Over the past year, Brown and his colleagues alone have done at least 800 different measurements of how every single gene in yeast is expressed under varying conditions. They have moved in other directions, too. The tools that have been developed for analyzing genomes are "all-purpose," Brown points out; they can be used with any organism. Working with Gary Schoolnik and others at Stanford, Brown applied them to the bacterium that causes tuberculosis, Mycobacterium tuberculosis, whose DNA sequence had just been published.
"The minute a genome is sequenced, you can have an experimental tool. Bang! It's fast," says Brown. "We've already printed an array of this one. We've even done experiments looking at the response of M. tb to various antibiotics and trying to get an idea of the genetic basis for its high virulence."
In addition, Brown's coworkers have helped Stuart Kim and other Stanford scientists who study C. elegans make a microarrayer of the worm's genes. Human genes are not far behind. In fact, work with human genes started even before a rough draft of the gigantic human genome had been completed.
"As people look at large-scale pictures of the expression programs in genomes, they've begun to realize that there's at least as much information in genomes entirely devoted to controlling where and at what level the genes are expressed [as to defining protein end products]," Brown points out. Gene expression is what really distinguishes one cell from another, he says, "and suddenly, that's just an open book."
Brown's microarrays are not the only kind available to researchers. There are several different types to choose from, including the popular DNA chips made by Affymetrix, a biotech company in Santa Clara, California. These chips have much in common with silicon chips, and the technique with which they are producedphotolithographyis normally used in the semiconductor industry. Each chip is a half-inch square of glass on which thousands of short filaments of DNA have been imprinted. The DNA filaments are synthesized from lab chemicals and represent known sequences of DNA. When a liquid that contains chopped-up genes (or mRNA) from a particular cell is poured over the chip, only those bits of genetic material that perfectly complement a synthetic filament on the chip will stick to the chip and glow. A scanner then reads out their pattern.
The DNA chip technology has certain advantages, but it is still quite expensive, requiring an outlay of at least $200,000 plus the cost of additional chips. To bring whole-genome analysis within the reach of all researchers, Pat Brown recently posted a do-it-yourself guide on his Web site. The guide provides a complete list of necessary materials for his type of microarrayer. It also shows where to order these parts and explains how to put them together.
The basic equipment for the microarrayer plus the scanner costs less than $80,000, Brown says. Printing a microarray that contains the entire yeast genome now costs as little as $10, since the DNA is spotted onto conventional microscope slides. Hundreds of copies of such microarrays can be printed in just one day.
Thousands of scientists have logged on to this site in recent months. More than 100 homemade microarrayers are now in operation in labs around the country, and Brown has started to run hands-on courses through which many more researchers may learn to build their own.
Being able to do experiments with microarrays is "the main immediate benefit of having genome sequences," Brown says. He wants to make sure that this benefit spreads far and wide.
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