Microarrays offer new approach to studies of chronic fatigue syndrome, cervical cancer

Scientists in the Viral Exanthems and Herpesvirus Branch (VEHB), Division of Viral and Rickettsial Diseases, are fine-tuning an exciting new research strategy—gene expression profiling with DNA microarrays—for application in studies of chronic fatigue syndrome (CFS) and human papillomavirus (HPV) and cervical cancer.

"Microarray analysis is a powerful analytical tool that allows us to develop new hypotheses about genetic function and disease causation," said Elizabeth Unger, chief of VEHB’s Human Papillomavirus Section.

Developed in the mid-1990s, microarrays are "biochips" with surface collections of hundreds to thousands of immobilized genes that can be simultaneously detected and evaluated by using specialized equipment and bioinformatics. A variety of commercial and in-house arrays are available, most commonly complementary DNA and oligonucleotide arrays. The arrays are used in experiments to analyze messenger RNA extracted from human tissue and examine patterns of gene expression. The gene expression profiles between samples can be compared with each other to identify differences that may yield clues for genetic function, altered physiological pathways, or diagnostic markers.

To establish a microarray-based research program within VEHB, the team has overcome several technical hurdles, including developing optimal methods for extracting total RNA from cells and tissue specimens, refining hybridization techniques, and identifying false-positive results in microarray datasets. The most challenging part of the work has been in recording, processing, and analyzing the vast amounts of data produced in microarray experiments.

VEHB collaborated with the National Cancer Institute (NCI) and a private firm to develop an integrated CDC microarray database, called CDC MADB. "This software system will enable us to perform gene expression studies with collaborators anywhere in the world, integrate gene expression results with clinical and epidemiologic parameters, and link to public genome databases worldwide and analyze the data in real time," said Suzanne Vernon, VEHB microbiologist.

Microarray technology has had an important impact on cancer research. As a member of the NCI-sponsored Early Detction Network, VEHB is collaborating on microarray-based gene expression studies of HPV and preinvasive cervical lesions in a high-risk population. The group is also using microarray technology to study patients with CFS, for which there is no known diagnostic marker. In a study in which peripheral blood mononuclear blood cells were analyzed by using microarray-based gene expression profiling, the team was able to distinguish CFS patients from control subjects.

VEHB’s work to establish a framework for microarray technology may have benefits for other NCID research programs, according to Dr. Vernon. MADB will be available to scientists who wish to use it, and some of the group’s microarray and computational systems are housed in NCID’s Biotech Core facility, where they may have broader applications.

Reprinted from NCID Focus, Fall 2002 with permission from the National Center for Infectious Diseases, Centers for Disease Control and Prevention