Equilibrium frequencies of alpha-globin genes.

A mathematical model has been developed to study the mechanism of the maintenance of variable numbers of alpha-globin genes in human populations. The model incorporates both selection and unequal crossing-over. The selection is formulated so that a homozygous individual with a double deletion is lethal and a heterozygous individual with a deletion or addition of an alpha-globin gene in a chromosome has decreased fitness. This differs from the previous models of stabilizing selection studied by Ohta (1981) and Takahata (1981). The effect of random genetic drift on the alpha-thalassemia polymorphims has also been studied. It has been shown that, although the results obtained are compatible with the observation of the low frequency of triple alpha-globin loci, it cannot explain the high frequency of single and double deletions in Asian populations. For the latter case, some type of heterozygote advantage may be operating.