Excess Polymorphisms in Genes for Membrane Proteins in Plasmodium falciparum

Author:

Volkman Sarah K.1,Hartl Daniel L.2,Wirth Dyann F.1,Nielsen Kaare M.23,Choi Mehee2,Batalov Serge4,Zhou Yingyao4,Plouffe David4,Le Roch Karine G.4,Abagyan Ruben4,Winzeler Elizabeth A.45

Affiliation:

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.

Abstract

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 oligonucleotide arrays provides rapid and convenient detection of single-nucleotide polymorphisms in Plasmodium falciparum , despite its exceptionally high adenine-thymine (AT) content (82%). A disproportionate number of polymorphisms are found in genes encoding proteins associated with the cell membrane. These genes are targets for only 22% of the oligonucleotide probes but account for 69% of the polymorphisms. Genetic variation is also enriched in subtelomeric regions, which account for 22% of the chromosome but 76% of the polymorphisms.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference16 articles.

1. Sequence data for P. falciparum chromosomes 1 3 through 9 and 13 can be obtained from The Sanger Institute (www.sanger.ac.uk/Projects/P_falciparum/).

2. Sequence data for P. falciparum chromosome 12 can be obtained from the Stanford Genome Technology Center (www-sequence.stanford.edu/group/malaria).

3. Preliminary sequence data for P. falciparum chromosomes 10 11 and 14 can be obtained from The Institute for Genomic Research (www.tigr.org).

4. Accessing Genetic Information with High-Density DNA Arrays

5. Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis

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