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New Machine at Wake Forest to Speed Hunt For Defective Genes

WINSTON-SALEM, N.C. – A new machine is automating the hunt for genes that cause diseases, greatly simplifying the search for a needle in a haystack.

Researchers at Wake Forest University Baptist Medical Center use the new technology to rapidly analyze a specimen for the entire human genome -- 30,000 genes -- in just two steps. By comparing a specimen from a tumor with nearby normal tissue, they can spot which gene or genes have mutated to cause the cancer. Finding which gene is linked to specific diseases is an important step in developing treatments.

The machine is the key element of the Microarray Core Facility which is directed by Yong Q. Chen, Ph.D., associate professor of cancer biology and endowed professor of the Prostate Cancer Center of Excellence.

Initially at least, the Microarray Core Facility will be used primarily for research. However, the system, which cost more than $250,000, has clinical applications as well.

"One hospital in the Netherlands is using a similar machine as a routine diagnostic tool, to decide how to treat a patient," he said. "It is a very useful tool for diagnosis and for determining prognosis." Chen explained that most cancers come from what are called somatic mutations, where the change in gene expression -- the gene mutation -- occurs only in the tumor. That opens the door for targeting just the mutated cells in the tumor as a treatment strategy.

Much rarer are germ line mutations, where the genetic defect is inherited, like BRCA1 and BRCA2, which account for 5-10% of breast cancer incidence.

The 30,000 genes are encoded on the DNA (deoxyribonucleic acid) in each cell in the body, which are the permanent record of the inherited coded instructions for the cell''s activity.

The DNA produces messenger RNA (ribonucleic acid), which in turn produces the cell''s proteins. Some diseases turn out to be caused by a mutation in a single gene. For instance, Huntington''s disease is caused by the mutation in a single gene which leads to a defective protein.

The new Microarray Core Facility greatly speeds the ability to look for defective genes, because it looks at so many at one time. The facility uses Affymetrix GeneChips, chips that are just one centimeter square, but which contain tens of thousands of probes. The entire human genome of 30,000 genes is represented on just two chips. The analysis takes about 24 hours, once RNA samples are prepared.

Until 10 years ago, scientists looked for defective genes in the painstakingly slow process of one gene at a time. Then came devices called arrays that could look at 588 genes at a time, then 1,200 genes.

Purchase of the Microarray Core Facility was financed half by Wake Forest University School of Medicine and half by charitable donations to the Comprehensive Cancer Center, and a growing number of researchers are using it. Chen already employs a full-time technician, Amanda Kuber, to operate the machine.

"Potentially, just about every investigator could use it," said Chen. Of the 44 core facilities available at the Medical Center as resources for all researchers, the Microarray Core Facility "could become our most-used core facility."

The facility also uses a second machine called a bioanalyzer to check on the quality of RNA samples submitted by investigators. "That is especially important for clinical samples from patients," he said. "We have to make sure we get a high quality samples."

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Contact: Robert Conn (rconn@wfubmc.edu), Karen Richardson (krchrdsn@wfubmc.edu) or Lisa Long (lclong@wfubmc.edu) at (336) 716-4587.

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