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

Abstract

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.

• Consanguinity
• alpha-thalassemia
• malaria
• inbreeding
• computer modeling