. In the United States, about 1 in 500 African-Americans develops sickle cell anemia. In Africa, about 1 in 100 individuals develops the disease. The answer is related to another potentially fatal disease, malaria.
Malaria is characterized by chills and fever, vomiting, and severe headaches.
Anemia and death may result. When malarial parasites invade the bloodstream, the red cells that contain defective hemoglobin become sickled and die, trapping the parasites inside them and reducing infection. Death of AA homozygotes results in removal of A alleles from the gene pool. Individuals with the AS genotype do not develop sickle cell anemia and have less chance of contracting malaria. They are able to survive and reproduce in malaria-infected regions.