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Scientists identify genes reducing risk of severe malaria by 40% Scientists identify genes reducing risk of severe malaria by 40%
(about 4 hours later)
Genes have been identified in African children that reduce their risk of contracting severe malaria by up to 40%.Genes have been identified in African children that reduce their risk of contracting severe malaria by up to 40%.
The locus, or position of the resistant genes on the genome, was found near a cluster of genes called glycophorins, which are involved in the malaria parasite’s invasion of red blood cells.The locus, or position of the resistant genes on the genome, was found near a cluster of genes called glycophorins, which are involved in the malaria parasite’s invasion of red blood cells.
The findings, published in Nature on Wednesday, could help to evaluate individual and population risk of the disease, which is estimated to have killed 584,000 people – 90% of them under five in Africa – and infected 198 million in 2013.The findings, published in Nature on Wednesday, could help to evaluate individual and population risk of the disease, which is estimated to have killed 584,000 people – 90% of them under five in Africa – and infected 198 million in 2013.
A particularly strongly protective variant, was found most commonly among children in Kenya, where it reduced the risk of severe malaria by about 40%, with a slightly smaller effect across the other African populations studied. A particularly strongly protective variant was found most commonly among children in Kenya, where it reduced the risk of severe malaria by about 40%, with a slightly smaller effect across the other African populations studied.
“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,” said one of the lead authors of the paper, Prof Dominic Kwiatkowski, of the Wellcome Trust’s Sanger Institute and Centre for Human Genetics.“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,” said one of the lead authors of the paper, Prof Dominic Kwiatkowski, of the Wellcome Trust’s Sanger Institute and Centre for Human Genetics.
“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 characterise these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”“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 characterise these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act.”
The research was conducted by MalariaGen, an international network of scientists and clinicians in Africa, Asia and other malaria-endemic regions of the world that is largely funded by the Wellcome Trust.The research was conducted by MalariaGen, an international network of scientists and clinicians in Africa, Asia and other malaria-endemic regions of the world that is largely funded by the Wellcome Trust.
Analysing data from eight African countries – Burkina Faso, Cameroon, Ghana, Kenya, Mali, the Gambia and Tanzania – the researchers examined common genetic variants in individuals to see if any variant was associated with a trait. Analysing data from eight African countries – Malawi, Burkina Faso, Cameroon, Ghana, Kenya, Mali, the Gambia and Tanzania – the researchers examined common genetic variants in individuals to see if any variant was associated with a trait.
The genome-wide association study compared the DNA of 5,633 children who had severe malaria with the DNA of 5,919 who did not. The researchers then replicated their key findings in a further 14,000 children.The genome-wide association study compared the DNA of 5,633 children who had severe malaria with the DNA of 5,919 who did not. The researchers then replicated their key findings in a further 14,000 children.
The researchers believe the differences in the risk of severe malaria between different populations in the eight countries, could be down to the genetic features of the local malaria parasite in east Africa. The researchers believe the differences in the risk of severe malaria between different populations in the eight countries could be down to the genetic features of the local malaria parasite in east Africa.
Prof Kevin Marsh, a co-author from the Kemri-Wellcome research programme in Kilifi, Kenya, said: “This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”Prof Kevin Marsh, a co-author from the Kemri-Wellcome research programme in Kilifi, Kenya, said: “This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.”
The authors said that although many different malaria resistance loci have been postulated over the years, this was one of few that have stood up to stringent testing in a large multi-centre study. Others include the genes for sickle cell and the type O blood group. The authors said that although many different malaria resistance loci have been postulated over the years, this was one of few that have stood up to stringent testing in a large multi-centre study. Others include the genes for sickle-cell anaemia and the type O blood group.
The newly discovered genetic resistance locus is believed to have been present in some variation for millions of years, as it lies within a region of the genome where humans and chimpanzees have been know to share particular variations of DNA.The newly discovered genetic resistance locus is believed to have been present in some variation for millions of years, as it lies within a region of the genome where humans and chimpanzees have been know to share particular variations of DNA.
This also suggests that it is the subject of “balancing selection”, where a genetic variant is maintained and not reduced over time – as is normal – because it confers a health benefit. However, it is only carried by a proportion of the population because it also has some other negative consequences.This also suggests that it is the subject of “balancing selection”, where a genetic variant is maintained and not reduced over time – as is normal – because it confers a health benefit. However, it is only carried by a proportion of the population because it also has some other negative consequences.