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Suggesting genes’ friends, facebook-style: New method reveals genes’ combined effects

No. 13 | 07/03/2011 | by (Sel)

Scientists at the European Molecular Biology Laboratory (EMBL) and the German Cancer Research Centre (DKFZ), both in Heidelberg, Germany, have developed a new method that uncovers the combined effects of genes. Published online today in Nature Methods, it helps understand how different genes can amplify, cancel out or mask each others’ effects, and enables scientists to suggest genes that interfere with each other in much the same manner that facebook suggests friends.

By silencing genes two at a time in cells like these, the scientists can analyse the genes’ combined effects. In this microscopy image of human cells, nuclei are shown in red, cell membranes in green, and the cellular scaffolding in blue.
© dkfz.de

To understand the connections between genetic make-up and traits like disease susceptibility, scientists have been turning to genome-wide association studies, in which they compare genetic variants of people with a particular disease to those of healthy people. Such studies have linked many genes to diseases, but these links were often weak and not clear-cut, possibly because individual genes often do not act alone. The effects of a particular gene can depend on what other genes a person carries, and the new method developed by the teams of Wolfgang Huber at EMBL and Michael Boutros at DKFZ enables scientists to uncover and measure those combined effects.

The scientists took a set of genes that are important for cell signalling and, using a technique called RNA interference, silenced those genes two at a time, and compared the effect to what happens when you silence only one or the other member of each pair. In so doing, they were able to identify a new component in a cell-signalling process known as the Ras pathway, which is involved in cellular proliferation, and is known to go awry in tumour cells.

If two people have many friends in common on facebook, the odds are that those two people know each other – even if they themselves are not facebook friends. Similarly, genes that have similar genetic interaction profiles are likely to influence each other’s effects, and Huber, Boutros and colleagues can now suggest such ‘friends’ – i.e. genes that are likely to affect the same cellular processes. In the long run, this could help predict patient outcomes and adapt treatments for diseases such as cancer.

This project was supported by the CellNetworks Cluster, a novel institution at Heidelberg University supported by the Excellence Initiative (www.cellnetworks.uni-hd.de).

Source Article
Horn, T., Sandmann, T., Fischer, B., Axelsson, E., Huber, W. & Boutros, M. Mapping of Signalling Networks through Synthetic Genetic Interaction Analysis by RNAi. Nature Methods, Advance Online Publication 6 March 2011. DOI: 10.1038/nmeth.1581.

A picture for this press release is available at:
http://www.dkfz.de/de/presse/pressemitteilungen/2011/images/bild_pm_13.jpg
Picture caption: By silencing genes two at a time in cells like these, the scientists can analyse the genes’ combined effects. In this microscopy image of human cells, nuclei are shown in red, cell membranes in green, and the cellular scaffolding in blue.

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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