Method quickly surveys yeast genome by gene function, not sequence

stinguish brands and sizes of packaged foods. (Mutations in the remaining genes are fatal regardless of environment, so those are not considered.)

The genetic barcodes, first reported in 1996, are unique, 20-block-long pieces of DNA inserted into the genetic material of each mutant. Shoemaker now has barcodes in all of the existing yeast mutants. He's also developed a microarray that acts as a "checkout scanner" to read these barcodes.

The microarray is a grid of thousands of tiny spots on a piece of glass roughly one-fourth the size of a dollar bill. Each spot holds a unique "sensor," a strand of DNA that precisely matches one of the barcodes. Machines then read the microarray "chip" to determine which of the sensors found matching barcodes.

"While regular checkout scanners at the grocery store can only read one barcode at a time, the chip can read all the barcodes at once," says Boeke, co-director of a new microarray facility that will soon open to serve researchers at the Johns Hopkins School of Medicine. Initial funding for the facility was provided by the school's Institute for Cell Engineering. The facility is co-directed by Forrest Spencer, Ph.D., of the school's McKusick-Nathans Institute of Genetic Medicine.

To prove they could identify genes' functions by pooling the mutants and using the barcodes, Boeke turned to his lab's study of how cells fix DNA, a process that is crucial in the immune system and in preventing cancer cells from forming, he says. For their experiments with yeast, the process also was crucial for the organism's survival.

"We're interested in how cells break strands of DNA and put them back together again, so we used the technique to search all the yeast mutants to find ones that couldn't 'fix' a test piece of DNA," says Boeke, whose studies were funded by the National Institutes of Health.


Contact: Joanna Downer
Johns Hopkins Medical Institutions

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