July 15, 2009
UI biologist and colleagues describe new technique to assist genetic researchers
A University of Iowa biologist and researcher in the Department of Biology and Roy J. Carver Center for Genomics, and his colleagues at Harvard University and the Carver Center for Genomics, describe a new and more effective way of identifying where important RNA (Ribonucleic acid) transcripts are located on the human genome in a paper published in the June 28 online issue of the journal Nature Genetics.
The studies helped demonstrate that mutations that cause colorectal cancer were not altering the expression of novel RNA transcripts on a region of the eighth chromosome and helped show that the mutations were likely altering regulatory regions of a known cancer gene, referred to as c-Myc.
John Manak, assistant professor of biology in the UI College of Liberal Arts and Sciences, said that the new technique should help researchers to discover new genes as well as new RNA transcript isoforms for any organism, including humans, with much greater precision and with less worry of identifying false positives. Manak worked with another Iowa colleague, Harsha Doddapaneni, to employ the methodology.
"This methodology sorts through complex data generated from a genomics platform called a tiling microarray and allows researchers to get to the real genes associated with disease much faster than previously possible," said Manak. "Imagine a gumball in a jar of marbles. If you are able to identify the gumball with a high degree of accuracy, you won't wind up with a mouthful of broken teeth. You want to get to the relevant stuff and leave the rest behind."
"The technique changes the way of analyzing this type of genomic data. In the past, this technique was prone to erroneously identifying new transcripts and genes due to the fact that the technique did not have the proper internal controls. The old way of doing it provided evidence for RNA transcripts that really weren't there at all. Using our new method, researchers can now subtract artifacts, or false data, from their results, and they will have the real data," he said.
Manak's collaborators at Harvard University found that an inherited variant located on a particular region of the eighth chromosome of the human genome (8q24) has a significant association with colorectal cancer. Manak and his fellow researchers found that the region containing the variant is not transcribed but is actually a "transcriptional enhancer" of the known cancer gene c-myc (enhancers are short regions of DNA that regulate transcription, which, in turn, is defined as the synthesis of RNA from a DNA template). That information and other data provide strong support for c-Myc being the causative gene for this type of colorectal cancer.
"Years of work are now called into question," Manak said. "Basically, any transcriptional data generated with tiling arrays, especially studies that propose large amounts of novel transcription, must be re-examined. With this new technique, we force researchers to carefully re-evaluate their old data."
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