Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inherited mutation leads to overproduction of EPO

08.03.2018

A newly-discovered hereditary mutation is responsible for an increased production of erythropoietin (EPO) in the blood. This mutation causes a messenger RNA (mRNA) that is not normally involved in the formation of proteins to be reprogrammed so that it produces EPO, thus abnormally increasing the number of red blood cells. Researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel reported these findings in The New England Journal of Medicine.

In patients suffering from erythrocytosis, the red blood cell mass (erythrocytes) is exceptionally high. The disease is usually triggered by a genetic disorder in the bone marrow, which leads to increased production of red blood cells.


Inheritance of the familial erythrocytosis.

(Image: University of Basel, Department of Biomedicine)

Researchers from the University of Basel and University Hospital Basel have now identified the first mutation in the EPO gene in a family with hereditary erythrocytosis. Ten affected family members from four generations took part in the study.

Using a genome-wide linkage analysis and gene sequencing, the researchers discovered that all of the affected family members lacked a single base in the EPO gene. As the EPO hormone increases the production of red blood cells, it was likely that this mutation caused the disease.

Overproduction instead of failure

However, the researchers were initially puzzled. This mutation would actually lead to a loss of function of the EPO gene, because the absence of the base shifts the reading frame of the genetic code, meaning that no more EPO protein can be formed. Despite this, the concentration of EPO hormone in the patients’ blood measurably increased rather than decreased.

The explanation was found using the CRISPR method, which allowed the researchers to engineer cells carrying the EPO mutation. There is a second, hidden mRNA in the EPO gene that is not normally involved in the production of a protein. As the researchers show, the mutation also leads to a shift in the reading frame of this second mRNA, this time with the result that more biologically active EPO hormone is produced.

“The mechanism is intriguing,” says study leader Professor Radek Skoda from the University of Basel’s Department of Biomedicine. “The mutation reprograms the gene product so that it gains a new function and is misused to overproduce EPO.” With consequences for the patients, who suffer from headaches and dizziness thanks to the increased red blood mass.

Mutations in the EPO gene should be taken into account in future searches for the causes of hereditary erythrocytosis, write the researchers in The New England Journal of Medicine.

Original source

Jakub Zmajkovic, Pontus Lundberg, Ronny Nienhold, Maria L. Torgersen, Anders Sundan, Anders Waage, and Radek C. Skoda
A Gain-of-Function Mutation in EPO in Familial Erythrocytosis
The New England Journal of Medicine (2018), doi: 10.1056/NEJMoa1709064

Further information

Prof. Dr. Radek Skoda, University of Basel, Department of Biomedicine / University Hospital Basel, tel. +41 61 265 23 24, e-mail: radek.skoda@unibas.ch

Weitere Informationen:

https://www.unibas.ch/en/News-Events/News/Uni-Research/Inherited-mutation-leads-...

Cornelia Niggli | Universität Basel
Further information:
http://www.unibas.ch

Further reports about: EPO blood cells bone marrow gene sequencing genetic disorder hormone mRNA red blood cells

More articles from Life Sciences:

nachricht Hopkins researchers ID neurotransmitter that helps cancers progress
25.04.2019 | Johns Hopkins Medicine

nachricht Trigger region found for absence epileptic seizures
25.04.2019 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Full speed ahead for SmartEEs at Automotive Interiors Expo 2019

Flexible, organic and printed electronics conquer everyday life. The forecasts for growth promise increasing markets and opportunities for the industry. In Europe, top institutions and companies are engaged in research and further development of these technologies for tomorrow's markets and applications. However, access by SMEs is difficult. The European project SmartEEs - Smart Emerging Electronics Servicing works on the establishment of a European innovation network, which supports both the access to competences as well as the support of the enterprises with the assumption of innovations and the progress up to the commercialization.

It surrounds us and almost unconsciously accompanies us through everyday life - printed electronics. It starts with smart labels or RFID tags in clothing, we...

Im Focus: Energy-saving new LED phosphor

The human eye is particularly sensitive to green, but less sensitive to blue and red. Chemists led by Hubert Huppertz at the University of Innsbruck have now developed a new red phosphor whose light is well perceived by the eye. This increases the light yield of white LEDs by around one sixth, which can significantly improve the energy efficiency of lighting systems.

Light emitting diodes or LEDs are only able to produce light of a certain colour. However, white light can be created using different colour mixing processes.

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

High-efficiency thermoelectric materials: New insights into tin selenide

25.04.2019 | Materials Sciences

Salish seafloor mapping identifies earthquake and tsunami risks

25.04.2019 | Earth Sciences

Using DNA templates to harness the sun's energy

25.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>