Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The importance of gene regulation for common human disease

17.09.2007
A new study published in Nature Genetics on Sunday 16 September 2007 show that common, complex diseases are more likely to be due to genetic variation in regions that control activity of genes, rather than in the regions that specify the protein code.

This surprising result comes from a study at the Wellcome Trust Sanger Institute of the activity of almost 14,000 genes in 270 DNA samples collected for the HapMap Project. The authors looked at 2.2 million DNA sequence variants (SNPs) to determine which affected gene activity.

They found that activity of more than 1300 genes was affected by DNA sequence changes in regions predicted to be involved in regulating gene activity, which often lie close to, but outside, the protein-coding regions.

"We predict that variants in regulatory regions make a greater contribution to complex disease than do variants that affect protein sequence," explained Dr Manolis Dermitzakis, senior author from the Wellcome Trust Sanger Institute. "This is the first study on this scale and these results are confirming our intuition about the nature of natural variation in complex traits.

... more about:
»Complex »DNA »HapMap »Variation »regulatory

"One of the challenges of large-scale studies that link a DNA variant to a disease is to determine how the variant causes the disease: our analysis will help to develop that understanding, a vital step on the path from genetics to improvements in healthcare."

Past studies of rare, monogenic disease, such as cystic fibrosis and sickle-cell anaemia, have focused on changes to the protein-coding regions of genes because they have been visible to the tools of human genetics. With the HapMap and large-scale research methods, researchers can inspect the role of regions that regulate activity of many thousands of genes.

The HapMap Project established cell cultures from participants from four populations as well as, for some samples, information from families, which can help to understand inheritance of genetic variation. The team used these resources to study gene activity in the cell cultures and tie that to DNA sequence variation

‘We have generated an information resource readily available to investigators working in the mapping of variants underlying complex traits. Regions of association can be correlated with signatures of regulatory regions affecting gene expression' explained Dr Panos Deloukas, Senior Investigator at the Wellcome Trust Sanger Institute

"We found strong evidence that SNP variation close to genes - where most regulatory regions lie - could have a dramatic effect on gene activity," said Dr Barbara Stranger, postdoctoral fellow at WT Sanger Institute. "Although many effects were shared among all four HapMap populations, we have also shown that a significant number were restricted to one population."

They also showed that genes required for the basic functions of the cell - so-called housekeeping genes - were less likely to be subject to genetic variation. "This was exactly as we would expect: you can't mess too much with the fundamental life processes and we predicted we would find reduced effects on these genes," said Dr Dermitzakis.

The study also detected SNP variants that affect the activity of genes located a great distance away. Genetic regulation in the human genome is complex and highly variable: a tool to detect such distant effects will expand the search for causative variants. The authors note, however, that the small sample size of 270 HapMap individuals is sensitive enough to detect only the strongest effects.

The results of this study are becoming available in public databases such as Ensembl for researchers to use.

The paper is accompanied by two others examining effects of changes to regulatory DNA in samples from asthma and from heart study patients.

Don Powell | alfa
Further information:
http://www.sanger.ac.uk
http://www.wellcome.ac.uk/

Further reports about: Complex DNA HapMap Variation regulatory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>