Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inheritance of mitochondrial diseases: new findings in basic biological research

08.10.2012
Max Planck researchers shed light on hereditary processes with new model system:
Whether mitochondrial diseases will be inherited is largely decided when the future mother herself is still an embryo.

Malfunctioning of the mitochondria can lead to metabolic disorders in the person affected. Furthermore, mutations in the mitochondrial DNA (mtDNA) are causing muscle weakness, neurodegenerative diseases, cardiac disorders as well as diabetes, and are linked to the ageing process.

But how and when is the proportion of pathogenic mtDNA mutations that will be inherited determined? Up to now there has been no suitable model system available to explore this question. Max Planck researcher Christoph Freyer has developed a new model and, together with an international research team, has got some answers: Intra-family differences in the degree of mutation of the mitochondrial genes are largely established before the mother herself is born.

The genetic blueprint of a living organism is predominantly held in the cell nucleus, in the form of DNA. However, the mitochondria of a cell also carry hereditary information of their own. This is referred to as “mtDNA”. Since the mitochondria play a central role in energy supply within the body, mutations in the genes of the mtDNA can have a serious effect on health. The respective disease can also be passed down to the next generation via the mutated genes, but only the maternal mtDNA is transmitted.

Opinions have been divided as to exactly how and when health-endangering mitochondrial mutations are inherited, as the transmission of mtDNA does not follow the classic Mendelian laws of inheritance whereby both mother and father contribute to each piece of hereditary information. This prompted Christoph Freyer, research scientist at the Max Planck Institute for Biology of Ageing in Cologne and the Karolinska Institute in Stockholm, to develop a new mouse model: The main player here is a pathogenic, i.e. a disease-inducing mutation in a mitochondrial gene known as “tRNA methionine”. Mutations in mitochondrial tRNA genes cause a high percentage of the known mitochondrial diseases, although tRNA genes constitute only a fraction of the total mtDNA. This discrepancy has never been satisfactorily explained.

With the aid of tRNA methionine, Freyer has been looking at the ratio of mutated to non-mutated genes, or mutation level, in three different phases of the hereditary process: First he analysed germ cells from mouse embryos and established how the degree of mutation varies from germ cell to germ cell. After birth he looked at that degree in the immature egg cells of the mouse. And later he examined the degree of mutation in the mtDNA of the offspring.

These basic research findings uncover a feature of maternal genetics that may pave the way to novel possibilities for genetic diagnosis

Freyer’s main breakthrough was to show that in contrast to the protein-coding genes, shown by recent research to be subject to prenatal selection, tRNA genes are not selected out by the female germ line. So whether and to what extent mutant genes can be transmitted to the next generation is decided when the future mother is still herself an embryo, during the development of her germ cells. Mutant genes often coexist with normal genes, a condition called heteroplasmy, in the affected egg cells. In other words, mutated and non-mutated genes occur in each egg cell in a particular ratio and thus the mutation may or may not be transmitted to the next generation. This also explains the differences arising within a family.

With these scientific findings, the researchers uncovered a feature of maternal genetics that may pave the way to novel possibilities for genetic diagnosis.

Moreover, the observation that in this model, too, the mice mitochondria try to compensate potential defects caused by mutations provides further insight into the hereditary mechanisms underlying mitochondrial disease. “Perhaps,” suggests Freyer, “this compensation could be stimulated by medical means.” The young researcher plans to use his mouse model in future to test therapies that could possibly prevent the hereditary transmission of mtDNA mutations.

Original publication:
Christoph Freyer, Lynsey M. Cree, Arnaud Mourier, James B. Stewart, Camilla Koolmeister, Dusanka Milenkovic, Timothy Wai, Erik Hagström, Emmanouella E. Chatzidaki, Rudolph Wiesner, David C. Samuels, Nils-Göran Larsson, Patrick F. Chinnery.
Variation in germ line mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission.
Nature Genetics.
nature genetics November 2012 – Vol 44 No 11 (Epap ahead of print: Oct 07, 2012)

Contact:
Dr. Christoph Freyer
Max Planck Institute for Biology of Ageing, D-Cologne
Mobil: +46 734 424959
E-mail: christoph.freyer@age.mpg.de

Press & Public Relations:
Sabine Dzuck
Tel.: +49 (0)221 478 89605
E-mail: sabine.dzuck@age.mpg.de

Sabine Dzuck | Max-Planck-Institut
Further information:
http://www.age.mpg.de

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>