Simons Searchlight is an initiative of the Simons Foundation Autism Research Initiative (SFARI) that aims to better understand genetic neurodevelopmental conditions, specifically those associated with autism spectrum disorder (ASD).
Previously named Simons Variation in Individuals Project (Simons VIP), the name change aims to better reflect the program’s mission to shed light on these conditions by building strong partnerships between researchers and families. In addition to the name, other recent changes include updating the community website, as well as streamlining the online registration process.
Currently, Simons Searchlight collects family, medical, developmental and behavioral information through online surveys and phone interviews with families and individuals. Biospecimen collection is performed either remotely or at in-person family meetings. Recently the scope has expanded to include new rare genetic disorders. Today, 151 genes and 23 CNVs are part of the Simons Searchlight community.
This expansion has been made possible through new coordinated efforts with SPARK (Simons Foundation Powering Autism Research for Knowledge), a SFARI initiative that aims to recruit, engage and retain a community of 50,000 individuals with autism and their family members living in the United States. SPARK returns genetic findings to participants who are found to carry ASD risk variants.
SPARK participants who receive a genetic diagnosis — together with any individual (worldwide) who has been given a professional diagnosis for one of the genetic conditions that are being studied by Simons Searchlight — will now have the opportunity to join Simons Searchlight. Joining such a community enables families to find and engage with others with the same genetic condition, as well as providing opportunities to connect with researchers and participate in studies aimed at bettering our understanding of these disorders and, in some cases, clinical trials to advance treatments.
Over 1,500 individuals with rare disorders and their families are currently registered in Simons Searchlight and more than 50 research papers have resulted from data collected from Searchlight families. These numbers are expected to grow significantly in the coming years, and so are the research opportunities for participants as well as investigators studying these conditions.
The initial phase of Simons Searchlight (Simons VIP Phase 1), which ended in early 2014, involved in-person evaluations at clinical study sites. There, participants underwent extensive psychological and neurological testing, along with neuroimaging — including magnetic resonance imaging (MRI), functional MRI and magnetoencephalography (MEG) — with a uniform protocol and collection of biospecimens.
Gene/CNV list
The Simons Searchlight gene list contains 151 gene changes (orange) and 23 copy number variants (purple) that are known to be associated with autism and other neurodevelopmental disorders. Any result returned by SPARK, another SFARI initiative, are eligible in Simons Searchlight.
Genetic variants
A list of genetic variants observed in Simons Searchlight participants can be found here (.xlsx). Where variants are found in more than one participant, counts are indicated. Variants included are classified as pathogenic, likely pathogenic, or variants of uncertain significance (VUS).
For more details, see data sets available through SFARI Base.
Phenotypic data
Phenotypic data from the following individuals are currently available to approved researchers via SFARI Base.
Copy number variants (individuals enrolled in Phase 1 and/or Phase 2):
- 38 carriers of the 15q11.2 BP1-BP2 deletion
- 9 carriers of the 15q13.3 deletion
- 332 carriers of the 16p11.2 deletion
- 226 carriers of the 16p11.2 duplication
- 54 individuals with Distal 16p11.2 deletion
- 20 individuals with Distal 16p11.2 duplication
- 8 carriers of the 16p12.1 deletion
- 6 individuals with 17q12 duplication
