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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

Whole exome sequencing of Simons Simplex Collection quads

Principal Investigator

Principal Investigator

Eichler, Evan

Description

Description

There is definitive evidence that rare mutations, including spontaneous, or de novo, structural variations, contribute to autism spectrum disorders. However, recent findings highlight important remaining areas for investigation. Approximately six to ten percent of families in the Simons Simplex Collection (SSC) carry large multi-genic de novo copy-number variants (CNVs), those most clearly associated with autism risk. This suggests that higher-resolution detection of de novo point mutations and insertions or deletions may lead to discovery of multiple additional bona fide autism risk genes. The findings also highlight the question of whether these CNVs carry risk as a consequence of being large and therefore more likely to encompass a critical gene, or because they simultaneously disrupt multiple coding or regulatory units. Whole-exome sequencing is an ideal way to pursue these questions: to explore the genome for rare autism-related de novo and transmitted mutations that disrupt proteins, to evaluate whether multiple de novo events in the same individual increase risk, and to determine whether de novo and transmitted point mutations begin to clarify the nature of the risk posed by large multi-genic CNVs. This project represents a collaboration among the labs of Matthew State, Evan Eichler and Daniel Geschwind. The goal is to carry out whole-exome sequencing and analysis of 400 SSC families. The researchers plan to evaluate 200 SSC trios — including parents and affected child — at the University of Washington in Seattle, and 200 SSC quartets, including an unaffected sibling in each pedigree, at Yale University. Geschwind’s team at the University of California, Los Angeles, aims to develop bioinformatics tools for integrated analysis with other types of genomic and transcriptomic data.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

0

Current Award Period

Current Award Period

2012-2014

Strategic Plan Question

Strategic Plan Question

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

Strategic Plan Objective

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.

Project Link

Project Link

Whole exome sequencing of Simons Simplex Collection quads (External web link)

Institution

Institution

University of Washington

State/Country

State/Country

Washington

Project Number

Project Number

191889EE

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Whole exome sequencing of Simons Simplex Collection quads | 1835440 | 2012 | 191889EE
Whole exome sequencing of Simons Simplex Collection quads | 2110073 | 2012 | 191889MS
Whole exome sequencing of Simons Simplex Collection quads | 1495957 | 2013 | 191889EE
Whole exome sequencing of Simons Simplex Collection quads | 536779 | 2013 | 191889MS

 
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