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July 25, 2013

Down syndrome's extra chromosome silenced in lab cells

Scientists silenced the extra copy of a chromosome that causes Down syndrome in laboratory stem cells, offering the first evidence that it may be possible to correct the genes responsible for the disorder.

The findings, published Wednesday in the journal Nature, offer new cell models for developing potential treatments, researchers said. The models, aided by gene-manipulating technology from Sangamo Biosciences Inc., may help researchers discover drug targets for other ill health effects that come with the syndrome, including heart disease, hearing difficulties, and weakened muscles.

Down syndrome slows physical and intellectual development. About 6,000 babies are born every year with the condition, which is caused by an extra copy of chromosome 21, according to the U.S. Centers for Disease Control and Prevention. While some genetic disorders have been easier to study because a single gene drives them, Down syndrome is more complex, said Robert Nussbaum, chief of genomic medicine at the University of California, San Francisco.

"It's a technical tour-de-force," Nussbaum said of the research, in a telephone interview. "We don't really understand why the extra copy of chromosome 21 causes the problems it does. So this might allow us to have a thorough description of what goes wrong." Nussbaum wasn't involved in the study.

While the findings aren't a cure for Down syndrome, they make what was once a mysterious disorder much easier to study, Nussbaum said.

In Wednesday's paper, researchers led by Jeanne Lawrence, a professor of the department of cell and developmental biology at the University of Massachusetts Medical School, used a gene called Xist. The gene creates a regulating piece of RNA that ordinarily quiets the second X chromosome in women. In women, the extra RNA makes copies that coat the whole second X chromosome, preventing it from producing proteins. The scientists wondered if this quieting effect could be used specifically to silence the third copy of chromosome 21.

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