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Originally published in Science Express on 21 June 2001
Science 20 July 2001:
Vol. 293. no. 5529, pp. 455 - 462
DOI: 10.1126/science.1061573
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Research Articles

Haplotype Diversity and Linkage Disequilibrium at Human G6PD: Recent Origin of Alleles That Confer Malarial Resistance

Sarah A. Tishkoff,12* Robert Varkonyi,2 Nelie Cahinhinan,2 Salem Abbes,3 George Argyropoulos,4 Giovanni Destro-Bisol,5 Anthi Drousiotou,6 Bruce Dangerfield,7 Gerard Lefranc,8 Jacques Loiselet,9 Anna Piro,10 Mark Stoneking,11 Antonio Tagarelli,10 Giuseppe Tagarelli,10 Elias H. Touma,9 Scott M. Williams,12dagger Andrew G. Clark2

The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.

1 Department of Biology, Biology/Psychology Building, University of Maryland, College Park, MD 20742, USA.
2 Institute of Evolutionary Genetics, Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.
3 Faculty of Medicine and Pasteur Institute, Tunis, Tunisia.
4 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
5 Department of Human and Animal Biology, University "La Sapienza," Rome, Italy.
6 Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
7 Department of Human Genetics, South African Institute of Medical Research, University of the Witwatersrand, Johannesburg, South Africa.
8 University of Sciences and CNRS, Montpellier, France.
9 University St. Joseph, Beirut, Lebanon.
10 Istituto di Medicina Sperimentale e Biotecnologie-CNR, Mangone (Cosenza), Italy.
11 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
12 Department of Microbiology, Meharry Medical College, Nashville, TN 37208, USA.
*   To whom correspondence should be addressed. E-mail: st130{at}umail.umd.edu

dagger    Temporary address: Montreal Genome Center, Montreal General Hospital Research Institute, Montreal, Quebec H3G 1A4, Canada.

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