Technology Discussion—DNA Chips

Several chip platforms have been developed to facilitate molecular biology research. For example, industry leader Affymetrix (www.affymetrix.com ) has developed chips programmed to act like living cells. These chips can run thousands of tests in short order to help scientists determine a specific gene’s expression.

Scientists know that a mutation—or alteration—in a particular gene’s DNA often results in a certain disease. However, it can be very difficult to develop a test to detect these mutations, because most large genes have many regions where mutations can occur. For example, researchers believe that mutations in the genes BRCA1 and BRCA2 cause as many as 60 percent of all cases of hereditary breast and ovarian cancers. But there is not one specific mutation responsible for all of these cases. Researchers have already discovered over 800 different mutations in BRCA1 alone.

The DNA chip is a tool used to identify mutations in genes, such as BRCA1 and BRCA2. The chip, which consists of a small glass plate encased in plastic, is manufactured somewhat like a computer microchip. On the surface, each chip contains thousands of short, synthetic, single-stranded DNA sequences, which together, add up to the normal gene in question. To determine whether an individual possesses a mutation for BRCA1 or BRCA2, a scientist first obtains a sample of DNA from the patient's blood as well as a control sample—one that does not contain a mutation in either gene.

The researcher then denatures the DNA in the samples, a process that separates the two complementary strands of DNA into single-stranded molecules. The next step is to cut the long strands of DNA into smaller, more manageable fragments and then to label each fragment by attaching a fluorescent dye. The individual’s DNA is labeled with green dye and the control, or normal, DNA is labeled with red dye. Both sets of labeled DNA are then inserted into the chip and allowed to hybridize (bind) to the synthetic BRCA1 or BRCA2 DNA on the chip. If the individual does not have a mutation for the gene, both the red and green samples will bind to the sequences on the chip.

If the individual does possess a mutation, the individual's DNA will not bind properly in the region where the mutation is located. The scientist can then examine this area more closely to confirm that a mutation is present. (Explanation provided courtesy of National Institutes of Health.)

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