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Infused spleen cells found not to impact islet recovery and reversal of type 1 diabetes in mice

Researchers at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins have invented a cost-effective and highly efficient way of analyzing what many have termed "junk" DNA and identified regions critical for controlling gene function. And they have found that these control regions from different species don't have to look alike to work alike.

The study will be published online at Science Express March 23.

The researchers developed a new system that uses zebrafish to test mammalian DNA and identify DNA sequences, known as enhancers, involved in turning on a gene. In studying RET, the major gene implicated in Hirschsprung disease and multiple endocrine neoplasia (MEN2), the team identified DNA sequences that can control RET but had not been identified using standard methods. Hirschsprung disease, also known as congenital megacolon, is a relatively common birth defect marked by bowel obstruction. MEN2 is an inherited predisposition to neuroendocrine cancers.

The notion that mutations in enhancers play a role in human disease progression has been difficult to confirm because usually enhancers are located in the 98 percent of the human genome that does not code for protein, termed non-coding DNA. Unlike DNA sequences that code for protein, non-coding DNA, sometimes referred to as "junk" DNA, follows few rules for organization and sequence patterns and therefore is more difficult to study.

"The difficulty with human genetic approaches to common disease is that we lack the power to precisely localize DNA sequences that are associated with disease, often leaving us immense stretches of DNA to look at," says one of the study's corresponding authors, Andy McCallion, Ph.D., an assistant professor in the McKusick-Nathans Institute. Most often one is limited to looking in the most obvious places, which may not yield the best results. "Until now," he says, "we've only been able to look under the lamplights for the car keys."

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Source:Joslin Diabetes Center


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