- 93 carriers of the 1q21.1deletion
- 110 carriers of the 1q21.1 duplication
- 8 carriers of the 2p16.3 deletion
- 25 carriers of the 7q11.23 duplication
Single genes (all individuals enrolled in Phase 2):
- 31 individuals with ADNP mutations
- 10 individuals with ANK2 mutations
- 27 individuals with ANKRD11 mutations
- 22 individuals with ARID1B mutations
- 9 individuals with ASH1L mutations
- 75 individuals with ASXL3 mutations
- 15 individuals with AUTS2 mutations
- 5 individuals with BRSK2 mutations
- 44 individuals with CHAMP1 mutations
- 15 individuals with CHD2 mutations
- 6 individuals with CHD3 mutations
- 22 individuals with CHD8 mutations
- 16 individuals with CLCN4 mutations
- 9 individuals with CSDE1 mutations
- 74 individuals with CSNK2A1 mutations
- 17 individuals with CSNK2B mutations
- 5 individuals with CTBP1 mutations
- 142 individuals with CTNNB1 mutations
- 12 individuals with CUL3 mutations
- 8 individuals with DDX3X mutations
- 10 individuals with DEAF1 mutations
- 26 individuals with DLG4 mutations
- 9 individuals with DNMT3A mutations
- 6 individuals with DYNC1H1 mutations
- 47 individuals with DYRK1A mutations
- 11 individuals with EHMT1 mutations
- 6 individuals with EIF3F mutations
- 17 individuals with FOXP1 mutations
- 5 individuals with GIGYF1 mutations
- 13 individuals with GRIN1 mutations
- 11 individuals with GRIN2A mutations
- 92 individuals with GRIN2B mutations
- 9 individuals with HECW2 mutations
- 40 individuals with HIVEP2 mutations
- 43 individuals with HNRNPH2 mutations
- 7 individuals with HNRNPU mutations
- 15 individuals with IRF2BPL mutations
- 10 individuals with KDM5B mutations
- 14 individuals with KDM6B mutations
- 11 individuals with KMT2C mutations
- 8 individuals with KMT2E mutations
- 11 individuals with KMT5B mutations
- 7 individuals with MBD5 mutations
- 12 individuals with MED13 mutations
- 84 individuals with MED13L mutations
- 11 individuals with MEF2C mutations
- 9 individuals with MYT1L mutations
- 7 individuals with NEXMIF mutations
- 8 individuals with NR4A2 mutations
- 6 individuals with NRXN1 mutations
- 34 individuals with PACS1 mutations
- 15 individuals with PPP2R1A mutations
- 130 individuals with PPP2R5D mutations
- 14 individuals with PPP3CA mutations
- 11 individuals with PTCHD1 mutations
- 7 individuals with SCN1A mutations
- 5 individuals with SCN1B mutations
- 199 individuals with SCN2A mutations
- 59 individuals with SETBP1 mutations
- 16 individuals with SETD5 mutations
- 7 individuals with SIN3A mutations
- 114 individuals with SLC6A1 mutations
- 5 individuals with SMARCA4 mutations
- 5 individuals with SMARCC2 mutations
- 5 individuals with SOX5 mutations
- 187 individuals with STXBP1 mutations
- 86 individuals with SYNGAP1 mutations
- 16 individuals with TANC2 mutations
- 10 individuals with TAOK1 mutations
- 17 individuals with TBR1 mutations
- 7 individuals with TCF20 mutations
- 7 individuals with TLK2 mutations
- 11 individuals with TRIO mutations
- 19 individuals with TRIP12 mutations
- 5 individuals with UPF3B mutations
- 8 individuals with USP9X mutations
- 21 individuals with VPS13B mutations
- 6 individuals with WAC mutations
- 15 individuals with WDFY3 mutations
Biospecimens
The following biospecimens are currently available for request via SFARI Base. Please note that not every sample type listed here is available for each donor.
Associated costs for obtaining and shipping these samples can be found here.
Induced pluripotent stem cells (iPSCs) that are available from other Simons Foundation collections can be found here.
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Click to expand the table.
