Abstract:
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Malaria is one of the strongest selective pressures
in recent human evolution. African populations have
been and continue to be at risk for malarial infections.
However, few studies have re-sequenced malaria susceptibility
loci across geographically and genetically diverse
groups in Africa. We examined nucleotide diversity at
Intercellular adhesion molecule-1 (ICAM-1), a malaria
susceptibility candidate locus, in a number of human
populations with a specific focus on diverse African ethnic
groups. We used tests of neutrality to assess whether natural
selection has impacted this locus and tested whether
SNP variation at ICAM-1 is correlated with malaria endemicity.
We observe differing patterns of nucleotide and
haplotype variation in global populations and higher levels
of diversity in Africa. Although we do not observe a
deviation from neutrality based on the allele frequency
distribution, we do observe several alleles at ICAM-1,
including the ICAM-1Kilifi allele, that are correlated with
malaria endemicity. We show that the ICAM-1Kilifi allele,
which is common in Africa and Asia, exists on distinct
haplotype backgrounds and is likely to have arisen more
recently in Asia. Our results suggest that correlation analyses
of allele frequencies and malaria endemicity may be
useful for identifying candidate functional variants that
play a role in malaria resistance and susceptibility. |