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Rowlands, K.

Publications and source records attributed to Rowlands, K..

2 recordsLinked to original sources

Natural diversity of the malaria vector Anopheles gambiae

The sustainability of malaria control in Africa is threatened by rising levels of insecticide resistance, and new tools to prevent malaria transmission are urgently needed. To gain a better understanding of the mosquito populations that transmit malaria, we sequenced the genomes of 765 wild specimens of Anopheles gambiae and Anopheles coluzzii sampled from 15 locations across Africa. The data reveal high levels of genetic diversity, with over 50 million single nucleotide polymorphisms across the 230 Mbp genome. We observe complex patterns of population structure and marked variations in local population size, some of which may be due at least in part to malaria control interventions. Insecticide resistance genes show strong signatures of recent selection associated with multiple independent mutations spreading over large geographical distances and between species. The genetic variability of natural populations substantially reduces the target space for novel gene-drive strategies for mosquito control. This large dataset provides a foundation for tracking the emergence and spread of insecticide resistance and developing new vector control tools.

genomics

A structural variant encoding hybrid glycophorins is associated with resistance to severe malaria

Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. Here we analyse whole genome sequence data from worldwide human populations, including 765 new genomes from across sub-Saharan Africa, and identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB. We find that a nearby reported association with severe malaria is explained by a complex structural variant that involves the loss of GYPB and gain of two hybrid genes, each with a GYPB extracellular domain and GYPA intracellular domain. This variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya. We show that the structural variant encodes the Dantu blood group antigen, and therefore a serologically distinct red cell phenotype. These findings demonstrate that structural variation of red blood cell invasion receptors is associated with natural resistance to P. falciparum malaria.

genomics