Presentation Abstract

Session: Malaria: Molecular Biology: Genes to Genomes
Abstract Number: 503
Title: Genome-wide analysis of natural selection in Plasmodium falciparum populations in West Africa
Presentation Start: 11/13/2012 9:15:00 AM
Authors: Victor A. Mobegi1, Alfred Amambua-Ngwa2, Kovana Loua3, Ambroise Ahouidi4, Judith Satoguina2, Davis Nwakanma2, Bronwyn MacInnis5, Jack O’Brien6, Magnus Manske5, Taane Clark1, Dominic Kwiatkowski5, David Conway1
1London School of Hygiene and Tropical Medicine, London, United Kingdom, 2Medical Research Council Unit, Fajara, Gambia, 3National Institute of Public Health, Conakry, Guinea, 4Universite Cheikh Anta Diop, Dakar, Senegal, 5Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 6Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
Abstract: When Plasmodium falciparum competes with other genotypes in same host or when under drug and host immunity pressure there is selection on the genome which leaves marks that can be identified by population genetic methods. Selective pressure will vary in different geographical locations and the varying marks detected in this case will correspond to genes involved in local adaptation. To explore this, we first analysed population structure by genotyping ten polymorphic P. falciparum microsatellite loci in 268 infections from eight locations in four West African countries (Republic of Guinea, Guinea Bissau, The Gambia and Senegal), spanning a highly endemic forested region in the south to a low endemic Sahelian region in the north. This showed that each location had similar levels of genotypic diversity, although there were many more mixed parasite genotype infections in the south. Genetic differentiation between populations was low and an overall test for isolation by distance was not significant. Given the high levels of recombination and minimal reproductive isolation of parasite populations in West Africa, differential signatures of selection in particular populations should be detectable against a background of neutral genomic variation that is more spatially homogeneous. To address this, we undertook a population genomic analysis of parasites at a highly endemic site in the Republic of Guinea, with whole genome sequencing using Illumina 76 base paired-end reads mapped to the reference genome of P. falciparum. Genome-wide analysis of SNPs in 100 P. falciparum clinical isolates from this population was used to identify genes under natural selection, and we compare the findings with those of a lower endemic site in The Gambia.





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