News from the zebrafish cousin of the human genome: A radiation hybrid map of the zebrafish genome

October 25, 1999

A map of the zebrafish genome based on the radiation hybrid technique has been published by scientists from the Max Planck Institute for Developmental Biology in Tuebingen/Germany (Nature Genetics, September 1999). This map allows scientists to match the map positions of candidate genes with the positions of genetically mapped mutations, and finally sequence the mutations.

In recent years large-scale screens for mutant zebrafish have been conducted in the laboratories of Christiane Nüsslein-Volhard in Tuebingen and Wolfgang Driever in Boston, yielding hundreds of mutations that can potentially provide insight into human development. These mutations give the zebrafish a unique advantage over other model organisms used in the human genome project, such as the mouse and rat. However, they must be analyzed on the DNA sequence level to be useful. Scientists at the Max Planck Institute for Developmental Biology in Tuebingen have now published a map of the zebrafish genome based on the radiation hybrid technique. With this map in hand, researchers will be able to match the map positions of candidate genes with the positions of genetically mapped mutations, and finally sequence the mutations.

The foundation for the map was laid by the lab of Peter Goodfellow (London), who fused irradiated zebrafish cells with rodent cells, producing a panel of hybrid cell lines each of which contains a large number of random fragments of the zebrafish DNA. To map a known piece of DNA (referred to as a marker), each of the cell lines must be tested for its presence or absence using the polymerase chain reaction (PCR) technique. Whenever two markers are retained in many of the same cell lines, they are placed next to each other on the map, until a map of the whole genome emerges.

Throughout the summer of 1998, more than thirty researchers from the departments of Christiane Nüsslein-Volhard and Friedrich Bonhoeffer worked long hours on the zebrafish map. 1275 markers were placed on the Tuebingen map, covering 82 % of the zebrafish genome at a resolution of 350 kb. The markers on the map include genetic markers (SSLPs) suitable for mapping mutations, developmental control genes known from other organisms, and partially sequenced random genes (ESTs). Even though only a tiny fraction of the zebrafish genes have been mapped, researchers could already match three mutations with candidate genes using the radiation hybrid data.

In the human genome project, ESTs play a crucial role because they allow to map genes and deduce their biological function before a complete sequence is available. They will soon become equally important for the zebrafish, as labs in Europe and U.S. are generating tens of thousands of ESTs, many of which will be candidate genes for the Tuebingen mutations. To make use of this wealth of potentially interesting genes, the Tuebingen group is now preparing for an even bigger task: they want to add another 20,000 ESTs to the map, more than the total number of human ESTs mapped until 1996.

The most current results and further information about the Zebrafish Genome Mapping Project are available from the Tuebingen website: http://wwwmap.tuebingen.mpg.de
-end-
Original article:

Geisler, R., Rauch, G.-J., Baier, H., van Bebber, F., Broß, L., Davis, R. W., Dekens, M., Finger, K., Fricke, C., Gates, M. A., Geiger, H., Geiger-Rudolph, S., Gilmour, D., Glaser, S., Gnügge, L., Habeck, H., Hingst, K., Holley, S., Keenan, J., Kirn, A., Knaut, H., Lashkari, D., Maderspacher, F., Martyn, U., Neuhauss, S., Neumann, C., Nicolson, T., Pelegri, F., Ray, R., Rick, J., Roehl, H., Roeser, T., Schauerte, H. E., Schier, A. F., Schönberger, U., Schönthaler, H.-B., Schulte-Merker, S., Seydler, C., Talbot, W. S., Weiler, C., Nüsslein-Volhard, C. and Haffter, P. (1999). A radiation hybrid map of the zebrafish genome. Nature Genetics 23, 86-89.

Published: 26-10-99
Contact: Robert Geisler
E-Mail: robert.geisler@tuebingen.mpg.de
Max Planck Institute for Developmental Biology, Tuebingen/Germany
Phone: +49-7071-601443
Fax: +49-7071-601384

Max-Planck-Gesellschaft

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