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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

A systematic test of the relation of ASD heterogeneity to synaptic function

Principal Investigator

Principal Investigator

Sudhof, Thomas

Description

Description

Although autism spectrum disorders (ASDs) are highly heritable, ASDs are heterogeneous, and no single genetic cause contributes to ASDs in a large proportion of patients. Instead, heterogeneous genetic changes, including many single gene mutations and copy-number variations (CNVs) are found in ASDs. Thus, a key question is whether different genetic changes contribute to ASDs via multiple, independent, pathogenic pathways, or whether the various genetic changes in ASDs converge onto a single pathogenic pathway. Several independent mutations in genes encoding synaptic proteins suggest that ASDs may generally involve an impairment of synaptic communication between neurons. Thus, the major goal of this project is to conduct a large scale, systematic analysis of the changes in neuron-to-neuron communication caused by the genes associated with autism. The approach will be to over express (to mimic gene duplications) or knock down (to mimic gene inactivations) mRNAs corresponding to 81 ASD candidate genes and to test the effect of these manipulations on synapses using standardized assays. Cell viability, neuronal development, synapse density, and synapse function will be assessed in cultured mouse neurons using optical and electro-physiological assays. The results of this project will provide a standardized reference point for the function of ASD candidate genes and provide an initial test of the hypothesis that despite their clinical and genetic heterogenity, ASDs involve a common, if diverse, pathway acting on synaptic communication in the brain.

Funder

Funder

National Institutes of Health

Fiscal Year Funding

Fiscal Year Funding

898037

Current Award Period

Current Award Period

na

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 2SG. Support five studies that associate specific genotypes with functional or structural phenotypes, including behavioral and medical phenotypes (e.g., nonverbal individuals with ASD and those with cognitive impairments) by 2015. IACC Recommended Budget: $22,600,000 over 5 years.

Project Link

Project Link

A systematic test of the relation of ASD heterogeneity to synaptic function (External web link)

Institution

Institution

Stanford University

State/Country

State/Country

California

Project Number

Project Number

1R01MH089054-01

Federal or Private?

Federal or Private?

Federal

Received ARRA Funding?

Received ARRA Funding?

Yes

History/Related Projects

History/Related Projects

A systematic test of the relation of ASD heterogeneity to synaptic function | 875864 | 2010 | 5R01MH089054-02

 
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