Consanguinity affects selection of alpha-thalassemia genotypes and the size of populations under selection pressure from malaria

Background: In populations with α+-thalassemia gene deletion, the practice of consanguineous marriages is common. Aim: The study explored the impact of consanguinity (inbreeding) on the selection of α+-thalassemia genotypes in a computer model. Method: In a population under selection pressure from malaria, a single protective mutation (-α/αα genotype) was introduced among normal genotypes (αα/αα), and mating allowed to proceed. Heterozygote (-α/αα) and homozygote (-α/-α) children were 1.5 and 2.5 times more likely to survive malaria than those with normal genotypes. Using different coefficients of inbreeding (F, range 0-0.12), we examined the effect of population size, and the mean number of generations required for the homozygote frequency to reach 0.5. Results: On average, consanguineous populations were larger than randomly mating populations and the size was directly proportional to F. In more inbred populations,-α/-α homozygotes reached a frequency of 0.5 faster than in less inbred populations. As the frequency of the α+-thalassemia allele in a population increases, however, the positive effect of inbreeding on the population growth decreases. Conclusion: Under selection pressure from malaria, consanguinity may increase the speed of selection of-α/-α homozygotes and provide an advantage regarding population growth over non-consanguineous populations.