Introduction
In its natural hosts, P. falciparum rapidly undergoes genetic adaptation and natural selection in response to several environmental pressure including drugs and host immune response. Analysis of the resulting acquired genetic changes will enhance understanding of the basis of these adaptations and infer efforts to control it – such as in identification of important drug and vaccine targets, but also proper use of currently available malaria interventions.
Methodology
A total of 314 malaria positive samples from under fives were collected from a rural district in Malawi. We performed DNA extraction, QC and processing at the Malawi-Liverpool-Wellcome Trust laboratories. DNA was shipped to Wellcome Trust Sanger Institute for sequencing using illumina sequencing technology. Population genomics and genetics analysis were performed on raw data generated from the Sanger at the London School of Hygiene & Tropical Medicine.
Results
We have sequenced 93 paediatric isolates and catalogued 118,000 Malawi specific SNPs. We have also identified genomic regions harbouring possible novel drug and vaccine targets including previously known genes using tests of selection - Tajima’s D test (balancing selection, possible vaccine targets) and iHS, FST, and XP-EHH (positive selection, possible drug targets).
Conclusion
Characterization of genetic variation and identification of loci under selection will greatly help in surveillance of drug resistant alleles and infer drug and vaccine development. These and other identified targets of selection will be prioritized for functional studies.
Supervisors:
Alister Craig (LSTM) & Taane Clark (LSHTM)
Advisors:
Mwapatsa Mipando (CoM)