The population genetics of the haemoglobinopathies

The haemoglobinopathies are the commonest single-gene disorders known, almo st certainly because of the protection they provide against malaria, as att ested by a number of observations. The geographical distributions of malari a and haemoglobinopathies largely overlap, and microepidemiological surveys confirm the close relationship between them. For two of the commonest diso rders, haemoglobin S and alpha(+)-thalassaemia, there is also good clinical evidence for protection against malaria morbidity. However, not all the ev idence appears to support this view. In some parts of the world malaria and haemoglobinopathies are not, and never have been, coexistent. It is also d ifficult to explain why the majority of haemoglobinopathies appear to be re cent mutations and are regionally specific. Here we argue that these appare nt inconsistencies in the malaria hypothesis are the result of processes su ch as genetic drift and migration and of demographic changes that have occu rred during the past 10 000 years. When these factors are taken into accoun t, selection by malaria remains the force responsible for the prevalence of the haemoglobinopathies.