Genetic Map Offers New Tool for Malaria Research

An international research team announced today the completion of a genome-wide map that charts the genetic variability of the human malaria parasite Plasmodium falciparum. Published in the December 10 advance online edition of Nature Genetics, the study reveals striking variation within the pathogen's genome, including an initial catalog of nearly 47,000 specific genetic differences among parasites sampled worldwide. These differences lay the foundation for dissecting the functions of important parasite genes and for tracing the global spread of malaria. Led by scientists at the Harvard School of Public Health and the Broad Institute of MIT and Harvard, together with researchers in Senegal, the work has already unearthed novel genes that may underlie resistance to current drugs against the disease.

"Malaria remains a significant threat to global public health, driven in part by the genetic changes in the parasite that causes the disease," said senior author Dyann Wirth, a professor and chairman of the department of immunology and infectious diseases at the Harvard School of Public Health and the co-director of the Broad Institute's Infectious Disease Initiative. "This study gives us one of the first looks at genetic variation across the entire malaria parasite genome - a critical step toward a comprehensive genetic tool for the malaria research community."

Plasmodium falciparum - the deadliest of the four parasites that cause malaria in humans - kills one person every 30 seconds, mostly children living in Africa. Despite decades of research, the genetic changes that enable it to escape the body's natural defenses and to overcome malaria drugs remain largely unknown.

To gain a broad picture of genetic variability - worldwide and genome-wide - the scientists analyzed more than 50 different P. falciparum samples from diverse geographic locations. This includes the complete genome sequencing of two well-studied samples as well as extensive DNA analyses of 16 additional isolates. The work is one of three large-scale studies of the parasite's DNA that appear together in Nature Genetics, and it represents a collaborative effort among Boston area researchers and a scientific team led by Souleymane Mboup, a professor at the Cheikh Anta Diop University in Senegal where malaria is endemic. "We are grateful for the contributions of our colleagues in Senegal. They are a crucial part of this collaboration," said Wirth.

By comparing the DNA sequences to each other and to the P. falciparum genome sequenced in 2002, the researchers uncovered extensive differences, including ~ 47,000 single letter changes called single nucleotide polymorphisms (SNPs). This represents more than double the expected level of diversity in the parasite's DNA. Although there are probably many more SNPs to be found, this initial survey - like the recent HapMap project in humans - provides a launching point for future systematic efforts to identify parasite genes that are essential to malaria.