DUP4 is a complex structural genomic variant that carries extra copies of a glycophorin A-glycophorin B fusion gene and has a dramatic effect on malaria risk by reducing the risk of severe malaria by up to 40%.
By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy-number variants affecting the host invasion receptor genes <i>GYPA</i> and <i>GYPB</i> We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of <i>GYPB</i> and gain of two <i>GYPB-A</i> hybrid genes, which encode a serologically distinct blood group antigen known as Dantu.