Genetic change Biospecimens available Cell Lines DNA Total # of donors per genetic change Fibroblasts Lympho-blastoids iPSCs Saliva Lympho-blastoids Whole Blood 15q11.2 BP1-BP2 deletion 0 0 0 0 0 0 0 15q13.3 deletion 0 0 0 0 0 2 2 16p11.2 deletion 59 29 15 19 27 149 195 16p11.2 duplication 44 34 5 10 33 109 153 Distal 16p11.2 deletion 0 0 0 0 0 3 3 Distal 16p11.2 duplication 0 0 0 0 0 4 4 16p11.2 triplication 0 0 0 0 0 3 3 16p12.1 deletion 0 0 0 0 0 1 2 17q12 duplication 0 0 0 0 0 3 4 1q21.1 deletion 11 5 0 7 5 25 42 1q21.1 duplication 8 10 0 6 9 29 43 2p16.3 deletion 0 0 0 0 0 0 0 7q11.23 duplication 0 1 0 0 1 4 7 ADNP 0 2 4 3 2 5 10 ANK2 0 0 0 0 0 1 2 ANKRD11 0 0 0 1 0 4 8 ARID1B 0 2 0 0 2 2 4 ASH1L 0 0 0 0 0 0 0 ASXL3 0 15 1 4 12 15 30 AUTS2 0 0 0 0 0 0 0 BRSK2 0 0 0 0 0 2 3 CHAMP1 0 0 0 0 0 1 5 CHD2 0 1 0 0 1 3 3 CHD3 0 0 0 0 0 3 3 CHD8 0 0 0 1 0 2 3 CLCN4 0 0 0 0 0 1 4 CSDE1 0 0 0 0 0 1 1 CSNK2A1 0 6 9 2 4 12 21 CSNK2B 0 0 0 0 0 0 0 CTBP1 0 0 0 0 0 0 0 CTNNB1 0 0 0 0 0 9 16 CUL3 0 0 0 0 0 3 4 DDX3X 0 0 0 0 0 0 0 DEAF1 0 0 0 0 0 0 2 DLG4 0 0 0 0 0 5 7 DNMT3A 0 0 0 0 0 1 1 DYNC1H1 0 0 0 0 0 1 1 DYRK1A 0 1 6 4 1 11 14 EHMT1 0 0 0 0 0 1 1 EIF3F 0 0 0 0 0 3 3 FOXP1 0 0 0 1 0 0 1 GIGYF1 0 0 0 0 0 1 1 GRIN1 0 0 0 0 0 0 0 GRIN2A 0 1 0 0 0 2 3 GRIN2B 0 8 10 3 8 16 29 HECW2 0 0 0 0 0 1 1 HIVEP2 0 2 1 1 2 12 18 HNRNPH2 3 3 2 0 3 6 12 HNRNPU 0 0 0 0 0 0 1 IRF2BPL 0 0 0 0 0 2 4 KDM5B 0 0 0 0 0 2 2 KDM6B 0 0 0 0 0 1 1 KMT2C 0 0 0 0 0 0 0 KMT2E 0 0 0 0 0 0 0 KMT5B 0 0 0 1 0 1 2 MBD5 0 0 0 1 0 4 5 MED13 0 0 0 0 0 4 4 MED13L 0 2 0 2 2 15 24 MYT1L 0 0 0 0 0 1 1 NEXMIF 0 0 0 0 0 0 0 NR4A2 0 0 0 0 0 2 2 NRXN1 0 0 2 0 0 2 2 PACS1 0 2 0 2 2 9 13 PPP2R1A 0 0 0 0 0 0 2 PPP2R5D 5 16 13 0 15 43 71 PPP3CA 0 0 0 0 0 2 4 PTCHD1 0 0 0 0 0 1 1 SCN1A 0 0 0 0 0 3 3 SCN1B 0 0 0 0 0 0 0 SCN2A 0 20 9 10 20 34 67 SETBP1 0 0 3 1 0 12 17 SETD5 0 1 0 1 1 2 4 SIN3A 0 0 0 0 0 0 0 SLC6A1 0 1 1 0 1 8 13 SMARCA4 0 0 0 0 0 1 2 SMARCC2 0 0 0 0 0 0 0 SOX5 0 0 0 0 0 0 0 STXBP1 0 5 5 4 4 25 48 SYNGAP1 0 1 3 3 1 9 15 TANC2 0 0 0 0 0 0 0 TAOK1 0 0 0 0 0 1 1 TBR1 0 0 0 0 0 3 4 TCF20 0 0 0 0 0 0 0 TLK2 0 0 0 0 0 1 2 TRIO 0 0 0 0 0 0 0 TRIP12 0 0 0 0 0 0 1 UPF3B 0 0 0 0 0 1 1 USP9X 0 0 0 0 0 0 0 VPS13B 0 0 0 0 0 1 1 WAC 0 0 0 0 0 0 0 WDFY3 0 0 0 0 0 1 1
Genetic data
Genetic data are available for a subset of individuals and their families enrolled in Phase 1.
More information is available in SFARI Base and in the publications listed below:
Single nucleotide polymorphism (SNP) genotype data
- Duyzend M.H. et al. Am. J. Hum. Genet. 98, 45-57 (2016) PubMed, Data available through SFARI Base
Targeted sequencing data
- Nuttle X. et al. Nature 536, 205-209 (2016) PubMed, Data available through SFARI Base (targeted sequencing around the 16p11.2 rearrangement breakpoints; please reference accession SFARI_SVIP_MIPS_1)
- Fiddes I.T. et al. Cell 173, 1356-1369 (2018) PubMed (targeted sequencing around the 1q21.1 rearrangement breakpoints; please reference accession SFARI_SVIP_VSV_1)
Whole-exome sequencing data
- Daly M.J. et al. (in preparation) Data available through SFARI Base
Whole-genome sequencing data
- Nuttle X. et al. Nature 536, 205-209 (2016) PubMed, Data available through SFARI Base (please reference accession SFARI_SVIP_WGS_1)
Additional links
- A paper published in Neuron further details the motivation behind the project and its design; click here to download the article
- Publications resulting from Simons Searchlight data are available here (select the filter “Uses Resources From: Simons Searchlight”)
- Families interested in participating in Simons Searchlight can register online (or call 855-329-5638 for more information)
- Simons Searchlight Investigators
- Researcher welcome packet (PDF)
- Simons Collection Researcher Distribution Agreement (PDF)
- How to access SFARI Base and request SFARI resources
- Online tools to visualize and analyze SFARI genomic and phenotypic data
- Biospecimen prices
- List of neuropsychological tests and other phenotypic instruments used in the Phase 1 study (PDF)
- Definition of phenotypic data points for Simons Searchlight (xlsx)
- Simons Searchlight Institutional Review Protocol (PDF)
- Simons Searchlight consent form (PDF)
- Induced pluripotent stem cell lines from Simons Searchlight participants