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Switching: a light on gene regulation

  April, 12 2006 15:25
your information resource in human molecular genetics
It used to be simple, genetic disease was caused by genetic mutation. Of course, as we all know, molecular biology is never simple. The discovery of chromatin as a transcriptional regulator, followed by antisense, antigene, RNAi, microRNA all showed how very naïve we had been. Knowing, as we do now, that gene regulation can occur through gene switches mediated by any of the above, the problem has been how to identify these regions as targets for research and eventually therapeutic attack.

In the current issue of Genome Research, the way forward has been eloquently shown.

The discovery, made by researchers from McGill University, L’Institut de recherches cliniques de Montreal (IRCM), and the McGill University Health Centre (MUHC) and published in the current issue of Genome Research, may revolutionize the way we think about gene regulation and speed up discovery for diagnostics and treatments, according to the researchers. Investigators worldwide will now be able to focus on these important regions, which are responsible for diseases such as cancer, neurodegenerative diseases, diabetes, and genetic malformations, they add.

Diseases are not only caused by gene mutations, but by defects in the way genes are controlled. Although the locations of genes in the human genome are now well-characterized thanks to the work of the Human Genome Project, the mechanism by which genes are regulated was poorly understood. Until now that is.

The McGill, IRCM and MUHC research team, lead by McGill Prof. Mathieu Blanchette, School of Computer Science, and François Robert, Director of the Laboratory of Chromatin and Genomic Expression at the IRCM, created a computer algorithm that analyzes the billions of bases that make up the human genome to identify “signatures” for gene switches. Their work describes a map consisting of more than 100,000 switches involved in controlling human genes.

The theoretical algorithms were then tested using data provided by Vincent Giguere, an MUHC-based researcher and professor in the Faculty of Medicine at McGill University. “We used the breast cancer model that we documented in a research paper last year,” says Dr. Giguere. “We found that the algorithms predicted the gene switch sites very nicely.”

The map sheds new light on our understanding of cellular function and is expected to greatly enhance research on many diseases, continues Giguere. “The map will speed up discovery for diagnostics and treatments by allowing researchers worldwide to focus on these important regions,” adds Blanchette.

Message posted by: Simon Chandler

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