Left Menu
Development News Edition

A large-scale tool to investigate the function of autism spectrum disorder genes

Scientists at Harvard University, the Broad Institute of MIT and Harvard, and MIT have developed a technology to investigate the function of many different genes in many different cell types at once, in a living organism.

ANI | Washington DC | Updated: 01-12-2020 11:32 IST | Created: 01-12-2020 11:32 IST
A large-scale tool to investigate the function of autism spectrum disorder genes
Representative image. Image Credit: ANI

Scientists at Harvard University, the Broad Institute of MIT and Harvard, and MIT have developed a technology to investigate the function of many different genes in many different cell types at once, in a living organism. They applied the large-scale method to study dozens of genes that are associated with autism spectrum disorder, identifying how specific cell types in the developing mouse brain are impacted by mutations.

The "Perturb-Seq" method, published in the journal Science, is an efficient way to identify potential biological mechanisms underlying autism spectrum disorder, which is an important first step toward developing treatments for the complex disease. The method is also broadly applicable to other organs, enabling scientists to better understand a wide range of disease and normal processes.

"For many years, genetic studies have identified a multitude of risk genes that are associated with the development of autism spectrum disorder. The challenge in the field has been to make the connection between knowing what the genes are, to understanding how the genes actually affect cells and ultimately behaviour," said co-senior author Paola Arlotta, the Golub Family Professor of Stem Cell and Regenerative Biology at Harvard. "We applied the Perturb-Seq technology to an intact developing organism for the first time, showing the potential of measuring gene function at scale to better understand a complex disorder," added Arlotta.

The study was also led by co-senior authors Aviv Regev, who was a core member of the Broad Institute during the study and is currently Executive Vice President of Genentech Research and Early Development, and Feng Zhang, a core member of the Broad Institute and an investigator at MIT's McGovern Institute. To investigate gene function at a large scale, the researchers combined two powerful genomic technologies. They used CRISPR-Cas9 genome editing to make precise changes, or perturbations, in 35 different genes linked to autism spectrum disorder risk.

Then, they analyzed changes in the developing mouse brain using single-cell RNA sequencing, which allowed them to see how gene expression changed in over 40,000 individual cells. By looking at the level of individual cells, the researchers could compare how the risk genes affected different cell types in the cortex -- the part of the brain responsible for complex functions including cognition and sensation. They analyzed networks of risk genes together to find common effects.

"We found that both neurons and glia -- the non-neuronal cells in the brain -- are directly affected by different sets of these risk genes," said Xin Jin, lead author of the study and a Junior Fellow of the Harvard Society of Fellows. "Genes and molecules don't generate cognition per se -- they need to impact specific cell types in the brain to do so. We are interested in understanding how these different cell types can contribute to the disorder," added Jin.

To get a sense of the model's potential relevance to the disorder in humans, the researchers compared their results to data from post-mortem human brains. In general, they found that in the post-mortem human brains with autism spectrum disorder, some of the key genes with altered expression were also affected in the Perturb-seq data. "We now have a really rich dataset that allows us to draw insights, and we're still learning a lot about it every day. As we move forward with studying disease mechanisms in more depth, we can focus on the cell types that may be really important," Jin said.

"The field has been limited by the sheer time and effort that it takes to make one model at a time to test the function of single genes. Now, we have shown the potential of studying gene function in a developing organism in a scalable way, which is an exciting first step to understanding the mechanisms that lead to autism spectrum disorder and other complex psychiatric conditions, and to eventually develop treatments for these devastating conditions," said Arlotta, who is also an institute member of the Broad Institute and part of the Broad's Stanley Center for Psychiatric Research. "Our work also paves the way for Perturb-Seq to be applied to organs beyond the brain, to enable scientists to better understand the development or function of different tissue types, as well as pathological conditions," added Arlotta.

"Through genome sequencing efforts, a very large number of genes have been identified that, when mutated, are associated with human diseases. Traditionally, understanding the role of these genes would involve in-depth studies of each gene individually. By developing Perturb-seq for in vivo applications, we can start to screen all of these genes in animal models in a much more efficient manner, enabling us to understand mechanistically how mutations in these genes can lead to disease," said Zhang, who is also the James and Patricia Poitras Professor of Neuroscience at MIT and a professor of brain and cognitive sciences and biological engineering at MIT. (ANI)

(This story has not been edited by Devdiscourse staff and is auto-generated from a syndicated feed.)


TRENDING

OPINION / BLOG / INTERVIEW

China: A savior for emerging markets or a poison pill?

... ...

Future of Urban Planning: Artificial Intelligence guiding the way

Advances in emerging technologies like Artificial Intelligence and Machine Learning can help us understand our cities better and derive useful insights from real-time data collected through automated models....

Videos

Latest News

Tennis-Andreescu's coach tests positive for COVID-19 ahead of Australian Open

Sylvain Bruneau, the coach of 2019 U.S. Open champion Bianca Andreescu, said on Saturday he has tested positive for COVID-19 after arriving in Melbourne ahead of next months Australian Open. Bruneau said in a statement shared by Tennis Cana...

NASA's Boeing moon rocket cuts short 'once-in-a-generation' ground test

NASAs deep space exploration rocket built by Boeing briefly ignited all four engines of its behemoth core stage for the first time on Saturday, cutting short a crucial test to advance a years-delayed U.S. government program to return humans...

Guterres welcomes Palestinian announcement of elections as ‘crucial step’ towards unity

The holding of elections in the occupied West Bank, including East Jerusalem, and Gaza will be a crucial step towards Palestinian unity, said a statement issued on behalf of Antnio Guterres on Saturday which would give renewed legitimacy ...

Britain invites G7 leaders to Cornish resort for June summit

Britain announced plans to hold the first in-person meeting of the G7 for nearly two years in June, inviting the leaders of major developed economies to a picturesque seaside village to discuss rebuilding from the pandemic and climate chang...

Give Feedback