What protects the DNA

Which genes protect against deadly malaria? - Protection against tropical diseases is inherent in the genome

Malaria - also known as common fever or intermittent fever - is a tropical disease that is responsible for around 1.2 million deaths worldwide each year. It is transmitted by the bite of a female Anopheles mosquito and is triggered by unicellular parasites of the genus Plasmodium. Although malaria can be treated well in the early stages of the disease, it has so far not been contained in the poor areas due to a lack of medical care.

Genetic predispositions protect against disease

Research into possible protective mechanisms that prevent the outbreak of the disease or its fatal course is therefore an important area of ​​research. Since the discovery of sickle cell anemia, we have known that there are genetic predispositions that can protect their carriers from deadly malaria. In sickle cell anemia, those affected carry a mutation in the hemoglobin gene, the gene that is responsible for the formation of the red blood pigment. This system protects people almost completely from the deadly courses of malaria. Studies have shown, however, that the sickle cell system only accounts for a fraction of the protection against tropical diseases that can be brought about by genetic predispositions in humans. According to this, there are still numerous genetic variants to be discovered that also help protect against malaria.

A team of scientists from the Hamburg Bernhard Nocht Institute for Tropical Medicine has set itself this task. Under the direction of Prof. Dr. Rolf Horstmann was to use a special technique, the so-called genome-wide association study, GWAS for short (see info box), to identify previously unknown genetic protective mechanisms against malaria.

Infant with life-threatening brain involvement in malaria. The
The photo was taken at the Komfo Anokye Teaching Hospital in Kumasi, Ghana.
Image source: Mika Väisänen

3,000 young children examined in Ghana

The study was carried out in close cooperation with the University Hospital of Kumasi in Ghana and the Universities of Kiel and Lübeck and funded by the Federal Ministry of Education and Research (BMBF) in the National Genome Research Network (NGFN). The scientists examined the genome of almost 3,000 Ghanaian toddlers with life-threatening courses of malaria for 1 million mutations each. At the same time, blood samples were taken from around 2,000 unaffected children of the same age in the districts and villages from which the malaria-stricken children came for genetic comparison. “In malaria areas, life-threatening malaria is usually diseases affecting young children, who often suffer from severe anemia as a result of malaria. For this reason, we were only able to use remnants of blood samples for the genetic analysis that were already taken for diagnostics, ”explains Professor Horstmann.

A difficult initial situation that gave Professor Horstmann headaches in a completely different way: “Genome-wide association studies have already been used with great success in numerous diseases such as diabetes, heart attacks and schizophrenia. In the case of infectious diseases, however, there has been little success. ”Difficult conditions for the methodologically demanding and scientifically ambitious approach.

Geneticists identify new protective mechanisms

The Anopheles mosquito, the carrier of malaria But despite all the negative signs, the efforts of the scientists should be rewarded: The study was successful. “The most important thing about our study was to show that the method of the genome-wide association study can also be successfully applied to infectious diseases. We have also discovered two genes that may protect against malaria, ”says Professor Horstmann. One gene regulates the formation of ion channels in red blood cells, the second the sealing of cells in the blood vessel wall.

The key to the drug

But what's next? Genetic mutations as discovered in this study cannot be used directly for diagnostic, therapeutic or prophylactic measures. Genes form the basis for the production of proteins in our body, the proteins. In the end, it is the proteins that take on important functions, for example the transport of oxygen in the blood or the defense against pathogens. “We therefore have to understand the role of the proteins that are behind the genes,” explains Professor Horstmann. The researchers at the Bernhard Nocht Institute in Hamburg have now embarked on this path. It is still unclear what role the two proteins play in protecting against malaria. However, this understanding is the basis for drug and vaccine development. There is still a long way to go before then.

Genome-wide association study
The human genome has now been completely deciphered for ten years. The international human genome project, which has been publicly funded since 1990, together with the American scientist and entrepreneur Craig Venter, has made a significant contribution to this. Overall, the human genome contains around 20,000 to 25,000 genes. Their functions are being researched in large-scale projects such as the National Genome Research Network (NGFN). The first complete sequencing, i.e. the decoding of the sequence of all the individual building blocks of our genome, took more than ten years. With the latest methods and equipment, this can now be done in a few days. As a result, DNA sequencing has been part of the research routine for many years and has now also become part of clinical diagnostics. A direct comparison of certain parts of the genetic make-up of healthy and sick people can reveal certain genetic locations that are frequently changed in diseases. In other words: If a large number of people affected by a disease carry a certain mutation, it is assumed that this mutation also has something to do with the disease. Such studies are called genome-wide association studies (the abbreviation GWAS stands for the English expression: genome-wide association study).
Contact Person:
Prof. Dr. Rolf Horstmann
Bernhard Nocht Institute for Tropical Medicine
Bernhard-Nocht-Str. 74
20359 Hamburg
Tel .: 040 42818-260
Fax: 040 42818-265
Email: [email protected]