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
Scientists unveil completely human platform for testing age-specific vaccine responses
20.11.2018 | Boston Children's Hospital
From Receptor Structure to New Osteoporosis Drugs
20.11.2018 | Universität Zürich
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Physics and Astronomy
20.11.2018 | Medical Engineering
20.11.2018 | Physics and Astronomy