The relationship between blood groups and disease

The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. Red cells lacking or having altered forms of blood group-active molecules are commonly found in regions of the world in which malaria is endemic, notably the Fy(a-b-) phenotype and the S-s- phenotype in Africa and the Ge- and SAO phenotypes in South East Asia. Founder effects provide a more convincing explanation for the distribution of the D- phenotype and the occurrence of hemolytic disease of the fetus and newborn in Europe and Central Asia. (Blood. 2010;115(23):4635-4643)