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Genetic linkage and association analyses for trait mapping in Plasmodium falciparum

Nature Reviews Genetics volume 8, pages 497–506 (2007)Cite this article

Key Points

  • This article discuss the foundations for genetic linkage mapping and population association analysis of the human malaria parasite Plasmodium falciparum.

  • We review strategies of P. falciparum genetic crosses and of candidate-gene association, selection-based association and genome-wide association studies.

  • We present an example of a trait (P. falciparum chloroquine resistance) that has been mapped to a single gene.

  • We discuss the feasibility of dissecting complex traits that are determined by multiple genes.

  • We survey methods for systematic and large-scale analysis of gene expression, polymorphism and selection.

Abstract

Genetic studies of Plasmodium falciparum laboratory crosses and field isolates have produced valuable insights into determinants of drug responses, antigenic variation, disease virulence, cellular development and population structures of these virulent human malaria parasites. Full-genome sequences and high-resolution haplotype maps of SNPs and microsatellites are now available for all 14 parasite chromosomes. Rapidly increasing genetic and genomic information on Plasmodium parasites, mosquitoes and humans will combine as a rich resource for new advances in our understanding of malaria, its transmission and its manifestations of disease.

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Figure 1: The malaria parasite life cycle.
Figure 2: A laboratory cross of different Plasmodium falciparum clones.
Figure 3: Reduced microsatellite diversity from a chloroquine selective sweep on the pfcrt locus of Plasmodium falciparum chromosome 7.

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Acknowledgements

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health.

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  1. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike Bethesda, Maryland, 20892-8132, USA

    Xinzhuan Su, Karen Hayton & Thomas E. Wellems

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  1. Xinzhuan Su
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Correspondence to Thomas E. Wellems.

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FURTHER INFORMATION

Affymetrix molecular inversion probe

Johns Hopkins Malaria Research Institute

Malaria Research and Reference Reagent Resource Center

NCBI Malaria Genetics and Genomics

NIAID Laboratory of Malaria and Vector Research

The J. Craig Venter Institute

PlasmoDB

Glossary

Apicomplexa

A phylum of parasitic protozoa that is classified by the presence of an apical complex, which is used by the invasive stages.

Linkage analysis

Analysis by which genetic markers that are associated with a trait of interest are established from genetic crosses or family pedigrees.

Linkage disequilibrium

A tendency of genetic loci to segregate together more frequently than expected by chance.

Selection valley

A chromosome region with reduced allelic diversity or reduced marker intensity owing to selection.

Hitchhiking

Spread in a population of neutral or, in some cases, deleterious variants, when they are linked to beneficial mutations.

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Su, X., Hayton, K. & Wellems, T. Genetic linkage and association analyses for trait mapping in Plasmodium falciparum. Nat Rev Genet 8, 497–506 (2007). https://doi.org/10.1038/nrg2126

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