: As the causative agent of the most severe form of the malaria in humans, Plasmodium falciparum is the source of significant global morbidity and mortality. In addition malaria imposes significant economic and social burdens on society. Though the malaria was eliminated from Europe and North America this century, mortality is probably now increasing, especially in sub-Saharan Africa (Greenwood and Mutabingwa, Nature 415:670-672, 2002). Part of this increase can likely be attributed to the spread of parasites that are resistant to inexpensive chemotherapies such as chloroquine. While the production of an effective vaccine would reduce the need for chemotherapy, attempts to produce protective immunity have met with little success as protection is short-lived (Richie and Saul, Nature 415:694-701, 2002). In both cases, genetic variation in the parasite population is an issue-because drug resistance is spread by variant alleles of drug pumps or drug targets and because the establishment of variation allows the parasite to evade the host's immune system. Because of the importance of genetic variation to the pathogenesis of P. falciparum new methods are needed to quickly discover variation in the parasite. In other species oligonucleotide-array-based hybridization methods allow allelic variation to be identified and scored, inexpensively and quickly, and on a genome-wide scale. An oligonucleotide array that contains 367226 different 25mer probes derived from the P. falciparum genome sequence is now available. By hybridizing genomic DNA to this array, in theory up to one-third of the variation in the 26 Mb genome could be detected as well as scored in genetic crosses. It is thus worthwhile to develop methods for using this array to identify allelic variation on genome-wide scale in P. falciparum. The exploratory work described herein should also be useful in determining whether hybridization-based methods could be used to identify particular isolates of other microbial pathogens, including those that may be used in bioterrorism. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI054687-02
Application #
6726049
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rogers, Martin J
Project Start
2003-04-01
Project End
2005-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$93,850
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kidgell, Claire; Volkman, Sarah K; Daily, Johanna et al. (2006) A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathog 2:e57