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PMID: 16001361 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

How malaria has affected the human genome and what human genetics can teach us about malaria.

American journal of human genetics ·Vol. 77 ·No. 2 ·2005-08-00 ·Pages 171-92

Kwiatkowski DP

Abstract

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, alpha+ 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.

MeSH Terms
Animals Biological Evolution Disease Models, Animal Erythrocytes/cytology Family Health Genetic Predisposition to Disease Genome, Human Globins/genetics Humans Immune System Immunity, Innate Malaria/epidemiology,genetics Mice Oxidative Stress Plasmodium falciparum
Chemicals
Globins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kwiatkowski Dominic P
Wellcome Trust Centre for Human Genetics and University Department of Paediatrics, Oxford, United Kingdom. [email protected]
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/432519
Email
[email protected]
Published
2005-08-00
Epub
2005-00-06
Pages
171-92
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1224522
Subset
IM
External Links
PubMed source DOI: 10.1086/432519 PMC Full Text View journal details
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