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Studies of postmortem brain searching for epigenetic defects causing autism  

Autism can arise from mutations that disrupt the activity of some genes, but the mutations discovered so far explain only a modest fraction of autism cases. Arthur Beaudet and his colleagues at Baylor College of Medicine are instead focusing on the epigenetic systems that control whether a gene is turned on or off through the regulation of genome structure. In the nucleus, DNA wraps around proteins to form a structure known as chromatin, and epigenetic modifications to either the proteins or the DNA can determine whether the chromatin hides or exposes a gene for RNA production. These modifications can include methylation of DNA at cytosine bases in the gene regulatory regions or adding methyl-, phosphate- or acetyl-groups to the wrapped histone proteins. Chromatin modifications can have a wide-ranging impact on which genes are expressed, even without a mutation in the DNA sequence. Beaudet and his colleagues are looking for unusual patterns of chromatin modifications associated with autism, using techniques that uncover these marks on the proteins and DNA recovered from the nuclei of neurons. From the postmortem brain tissue from people with autism, the team plans to isolate chromatin and use antibodies to detect particular histone modifications known to affect gene expression. The researchers will also sequence the isolated DNA, looking for both mutations and methylation marks; they have already used these techniques to detect known epigenetic abnormalities associated with Prader-Willi and Angelman syndromes, developmental disorders that present with learning disabilities and some autism-like symptoms. This combined strategy allows unbiased screening of the chromatin in the neuron nuclei across the entire genome but the researchers will also meticulously analyze autism-associated genomic regions with even higher resolution to detect any epigenetic changes that would not be detected by traditional sequencing. In a complementary set of experiments, the investigators are carefully assaying the neurons' RNA profiles to determine which genes are up- or down-regulated in autism, which may point to new genes or pathways. Epigenetic modifications can vary between tissues, so the researchers are starting with brain samples. But if the marks they discover are also found in other tissues, such as blood or skin, a simpler screen could perhaps be developed for earlier and more accurate diagnoses of autism. Project Status


Funder Simons Foundation
Fiscal Year Funding $400,000.00
Current Award Period 2008-2011
Project Number 95252
Principal Investigator Beaudet, Arthur
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Epigenetics
Strategic Plan Objective New! Green dot: Objective has greater than or equal to the recommended funding. 3SJ. Support at least three studies that focus on the role of epigenetics in the etiology of ASD, including studies that include assays to measure DNA methylations and histone modifications and those exploring how exposures may act on maternal or paternal genomes via epigenetic mechanisms to alter gene expression, by 2012. IACC Recommended Budget: $20,000,000 over 5 years.
Federal or Private? Private
Institution Baylor College of Medicine
State/Country Texas
Web Link 1 Studies of postmortem brain searching for epigenetic defects causing autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Studies of postmortem brain searching for epigenetic defects causing autism | $400,000.00 | 2009 | 95252
Studies of postmortem brain searching for epigenetic defects causing autism | $400,000.00 | 2008 | Project number unavailable