How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria

Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have...

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Bibliographic Details
Published in:	American journal of human genetics 2005-08, Vol.77 (2), p.171-192
Main Author:	Kwiatkowski, Dominic P.
Format:	Article
Language:	eng
Subjects:	Animals Biological and medical sciences Biological Evolution Children & youth Disease Models, Animal Epidemiology Erythrocytes - cytology Family Health General aspects. Genetic counseling Genetic Predisposition to Disease Genetic research Genome, Human Globins - genetics Human protozoal diseases Humans Immune System Immunity, Innate Infectious diseases Malaria Malaria - epidemiology Malaria - genetics Medical genetics Medical immunity Medical sciences Mice Oxidative Stress Parasitic diseases Plasmodium falciparum Prevention Protozoal diseases Review Vaccines
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Summary:	Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have arisen in different populations: epidemiological confirmation of the hypotheses that G6PD deficiency, α + thalassemia, and hemoglobin C protect against malaria mortality; the application of novel haplotype-based techniques demonstrating that malaria-protective genes have been subject to recent positive selection; the first genetic linkage maps of resistance to malaria in experimental murine models; and a growing number of reported associations with resistance and susceptibility to human malaria, particularly in genes involved in immunity, inflammation, and cell adhesion. The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine.
ISSN:	0002-9297 1537-6605