Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex

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• dc.contributor.author Werling, Donna M.
• dc.contributor.author Santpere Baró, Gabriel, 1981-
• dc.contributor.author Sestan, Nenad
• dc.date.accessioned 2021-03-15T06:56:14Z
• dc.date.available 2021-03-15T06:56:14Z
• dc.date.issued 2020
• dc.description.abstract Gene expression levels vary across developmental stage, cell type, and region in the brain. Genomic variants also contribute to the variation in expression, and some neuropsychiatric disorder loci may exert their effects through this mechanism. To investigate these relationships, we present BrainVar, a unique resource of paired whole-genome and bulk tissue RNA sequencing from the dorsolateral prefrontal cortex of 176 individuals across prenatal and postnatal development. Here we identify common variants that alter gene expression (expression quantitative trait loci [eQTLs]) constantly across development or predominantly during prenatal or postnatal stages. Both "constant" and "temporal-predominant" eQTLs are enriched for loci associated with neuropsychiatric traits and disorders and colocalize with specific variants. Expression levels of more than 12,000 genes rise or fall in a concerted late-fetal transition, with the transitional genes enriched for cell-type-specific genes and neuropsychiatric risk loci, underscoring the importance of cataloging developmental trajectories in understanding cortical physiology and pathology.
• dc.format.mimetype application/pdf
• dc.identifier.citation Werling DM, Pochareddy S, Choi J, An JY, Sheppard B, Peng M, et al. Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex. Cell Rep. 2020; 31(1):107489. DOI: 10.1016/j.celrep.2020.03.053
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2020.03.053
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/46756
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep. 2020; 31(1):107489
• dc.rights © 2020 The Author(s). This is an open access article under the CC BY license http://creativecommons.org/licenses/by/4.0/
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword BrainVar
• dc.subject.keyword DLPFC
• dc.subject.keyword LOC101926933 RP11-298I3.1 AL132780.1 ENSG00000257285
• dc.subject.keyword PsychENCODE
• dc.subject.keyword RHEBL1
• dc.subject.keyword Dorsolateral prefrontal cortex
• dc.subject.keyword Fetal transition
• dc.subject.keyword mTOR
• dc.subject.keyword Prenatal eQTL
• dc.title Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion