Harnessing genomics and genome biology to understand malaria biology

• Published in: Nature reviews. Genetics Vol. 13; no. 5; pp. 315 - 328
• Main Authors: Volkman, Sarah K., Neafsey, Daniel E., Schaffner, Stephen F., Park, Daniel J., Wirth, Dyann F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2012; Nature Publishing Group
• Subjects: 631/326/417/2550; 692/699/255/1629; Agriculture; Animal Genetics and Genomics; Animals; Anopheles - parasitology; Anopheles - physiology; Antimalarial agents; Antimalarials - therapeutic use; Biological and medical sciences; Biology; Biomedical and Life Sciences; Biomedicine; Blood parasites; Cancer Research; Chromosomes; Disease transmission; Diverse techniques; Drug resistance; Drug Resistance - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Gene loci; Genetic aspects; Genetic diversity; Genetic Linkage; Genetic Loci; Genetics of eukaryotes. Biological and molecular evolution; Genome, Protozoan; Genome-wide association studies; Genomes; Genomics; Health aspects; Human Genetics; Human protozoal diseases; Humans; Immunosuppressive agents; Infectious diseases; Influenza; Informatics; Linkage disequilibrium; Malaria; Malaria - parasitology; Male; Medical sciences; Methods; Molecular and cellular biology; Natural selection; Parasite resistance; Parasites; Parasitic diseases; Pathogens; Phenotypes; Physiological aspects; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Population genetics; Population structure; Protozoal diseases; review-article; Selection, Genetic; Therapeutic applications; United States; United States > US; Massachusetts; Infection; Protozoal disease; Malaria; Genomics; Parasitosis; Review; Genome
• ISSN: 1471-0056; 1471-0064; 1471-0064
• DOI: 10.1038/nrg3187

Key Points 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. This Review describes how genome-wide analyses have provided various insights into the most lethal malarial parasite, Plasmodium falciparum , including determinants of antimalarial drug resistance. The authors also propose how genetic tools can be refined to monitor future therapeutic interventions. Malaria is an important human disease and is the target of a global eradication campaign. New technological and informatics advancements in population genomics are being leveraged to identify genetic loci under selection in the malaria parasite and to find variants that are associated with key clinical phenotypes, such as drug resistance. This article provides a timely Review of how population-genetics-based strategies are being applied to Plasmodium falciparum both to identify genetic loci as key targets of interventions and to develop monitoring and surveillance tools that are crucial for the successful elimination and eradication of malaria.