Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fishing for answers to autism puzzle

20.06.2012
Biologists take a new approach to deciphering the roles of genes associated with autism.

Fish cannot display symptoms of autism, schizophrenia or other human brain disorders. However, a team of MIT biologists has shown that zebrafish can be a useful tool for studying the genes that contribute to such disorders.

Led by developmental biologist Hazel Sive, the researchers set out to explore a group of about two dozen genes known to be either missing or duplicated in about 1 percent of autistic patients. Most of the genes’ functions were unknown, but the MIT study revealed that nearly all of them produced brain abnormalities when deleted in zebrafish embryos.

The findings should help researchers pinpoint genes for further study in mammals, says Sive, a professor of biology and associate dean of MIT’s School of Science. Autism is thought to arise from a variety of genetic defects; this research is part of a broad effort to identify culprit genes and develop treatments that target them.

“That’s really the goal — to go from an animal that shares molecular pathways, but doesn’t get autistic behaviors, into humans who have the same pathways and do show these behaviors,” says Sive, who is also a member of the Whitehead Institute for Biomedical Research.

Sive and her colleagues described their findings a recent paper in the online edition of the journal Disease Models and Mechanisms. Lead authors of the paper are Whitehead postdocs Alicia Blaker-Lee, Sunny Gupta and Jasmine McCammon.

A logical starting point

Sive recalls that some of her colleagues chuckled when she first proposed studying human brain disorders in fish, but it is actually a logical starting point, she says. Brain disorders are difficult to study because most of the symptoms are behavioral, and the biological mechanisms behind those behaviors are not well understood, she says.

“We thought that since we really know so little, that a good place to start would be with the genes that confer risk in humans to various mental health disorders, and to study these various genes in a system where they can readily be studied,” she says.

Those genes tend to be the same across species — conserved throughout evolution, from fish to mice to humans — though they may control somewhat different outcomes in each species.

In the Disease Models and Mechanisms paper, Sive and her colleagues focused on a genetic region known as 16p11.2, first identified by Mark Daly, a former Whitehead researcher who identified a type of genetic defect known as a copy number variant. A typical genome includes two copies of every gene, one from each parent; copy number variants occur when one of those copies is deleted or duplicated, and can be associated with pathology.

The “core” 16p11.2 region includes 25 genes. Both deletions and duplications in this region have been associated with autism, but it was unclear which of the genes might actually produce symptoms of the disease. “At the time, there was an inkling about some of them, but very few,” Sive says.

Sive and her postdocs began by identifying zebrafish genes analogous to the human genes found in this region. (In zebrafish, these genes are not clustered in a single genetic chunk, but are scattered across many chromosomes.) The researchers studied one gene at a time, silencing each with short strands of nucleic acids that target a particular gene and prevent its protein from being produced.

For 21 of the genes, silencing led to abnormal development. Most produced brain deficits, including improper development of the brain or eyes, thinning of the brain, or inflation of the brain ventricles, cavities that contain cerebrospinal fluid. The researchers also found abnormalities in the wiring of axons, the long neural projections that carry messages to other neurons, and in simple behaviors of the fish. The results show that the 16p11.2 genes are very important during brain development, helping to explain the connection between this region and brain disorders.

Furthermore, the researchers were able to restore normal development by treating the fish with the human equivalents of the genes that had been repressed. “That allows you to deduce that what you’re learning in fish corresponds to what that gene is doing in humans. The human gene and the fish gene are very similar,” Sive says.

Genes with impact

To figure out which of these genes might have a strong effect in autism or other disorders, the researchers set out to identify genes that produce abnormal development when their activity is reduced by 50 percent, which would happen in someone who is missing one copy of the gene. (This correlation is not seen for most genes, because there are many other checks and balances that regulate how much of a particular protein is made.)

The researchers identified two such genes in the 16p11.2 region. One, called kif22, codes for a protein involved in the separation of chromosomes during cell division; another, aldolase a, is involved in glycolysis — the process of breaking down sugar to generate energy for the cell.

Though zebrafish have long been studied as a model of brain development, the new MIT research adds a new dimension to their usefulness, says Su Guo, an associate professor of pharmaceutical sciences at the University of California at San Francisco.

“This is really nice work that shows the importance of zebrafish in revealing disease mechanisms related to human mental disorders — in this case, autism,” says Guo, who was not involved in this study.

In work that has just begun, Sive’s lab is working with Stanford University researchers to explore in mice predictions made from the zebrafish study. They are also doing molecular studies in zebrafish of the pathways affected by these genes, to get a better idea of how defects in these might bring about neurological disorders.

Sive is a member of the Simons Center for the Social Brain at MIT; this research was funded by the Simons Foundation Autism Research Initiative.

Written by: Anne Trafton, MIT News Office

Caroline McCall | EurekAlert!
Further information:
http://www.mit.edu

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>