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Excess Polymorphisms in Genes for Membrane Proteins in Plasmodium falciparum
Sarah K. Volkman,1Daniel L. Hartl,2Dyann F. Wirth,1Kaare M. Nielsen,23Mehee Choi,2Serge Batalov,4Yingyao Zhou,4David Plouffe,4Karine G. Le Roch,4Ruben Abagyan,4Elizabeth A. Winzeler45*
The detection of single-nucleotide polymorphisms in
pathogenic microorganisms has normally been carried out by trial and
error.Here we show that DNA hybridization with high-density
oligonucleotidearrays provides rapid and convenient detection of
single-nucleotidepolymorphisms in Plasmodium falciparum,
despite its exceptionallyhigh adenine-thymine (AT) content
(82%). A disproportionate numberof polymorphisms are found in genes
encoding proteins associatedwith the cell membrane. These genes are
targets for only 22% ofthe oligonucleotide probes but account for
69% of the polymorphisms.Genetic variation is also enriched in
subtelomeric regions, whichaccount for 22% of the chromosome but 76%
of the polymorphisms.
1 Department of Immunology and Infectious
Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
2 Department of Organismic and Evolutionary Biology,
Harvard University, Cambridge, MA 02138, USA.
3 Department of Pharmacy, University of Tromso,
Tromso N-9037, Norway.
4 Genomics Institute of the
Novartis Research Foundation, San Diego, CA 92121, USA.
5 Department of Cell Biology, The Scripps Research
Institute, La Jolla, CA 92037, USA.
*
To whom correspondence should be addressed. E-mail:
winzeler{at}gnf.org
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