Whole-Genome Analysis for Autism Risk Variants, Request for Applications

About this funding opportunity

Search SFARI Home Funding Email Intent to Submit Proposal

July 28, 2015 Application Deadline

August 14, 2015 Notification of Award

October 15, 2015 Funding Expected to Begin

November 1, 2015 SFARI Grant Programs

sciencerfa@simonsfoundation.org Email Intent to Submit Proposal

July 28, 2015 Application Deadline

August 14, 2015 Notification of Award

October 15, 2015 Funding Expected to Begin

November 1, 2015 SFARI Grant Programs

sciencerfa@simonsfoundation.org

Grants awarded through this request for applications (RFA) were intended to advance our understanding of the genetic basis of autism, and in particular, to begin to assess genetic variants conferring risk in non-coding regions and in coding regions of the genome that may be less accessible to whole-exome sequencing (WES).

The Simons Simplex Collection (SSC) is a rigorously characterized collection optimized to support the discovery of genetic events that increase risk of developing autism. The collection consists of approximately 2,600 simplex families, all of which have one child with autism, unaffected parents, and in over 80 percent of families at least one unaffected sibling. Analyses based on WES data from the SSC have already identified at least 30 risk genes for autism and have nominated several hundred other genes as strong candidates.

Whole-genome sequencing (WGS) of the SSC is expected to increase the detection of rare variants of clinical importance. In addition to identifying variants in non-coding regions of the genome, WGS analyses are anticipated to identify novel copy number variants (CNVs) and single nucleotide variants (SNVs) in protein-coding regions that have not previously been detected with WES. _Preliminary_ WGS analyses of a separate group of 40 families (160 genomes) from the SSC compared WGS results with WES data from the same 40 families and support the value of WGS in identifying additional variants of potential clinical significance for autism.

To this end, SFARI partnered with the New York Genome Center (NYGC) to sequence whole-genomes from the whole blood DNA of 500 SSC quartet families (2,000 genomes at 30X sequence coverage). SFARI later made the alignment and variant call data available to all eligible researchers (i.e., not contingent on funding through this RFA) without delay following standard quality control and data processing steps by the NYGC.

SFARI worked with successful applicants to make the WGS data (estimated to be about 400 TB) available to their academic or cloud-based computing resources. SFARI understood that validation of prioritized hits was a key part of this project and coordinated some of this confirmation of _de novo_ calls with awardees and the NYGC.

This RFA sought applications from investigators who plan to develop innovative and efficient ways to analyze WGS data from the 500 SSC families. Proposals of particular relevance to this RFA included, but were not limited to: Analyses of _de novo_ and inherited mutations in exomes to identify coding variants not originally identified by WES. Analyses of _de novo_ and inherited CNVs that were not identified by WES. Identification of non-coding variants associated with autism risk, including the potential development of novel algorithms/tools to analyze intronic and regulatory regions of the genome. Comparison of the current dataset with sequencing data from other autism and other neurodevelopmental disorders cohorts (including comparisons with WES data from SSC). Analyses of mitochondrial DNA.

Recognizing that successful analyses of such large datasets are likely to require multidisciplinary approaches, we encouraged collaborations between investigators with complementary expertise. Contacts

Scientific Inquiries

sciencerfa@simonsfoundation.org

646-654-0066

Administrative Inquiries

grants@simonsfoundation.org

646-654-0066

SSC Collection Inquiries

collections@sfari.org

646-654-0066 Email Intent to Submit Proposal

July 28, 2015 Application…

Topic areas: Life Sciences and Health.

Funding amount

This grant provides Varies in funding.

Deadline

Applications are accepted on a rolling basis; there is no single fixed deadline.

Who can apply

This opportunity is open to the following applicant types:

• Not specified by the program.

Eligibility

The program did not publish a separate eligibility statement. See the official opportunity page for the full eligibility criteria.

Agency

Whole-Genome Analysis for Autism Risk Variants, Request for Applications is administered by Simons Foundation (Simons), listed via Simons Foundation.