Malaria Protection Linked to Receptor Mutations

Resistance to malaria in some parts of Africa has been linked to mutations in the genes that code for the glycophorin receptors on the surface of the red blood cells that are attacked and invaded by the parasite.

The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. To better understand these interactions, an international research conglomerate - coordinated by the Wellcome Trust Sanger Institute - investigated the glycophorin area of the genome in more detail than ever before using new whole-genome sequence data from healthy and ill volunteers in the Gambia, Burkina Faso, Cameroon, and Tanzania.

The investigators reported in the May 18, 2017, online edition of the journal Science that they had identified a diverse array of large copy number variants affecting the host invasion receptor genes GYPA (Glycophorin A) and GYPB (Glycophorin B). They found that a nearby association with severe malaria was explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encoded a serologically distinct blood group antigen known as Dantu.

Dantu is a minor member of the MNS human blood group system, which is a based on the two glycophorin genes on chromosome four. There are 46 antigens in the system; the most common are called M, N, S, s, and U. The Dantu variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya, yet it appears to be absent from West Africa.

Senior author Dr. Dominic Kwiatkowski, professor of tropical pediatrics at the Wellcome Trust Sanger Institute, said, "We are starting to find that the glycophorin region of the genome has an important role in protecting people against malaria. Our discovery that a specific variant of glycophorin invasion receptors can give substantial protection against severe malaria will hopefully inspire further research on exactly how Plasmodium falciparum invade red blood cells. This could also help us discover novel parasite weaknesses that could be exploited in future interventions against this deadly disease."