Group identifies malaria resistance locus

Children from a village

outside of Nairobi, Kenya

Photo by Gabrielle Tenenbaum

Researchers say they have identified genetic variants that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the disease.

The variants are at a locus located next to a cluster of genes that are responsible for creating the receptors the malaria parasite Plasmodium falciparum uses to infect red blood cells.

The researchers described their findings in a letter to Nature.

“The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell,” said Dr Kevin Marsh, of the Kemri-Wellcome Research Programme in Kilifi, Kenya.

“This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”

For this study, Dr Marsh and his colleagues analyzed data from 8 different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia, and Tanzania.

They compared the DNA of 5633 children with severe malaria and the DNA of 5919 children without severe malaria. The researchers then replicated their key findings in a further 14,000 children.

The locus the team identified is near a cluster of genes that code for glycophorins, which are involved in P falciparum’s invasion of red blood cells.

The researchers also found an allele that was common among children in Kenya. Having this allele reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

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

Balancing selection

The newly identified malaria resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of 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.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history,” said Dr Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite’s invasion machinery. We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”

Children from a village

outside of Nairobi, Kenya

Photo by Gabrielle Tenenbaum

Researchers say they have identified genetic variants that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the disease.

The variants are at a locus located next to a cluster of genes that are responsible for creating the receptors the malaria parasite Plasmodium falciparum uses to infect red blood cells.

The researchers described their findings in a letter to Nature.

“The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell,” said Dr Kevin Marsh, of the Kemri-Wellcome Research Programme in Kilifi, Kenya.

“This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”

For this study, Dr Marsh and his colleagues analyzed data from 8 different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia, and Tanzania.

They compared the DNA of 5633 children with severe malaria and the DNA of 5919 children without severe malaria. The researchers then replicated their key findings in a further 14,000 children.

The locus the team identified is near a cluster of genes that code for glycophorins, which are involved in P falciparum’s invasion of red blood cells.

The researchers also found an allele that was common among children in Kenya. Having this allele reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

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

Balancing selection

The newly identified malaria resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of 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.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history,” said Dr Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite’s invasion machinery. We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”

Children from a village

outside of Nairobi, Kenya

Photo by Gabrielle Tenenbaum

Researchers say they have identified genetic variants that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the disease.

The variants are at a locus located next to a cluster of genes that are responsible for creating the receptors the malaria parasite Plasmodium falciparum uses to infect red blood cells.

The researchers described their findings in a letter to Nature.

“The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell,” said Dr Kevin Marsh, of the Kemri-Wellcome Research Programme in Kilifi, Kenya.

“This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”

For this study, Dr Marsh and his colleagues analyzed data from 8 different African countries: Burkina Faso, Cameroon, Ghana, Kenya, Malawi, Mali, The Gambia, and Tanzania.

They compared the DNA of 5633 children with severe malaria and the DNA of 5919 children without severe malaria. The researchers then replicated their key findings in a further 14,000 children.

The locus the team identified is near a cluster of genes that code for glycophorins, which are involved in P falciparum’s invasion of red blood cells.

The researchers also found an allele that was common among children in Kenya. Having this allele reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

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

Balancing selection

The newly identified malaria resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of 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.

“These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history,” said Dr Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite’s invasion machinery. We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”