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Non-coding DNA implicated in type 2 diabetes

Variations in non-coding sections of the genome might be important contributors to type 2 diabetes risk, according to a new study.

DNA sequences that don't encode proteins were once dismissed as "junk DNA", but scientists are increasingly discovering that some regions are important for controlling which genes are switched on.

The new study, published in Nature Genetics, is one of the first to show how such regions, called regulatory elements, can influence people's risk of disease.

Type 2 diabetes affects over 300 million people worldwide. Genetic factors have long been known to have an important role in determining a person's risk of type 2 diabetes, alongside other factors such as body weight, diet and age.

Many studies have identified regions of the genome where variations are linked to diabetes risk, but the function of many of these regions is unknown, making it difficult for scientists to glean insights into how and why the disease develops. Only around two per cent of the genome is made up of genes: the sequences that contain code for making proteins. Most of the remainder is shrouded in mystery.

"Non-coding DNA, or junk DNA as it is sometimes known, is the dark matter of the genome. We're only just beginning to unravel what it does," said leading author Professor Jorge Ferrer, a Wellcome Trust Senior Investigator from the Department of Medicine at Imperial College London.

In the new study scientists mapped the regulatory elements that orchestrate gene activity in the cells of the pancreas that produce insulin, a hormone that regulates blood sugar.

In type 2 diabetes, the tissues become less responsive to insulin, resulting in blood sugar levels being too high. Most people can compensate when this happens by producing more insulin, but in people with type 2 diabetes, the pancreas cannot cope with this increased demand.

"The cells that produce insulin appear to be programmed to behave differently in people with type 2 diabetes," said co-author Mark McCarthy, a Wellcome Trust Senior Investigator at the University of Oxford. "This study provides some important clues to the mechanisms which are disturbed in the earliest stages of the development of type 2 diabetes, and may point the way to novel ways of treating and preventing the disease."

The team identified genome sequences that drive gene activity in insulin-producing cells specifically. They found that these sequences are located in clusters, and that genetic variants known to be linked to diabetes risk are also found in these clusters.

"Many people have small DNA variants in such regulatory elements, and these variants affect gene expression in the cells that produce insulin. This knowledge will allow us to understand the detailed mechanisms whereby specific DNA variants predispose to diabetes," said Professor Ferrer.

For more information please contact:

Sam Wong
Research Media Officer
Imperial College London
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248
Notes to editors
1. L. Pasquali et al. 'Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants.' Nature Genetics, 12 January 2014.

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Sam Wong | EurekAlert!
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