TY - JOUR T1 - Genome-Wide Linkage Analysis of Malaria Infection Intensity and Mild Disease A1 - Timmann, Christian A1 - Evans, Jennifer A A1 - König, Inke R A1 - Kleensang, André A1 - Rüschendorf, Franz A1 - Lenzen, Julia A1 - Sievertsen, Jürgen A1 - Becker, Christian A1 - Enuameh, Yeetey A1 - Kwakye, Kingsley Osei A1 - Opoku, Ernest A1 - Browne, Edmund N. L A1 - Ziegler, Andreas A1 - Nürnberg, Peter A1 - Horstmann, Rolf D Y1 - 2007/03/23 N2 -
In tropical Africa, virtually all children become infected with malaria parasites. Most of them experience several malaria attacks per year, and over a million die from disease complications. Sickle-cell anemia, thalassemias, and other inherited red blood cell disorders indicate that malaria has selected for human genetic variants, but no attempts have so far been reported to systematically screen the human genome for malaria-resistance factors. We describe a genome-wide linkage analysis performed in children living in rural Ghana, West Africa, including approaches to select an informative study cohort and to assess, over a period of 8 mo, individual disposition to malaria parasitemia, fever episodes, and anemia. Families carrying the known malaria-protective red blood cell disorders were excluded, infection intensities were adjusted to the use of mosquito-protection devices, and parasitological and clinical findings were corrected according to the state of partial malaria immunity, which, under constant exposure, gradually develops over the first 10 y of life. The study revealed several genomic regions showing evidence for linkage to the various malaria phenotypes recorded, among them a prominent signal on Chromosome 10 correlated to the frequency of fever episodes. Future identification of genes involved is expected to reveal previously unrecognized pathways that may protect children against malaria.