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 What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>