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Genome Annotation by Mutation

thus learn the normal job of that piece of DNA.

Capecchi says the same method also can be used to make two chromosomes break and recombine, with each new chromosome containing a piece of each of the two old ones. The process, translocation, also can create new genes from two other genes. Many cancers certain sarcomas, leukemias and lymphomas start with translocation.

Existing methods result in the desired translocation of two chromosomes in one of every 1 million to 10 million cells cultured, Capecchi says, while the new method produces the desired result in one of every 100 cells. So it is 10,000-100,000 times better.

That is important, because multiple molecular steps are needed for a mouse to develop a human cancer and such mice are used to learn how to treat or prevent cancers, says Capecchi. In many cancers, translocation of two chromosomes is the first step, and if it occurs only in one of every million cells, not enough cells are present in which subsequent steps can occur so that cancer develops.

If we now improve that 10,000-fold, the pool of cells [with translocated chromosomes] may be large enough to create a mouse that develops the cancer, so the new method makes it easier to breed mice with human cancers, Capecchi says.

Jumping Genes Help Make More Mutant DNA Wu and Capecchi improved their new method by using it in combination with a transposon or so-called jumping gene named piggyBac, which comes from a moth. They used piggyBac to insert pieces of loxP DNA randomly into numerous spots on the mouse genome. So scientists easily can breed multiple generations of mice with loxP surrounding various large stretches of DNA.

Then the first part of the new method is used: The mice are bred with mice that carry the Cre gene so any large stretch of DNA that is located between two short pieces of loxP DNA can be mutated.

Because the whole mouse genome has been sequenced
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