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تسجيل

Genetic Epidemiology of the Sickle Gene

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P599

2026-05-09

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Heterozygotes for the sickle gene (sickle trait or HbAS) who are generally asymptomatic have a substantial survival advantage in malaria-endemic environments. HbAS individuals are not only protected from effects of severe Plasmodium falciparum malaria but also from consequences of malaria infection, including malnutrition and bacterial infections, a result of which is the very high population frequencies of 10% to 20% in historically malaria-endemic regions.  However, with the increased premature death rate of patients with SCD, the sickle cell gene represents a balanced polymorphism.  Early genetic studies based on β S haplotypes generated by restriction fragment length polymorphisms in the globin-gene cluster on chromosome 11, hypothesized that the β S mutation arose and amplified separately in at least four African locations between 2000 and 4000 years ago and once in the Middle East or India.  Recent studies based on whole genome sequence data and phased single nucleotide polymorphisms (SNPs), however, suggest that rs334 arose once approximately 7300 years ago in West Africa on HAP1 haplotype from which the other haplotypes were then derived.  Another study based on sequencing of the β -globin gene (HBB) cluster supported a single origin of rs334 but estimated an earlier origin about 22,000 years ago.