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Genome-Wide Mouse BAC Brought to Microarray

NEW YORK, April 1 - Researchers have for the first time used genome-wide mouse BAC arrays to hunt for genetic links to tumors, according to results of a recent study.


Studying the way a 960-mouse BAC array can detect the loss of heterozygosity compared with the more conventional microsatellite approach, the researchers found that "BACs are great for detecting absolute copy number changes in tumors," according to Allan Balmain, a professor of cancer genetics at the University of California, San Francisco Cancer Center, and a study author.

"It enables you to detect absolute changes in copy numbers or deletion numbers of genes," he added. "We needed a genome-wide method for rapidly narrowing down important areas for research."


The research, published in April's Nature Biotechnology, marked the first time that use of genome-wide mouse BAC arrays was reported, Balmain said. Research for this paper was also performed by scientists at Baylor College of Medicine in Houston and the Wellcome Trust Sanger Institute in the UK. Researchers used glass microarrays made by Spectral Genomics, of Houston.


While scientists using the BAC approach were able to detect absolute copy number changes with high fidelity, the microsatellite analysis often provided better qualitative indications of allele loss or imbalance, the authors write. This led the team to recommend using a combination of both approaches to help detect genetic links to tumors.


However, the speed of doing a BAC study, in which a thousand BACs on one chip can be hybridized in several hours versus conventional microsatellite analysis, which often take weeks, may prove more applicable to drug- and diagnostic-development, said Balmain.


"The primary application is for tumor screening," he said. "You could use BAC-array profiles as a diagnostic tool to show how nasty a tumor is."


Then there's drug discovery: "BAC arrays at high resolution allow us to find the [onco]genes. When you find specific genes, they are good targets for drug discovery," Balmain said.


The number of BACs on a single chip could rise to 30,000 within two or three years, according to Balmain.

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