Sickle cell variants descended from this ancestral haplotype comprise five haplotypes named after toponyms or ethnolinguistic groups (the Arabian/Indian, Benin, Cameroon, Central African Republic/Bantu, and Senegal variants), and another designation earmarked for atypical sickle-cell haplotypes. Their clinical importance is because some are associated with higher HbF levels (e.g., Senegal and Saudi-Asian variants tend to have milder disease). In athletes
In some cases, athletes with sickle cell trait do not achieve the same level of performance as elite athletes with normal hemoglobin (AA). Athletes with sickle cell trait and their instructors must be aware of the dangers of the condition during anaerobic exertion especially in hot and dehydrated conditions. In rare cases, exercise-induced dehydration or exhaustion may cause healthy red blood cells to turn sickle-shaped, which can cause death during sporting activities.While more research is necessary on the topic, the correlation found between individuals with sickle cell trait and an increased risk of sudden death appears to be related to microcirculatory disorders, during exercise. In recent years the NCAA has partnered with the ACSM and issued a joint statement, warning athletes about both the prevalence and the potential risk factors of sickle cell trait.
Sickle cell anemia affects about 72,000 people in the United States. Most Americans who have sickle cell anemia are of African descent. The disease also affects Americans from the Caribbean, Central America, and parts of South America, Turkey, Greece, Italy, the Middle East and East India. Sickle-cell disease and the associated trait are most prevalent in Africa and Central America, which is attributed to natural selection:  the sickle-cell trait confers a survival advantage in areas with a high occurrence of malaria, which has a high death rate among individuals without the trait.There also have been studies that show changes in the globin genes. There have been noted changes in the beta-globin sequence, to what is known as the sickle hemoglobin. The significance of the sickle-cell trait is that it does not show any symptoms, nor does it cause any major difference in blood cell count. The trait confers about 30% protection against malaria and its occurrence appears to have risen tremendously in Africa, India and the Middle East. Some findings also show the reduction of the sickle-cell trait in those who retain much more fetal hemoglobin than usual in adulthood. Fetal hemoglobin likely plays a role in the prevention of sickling. Elevated fetal hemoglobin levels have been observed in populations where sickle-cell disease is prevalent. Whole genome sequence analysis has identified a single origin of the sickle trait, with one haplotype ancestral to all sickle-cell variants. This haplotype is thought to have originated in the Sahara during the Holocene Wet Phase around 7,300 years ago.