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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Haemoglobin S and haemoglobin C: 'Quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria
Human Molecular Genetics, Volume 17, No. 6, Year 2008
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Description
Haemoglobin S (HbS; β6Glu→Val) and HbC (β6Glu→Lys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox, we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (SBenin) and the C alleles are common (0.05 and 0.13). Here we show that: both C and SBenin are monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the SBenin allele (P = 0.003) implying higher antiquity; for a long initial lag period, the C alleles did apparently remain very few. These results, consistent with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a 'slow but gratis' genetic adaptation to malaria through a transient polymorphism, compared to the polycentric 'quick but costly' adaptation through balanced polymorphism of HbS. © The Author 2007. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Modiano, David
Italy, Rome
Sapienza Università Di Roma
Bancone, Germana
Italy, Rome
Sapienza Università Di Roma
Ciminelli, Bianca Maria
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Pompei, Fiorenza
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Blot, Isa
Burkina Faso, Ouagadougou
Centre National de Transfusion Sanguine
Simpore, J.
Burkina Faso, Ouagadougou
Centre de Recherche Biomoléculaire Pietro Annigoni Cerba
Modiano, Guido
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Statistics
Citations: 46
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1093/hmg/ddm350
ISSN:
09646906
e-ISSN:
14602083
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
Burkina Faso