HARVARD COLLEGE, PRESIDENT & FELLOWS OF

Malaria is a major cause of global morbidity and mortality, with its greatest impact on African children who account for most of the 1 to 2.7 million annual deaths (WHO, 2000). P falciparum, the major causative agent of human malaria, has remained a major health threat in part through the evolution of drug resistant organisms, such that the most affordable antimalarial drugs are no longer effective and resistance is emerging to newer drugs. Vaccine development has been hampered in part by antigenic variation in parasite proteins, and global climate changes have led to new adaptations of the parasite and the mosquito vector. Genetic differences among parasites are likely to be associated with many of the adaptive changes. Understanding the frequency and distribution of polymorphisms in the extant parasite population is essential for the development of genetic mapping tools that can provide a powerful approach to identify genetic loci responsible for important phenotypes such as drug resistance and clinical outcomes of disease. We expect to carry out genome-wide single-nucleotide polymorphism genotyping of a worldwide sampling and use this genotyping to detect phenotype/genotype associations for drug resistance in P. falciparum. Funds will be subcontracted to the University of Notre Dame. They will scan the parasite genome and hope to find associations with drug resistance during these sweeps and provide Harvard with their results.

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