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 Are there sustainable solutions in dealing with dwindling phosphorus resources?
16.10.2017 | Leibniz-Institut für Nutzierbiologie (FBN)

nachricht Strange undertakings: ant queens bury dead to prevent disease
13.10.2017 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

Im Focus: New nanomaterial can extract hydrogen fuel from seawater

Hybrid material converts more sunlight and can weather seawater's harsh conditions

It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...

Im Focus: Small collisions make big impact on Mercury's thin atmosphere

Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.

Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

Conference Week RRR2017 on Renewable Resources from Wet and Rewetted Peatlands

28.09.2017 | Event News

 
Latest News

A single photon reveals quantum entanglement of 16 million atoms

16.10.2017 | Physics and Astronomy

The melting ice makes the sea around Greenland less saline

16.10.2017 | Earth Sciences

On the generation of solar spicules and Alfvenic waves

16.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>