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Resistance and genetic sensitivity to sleeping sickness

degree of parasite virulence or pathogenicity and the environment.

An IRD team focused particularly on the role of host genetic diversity in response to T. b. gambiense infection (whether or not the disease develops). As human experimentation is excluded, genetic, epidemiological and statistical methods, all brought under the term genetic epidemiology, were developed in order to identify the chromosome regions and/or DNA mutations involved in the development of the disease. The researchers used association techniques in order to determine the influence of certain mutations on the DNA of genes coding for particular immune system proteins (cytokines) in manifestation of the disease. This type of study consists in comparing the frequency of a mutation in subjects with symptoms and in healthy individuals. When the frequency of a mutation is significantly higher in the sick subjects than in the healthy ones, this mutation is associated with an enhanced risk of developing the disease. Conversely, a significantly lower frequency is an expression of a protective effect conferred by the mutation.

The two studies conducted in two distinct foci of the disease, respectively at Sinfra in the Ivory Coast and at Bandundu in the Democratic Republic of Congo (1), revealed evidence of three associations between a DNA mutation and the development of the disease. Depending on their position on certain cytokines genes, the mutations investigated were shown to be capable of inducing in the subject carrying them an increased risk of developing this human trypanosomiasis, or conversely a higher chance of a protector effect (2).

The associations brought out between these mutations and the disease necessitate work to confirm this in different populations and environments. New investigations, particularly in genetic epidemiology, are currently being put into operation in order to check up on possible effects of genetic predisposition already observed. The results
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Source:Institut de Recherche Pour le D茅veloppement


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