Consortial Project 4

Genetic linkage studies of resistance to malaria

Consortial Project 4 builds on previous family-based studies conducted in three different rural communities where malaria is endemic. These studies used a method known as genetic linkage analysis to identify a number of regions of the genome that appear to influence an individual's ability to control the level of parasites in the blood, or the frequency with which an individual becomes ill with malaria fever. The purpose of Consortial Project 4 is to identify the specific genes responsible for malaria resistance within the genomic regions identified by these previous genetic linkage studies.

Study sites

• Ghana: Kwame Nkrumah Institute of Science and Technology
• Senegal: Institut Pasteur de Dakar
• Thailand: Mahidol University

Scientific rationale

Consortial Project 4 is led by MalariaGEN investigators in France, at the Institut Pasteur,  and in Germany, at the Bernard Nocht Institute. It is based on the genetic linkage studies that these investigators have been conducting for a period of more than a decade, in collaboration with MalariaGEN investigators in Ghana, Senegal and Thailand. 

The first step in this Consortial Project was to compare the results of these previous genetic linkage studies and to identify regions of the genome that have strong evidence of a genetic effect on the intensity of infection or the rate of clinical illness due to malaria. The next step was to design a method of fine mapping these genomic regions by genotyping a high density of single nucleotide polymorphisms in the subjects of the previous genetic linkage studies. So far, the main focus of this work has been on fine mapping the genomic region around chromosome 5p15, which has been linked to malaria resistance both in Senegal and in Thailand.