Spontaneous mutations in key brain gene are a cause of the disorder
Disorders such as autism are often caused by genetic mutations. Such mutations can change the shape of protein molecules and stop them from working properly during brain development. However, the genetic foundation of autism is complicated and there is no single genetic cause. In some individuals, inherited genetic variants may put them at risk. But research in recent years has shown that severe cases of autism can result from new mutations occurring in the sperm or egg - these genetic variants are found in a child, but not in his or her parents, and are known as de novo mutations. Scientists have sequenced the DNA code of thousands of unrelated children with severe autism and found that a handful of genes are hit by independent de novo mutations in more than one child. One of the most interesting of these genes is TBR1, a key gene in brain development. Researchers from the Max Planck Institute for Psycholinguistics in Nijmegen, Netherlands, describe how mutations in TBR1 disrupt the function of the encoded protein in children with severe autism. In addition, they uncover a direct link between TBR1 and FOXP2, a well-known language-related protein.
Mutations in the TBR1 gene in children with autism affect the location of the TBR1 protein in human cells. In cells, the normal TBR1 protein, shown in red, is found together with DNA, shown in blue. In contrast, the mutant TBR1 protein is found throughout the cell.
© MPI f. Psycholinguistics/ Deriziotis
Autism is a disorder of brain development which leads to difficulties with social interaction and communication. One third of individuals never learn to speak, whereas others can speak fluently but have difficulties maintaining a conversation and understanding non-literal meanings. Studying autism can therefore help us understand which brain circuits underlie social communication, and how they develop.
In the new study, researchers from the Max Planck Institute’s Language and Genetics Department, together with colleagues from the University of Washington, investigated the effects of autism risk mutations on TBR1 protein function. The scientists were interested in directly comparing the de novo and inherited mutations found in autism, because it is speculated that de novo mutations have more severe effects. They used several cutting-edge techniques to examine how the mutations affected the way the TBR1 protein works, using human cells grown in the laboratory. According to the scientists de novo mutations disrupt subcellular localization of TBR1. ‘We found that the de novo mutations had much more dramatic effects on TBR1 protein function compared to the inherited mutations that we studied’, says lead author Pelagia Deriziotis, ‘It is a really striking confirmation of the strong impact that de novo mutations can have on early brain development’.
The human brain depends on many different genes and proteins working together in combination. So, novel research horizons could be opened up by identifying proteins that interact with TBR1. ‘We can think of it like a social network for proteins’, says Deriziotis, ‘There were initial clues that TBR1 might be "friends" with a protein called FOXP2. This was intriguing because FOXP2 is one of the few proteins to have been clearly implicated in speech and language disorders’. The researchers discovered that, not only does TBR1 directly interact with FOXP2, mutations affecting either of these proteins abolish the interaction.
According to senior author Simon Fisher, ‘It is very exciting to uncover these fascinating molecular links between different disorders that affect language. By coupling data from genome screening with functional analysis in the lab, we are starting to build up a picture of the neurogenetic pathways that contribute to fundamental human traits.’
Dr. Pelagia Deriziotis | Max-Planck-Institute
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Trade Fair News
22.03.2018 | Earth Sciences
22.03.2018 | Earth Sciences