Scientists have for the first time instantly mapped an entire genome with DNA chips, postage stamp-sized arrays of DNA snippets. The success, reported in today's Science , could pave the way to a better understanding of conditions--such as susceptibility to heart disease--thought to be caused by contributions of several genes.
Pinpointing the location of the genes for traits controlled by single genes is relatively straightforward. But it's much harder to track traits that may be caused by the combined workings of several genes scattered throughout the genome. To circumvent that problem, geneticists Elizabeth Winzeler, Dan Richards, and Ronald Davis, along with their colleagues at Stanford and Duke universities, turned to DNA chip technology currently under development at the biotech firm Affymetrix in Santa Clara, California. Affymetrix researchers had previously designed chips composed of over 150,000 snippets of yeast DNA dotted across a silicon wafer. These snippets correspond to overlapping DNA fragments from a complete yeast genome sequenced in 1996.
To map yeast genes, the team obtained DNA from two different yeast strains, called S96 and YJM789, and used enzymes to break them into small pieces. After tagging the pieces with a fluorescent compound, the team applied the fragments to the chips, one yeast strain at a time. If the fragment exactly matched a snippet on the chip, it would bind. Because the S96 genome is virtually identical to that of the strain used to prepare the chip, almost all of the S96 fragments matched those on the chip. But tests on the second strain--YJM789--revealed over 3000 spots on the array with little fluorescence, denoting mismatches, or differences, with the reference strain. By comparing the sequences of the snippets that didn't bind to any of the test fragments with the known genome sequence, the researchers could determine where each of these mismatches fell on the genome.
"This is a brand-new age. It's really exciting," says Jasper Rine, a geneticist at the University of California, Berkeley. He says the work is "a terrific demonstration" of how researchers can now analyze entire genomes in a single step--an achievement that should aid efforts to map multigene traits. Still, because current chips offer complete surveys only of relatively small genomes, or samples of larger ones, advances in identifying the microbial genes are expected to come much faster.