Project Detail
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Office of Autism Research Coordination (OARC) logo

Genomic imbalances at the 22q11 locus and predisposition to autism  

Autism has been linked to small genomic rearrangements such as deletions, insertions and duplications, but how these aberrations lead to the disorder is unclear. Joseph Gogos of Columbia University and his colleagues aim to address this question by studying mice with a deletion similar to one frequently seen in people with autism. Copy-number variations (CNV), or the gain or loss of a chunk of DNA, can change cell physiology by altering the dosage of genes in that region. The technological advances of the past few years have made it possible to systematically detect small genomic rearrangements (~1Mb) and identify their high frequency in neurological disorders such as autism and schizophrenia. These CNVs can be found at many sites in the genome, but some locations, such as the human chromosomal region 22q11, appear to be rearranged in several cases of autism. Gogos and colleagues have generated a mouse with a small deletion in the chromosomal region equivalent to the human 22q11 region, and found that the deletion disrupts two cellular processes: the production of microRNAs — small RNAs that regulate gene expression — and the addition of palmitoyl groups to proteins. In the absence of microRNAs, cells have abnormal gene expression; without protein palmitoylation, important signaling proteins are improperly distributed within the cell. Either malfunction can lead to deficits in neuronal communication and function, the researchers reported in 2008. Gogos and colleagues now plan to more thoroughly characterize these mice and determine whether miRNAs or protein palmitoylation may underlie the neurobiological abnormalities in autism. Signaling complexes between neurons, called synapses, tend to be sparse and weaker in autistic brains. The researchers plan to look at neuronal morphology in these mice, following synapse formation through initial construction to maturation. They also plan to measure the electrical activity of the mouse neurons to determine how the abnormal development affects neuronal function and how these cellular phenotypes manifest in terms of cognition and social behavior. Their exploration of this deletion may show how other CNVs interfere with neural development, and perhaps uncover new targets for autism therapies or diagnostic tests. Project Status


Funder Simons Foundation
Fiscal Year Funding $400,000.00
Current Award Period 2008-2011
Project Number 95470
Principal Investigator Gogos, Joseph
Received ARRA Funding? No
Strategic Plan Question Question 4: Which Treatments And Interventions Will Help? (Treatments)
Subcategory Model Systems/Therapeutic Targets
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.
Federal or Private? Private
Institution Columbia University
State/Country New York
Web Link 1 Genomic imbalances at the 22q11 locus and predisposition to autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Genomic imbalances at the 22q11 locus and predisposition to autism | $400,000.00 | 2009 | 95470
Genomic imbalances at the 22q11 locus and predisposition to autism | $400,000.00 | 2008 | Project number unavailable