Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic mutations identified that suggest link between type 1 diabetes and common viral infection

09.03.2009
The rare genetic mutations also reduce the risk of developing the disease

Scientists from Cambridge University have discovered four rare mutations of a gene associated with type 1 diabetes (T1D) that reduce the risk of developing the disease. Their findings, published today in the journal Science Express, suggest a link between T1D and the enterovirus (a common virus that enters via the gastrointestinal tract but is often non-symptomatic).

Everyone carries the IFIH1 gene, which plays a role in the body's antiviral responses. Importantly, it is also located in the region of the human genome associated with T1D, an autoimmune disorder which results in the body attacking its own insulin-producing pancreatic cells. The IFIH1 gene codes for a protein that recognizes the presence of viruses in the cell and controls immune activation. It is within this gene that scientists have identified four gene variants that protect against T1D.

Enteroviruses are well known to be associated with T1D: enterovirus infections are more common among newly diagnosed T1D patients and pre-diabetic subjects than in the general population and often precede the appearance of biological markers for pre-diabetes. However, no one knows if these infections are a cause of type 1 diabetes.

The study by Nejentsev et al., which was conducted at the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, establishes that the IFIH1 protein is involved in T1D, highlighting a molecular pathway by which enterovirus infections may contribute to the development of the disease. The four rare variants they identified, which are predicted to reduce function of the IFIH1 protein, consistently decrease the risk of T1D, rather than predispose to it. This suggests a model where normal immune activation caused by enterovirus infection and mediated by IFIH1 protein stimulates autoimmunity that eventually leads to T1D.

Professor John Todd, senior author on the study, said: "We have been able to pin-point one particular gene among a long list of candidates. Now we and others can begin to study the biology of IFIH1 in the context of type 1 diabetes knowing that it is part of the cause of the disease."

In the past three years genome-wide association studies have been a major success, revealing dozens of regions in the human genome that harbour genes which predispose individuals to various diseases, such as diabetes or cancers. Nevertheless, as disease-associated regions may contain several genes with different functions, scientists rarely know which gene or gene variant (mutations of the gene) in these regions cause the disease.

In order to overcome this limitation, the scientists searched for variants that had obvious biological effects, e.g. those affecting gene expression or protein function. They hypothesized that if a gene harbors several such variants, then it is likely to be causative. Most of such variants are rare in the population and are not tested in genome-wide association studies. Nevertheless, they could be discovered by sequencing (examining the sequence of the pairs of nucleotides which make up a gene).

The researchers studied 10 candidate genes associated with T1D. Using a novel technique (high throughput sequencing of DNA pools) in collaboration with 454 Life Sciences, a Roche company, they examined the DNA of 480 T1D patients and 480 healthy controls. This approach allowed them to not only discover several rare variants associated with T1D, but also to accurately measure their frequency in the pools of patients and controls.

The researchers then genotyped approximately 30,000 individuals who were either T1D patients, controls or family members and proved that four rare variants or versions that reside in the gene IFIH1 reduce the risk of developing T1D.

The study demonstrates that re-sequencing genes associated with diseases can help pinpoint the specific gene or genes that lead to the disease.

"Finding several new rare disease variants with clear biological functions was crucial. Not only has this proved that IFIH1 is involved in type 1 diabetes, it also gave us clues to understand the mechanism" said Dr. Sergey Nejentsev, Royal Society Research Fellow at the Department of Medicine, the first author of the study. He added: "This experiment shows the way to identify causative genes contributing to various common diseases."

Genevieve Maul | EurekAlert!
Further information:
http://www.cam.ac.uk

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>