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Series GSE186347 Query DataSets for GSE186347
Status Public on Feb 10, 2023
Title Extensive sex differences in depression-linked variants functionally assayed in mouse brain [P0&P10]
Organisms Mus musculus; Adeno-associated virus 9
Experiment type Expression profiling by high throughput sequencing
Summary Here, we selected >1000 variants from over 30 depression-associated loci using brain epigenomic data, and functionally assayed them using in vivo functional assays in the mouse brain to examine sex-by-genotype interactions. We identify extensive sex-by-allele effects in mature hippocampus, suggesting genetic risk and thus disease mechanisms may be distinct between the sexes. Unbiased informatics approaches indicated a role for nuclear hormone receptors, which was supported by . Further, comparative analysis of allelic function in the neonatal mouse brain, during a key between developmental neonates during the masculinizing testosterone surge, and in the adult hippocampus—a region of interest in depression pathology—but not at 10 days old, a older hormonally quiescent developmental stage juveniles. Our study provides novel insights into depression genetics as influenced by age, biological sex, and cell type, and provides a framework for in vivo parallel assays at a scale not previously shown possible to functionally define interactions between sex and disease variation.
Overall design AAV9 MPRA library was delivered into the mouse brain in utero (embryonic day 15). Mice were screened at birth for reporter-driven red fluorescence (visible through the skull by eye by green light illumination). Brains were collected WITHOUT cerebellum for RNA extraction at postnatal day 0 (P0) (n=9 male, n=6 female) or P10 (n=7 male, 6 female).

Additional grant information: 571009 - Joseph Dougherty - Simons Foundation
Contributor(s) Mulvey B, Dougherty JD, Selmanovic D
Citation(s) 36803612
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 MH116999 Highly parallel analysis of 5' and 3' UTR variants in Autism Spectrum Disorders WASHINGTON UNIVERSITY JOSEPH D DOUGHERTY
F30 MH116654 Identification and characterization of common, noncoding regulatory variants associated with Major Depressive Disorder. WASHINGTON UNIVERSITY Bernard John Mulvey
Submission date Oct 21, 2021
Last update date May 12, 2023
Contact name Joseph Dougherty
Organization name Washington University in St. Louis
Department Genetics
Lab Dougherty
Street address 660 S Euclid Ave, Campus Box 8232
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL30885 Illumina NovaSeq 6000 (Adeno-associated virus 9)
Samples (44)
GSM5645947 P0_A2
GSM5645948 P0_A3
GSM5645949 P0_A4
This SubSeries is part of SuperSeries:
GSE186348 Extensive sex differences in depression-linked variants functionally assayed in mouse brain
BioProject PRJNA773476
SRA SRP342578

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE186347_P010_unfiltered_counts.txt.gz 2.2 Mb (ftp)(http) TXT
GSE186347_Reference-Barcode_Sequences__their_paired_internal_identifiers__and_the_corresponding_sequence_placed_upstream_of_min_promoter.txt.gz 1.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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