Search For The 'On' Switches May Reveal Genetic Role In Development And Disease

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Search For The 'On' Switches May Reveal Genetic Role In Development

And Disease

http://www.sciencedaily.com/releases/2008/01/080124132515.htm

A new resource that identifies regions of the human genome that

regulate gene expression may help scientists learn about and develop

treatments for a number of human diseases, according to researchers

at Duke's Institute for Genome Sciences & Policy (IGSP).

" The majority of DNA in our bodies is packaged, or tightly

structured, " said Crawford, Ph.D., a researcher in the IGSP

and one of the senior investigators on this study. " Our goal was to

identify the areas of DNA across the entire genome that are not

packaged, because we know those are the regions that are important in

regulating gene activity. "

They combined two known processes to look at regulatory regions

across the whole human genome, Crawford said.

" We used an enzyme called DNase that has been known for decades to

preferentially identify unpackaged regions of DNA, " he said. " In this

study, we identified all unpackaged regions within the entire genome

using two extremely efficient methodologies: microarrays and

sequencing. "

Microarrays are glass slides on which scientists can simultaneously

look at millions of short pieces of DNA. New sequencing technologies

are able to determine the genetic code of millions of DNA fragments.

Together, these tools generated guides to understanding the location

of the unpackaged regions, and the researchers compared the results

found using each method and found high levels of agreement.

By combining the two methods, the researchers were able to scan the

entire genome efficiently.

" Scientists have used similar methods to look at tiny portions of the

genome in the past, but ours is the first technology to really allow

researchers to look at the whole genome, so we can see all of the

areas where gene regulation occurs, " said Terrence Furey, Ph.D., a

researcher in the IGSP and co-senior investigator on this

study. " Identifying these sites may help us understand the biological

basis for gene regulation expression patterns in different cell

types. We'll also compare patterns within and across species, in

response to external stimuli and in diseased tissues. "

The researchers said they looked at normal cells for this study

because in order to understand anything about disease or the aging

processes, it's important to first understand what a normal cell

looks like.

" Perhaps in the future, this data resource could help researchers

learn to turn a harmful gene off or increase the expression of

helpful ones, " Furey said.

The researchers published their findings in the January 25, 2008

issue of the journal Cell. The study was funded by the Duke IGSP and

the National Human Genome Research Institute.

Other researchers involved with this study were Alan Boyle of the

IGSP at Duke; , Elliott Margulies and Meltzer of the

National Institutes of Health; and Hennady Shulha and Zhiping Weng of

Boston University.