Identifying Darwinian selection acting on different human APOL1 variants among diverse African populations.
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Date
2013-07-11
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Publisher
The American Journal of Human Genetics
Abstract
Disease susceptibility can arise as a consequence of adaptation to infectious disease. Recent findings have suggested that higher rates of
chronic kidney disease (CKD) in individuals with recent African ancestry might be attributed to two risk alleles (G1 and G2) at the serum-
resistance-associated (SRA)-interacting-domain-encoding region of APOL1. These two alleles appear to have arisen adaptively, possibly as
a result of their protective effects against human African trypanosomiasis (HAT), or African sleeping sickness. In order to explore the
distribution of potential functional variation at APOL1, we studied nucleotide variation in 187 individuals across ten geographically
and genetically diverse African ethnic groups with exposure to two Trypanosoma brucei subspecies that cause HAT. We observed unusually
high levels of nonsynonymous polymorphism in the regions encoding the functional domains that are required for lysing parasites.
Whereas allele frequencies of G2 were similar across all populations (3%–8%), the G1 allele was only common in the Yoruba (39%). Addi-
tionally, we identified a haplotype (termed G3) that contains a nonsynonymous change at the membrane-addressing-domain-encoding
region of APOL1 and is present in all populations except for the Yoruba. Analyses of long-range patterns of linkage disequilibrium indi-
cate evidence of recent selection acting on the G3 haplotype in Fulani from Cameroon. Our results indicate that the G1 and G2 variants
in APOL1 are geographically restricted and that there might be other functional variants that could play a role in HAT resistance and CKD
risk in African populations.
Description
Keywords
Darwinian selection, Variants, African populations
Citation
Ko, W.Y., Rajan, P., Gomez, F., Scheinfeldt, L., An, P., Winkler, C.A., Froment, A., Nyambo, T.B., Omar, S.A., Wambebe, C. and Ranciaro, A., 2013. Identifying Darwinian selection acting on different human APOL1 variants among diverse African populations. The American Journal of Human Genetics, 93(1), pp.54-66.