Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Copy number variation may stem from replication misstep

03.01.2008
Genome rearrangements, resulting in variations in the numbers of copies of genes, occur when the cellular process that copies DNA during cell division stalls and then switches to a different genetic “template,” said researchers at Baylor College of Medicine in Houston in a report that appears today in the journal Cell.

The new mechanism is called replication “Fork Stalling and Template Switching,” said Dr. James R. Lupski, Cullen professor of molecular and human genetics and vice chair of the department at BCM. He is also professor of pediatrics. It not only represents a new way in which the genome generates DNA copy number variation, but it also demonstrates that copy number variation can occur at a different time point in the life of a cell. DNA replication takes place as the cell is dividing and becoming two.

Copy number variation involves structural changes in the human genome that result in the deletion or extra copies of genes (or parts of them). Often, this process is associated with disease, and also with evolution of the genome itself.

DNA (deoxyribonucleic acid) exists as two complementary strands that remain together because of the attraction between nucleotides. A or adenosine is always attracted to T (thymidine). C or cytosine is always attracted to G or guanine.

When a cell divides, it must reproduce its DNA so that each cell that results from the division has the same genetic code. That means it must replicate its DNA. During this process, an enzyme called a helicase separates the two strands, breaking the hydrogen bonds between the A – T and G – C base pairs holding the strands together. The two separating strands become the replication fork. On one strand, an enzyme called DNA polymerase reads the genetic material in the strand as a template and makes a strand (leading strand) of complementary DNA to pair to it. Again, the code is A to T and C to G. This process is continuous. On the other strand that comprises the fork, the complementary strand (lagging strand) is made in short, separated segments by a process that involves RNA and a series of enzymes.

Until the 1990s, researchers studying reasons for genetic mutations or changes looked at molecular “typos” in this process, tiny changes in the As, Ts, Cs or Gs called single nucleotide polymorphisms (SNPs). These SNPs changed the message of the gene. However, in the early 1990s, Lupski was one of the pioneers to elucidate a new mechanism in which the structure of the DNA itself was grossly duplicated or deleted, which changed numbers of copies of a gene that occurred in this genetic material. This “copy number variation” wrote a new chapter in the understanding of genetic variation.

Lupski and his former graduate student Dr. Jennifer Lee (now a postdoctoral fellow at BCM) found in their experiments that this process stalls when there is a problem with the DNA. In that case, the process switches to a different template, copying another similar but significantly different stretch of DNA, before it switches back to the appropriate area. Dr. Claudia M. B. Carvalho, also of BCM, took part in this research.

Previously, Lupski and colleagues had identified two different ways in which recombinations of genetic material resulted in copy number variation. However, when Lee was studying an inherited disease called Pelizaeus-Merzbacher disease, she found changes in the genome that the previous theories about DNA recombination did not explain.

Structural changes in the genome in people with the disease, a neurodevelopmental disorder, vary from person to person. In some places, genetic material that was duplicated was similar to that nearby but it was thrust into the middle of another duplication of material. The question was how they got there, Lee said.

The fork stalling, template switching mechanism explained the oddities, said Lupski.

“It stalls and rather than restart at the position where it is, it switches to a different template,” said Lupski. Usually this occurs in an area of the genome where there are many repeats of the nucleotides that form an unusual structure. This can actually aid in the template switching, he said.

“One could envision that it could happen anywhere in the genome and would be a way to make copy number changes in any gene you want,” he said. It might even play a role in evolution, allowing organisms to change. Some of the changes might make it easier for that organism to live in particular environment or survive in a stressed situation.

Glenna Picton | EurekAlert!
Further information:
http://www.bcm.edu
http://www.cell.com
http://www.bcm.edu/genetics/faculty/index.html

Further reports about: DNA Genome Lupski Nucleotide Variation genetic material replication

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>