Harnessing genomics and genome biology to understand malaria biology

Population-genetics approaches provide important insight into the causes and spread of human malaria caused by Plasmodium falciparum.New technological and informatics advancements are being leveraged in P. falciparum to identify genetic loci under selection and to find variants that are associated with key clinical phenotypes, such as drug resistance.P. falciparum parasite population structure and levels of genetic diversity, reflected in observed patterns of linkage disequilibrium (LD), generally follow continental lines — the greatest parasite population diversity is found in Africa, followed by Asia and then the Americas.P. falciparum parasites are subject to two broad classes of natural selection: balancing selection, which maintains genetic diversity among loci under immune selection, and directional selection which selects for mutations that are advantageous to survival under pressure from drug intervention.Genome-wide association studies in P. falciparum can identify genetic variants associated with key clinical phenotypes, such as drug resistance. Use of multiple independent tests can assist in the identification of the most likely candidate genes for functional follow-up.LD reflects transmission history of parasites within a population and can be used to measure the complexity of infection. Genomic tools based on population structure can be applied to monitor parasite dynamics related to transmission, to assess interventions such as drugs or vaccines and to identify sources of new infection.