Genetics

A Genotype Resource for Postmortem Brain Samples from the Autism Tissue Program

Source: 
Autism Res, Wintle et al.
Date Published: 
April 2011
Year Published: 
2011

The Autism Tissue Program (ATP) is a postmortem brain tissue program created by the National Alliance for Autism Research (NAAR) for the purpose of supplying research scientists with neurological tissue samples of deceased Autistic individuals. Scientists, however, are not supplied with tissue samples from any other parts of the deceased individual, leading to frustration over genotype/phenotype verification. In this study, scientists from the Hospital for Sick Children in Toronto verify the ethnicity and gender of a certain sample, and provide an algorithmic verification system for other researchers looking to provide accurate research into the genotype/phenotype makeup of their sample.

MIT Researchers Recreate Autism in Mice

Source: 
Medical News Today
Date Published: 
March 20, 2011
Abstract: 

By mutating a single gene, researchers at MIT and Duke have produced mice with two of the most common traits of autism - compulsive, repetitive behavior and avoidance of social interaction. In this study, the researchers focused on one of the most common of those genes, known as shank3. Shank3 is found in synapses - the junctions between brain cells that allow them to communicate with each other. Feng, who joined MIT and the McGovern Institute last year, began studying shank3 a few years ago because he thought that synaptic proteins might contribute to autism and similar brain disorders, such as obsessive compulsive disorder.

Gene Variants in Autism Linked to Brain Development

Source: 
Science Daily
Date Published: 
March 7, 2011
Abstract: 

New research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling.

Gene Variants in Autism Linked to Brain Development

Source: 
Journal of Molecular Psychiatry, Gai et al.
Date Published: 
March 2011
Year Published: 
2011

This research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling. While an association between genomic variants in certain nervous system processes and autism has been hypothesized in the past, this research definitively links these biological functions to autism. 

"This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both synaptic function and neurotransmission," said senior author Peter S. White, Ph.D., a molecular geneticist and director of the Center for Biomedical Informatics at The Children's Hospital of Philadelphia. Synapses are the contact points at which nerve cells communicate with other nerve cells, while neurotransmitters are the chemical messengers carrying those signals.

"Prior genomic studies of autism have successfully identified several genes that appear to confer risk for autism, but each gene appears to contribute to only a small percentage of cases," said the lead author, Xiaowu Gai, Ph.D. "Our approach considered whether groups of genes with common biological functions collectively accounted for a greater percentage of autism risk."

-- via Science Daily http://www.sciencedaily.com/releases/2011/03/110301111243.htm.

Researchers Reveal First Autism Candidate Gene That Demonstrates Sensitivity to Sex Hormones

Source: 
Journal of Molecular Psychiatry, Hu et al.
Date Published: 
March 2011
Year Published: 
2011

 

George Washington University researchers have found that male and female sex hormones regulate expression of an important gene in neuronal cell culture through a mechanism that could explain not only higher levels of testosterone observed in some individuals with autism, but also why males have a higher incidence of autism than females.

The gene, RORA, encodes a protein that works as a "master switch" for gene expression, and is critical in the development of the cerebellum as well as in many other processes that are impaired in autism. Dr. Hu's earlier research found that RORA was decreased in the autistic brain. In this study, the research group demonstrates that aromatase, a protein that is regulated by RORA, is also reduced in autistic brains.

This is significant because aromatase converts testosterone to estrogen. Thus, a decrease in aromatase is expected to lead in part to build up of male hormones that, in turn, further decrease RORA expression, as demonstrated in this study using a neuronal cell model. On the other hand, female hormones were found to increase RORA in the neuronal cells. The researchers believe that females may be more protected against RORA deficiency not only because of the positive effect of estrogen on RORA expression, but also because estrogen receptors, which regulate some of the same genes as RORA, can help make up for the deficiency in RORA.

Shank3 Mutant Mice Display Autistic-like Behaviors and Striatal Dysfunction

Source: 
Nature, Peça et al.
Date Published: 
March 2011
Year Published: 
2011

Currently, the neurological basis of autism spectrum disorders (ASDs) is poorly understood. “Shank3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs”. In this study, mice with the Shank3 deletion were seen to exhibit “self-injurious repetitive grooming and deficits in social interaction.” Cellular, electrophysiological, and biochemical analyses revealed defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. The study’s findings demonstrate that Shank3 plays a critical role in the development of neuronal connectivity. The study also established a causality between a disruption in the Shank3 gene and the beginning of autistic-like behaviors in mice.

Serotonin Plays Role in Many Autism Cases, Studies Confirm

Source: 
Science Daily
Date Published: 
February 24, 2011
Abstract: 

Georgianna Gould, Ph.D., research assistant professor of physiology in the Graduate School of Biomedical Sciences, is eyeing the role that serotonin plays in autism spectrum disorders. Serotonin is known for giving a sense of well-being and happiness. It is a neurotransmitter, a chemical that acts like a radio tower in the brain conveying signals among cells called neurons. Thirty percent of autism cases may have a serotonin component. In a recent paper in the Journal of Neurochemistry, Dr. Gould and colleagues showed that a medication called buspirone improved the social behaviors of mice. Buspirone is approved by the U.S. Food and Drug Administration for use in adults as an anti-anxiety and antidepressant adjuvant medication.

Researchers Reveal First Autism Candidate Gene That Demonstrates Sensitivity to Sex Hormones

Source: 
Science Daily
Date Published: 
February 17, 2011
Abstract: 

George Washington University researcher, Dr. Valerie Hu, Professor of Biochemistry and Molecular Biology, and her team at the School of Medicine and Health Sciences, have found that male and female sex hormones regulate expression of an important gene in neuronal cell culture through a mechanism that could explain not only higher levels of testosterone observed in some individuals with autism, but also why males have a higher incidence of autism than females.

Surprising View of Brain Formation: Discovery of a New Mechanism May Have Implications for a Host of Diseases

Source: 
Science Daily
Date Published: 
February 10, 2011
Abstract: 

A study from The Scripps Research Institute has unveiled a surprising mechanism that controls brain formation. In the new study, Mueller and colleagues focused on a protein called reelin. They found reelin is a key player in the migration of new nerve cells to the neocortex, the part of the brain responsible for higher-order functions, such as language and movement. The findings have implications for understanding a host of diseases, including some forms of mental retardation, epilepsy, schizophrenia, and autism.

Autism and Increased Paternal Age Related Changes in Global Levels of Gene Expression Regulation

Source: 
PloS One, Alter et al.
Date Published: 
February 2011
Year Published: 
2011

This study, performed by researchers at the University of Pennsylvania, analyzed the level of gene expression in children with autism, compared with a control group. The researchers hypothesized that the variability in the pattern of the overall of gene expression levels would be associated with variability in hippocampal-dependent behaviors, which include short-term memory and spatial navigation. Additionally, the group tested whether increased paternal age was associated with variance of gene expression. A decrease in the variability of gene expression levels was associated with the diagnosis of autism and increased paternal age. The research team believes this change to be caused by the down-regulation of gene expression pathways involved in protein synthesis regulation in the blood of children with autism and children with older fathers. Thus, the researchers concluded that alterations at the gene level of gene expression regulation are related to autism and increased paternal age.