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Genes that protect African children from malaria identified

Staff writer |
Variations in DNA at a specific location, locus, on the genome that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the life-threatening disease, have been identified in the largest genetic association study.

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The findings detail a new gene locus that can explain why, in communities where everyone is constantly exposed to malaria, some children develop severe malaria and others don’t. Now, researchers can be sure that this particular stretch of our DNA plays a crucial role in the progression of the disease.

The research was conducted by MalariaGEN, an international network of scientists and clinicians spread across Africa, Asia and other malaria-endemic regions of the world, largely funded by the Wellcome Trust. In this study they analysed data from eight different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia and Tanzania.

To identify the new locus, researchers performed a genome-wide association study (GWAS) that compared the DNA of 5,633 children with severe malaria with the DNA of 5,919 children without severe malaria. They then replicated their key findings in a further 14,000 children.

The new locus they have identified is near a cluster of genes which code for proteins called ‘glycophorins’ that are involved in the malaria parasite’s invasion of red blood cells.

Although many different malaria resistance loci have been postulated over the years, this is one of very few that have stood up to stringent testing in a large multi-centre study; the others include the genes for sickle cell and the O blood group.

A particularly strongly-protective variant, known in genetics as an allele, was found most commonly among children in Kenya in East Africa. Having this allele reduces the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

The authors speculate that this difference between populations could be due to the genetic features of the local malaria parasite in East Africa.

Intriguingly, the new genetic resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of DNA variants, known as haplotypes. This indicates that some of the variation seen in contemporary humans has been present for millions of years.

The finding also suggests that this region of the genome is the subject of "balancing selection".

Balancing selection happens when a particular genetic variant evolves because it confers health benefits, but it is carried by only a proportion of the population because it also has damaging consequences.

The classic example is the sickle cell gene – people with one copy of the gene are strongly protected against malaria but those with two copies of the gene develop a life-threatening condition known as sickle-cell disease.

Professor Dominic Kwiatkowski, one of the lead authors of the paper, from the Wellcome Trust Sanger Institute and the Wellcome Trust Centre for Human Genetics, said: “We can now say, unequivocally, that genetic variations in this region of the human genome provide strong protection against severe malaria in real-world settings, making a difference to whether a child lives or dies.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history.


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