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Wisconsin Partners Win $4.3M for Type 1 Diabetes Genes Research

NEW YORK (GenomeWeb News) – The Medical College of Wisconsin and the Children's Hospital of Wisconsin Research Institute plan to use a $4.3 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases to study a number of genes that may be involved in type 1 diabetes.

The partners plan to use zinc-finger nuclease (ZFN) technology and transcription activator-like effector nuclease (TALEN) technology to study and manipulate genes on a number of chromosome regions that have been identified as contributing to type 1 diabetes, MCW said today. They will test these technologies in a type 1 diabetes animal model and also plan to try to contribute new knowledge that could be used in approaches to treating this disease.

MCW said that using traditional genetic engineering methods for manipulating the many genes involved in this study "would take a tremendous amount of time and money."

The study will be led by principal investigators Aron Geurts, an associate professor of physiology at MCW, and Yi-Guang Chen, an assistant professor of pediatrics at MCW. Geurts received a National Institutes of Health Director's New Innovator Award in 2011 for efforts using zinc-finger nuclease technology to develop improved animal models for disease studies.

Type 1 diabetes accounts for around five percent of all diabetes cases in the US and affects about 1.3 million Americans, and its incidence has been increasing in recent years, MCW said.

"Through large-scale genetics studies in humans, others have recently identified about 50 different chromosome regions in the human genome likely containing genes that contribute to the risk or progression of T1D," the investigators explained in their project proposal. "Unfortunately, we still do not know for the most part which specific genes within these regions are playing a role," they wrote, adding that more research into these genes and regions could lead to better risk assessment and development of new therapeutic targets.

They said that the ZFN and TALEN technologies have made it much more efficient to genetically modify animal models, such as the Non-Obese Diabetic mouse model, for pursuing such research projects. These techniques enable them to knock in very specific mutations into mouse and rate genomes, where they will investigate a large number of potential human type 1 diabetes genes.

"We expect to uncover a significant number of new genes which are playing a role in this terrible disease and will represent new biomarkers for identifying at-risk individuals and provide new targets for therapies to be developed," the investigators said.

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