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Taking 'chips' to the next level of gene hunting

Researchers at the Johns Hopkins' High Throughput Biology Center have invented two new gene "chip" technologies that can be used to help identify otherwise elusive disease-causing mutations in the 97 percent of the genome long believed to be "junk."

A variety of DNA microarray technology, one of the two new chips, called the TIP-chip (transposable element insertion point) can locate in the genome where so-called jumping genes have landed and disrupted normal gene function. This chip is described online this week in the Proceedings of the National Academy of Sciences.

The most commonly used gene chips are glass slides that have arrayed on them neat grids of tiny dots containing small sequences of only hand-selected non-junk DNA. TIP-chips contain on them all DNA sequences. Because each chip can hold thousands of these dots - even a whole genome's worth of information - scientists in the future may be able to rapidly and efficiently identify, by comparing a DNA sample from a patient with the DNA on the chip, exactly where mutations lie.

"With standard chips, we're missing a big piece of the picture of mutations in humans because they look only at the meaty parts of genes, but the human genome is only 3 percent meaty parts," says Jef Boeke, Ph.D., Sc.D, professor of molecular biology and genetics and director of the HiT (High Throughput Biology Center), who spearheaded both studies at the Institute of Basic Biomedical Sciences at Hopkins. "The other 97 percent also can contain disease-causing mutations and is often systematically ignored," he says.

Boeke and his team have focused particularly on transposable elements, segments of DNA that hop around from chromosome to chromosome. These elements can, depending on where they land, wrongly turn on or off nearby genes, interrupt a gene by lodging in the middle of it, or cause chromosomes to break. Transposable elements long have been suspected of playing a role vital to disease-causing
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Source:Johns Hopkins Medical Institutions


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