Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The usual suspects: a new gene affecting diabetes

02.07.2007
According to a study to be published in the journal Nature Genetics, variations in the WFS1 gene – which is known to affect both the survival and function of insulin-producing cells in the pancreas – can be linked to type 2 diabetes susceptibility. The study has two major implications – it identifies a new risk factor in a disease reaching epidemic levels worldwide while also showing that variations in a gene – and not only mutations – can lead to type 2 diabetes.

The importance of the last finding resides in the fact that gene variations – contrary to the extremely rare mutations – are relatively common in the population. Also interesting is the fact that this gene, when mutated, is known to lead to a rare syndrome while the new study show that relatively common variations can predispose to diabetes revealing a larger spectrum of effects than previously thought.

Diabetes – which name comes from the Greek word “siphon” due to the excessive urination of patients – results from incapacity of using the glucose in the blood. The metabolism of glucose is mediated by insulin –a hormone produced by the beta cells in the pancreas – which controls the passage of this sugar from the blood and into the cells where it can be used as energy. When this does not happen, the glucose accumulates in the blood leading to the long-term health problems associated with diabetes, including eye, kidney, and nerve damage.

Type 2 diabetes - one of the two major types of diabetes accounting for 90% of all the cases– is caused by a combination of insulin resistance (where the cells of the body do not respond to the hormone) and low insulin production. The disease results from genetic and environmental factors where an unhealthy diet and decreased physical activity habits act on genetically susceptible individuals and although it used to be mostly prevalent on adults after the age of 40 but now, with the increasing obesity epidemic, cases among young children are becoming more and more common. At the moment there is no cure for diabetes consequently, studies to better understand the disease causing mechanisms so to improve control of its potentially catastrophic health and economic problems are now a major priority around the world.

Genetic approaches have so far been limited and although the disease is believed to be affected by multiple genes until last year only three had been identified. Recent large scale studies have led to five more genes being associated with the disease, but still much remains to be understood on the causes of type 2 diabetes.

And studies that search for disease causes, by comparing the full genome of patients and healthy controls, can, for example, miss genetic “variations” with mild effects on disease susceptibility. In this case, alternative studies capable of high-powered analysis of specific genes, such as those with functions directly related to the biology of the disease, can complement the genome-wide approaches allowing a more detailed idea of the disorder. Furthermore, the genome-wide approaches are not only expensive but also difficult to perform in large numbers of individuals.

With this in mind Manjinder S Sandhu, Inês Barroso and colleagues at Cambridge in collaboration with other groups in the UK, US and Israel, decided to look at 84 genes thought to be involved in beta-cell development, growth, function and/or survival, searching for associations with type 2 diabetes. Since beta-cells produce insulin and type 2 diabetes patients are known for their insulin problems, these genes seemed ideal candidates as possible susceptibility factors.

The study used a new weapon of genetic analysis called single nucleotide polymorphisms (SNPs). Nucleotides are the structural units of DNA, being DNA like a long chain of beads and each nucleotide one bead, while SNPs are, like the name indicates, variations in the DNA sequence of only one single nucleotide. SNPs, contrary to mutations, are relatively common with each variation existing in at least 1% of the population, and it is this abundance that makes them perfect tools to create ultra-fine-resolution genetic maps in humans associating different variations with distinct disorders.

Sandhu, Barroso and colleagues' study started by looking into four different groups - three UK and one North European Jewish population – and were able to describe the existence of 1536 different SNPs in the 84 genes linked to the insulin-producing beta cells of the pancreas.

In order to confirm the importance of these SNPs in disease, the next step was to analyse their presence in the diabetic and the healthy individuals. initially in the 3 UK groups where 18 SNPs were significantly more common among the diabetic patients than among the healthy controls, suggesting that they could in fact contribute to disease.

The next step, in order to confirm the link of these 18 SNPs to disease, was to test them against a population with a totally different genetic makeup, in this case a group of Ashkenazi individuals, which are a central and north Europeans descendant Jewish population. From this analysis only two SNPs remained linked to type 2 diabetes and interestingly, both variations in the same gene - the Wolfram syndrome 1or WFS1 gene.

WFS1 is a gene active in the pancreas where is known to affect the survival and proper function of the beta-cells. Mutation in this gene can cause a rare syndrome called the Wolfram syndrome 1, a genetic neurodegenerative disease with several diabetic-like symptoms.

Also interesting was the fact that none of two SNPs associated with type 2 diabetes affected the sequence of the protein produced by WFS1, which is the most common way to lead to disease, hhighlighting how little is still known on the roles of different types of DNA both in health and in human disease.

In conclusion, while genome-wide studies are good to find genetic alterations with a strong effect on disease, for variations with a milder effect, like WFS1, approaches based on higher-powered studies, using large numbers of individuals, may be a useful complement to find correlations that could be otherwise missed.

“Our study reinforces the idea that knowledge-based genetics can uncover the foundation of common disease,” - said Dr Barroso, a Portuguese researcher and the leading author of the study - “Our targeted approach efficiently surveys many of the genes that we consider might lead to onset of diabetes”.

Sandhu, Barroso and colleagues´ study is particularly interesting because not only it identifies a new risk factor to a disease with serious health and economical implications - the World Health Organization calculates that in 2006 more than 180 million type 2 diabetics exist worldwide – but also because it shows how a single gene, depending if it is mutated or simply have different variations, can result in totally different outcomes in the different individuals.

Catarina Amorim | alfa
Further information:
http://www.srl.cam.ac.uk
http://www.sanger.ac.uk
http://www.nature.com/ng/index.html

Further reports about: Barroso DNA Genetic Insulin SNP WFS1 approach factor pancreas studies type 2 diabetes

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | 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

 
Latest News

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

Metallic nanoparticles will help to determine the percentage of volatile compounds

20.10.2017 | Materials Sciences

Shallow soils promote savannas in South America

20.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>