Project Detail
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Comprehensive genetic variation detection to assess the role of the X chromosome in autism  

Using recent technological advances in genetics to rapidly acquire data, researchers have linked several genes and chromosomal aberrations to autism. Steve Warren of Emory University and colleagues plan to implement these high-throughput methods to address one mystery of autism: roughly four times as many males as females are affected by the disorder. There are few theories that can explain this gender imbalance. One possibility is that mutations on the X chromosome trigger the disorder. Consistent with this theory, four autism-associated genes — FMR1, NLGN3, NLGN4, MeCP2 — are located on the X chromosome. But mutations in these genes are either rare among cases of autism or are associated with more complicated syndromes, and they cannot account for the predominance of males with autism. Warren and colleagues plan to determine whether other properties of the X chromosome might make males more susceptible to autism by performing a series of genetic analyses on a group of nearly 300 males with autism, and compiling a complete list of autism-associated abnormalities on the X chromosome. The researchers first plan to use high-density microarrays to search for small genomic deletions and insertions in the genomes of these individuals. These types of aberrations have recently been implicated in autism, usually appearing for the first time in the autism-affected generation. Males would be particularly vulnerable to mutations arising anew on the X chromosome, and Warren's experimental approach may reveal the frequency of these aberrations in this population. The researchers also plan to sequence the entire coding regions of the 300 participants' X chromosomes to uncover mutations that could impede protein function. In a third project, the researchers plan to investigate the epigenetic modifications of the genome that regulate gene expression. The control of protein production is as important as protein structure, and by looking for epigenetic modifications, such as methylation, Warren and colleagues aim to uncover genes whose activity is altered without a clear change in the protein-coding sequence. Based on these studies, Warren and colleagues plan to assemble the most comprehensive picture of the X chromosome in autism to date. This information may give insights into the role of the chromosome in the disorder, and lead to specialized treatments for males affected with the autism. Project Status


Funder Simons Foundation
Fiscal Year Funding $764,847.47
Current Award Period 2007-2011
Project Number SFARI-07-44
Principal Investigator Warren, Stephen
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Genetic Risk Factors
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 3LB. Identify genetic risk factors in at least 50% of people with ASD by 2014. IACC Recommended Budget: $33,900,000 over 6 years.
Federal or Private? Private
Institution Emory University
State/Country Georgia
Web Link 1 Comprehensive genetic variation detection to assess the role of the X chromosome in autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects Comprehensive genetic variation detection to assess the role of the X chromosome in autism | $1,019,796.68 | 2009 | SFARI-07-44
Comprehensive genetic variation detection to assess the role of the X chromosome in autism | $0.00 | 2011 | SFARI-07-44