Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Secrets revealed about how disease-causing DNA mutations occur

02.07.2009
A team of Penn State scientists has shed light on the processes that lead to certain human DNA mutations that are implicated in hundreds of inherited diseases such as tuberous sclerosis and neurofibromatosis type 1.

The results one day could influence the way couples who seek to have children receive genetic counseling. The team, led by Kateryna Makova, an associate professor of biology, also includes Erika Kvikstad, a graduate student in the Department of Biology, and Francesca Chiaromonte, an associate professor of statistics. Their findings will be published in the July 2009 issue of the journal Genome Research.

The scientists examined insertions and deletions -- mutations in which small fragments of DNA are either added or subtracted from the genome -- and they found patterns in the DNA sequences immediately surrounding the mutations. "The patterns in the DNA sequences that surround insertions and deletions suggest mechanisms that may have generated the insertions and deletions," said Chiaromonte. According to the researchers, the study is the first to detect patterns in the DNA sequences adjacent to insertions and deletions of DNA fragments at the genome-wide scale.

The team also found striking differences between insertions and deletions. For example, they found that recognition sites for the enzyme topoisomerase, which is responsible for winding and unwinding DNA, were more prevalent near deletions than near insertions. "We were surprised to find that the patterns of DNA sequences surrounding insertions versus deletions are unique because scientists previously have lumped the two types of mutations together," said Kvikstad.

Scientists also previously had believed that insertions and deletions are formed mostly by errors taking place during DNA replication, but the team found that the mutations also can form by mechanisms related to recombination. "What's striking is that most insertions and deletions are thought to occur by replication errors and, while this is a primary source generating the mutations, we discovered that recombination also is very important," said Kvikstad.

For one of the first times in a genome-wide study, the team used a statistical method, called wavelet analysis, which allows scientists to look at variability in a sample at multiple scales simultaneously. For example, JPEG image files, which preserve an image's different qualities regardless of whether the image is made smaller or larger, use a similar wavelet-like method. According to Chiaromonte, "When you run a wavelet analysis you are characterizing the signals simultaneously at many scales. In our case, the signal was the composition of the DNA sequences surrounding insertions and deletions. To be able to look at these sequences with a multi-scale approach was really important for our ability to find interesting features."

Using the wavelet analysis, the team confirmed that scale is important in detecting patterns of DNA sequences adjacent to insertions and deletions. For example, they were able to detect an increased number of DNA sequences responsible for pausing DNA polymerase, an enzyme involved in DNA replication, at the finest scales (10 to 20 DNA base pairs), but not at larger scales.

Both replication and recombination errors can lead to disease-causing mutations in humans. According to the researchers, if we know that certain diseases are more likely to be caused by recombination than by replication errors, doctors can provide better advice to couples who want to have children. "For example, there is a difference among males and females in the number of replication rounds that their germline cells undergo. Males undergo more rounds of DNA replication than females and the number of replication rounds increases with a male's age. If we know that a disease is due to a replication error rather than a recombination error, doctors can provide better genetic counseling to couples," said Makova.

This research received support from the National Institutes of Health and Penn State University.

Barbara K. Kennedy | EurekAlert!
Further information:
http://www.psu.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>