Deadline for nominations:
April 12, 2019
Background and rationale
Neuronal precursors, neurons and other cell types derived from human induced pluripotent stem cells (iPSCs) have become a valuable tool in autism research, complementing other research done in humans and animal models. As iPSCs can be derived from individuals with autism spectrum disorder (ASD), they present one of the few ways to study human-specific cell and molecular biology in the context of a patient-specific genome.
As part of the Simons Simplex Collection (SSC) and Simons Variation in Individuals Project (Simons VIP) cohorts, SFARI has collected (and is continuing to collect) peripheral blood mononuclear cells (PBMCs) suited for iPSC derivation from individuals with ASD and other neurodevelopmental disorders, including many with well-validated genetic risk variants (Table 1). iPSCs from these individuals will be especially valuable for research as, in addition to the biospecimens, SFARI has collected detailed clinical and genetic information on many participants, which is accessible by approved researchers via SFARI Base.
Creation of iPSCs from the PBMC resource will add to the existing SFARI iPSC collection. We hope that standardized creation of iPSCs and their centralized storage will facilitate experiments that compare across different genetic etiologies and allow for easy access by many researchers.
Table 1. Summary of available peripheral blood mononuclear cell (PBMC) samples by risk gene/ copy number variant (CNV).
Click to expand the table.
Genes/CNVs total # proband samples1 # unique genetic variants2 # of samples from probands with ASD diagnosis # of samples with familial sample(s) available3 Simons cohort Genes ADNP 4 4 3 4 Simons VIP ANK2 1 1 1 1 SSC ANKRD11 2 2 2 2 SCC ARID1B 1 1 1 1 SSC ASH1L 1 1 1 1 SSC ASXL3 10 10 3 9 Simons VIP CHD2 1 1 1 1 SSC CHD8 4 4 4 4 SSC CNOT3 1 1 1 1 SSC CSNK2A1 8 7 1 8 Simons VIP DDX3X 1 1 1 1 SSC DSCAM 3 3 3 3 SSC DST 1 1 1 1 SSC DYRK1A 1 1 1 1 SSC FOXP1 1 1 1 1 SSC GIGYF1 1 1 1 1 SSC GIGYF2 1 1 1 1 SSC GRIN2B 10 10 2 10 Simons VIP SSC HIVEP2 1 1 N/A 1 Simons VIP HNRNPH2 3 2 1 0 Simons VIP KATNAL2 1 1 1 1 SSC KDM5B 2 2 2 2 SSC KDM6B 1 1 1 1 SSC KMT2A 1 1 1 1 SSC MBD5 1 1 1 1 SSC MED13L 2 2 1 2 SSC NBEA 1 1 1 1 SSC NCKAP1 1 1 1 1 SSC NLGN3 1 1 1 1 SSC NRXN1 2 2 2 2 SSC PACS1 1 1 N/A 0 Simons VIP POGZ 1 1 1 1 SSC PPP2R5D 6 4 4 6 SSC RAI1 1 1 1 1 SSC RERE 1 1 1 1 SSC RIMS1 2 2 2 2 SSC SCN2A 16 14 8 14 Simons VIP SSC SHANK2 1 1 1 1 SSC SHANK3 1 1 1 1 SSC SPAST 1 1 1 1 SSC SYNGAP1 2 2 N/A 2 Simons VIP TBR1 2 2 2 2 SSC UPF3B 1 1 1 1 SSC WAC 1 1 1 1 SSC WDFY3 2 2 2 2 SSC CNVs 16p11.2 deletion 60 N/A 18 43 Simons VIP 16p11.2 duplication 42 N/A 6 18 Simons VIP 1q21.1 deletion 11 N/A 2 4 Simons VIP 1q21.1 duplication 16 N/A 4 6 Simons VIP
1 Not all probands for whom samples are available have a diagnosis of ASD. Those who don’t, have another neurodevelopmental or neuropsychiatric diagnosis.
2 To learn what specific genetic variants are represented or for more specific information concerning diagnosis and other phenotypes, please place a request for data within SFARI Base. If you do not yet have an account, please register. In addition, to alert us of your request, please send us a short email at [email protected], subject: “iPSC RFI”.
3 Familial samples may be from the father, mother and/or siblings.
With this request for information (RFI), we are requesting nominations from investigators interested in using iPSC lines derived from particular PBMC samples (Table 1) from SFARI cohorts. We will use submitted nominations to prioritize samples for iPSC derivation. Importantly, nominations should demonstrate immediate interest in using the iPSC lines for research projects relevant to understanding the biological impact of mutations associated with ASD and related neurodevelopmental disorders.
As the PBMC samples are a limited resource, SFARI will coordinate the iPSC derivation for the prioritized biospecimens at a central facility; resulting iPSCs will be stored at and shared with the research community via the SFARI biorepository at RUCDR Infinite Biologics (formerly Rutgers University Cell and DNA Repository).
If well-justified interest for the creation of iPSC lines exceeds our current budget, SFARI may consider cost-sharing arrangements with investigators.
Available samples are listed in Table 1.
If you require more detailed information (e.g., details regarding genetic variants, diagnosis or phenotypic measures), please place a request for data within SFARI Base. If you do not yet have an account, please register. In addition, to alert us of your request, please send us a short email at [email protected], subject: “iPSC RFI”.
How to submit a nomination
The deadline of receipt for nominations is April 12, 2019. Nominations should be made using this online form.
Nominations will be evaluated by SFARI science staff. Information provided in the nomination will be used to prioritize PBMC samples for iPSC derivation. It will add to the weight of a nomination if immediate interest in using the resulting iPSC lines for research projects relevant to understanding the biological impact of mutations associated with ASD and related neurodevelopmental disorders can be demonstrated.
We will reach out to individual investigators if we require more information. Investigators will be informed of our final decisions in mid May, 2019.
Importantly, even samples that are not prioritized for iPSC derivation by SFARI at this time are available for iPSC generation to investigators at their own cost. However, as the samples are a limited resource, SFARI strongly prefers derivation at a central facility of our choosing, and resulting iPSCs will have to be stored at and shared with the research community via the SFARI biorepository at RUCDR.
Who is eligible to submit a nomination?
To submit a nomination, you must hold a Ph.D., M.D. or equivalent degree and have a faculty position or the equivalent at a college, university, medical school or other research facility. Any researcher from around the world can respond to this RFI.
Questions and further information
Additional information can be found in our FAQs.
If your question remains unanswered, please contact [email protected] with the subject “iPSC RFI.”