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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
CR1 Knops blood group alleles are not associated with severe malaria in the Gambia
Genes and Immunity, Volume 4, No. 5, Year 2003
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Description
The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens SI1/SI2 and McCa/McCb, we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with SI:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for SI 2 (0.800, 1365/1706) and McCb (0.385, 658/1706) were observed. Further, when compared to the SI 1/McCa allele observed in all populations, the African SI 2/McCb allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e. = 1.77, P-value < 0.05). Given the role of CR1 in host defense, our findings suggest that SI 2 and McCb have arisen to confer a selective advantage against infectious disease that, in view of these case - control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between SI 2 and McCb with severe malaria may involve variation in CR1 expression levels. © 2003 Nature Publishing Group All rights reserved.
Authors & Co-Authors
Zimmerman, Peter A.
United States, Cleveland
Case School of Medicine
Fitness, Jodene E.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Moulds, Joann M.
United States, Philadelphia
Drexel University College of Medicine
McNamara, David T.
United States, Cleveland
Case School of Medicine
Kasehagen, Laurin J.
United States, Cleveland
Case School of Medicine
Rowe, Jane Alexandra
United Kingdom, Edinburgh
The University of Edinburgh
Hill, Adrian V. S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Gambia, Banjul
Medical Research Council Laboratories Gambia
Statistics
Citations: 66
Authors: 7
Affiliations: 5
Identifiers
Doi:
10.1038/sj.gene.6363980
ISSN:
14664879
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Locations
Gambia