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SRX5001324: GSM3466728: FB_RNA_rep3; Mus musculus; RNA-Seq
1 ILLUMINA (Illumina HiSeq 2500) run: 89.1M spots, 17.8G bases, 10.7Gb downloads

Submitted by: NCBI (GEO)
Study: Parkinson-associated SNCA enhancer variants revealed by open chromatin in mouse dopamine neurons
show Abstracthide Abstract
The progressive loss of midbrain (MB) dopaminergic (DA) neurons defines the motor features of Parkinson disease (PD) and modulation of risk by common variation in PD has been well established through GWAS. Anticipating that a fraction of PD-associated genetic variation mediates their effects within this neuronal population, we acquired open chromatin signatures of purified embryonic mouse MB DA neurons. Correlation with >2,300 putative enhancers assayed in mice reveals enrichment for MB cis-regulatory elements (CRE), data reinforced by transgenic analyses of six additional sequences in zebrafish and mice. One CRE, within intron 4 of the familial PD gene SNCA, directs reporter expression in catecholaminergic neurons of transgenic mice and zebrafish. Sequencing of this CRE in 986 PD patients and 992 controls reveals two common variants associated with elevated PD risk. To assess potential mechanisms of action, we identify proteins whose binding is impacted by these enhancer variants. Additional genotyping across the SNCA locus identifies a single PD-associated haplotype, containing the minor alleles of both of the aforementioned PD-risk variants. Our work posits a model for how common variation at SNCA may modulate PD risk and highlights the value of cell context-dependent guided searches for functional non-coding variation. Overall design: 6 ATAC-seq libraries and 8 RNA-seq samples from sorted mouse Th-EGFP dopaminergic neurons collected at E15.5 from two distinct brain regions (midbrain and forebrain)
Sample: FB_RNA_rep3
SAMN10413955 • SRS4036040 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: Illumina HiSeq 2500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Pooled brain regions were dissociated using the Papain Dissociation System (Worthington Biochemical Corporation). The tissue was dissociated in the papain solution for 30 minutes at 37°C, with gentle trituration every 10 minutes using a sterile Pasteur pipette. Following dissociation, cells were passed through a 40µm cell strainer into a 50mL conical, centrifuged for 5 minutes at 300g, resuspended in albumin-inhibitor solution containing DNase, applied to a discontinuous density gradient, and centrifuged for 6 minutes at 70g. The resulting cell pellet was resuspended in HBSS with Mg2+ and Ca2+ and submitted to FACS. Aliquots of 50,000 EGFP+ cells were sorted directly into 300µL HBSS with Mg2+ and Ca2+ with 10% FBS for ATAC-seq. Aliquots containing ≥50,000 EGFP+ cells were sorted into kit-provided lysis buffer for RNA-seq. Total RNA was extracted using the Purelink RNA Micro Kit (Invitrogen). Following FACS isolation into kit-provided lysis buffer, samples were homogenized and RNA extraction proceeded using manufacturer's recommendations. Total RNA integrity was determined using the RNA Pico Kit (Agilent). RNA samples were sent to the Sidney Kimmel Comprehensive Cancer Center Next Generation Sequencing Core at Johns Hopkins for library preparation, using the Ovation RNA-Seq System V2 (Nugen), and sequencing.
Experiment attributes:
GEO Accession: GSM3466728
Links:
Runs: 1 run, 89.1M spots, 17.8G bases, 10.7Gb
Run# of Spots# of BasesSizePublished
SRR818133089,142,12417.8G10.7Gb2018-11-15

ID:
6743878

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