Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that allele (is homozygous). Those who are heterozygous for the sickle cell allele produce both normal and abnormal hemoglobin (the two alleles are codominant with respect to the actual concentration of hemoglobin in the circulating cells). Sickle cell disease is a blood disorder wherein there is a single amino acid substitution in the hemoglobin protein of the red blood cells, which causes these cells to assume a sickle shape, especially when under low oxygen tension. Sickling and sickle cell disease also confer some resistance to malaria parasitization of red blood cells, so that individuals with sickle-cell trait (heterozygotes) have a selective advantage in environments where malaria is present. Symptoms and signs Sickle cell trait is a hemoglobin genotype AS and is generally regarded as a benign condition. However, individuals with sickle cell trait may have rare complications. For example, in November 2010, Dr. Jeffery K. Taubenberger of the National Institutes of Health discovered the earliest proof of sickle-cell disease while looking for the virus of the 1918 flu during the autopsy of an African-American soldier. Taubenberger's autopsy results showed that the soldier had had a sickle-cell crisis that contributed to his death even though he had only one copy of the gene. There have been calls to reclassify sickle cell trait as a disease state, based on its malignant clinical presentations. Significance may be greater during exercise. Association with other medical conditions Malaria The sickle cell trait provides a survival advantage against malaria fatality over people with normal hemoglobin in regions where malaria is endemic. The trait is known to cause significantly fewer deaths due to malaria, especially when Plasmodium falciparum is the causative organism. This is a prime example of natural selection, evidenced by the fact that the geographical distribution of the gene for hemoglobin S and the distribution of malaria in Africa virtually overlap. Because of the unique survival advantage, people with the trait become increasingly numerous as the number of malaria-infected people increases. Conversely, people who have normal hemoglobin are more likely to succumb to the complications of malaria. The way in which sickle cell protects against malaria is attributed to several different things. One