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Weizmann Institute scientists show extra copies of a gene carry extra risk
Date:2/4/2009

Is more of a good thing better? A gene known as LIS1 is crucial for ensuring the proper placement of neurons in the developing brain. When an LIS1 gene is missing, brains fail to develop the characteristic folds; babies with lissencephaly or 'smooth brain' are born severely mentally retarded. But new research by Prof. Orly Reiner of the Institute's Molecular Genetics Department, which recently appeared in Nature Genetics, shows that having extra LIS1 genes can cause problems as well.

Reiner was the first to discover LIS1's tie to lissencephaly, in 1993. Their latest study shows that it works by helping to determine polarity in the cell how the various organelles are arranged inside the cell as well as where it connects to neighboring cells. Neurons alter their polarity several times during development, especially when they take on an elongated shape and migrate to new locations in the brain.

But what if, rather than too little, the body has too much LIS1? One of the surprises to come out of the recent spate of post-human-genome research is the number of genes that can be repeated or deleted in an individual's genome. Most extra copies of genes may be no more harmful than a computer backup disk, but scientists have been finding that some repeats can cause disease.

Research associate Dr. Tamar Sapir and lab technician Talia Levy, working in Reiner's lab, developed a mouse model in which additional LIS1 protein was produced in the brain. The scientists found that the brains of these mice were a bit smaller than average. On closer inspection, they discovered a range of subtle changes in cell polarity and movement: Nuclei within the proliferating zone tended to move faster, but with less control; rates of cell death were higher; and various factors in the cell became more disordered.

Reiner then asked whether their findings might apply to humans. Together with Jim Lupski and Drs. Weimin Bi and Oleg A. Shchelochkov of Ba
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Contact: Yivsam Azgad
news@weizmann.ac.il
972-893-43856
Weizmann Institute of Science
Source:Eurekalert

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