Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Elucidation of the genome for diabetics with DNA chips

15.02.2007
The genome of patients with type 2 diabetes (DT2) has been elucidated, for the first time, thanks to the use of new DNA chip technologies allowing 400,000 DNA mutations to be studied simultaneously.

New genes conferring a predisposition to DT2 have been identified. They include the zinc transporter of pancreatic insulin-secreting cells (ZnT8), which is a potential target for treatment. This study of the French population was carried out as a French-British-Canadian collaboration between the teams directed by Philippe Froguel (CNRS, University of Lille 2, Pasteur Institute, Imperial College London) and Rob Sladek (McGill University, Montreal, Canada). About 70% of the genetic risk of DT2 is accounted for by these new discoveries, published online in Nature on February 11 2007. This work opens up entirely new avenues of prevention and treatment for this disease.

There are more than 200 million diabetics worldwide, and it has been predicted that this number will double by 2030. This increase in the number of diabetics is linked to the obesity epidemic, which currently affects 1.1 thousand million people, including 150 million children. However, heredity also makes a major contribution to the development of DT2. Abnormalities in insulin secretion appear very early in the children of diabetic parents. These individuals become hyperglycaemic when they put on weight and are resistant to the insulin they produce. The team of Philippe Froguel was the first to identify a gene associated with DT2 — that encoding glucokinase — in 1992. Several other such genes have since been discovered, but together these genes account for only a small proportion of DT2 cases. Insufficient knowledge of the human genome and the absence of cheap, simple-to-use, rapid analytical techniques hampered progress in medical research for many years. The recent sequencing of the human genome and the establishment of a complete map of DNA variations in the human species have finally made it possible to explore genetic predisposition to DT2 in its entirety. In 2006, a revolutionary genetic analysis technique was developed in the United States. This method is based on the use of DNA chips, with a surface of only a few square centimetres, carrying almost half a million DNA mutations. Each of these chips can be used to dissect the entire genome of an individual.

Initially, DNA from non-obese patients with type 2 diabetes and a family history of the disease was compared with DNA from 669 non-diabetic subjects from the DESIR study, a prospective study run by INSERM and directed by Beverly Balkau. The key results of this first screening were then confirmed in more than 5500 French diabetic patients treated at Corbeil-Essonnes Hospital (Guillaume Charpentier) and Poitiers University Hospital (Samy Hadjadj) and in additional control subjects. These results demonstrate very strong associations between DT2 and at least four genes encoding proteins playing major roles in the development of the pancreas and of insulin-producing cells: TCF7L2, HHEX, EXT2 and SLC30A8.

... more about:
»DNA »DT2 »Insulin »ZnT8 »diabetic »obesity »pancreas

TCF7L2 and HHEX encode transcription factors (molecules regulating the activity of other genes) controlling the Wnt signalling pathway essential for cell survival. Studies in animals have shown that the absence of these genes impairs pancreatic function.

EXT2 encodes an enzyme involved in the foetal development of several organs, including the pancreas. This enzyme also regulates Wnt signalling.

Finally, the SLC30A8 gene encodes the ZnT8 protein, which is involved in zinc transport. This protein is involved in insulin binding in the pancreas. According to the work of the French team directed by P. Froguel and Mellitech, a biotech company from Grenoble, ZnT8 is the only molecule apart from insulin produced exclusively in the insulin-secreting beta cells of the pancreas. Zinc is a trace element present in very small amounts in the body, but essential for survival. Zinc deficiency is common in developing countries and has been associated with many diseases, including dabetes.

These four genes may account for up to 70% of the hereditary basis of DT2. Several tens of other strong "signals" have also been identified. If confirmed, these signals may complete the diabetic genome map.

This work has predictive value and has potential implications for DT2 prevention and treatment. At a time when the number of diabetics is soaring due to the increasing frequency of early, severe obesity, we need to be able to establish the profile of the young adults most at risk; this would allow personalised preventive strategies to be implemented. Some of the genes identified in this study, including the ZnT8 zinc transporter gene in particular, may be good targets for treatments to combat DT2.

These results from the analysis of very high-density DNA chips — the first in the world for a common disease like DT2 — demonstrate the validity of this approach. The method will be made available in France in March 2007, through the CNRS genotyping platform at Lille, largely funded by the Nord-pas-de-Calais Regional Council. These advances should make it possible to unravel genetic predisposition to vascular complications of diabetes and to solve the mysteries shrouding childhood obesity and certain cancers linked to obesity . The work of this French-British-Canadian team was financed principally by the Canadian government and by the province of Quebec. The DNA chips were produced at the genomics centre in Montreal.

Monica McCarthy | EurekAlert!
Further information:
http://www.cnrs-dir.fr

Further reports about: DNA DT2 Insulin ZnT8 diabetic obesity pancreas

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | 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

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>