NIH scientists create first detailed map of malaria parasite

November 10, 1999

NIH scientists create first detailed map of malaria parasite

A research effort led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) has produced the first high-resolution genetic map of Plasmodium falciparum, the deadliest malaria parasite. The map along with a report describing its construction appears in this week's journal Science.

"NIAID has made sequencing disease-causing microbes a priority, with an eye toward finding new targets for improved diagnostic tools, therapies and vaccines to relieve the burden of important infectious diseases," comments Anthony S. Fauci, M.D., NIAID director. "This map provides the scaffolding to accelerate efforts to sequence the entire genome of one of our greatest infectious foes, the malaria parasite." Complete sequences for two of the parasite's 14 chromosomes have recently been reported.

"Equally important," Dr. Fauci adds, "this genetic map, constructed from a classical genetic cross, will serve as a bridge between the genomic information and the biology of the parasite." As such, the map can help locate genes important to drug resistance and disease severity, for example.

Thomas E. Wellems, M.D., Ph.D., and Xin-zhuan Su, Ph.D., section chief and staff scientist, respectively, in NIAID's Laboratory of Parasitic Diseases, headed the study. Input and analysis by scientists from the National Center for Biotechnology Information at the National Institutes of Health (NIH), and from the People's Republic of China were key to the effort.

Each year, P. falciparum malaria affects up to 500 million people worldwide. More than 2 million of those people, primarily young children in sub-Saharan Africa, die, and many more are left debilitated by the disease.

Malaria researchers have stepped up efforts to understand the genetics and genome of the parasite, hoping to generate new strategies to fight this age-old scourge.

The team constructed their genetic map by crossing a drug-resistant type of P. falciparum with a drug-sensitive type. Examination of the resulting 35 progeny parasites yielded a wealth of information.

According to Dr. Wellems, small repeating patterns of the four chemical subunits of DNA pepper each and every one of the malaria chromosomes. These can be used to pinpoint important traits that come from each parent. When the mapping was complete, says Dr. Wellems, "It had all come together like pieces of a jigsaw puzzle."

They identified 901 markers that could be naturally sorted into 14 groups, correlating closely to the physical sizes of the 14 chromosomes of the parasite. This is one of the most detailed genetic maps of a eukaryotic organism.

Dr. Wellems has focused much of his laboratory's research on understanding the basis of resistance to chloroquine, an inexpensive malaria drug that is no longer effective in many areas of the world where drug-resistant strains have emerged and now predominate. "One way we can use this new information is to uncover the genetic changes that accompany the expanding problem of drug resistance and try to stay one step ahead of the parasite," he says.

Recently, scientists at the University of Wisconsin, Madison, reported that they had constructed an optical map of the P. falciparum genome. That map-a physical map that orders snipped DNA fragments of the chromosomes-and the genetic map provide complementary information to genome sequencers. But because the genetic map was derived from an actual breeding between parasites with different traits, it also provides insight into the biology of the parasite. It can, for example, help localize genes important in how drug resistance evolves and in how human infections develop. The map also will shed light on the clinical implications of genetic differences seen in parasites from various geographic regions around the world.

The new genetic map is posted on the National Center for Biotechnology Information Web site ( http://www.ncbi.nlm.nih.gov ). Dr. Wellems believes that Internet communication and information flow is important for "promoting a research environment in which new ideas about malaria will more readily evolve and synergize."

"I completely concur with Dr. Wellems' vision," comments David J. Lipman, M.D., NCBI director. "This genetic map is on the Web for the entire malaria research community. The genetic and computational work of NCBI biologists John Wootton and Chuong Huynh, in close collaboration with the NIAID group, is an important example of NCBI's continuing commitment to the public efforts against malaria and other infectious diseases."
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NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NCBI, a Center within the National Library of Medicine, creates public databases, conducts research in computational biology, and develops software tools for analyzing genome data. NIH is an agency of the U.S. Department of Health and Human Services.

Reference:

X-z Su, MT Ferdig, Y Huang, C Huynh, A Liu, J You, JC Wootton, and TE Wellems. A genetic map and recombination parameters of the human malaria parasite P. falciparum. Science 286:1351-53 (1999).

E Pennisi. Malaria genome comes into view. Science 286:1263-65 (1999).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov .

NIH/National Institute of Allergy and Infectious Diseases

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