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Infection and Immunity, February 2005, p. 953-955, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.953-955.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inverse Associations of Human Leukocyte Antigen and Malaria Parasite Types in Two West African Populations

Karen Young,1 Angela Frodsham,1 Ogobara K. Doumbo,2 Sunetra Gupta,3 Amagana Dolo,2 Jiang Ting Hu,1 Kathryn J. H. Robson,4,5 Andrea Crisanti,6 Adrian V. S. Hill,1* and Sarah C. Gilbert1

Wellcome Trust Centre for Human Genetics,1 Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology,3 M.R.C. Molecular Haematology Unit, Institute of Molecular Medicine, Oxford University,4 John Radcliffe Hospital, Oxford,5 Department of Pure and Applied Biology, Imperial College, London, United Kingdom,6 Departement d'Epidemiologie des Affections Parasitaires, University of Mali, Bamako, Mali2

Received 29 February 2004/ Returned for modification 22 April 2004/ Accepted 25 October 2004

Differences in allelic associations between populations continue to cause difficulties in the mapping and identification of susceptibility genes for complex polygenic diseases. Although well recognized, the basis of such interpopulation differences is poorly understood. We present an example of an inverse allelic association of an immune response genotype to an infectious disease in two neighboring West African populations. In this case, both the key environmental contributor, i.e., the malaria parasite, and a major biological mechanism are well defined. We show that this surprising result fits well with the predictions of a mathematical model describing the population genetics and dynamics of this interaction.

* Corresponding author. Mailing address: Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Dr., Oxford OX3 7BN, United Kingdom. Phone: 44 1865 287759. Fax: 44 1865 287686. E-mail: Adrian.hill{at}imm.ox.ac.uk.

Editor: S. H. E. Kaufmann

Infection and Immunity, February 2005, p. 953-955, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.953-955.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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