The effect on the equilibrium sickle cell allele frequency of the probable protection conferred by malaria and sickle cell gene against other infectious diseases

疟疾和镰状细胞基因对其他传染病的可能保护作用对镰状细胞等位基因平衡频率的影响

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Abstract

If a mutated gene with heterozygous advantage against malaria, e.g., hemoglobin S (HbS) gene, is introduced in a small tribe, the gene (allele) frequency (f(gene)) increases until it reaches a steady state value (f(eq)) where the total mortality from malaria and sickle cell disease is a minimum. This is a classic example of balanced-polymorphism named malaria hypothesis. In a previous in silico study, assuming realistic initial conditions, it has been shown that the f(eq) is around 14%, far less than the f(gene) observed in certain parts of Africa, 24%. It seems that the malaria hypothesis, per se, could not explain such a high f(gene), unless it is assumed that malaria and HbS gene can provide protection against other diseases. Using Monte-Carlo simulation, the current study was conducted to examine the effect on f(eq) of five scenarios was examined. The studied scenarios consisted of different combinations of mortality of other diseases and the possible amounts of protections conferred by malaria and HbS gene against the diseases. Taking into account other diseases causing mortality in the population makes the f(gene) rate of change steeper over generations. f(eq) is an increasing function of the amount of protection conferred by HbS gene against other diseases. The effect of protection provided by malaria against other diseases on f(eq), is however, variable-depending on the amount of protection conferred by HbS gene against other diseases, it may increase or decrease f(eq). If malaria and HbS gene provide protections of 1.5-fold and threefold against other diseases, respectively, the f(eq) is around 24%, the amount reported in certain tribes of Africa. Under certain scenarios, the f(eq) attained is even higher.

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