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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

Dosage effects of 22q11 region on autism-relevant neural systems

Principal Investigator

Principal Investigator

Bearden, Carrie

Description

Description

Recent discoveries of contrasting phenotypes caused by deletion vs. duplication events within the same genetic locus suggest that investigation of gene dosage effects may provide valuable clues into how copy number variations (CNVs), or duplications or deletions of stretches of DNA, disrupt the brain and ultimately contribute to disease pathogenesis. However, almost nothing is known about the consequences of such reciprocal imbalances on brain function or behavior. Carrie Bearden and her colleagues at the University of California, Los Angeles have collected extensive clinical, behavioral and brain imaging data from a large cohort of children with deletion of the 22q11.2 chromosomal region. The data reveal structural and functional disruptions of neural circuits relevant to language and social communication. Bearden plans to obtain comparable structural and functional brain anatomic data in a cohort of children with gain-of-function mutations (duplications of genetic material) in the same gene location. Preliminary data from Bearden's group indicate robust dose-dependent effects in brain regions critical for social processes. The researchers aim to use a novel artificial-language-learning paradigm that has revealed disruption of language-relevant neural circuits in both individuals with 22q11.2 deletions and children with idiopathic autism (autism of unknown cause). Extensive data from individuals with 22q11.2 deletions, typically developing children and children with idiopathic autism may allow for key comparisons across neural and behavioral levels of analysis. The investigators hope to use this ‘genetics-first’ approach to investigate whether brain structure and language-related neural circuitry, along with associated clinical phenotypes, differ meaningfully as a function of gene dosage. This information may reveal whether treatments are best tailored to a specific genetic event, or may be generalizable to those with autism of other or unknown etiologies.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

0

Current Award Period

Current Award Period

2014-2016

Strategic Plan Question

Strategic Plan Question

Question 3: What Caused This To Happen And Can This Be Prevented?

Strategic Plan Objective

Strategic Plan Objective

Yellow dot: Objective has some degree of funding, but less than the recommended amount. 3SA. Coordinate and implement the inclusion of approximately 20,000 subjects for genome-wide association studies, as well as a sample of 1,200 for sequencing studies to examine more than 50 candidate genes by 2011. Studies should investigate factors contributing to phenotypic variation across individuals that share an identified genetic variant and stratify subjects according to behavioral, cognitive, and clinical features. IACC Recommended Budget: $43,700,000 over 4 years.

Project Link

Project Link

Dosage effects of 22q11 region on autism-relevant neural systems (External web link)

Institution

Institution

University of California, Los Angeles

State/Country

State/Country

California

Project Number

Project Number

310629

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Dosage effects of 22q11 region on autism-relevant neural systems | 60000 | 2014 | 310629

 
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