Global Map of the Sickle Cell Gene Supports 'Malaria Hypothesis'
ScienceDaily (Nov. 2, 2010) — At a global scale, the sickle cell gene is most commonly found in areas with historically high levels of malaria, adding geographical support to the hypothesis that the gene, while potentially deadly, avoids disappearing through natural selection by providing protection against malaria.
These are maps showing the distribution of the HbS "sickle cell gene" and the endemicity of malaria. (Credit: Malaria Atlas Project)
In a study funded by the Wellcome Trust, geographers, biologists and statisticians at the University of Oxford, together with colleagues from the KEMRI-Wellcome Trust Programme in Kenya, have produced the first detailed global map showing the distribution of the sickle cell gene. The results are published in the journal Nature Communications.
Haemoglobin S (HbS) is known to cause sickle cell disease, which is usually fatal if untreated. Natural selection suggests that such a disadvantageous gene should not survive, yet it is common in people of African, Mediterranean and Indian origin.
More than sixty years ago, researchers observed that the sickle cell gene tended to be more common in populations living in, or originating from, areas of high malaria prevalence. This led to the 'malaria hypothesis', which suggested that, although deadly when inherited from both parents, the gene provided a degree of protection from malaria in children inheriting it from just one parent. This protective advantage was strong enough in areas of intense malaria transmission for the gene to survive.
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Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis
Frédéric B. Piel, Anand P. Patil, Rosalind E. Howes, Oscar A. Nyangiri, Peter W. Gething, Thomas N. Williams, David J. Weatherall & Simon I. Hay
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Nature Communications 1 ,
Article number: 104 doi:10.1038/ncomms1104
Received 01 June 2010 Accepted 01 October 2010 Published 02 November 2010
Abstract
It has been 100 years since the first report of sickle haemoglobin (HbS). More than 50 years ago, it was suggested that the gene responsible for this disorder could reach high frequencies because of resistance conferred against malaria by the heterozygous carrier state. This traditional example of balancing selection is known as the 'malaria hypothesis'. However, the geographical relationship between the transmission intensity of malaria and associated HbS burden has never been formally investigated on a global scale. Here, we use a comprehensive data assembly of HbS allele frequencies to generate the first evidence-based map of the worldwide distribution of the gene in a Bayesian geostatistical framework. We compare this map with the pre-intervention distribution of malaria endemicity, using a novel geostatistical area-mean comparison. We find geographical support for the malaria hypothesis globally; the relationship is relatively strong in Africa but cannot be resolved in the Americas or in Asia.
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