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 Lung images of twins with asthma add to understanding of the disease
05.12.2019 | University of Western Ontario

nachricht Between Arousal and Inhibition
05.12.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau

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: The coldest reaction

With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction

The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...

Im Focus: How do scars form? Fascia function as a repository of mobile scar tissue

Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.

Fibroblasts kit - ready to heal wounds

Im Focus: McMaster researcher warns plastic pollution in Great Lakes growing concern to ecosystem

Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.

In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...

Im Focus: Machine learning microscope adapts lighting to improve diagnosis

Prototype microscope teaches itself the best illumination settings for diagnosing malaria

Engineers at Duke University have developed a microscope that adapts its lighting angles, colors and patterns while teaching itself the optimal...

Im Focus: Small particles, big effects: How graphene nanoparticles improve the resolution of microscopes

Conventional light microscopes cannot distinguish structures when they are separated by a distance smaller than, roughly, the wavelength of light. Superresolution microscopy, developed since the 1980s, lifts this limitation, using fluorescent moieties. Scientists at the Max Planck Institute for Polymer Research have now discovered that graphene nano-molecules can be used to improve this microscopy technique. These graphene nano-molecules offer a number of substantial advantages over the materials previously used, making superresolution microscopy even more versatile.

Microscopy is an important investigation method, in physics, biology, medicine, and many other sciences. However, it has one disadvantage: its resolution is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Detailed insight into stressed cells

05.12.2019 | Life Sciences

State of 'hibernation' keeps haematopoietic stem cells young - Niches in the bone marrow protect from ageing

05.12.2019 | Life Sciences

First field measurements of laughing gas isotopes

05.12.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>