Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Towards a Global Map of Epigenetic Variation Human Epigenome Project generates DNA methylation profiles of three chromosomes

30.10.2006
A new DNA map, published in Nature Genetics today, provides the first large-scale study of biological inheritance in human that is not DNA-sequence based. The map of human chromosomes 6, 20 and 22 shows that as many as one in six of our human genes might be subject to modifications that could alter their activity by epigenetic changes - under the influence of the environment. Understanding these modifications will be important in diagnosis, drug development and disease study.

The epigenome is the interface of genetics and environment, where plasticity of epigenetic changes modifies the hard wiring of our genetic code. Increasingly it is thought that at this interface lie clues to how lifestyle and the environment affect our susceptibility to many diseases.

Epigenetic changes include modification of DNA bases, through addition or removal of simple chemical tags, such as a methyl group, and similar changes of the proteins that are closely entwined with DNA to form chromatin, the functional form of the genome. Collectively, these modifications are also referred to as the 'epigenetic code' which researchers believe defines how different genetic programmes can be executed from the same genome in different tissues.

To examine how and where DNA modification might vary, the team from the Wellcome Trust Sanger Institute and Epigenomics AG measured levels of DNA methylation across three chromosomes in twelve different tissues. The results, from almost two million measurements, looked for differences between tissues as well as differences that might be linked to age or sex.

... more about:
»Chromosome »DNA »genetic marker »methylation

Although DNA methylation can vary over a wide dynamic range, the study revealed the majority of sites to have on/off status (e.g. being unmethylated or methylated) and identified distinct regions in the genome where methylation differs between tissues but no significant differences were found between two age groups - average age 26 years old and average age 68 years old. Age has been suspected to influence the plastic changes in methylation, and perhaps influence disease processes, but these remarkable results suggest methylation states are more stable than previously thought. The authors do emphasize that discrete changes may occur in regions or tissues not examined here.

Moreover, the two sexes showed indistinguishable patterns of methylation of regions not on the sex chromosomes, X and Y, or part of imprinted regions which are known to have parent-of-origin specific methylation patterns. Except for those regions, the global patterns of methylation are thus the same in males and females.

"There is much less noise in the system than we feared," explained Dr Stephan Beck, Project Leader at the Wellcome Trust Sanger Institute, "Our data show DNA methylation to be stable, specific and essentially binary (that is, on or off) - all key hallmarks of informative clinical markers. Our conclusion is that epigenetic markers will be a powerful addition to the current repertoire of genetic markers for future disease association studies, particularly where non-genetic factors are known to play a role, for example in cancer, and where they are suspected, as in autoimmune disease."

Analysis of the global epigenetic landscape revealed methylation to be tissue- and cell-type specific with sperm showing the greatest difference (up to 20%) when compared to other cell types, emphasizing the extensive epigenetic reprogramming during gametogenesis.

The team found that tissue-specific methylation of one in three genes they studied was associated with changed levels of gene activity. Intriguingly, tissue-specific differences were enriched in regions called evolutionary conserved regions (ECRs), lying distant from genes, out in the 'junk' DNA. ECRs were more often differentially methylated than regions close to genes, suggesting they might have an undiscovered role in gene or chromosome activity.

The study also looked at predicted genes that have decayed and appear to have lost function - so-called pseudogenes - or lack experimental verification. The control regions for almost 90% were methylated, suggesting that methylation plays a role in silencing such genes and that many of the predicted genes might also be non-functional.

In 70% of cases, the patterns of methylation were also conserved between mouse and human tissues. Less than 5% differed to a great extent, supporting previous studies that suggest some epigenetic states to be conserved between these two species.

This stage of the HEP has defined the extent of methylation on a chromosomal scale and identified new possible roles for regions of the genome that we understand only poorly. But its importance goes beyond that.

"This is by far the most comprehensive study in understanding epigenetic differences," commented Professor Peter Jones, Director at the University of Southern California/Norris Comprehensive Cancer Center and a member of the Advisory Board of Epigenomics AG. "It is a breakthrough: we now have a sense of chromosome-wide epigenetics and this study shows what can be done to unravel this complex and clinically important process.

"The achievements serve to emphasize the need for genome-wide analysis of epigenetics - not only the study of methylation differences of DNA but also of chromatin changes. We know from individual studies that these changes are important in some diseases and we need now to establish a comprehensive study programme. The recently initiated international Alliance for Human Epigenomics and Disease (AHEAD) project by the American Association for Cancer Research can be expected to be invaluable for our understanding how genomes function and to take us toward a truly integrated (epi)genetic approach to common disease."

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

Further reports about: Chromosome DNA genetic marker methylation

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

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

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>