Skip Navigation


Human Molecular Genetics Advance Access first published online on November 28, 2007
This version published online on December 6, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm350
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
17/6/789    most recent
ddm350v2
ddm350v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Modiano, D.
Right arrow Articles by Modiano, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Modiano, D.
Right arrow Articles by Modiano, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Haemoglobin S and haemoglobin C: ‘quick but costly’ versus ‘slow but gratis’ genetic adaptations to Plasmodium falciparum malaria

David Modiano#,1, Germana Bancone#,1, Bianca Maria Ciminelli2, Fiorenza Pompei2, Isa Blot3, Jacques Simporé4 and Guido Modiano*,2

1 Dipartimento di Scienze di Sanità Pubblica, University of Rome "La Sapienza", Italy 2 Dipartimento di Biologia, University of Rome "Tor Vergata", Italy 3 Centre National de Transfusion Sanguine, Ouagadougou, Burkina Faso 4 Centre de Recherche Biomoleculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso

* Corresponding author: Guido Modiano Facoltà di Scienze Matematiche, Fisiche e Naturali, Dipartimento di Biologia, Università di Roma "Tor Vergata", Via della Ricerca Scientifica 00133 Rome, Italy, Tel. +39-06-72594341; +39-06-72594330;, Fax +39-06-2023500, e-mail: modiano{at}uniroma2.it

Received September 20, 2007; Revised November 27, 2007; Accepted November 27, 2007

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 fourfold 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, consistently 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.

# These authors contributed equally to this work.

This paper has been versioned to correct the order in which the parts of the author names are displayed.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.