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New technique to overcome genetic oddity of P. falciparum

Published on January 27, 2012 at 12:52 AM · No Comments

The parasite that causes malaria is a genetic outlier, which has prevented scientists from discovering the functions of most of its genes. Researchers at National Jewish Health and Yale University School of Medicine have devised a technique to overcome the genetic oddity of Plasmodium falciparum, the major cause of human malaria. This new approach led them discover a new gene involved in lipid synthesis, and opens the door to further genetic discovery for the entire organism. This should foster a much greater understanding of the parasite, and facilitate discovery of new medications for a disease that infects more than 200 million people and kills nearly 700,000 every year.

"The malarial genome has been a black box. Our technique allows us to open that box, so that we can learn what genes in the most lethal human parasite actually do," said Dennis Voelker, PhD, Professor of Medicine at National Jewish Health and senior author on the paper that appeared in the January 2, 2012 , issue of the Journal of Biological Chemistry. "This could prove tremendously valuable in the fight against a disease that has become increasingly drug-resistant."

The genome of P. falciparum was sequenced in 2002, but the actual functions of many of the organism's genes have remained elusive. One of the primary methods for discovering gene function is to copy a specific gene, insert it into a model organism that is easy to grow, often the yeast Saccharomyces cerevisiae, then draw on the incredible knowledge base about yeast and its abundant genetic variants to discover how that inserted gene changes the organism's biology.

DNA is composed of building blocks with the shorthand designations A,T,C and G. The genome of P. falciparum is odd because it is particularly rich in A's and T's. Because of this A-T-rich nature, P. falciparum genes generally do not function when they are inserted into other organisms. As a result, scientists have been largely stymied when trying to understand the functions of P. falciparum's genes.

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