Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Threaded through a Pore - Single-molecule detection of hydroxymethylcytosine in DNA

24.04.2013
Changes in the bases that make up DNA act as markers, telling a cell which genes it should read and which it shouldn’t.

In the journal Angewandte Chemie, a British team has now introduced a new method that makes it possible to enrich the rare gene segments that contain the modified base hydroxymethylcytosine and to identify individual hydroxymethylcytosine molecules in DNA. Such modifications are associated with autoimmune diseases and cancer.



The bases adenine, guanine, cytosine, and thymine make up the genetic code. Every cell of the body contains an identical set of complete genetic material. However, the various tissues in the body are very different from each other.

This is because the cells have the ability to transcribe only a specific selection of genes into proteins, leaving other genes unused. Epigenetic factors such as “markers” on the DNA control this process.

The base cytosine can be equipped with different side groups, such as a methyl or hydroxymethyl group. Dense methylation of regulatory gene segments switches off the corresponding genes. During development of the embryo, methylation patterns initiate cell differentiation.

Changes in the methylation patterns are associated with autoimmune diseases and cancer. Hydroxymethylcytosine patterns also seem to play a role in the differentiation of embryonic stem cells as well as in gene expression in cells of the central nervous system.

Sequencing techniques that can be used to specifically detect epigenetic bases are thus very important. To date, the identification of hydroxymethylcytosine has required complex, expensive, or error-prone processes. A team led by Hagan Bayley at the University of Oxford University has now developed a chemical modification that allows for the differentiation of hydroxymethylcytosine and methylcytosine through sequencing in nanopores.

Developed by Oxford Nanopore, a company formed by Hagan Bayley in 2005, the nanopore method is a highly promising alternative to the sequencing of individual DNA molecules without an amplification step. Fed by an enzyme, a single strand of DNA threads through a membrane-embedded protein pore.

Depending on which of the bases is in the narrowest part of the pore at a given time, there is a characteristic change in the flow of current through the pore.

A chemical reaction between hydroxymethylcytosine, bisulfite, and a cysteine-containing peptide that leaves the other bases—including methylcytosine—unchanged, greatly improves the resolution as the various bases result in differences in current.

Importantly, it is possible to attach a fluorescent marker to the modified site, or a molecular “eye” that can be used to attach the rare hydroxymethylcytosine-containing DNA fragments to “hooks” that allow the fragments to be enriched over unmodified fragments, enabling rapid sequence analysis.

About the Author
Hagan Bayley is the Professor of Chemical Biology at the University of Oxford, and the founder of Oxford Nanopore Technologies. He was recognized by the RSC as Chemistry World Entrepreneur of the Year in 2009 and was the society's Interdisciplinary Prize winner in 2012. He is a Fellow of the Royal Society.

Author: Hagan Bayley, University of Oxford (UK), http://bayley.chem.ox.ac.uk/hbayley/

Title: Single-Molecule Detection of 5-Hydroxymethylcytosine in DNA through Chemical Modification and Nanopore Analysis

Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201300413

Hagan Bayley | Angewandte Chemie
Further information:
http://pressroom.angewandte.org
http://bayley.chem.ox.ac.uk/hbayley/

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>