Study Pinpoints Cell Types And Brain Regions Affected By Autism Gene Mutations

redOrbit Staff & Wire Reports – Your Universe Online
Researchers from Yale University and the University of California, San Francisco (UCSF) have pinpointed the types of cells and regions of the brain affected by the genetic mutations associated with autism.
Their findings, which were reported in Thursday’s edition of the journal Cell, indicate that a common variety of neural circuits are affected by autism-risk genes. Furthermore, they determined how, when, where and in what types of cells those genes will influence a developing brain, leading to autism spectrum disorders.
As part of the study, senior author Matthew W. State, chair of the UCSF Department of Psychiatry at UCSF and an expert on the genetics of neurodevelopmental disorders, and his colleagues focused specifically on nine genes that had been most strongly associated with autism in recently-published sequencing studies.
State’s team “investigated their effects using precise maps of gene expression during human brain development,” UCSF added, and demonstrated that this set of genes play a role in abnormalities in specific brain cells. Those cells, which are known as cortical projection neurons, are located in the deepest regions of a person’s developing prefrontal cortex during the middle period of fetal development, the study authors said.
“Given the small subset of autism genes we studied, I had no expectation that we would see the degree of spatiotemporal convergence that we saw,” explained State. “This strongly suggests that though there are hundreds of autism risk genes, the number of underlying biological mechanisms will be far fewer. This is a very important clue to advance precision medicine for autism toward the development of personalized and targeted therapies.”
It has been difficult for researchers to pin-down the genetic causes of autism, as several hundred genes have been linked to autism spectrum disorders but no single set of them appears to explain all of the symptoms associated with the disorders. Even with these new discoveries, the authors explain that there are other genes and other neural circuits that also contribute to autism spectrum disorders and have not yet been discovered.
However, according to co-senior author and Yale neurobiology professor Nenad Sestan, the new study suggests that new targeted treatment approaches could be possible. “We know now that we may not have to treat the whole brain, that changes related to mutations in autism-risk genes may affect particular neural circuits at specific places at specific times,” he said.
In related work, UCLA neuroscientists have become the first researchers to map groups of autism-risk genes by function, and to identify the time and location where those genes typically play major roles in early brain development.
Furthermore, they found disturbances in neural circuits that define key pathways between areas of the cerebral cortex, and their findings suggest that those disruptions are not a result of autism itself.
Rather, the changes are formed by mutations in genes during fetal brain development, the study authors said. Their study, which was also published in Cell on Thursday, could help experts better understand how genetic changes cause autism spectrum disorders on a molecular level and should help shape future research.
“Identifying gene variants that boost risk is only the first step of unraveling a disease,” said lead author Dr. Daniel Geschwind, a professor of human genetics, neurology and psychiatry. “We need to figure out where genetic changes appear in the brain, at what stages during development and which biological processes they disrupt. Only then will we understand how mutations cause autism.”