Single cell methylation, RNA, and ATAC sequencing of amygdala brain tissue from inbred mouse strains
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE262259 | GEO | 2024/04/04
REPOSITORIES: GEO
Similar Datasets
Project description:Schizophrenia is a complex genetic and developmental disorder. We present a model of disease resulting from disruption of a specific stage of homeostatic scaling (HS). HS modifies synapses and circuits in response to changes in neuronal activity and underlies cortical development and memory consolidation. Neuronal pentraxin 2 (NPTX2) plays a critical role in HS and its homeostatic action requires exocytosis at excitatory synapses on parvalbumin interneurons (PV) whereupon a portion is later shed into the CSF. CSF NPTX2 is reduced in two independent cohorts of patients with schizophrenia. To understand the relationship of this biomarker to disease we confirmed that in normal volunteers CSF NPTX2 increases rapidly with sleep deprivation consistent with behavior-linked exocytosis/shedding. In mouse neocortex NPTX2 exocytosis/shedding are activity-dependent and coupled to circadian behavioral. By contrast, in mouse genetic models that interrupt early events in HS NPTX2 exocytosis/shedding are erratic and not linked to behavior. The vital contribution of NPTX2 to homeostasis is revealed in Nptx2-/- mice, which exhibit sensitivity to social isolation stress and multiple schizophrenia-domain phenotypes. NPTX2 is not implicated by human genome studies; rather we propose that diverse mutations linked to schizophrenia disrupt activity-dependent mechanisms required for NPTX2 function. The ability to monitor NPTX2 in human subjects provides an opportunity to translate fundamental neuroscience to human neuropsychiatric disease.
2021-05-15 | GSE150671 | GEO
Project description:The genetic contribution of additive versus non-additive (epistasis) effects in the regulation of hematologic and other complex traits is unclear. While genome-wide association studies typically ignore gene-gene interactions, in part because of the lack of statistical power for detecting them, mouse chromosome substitution strains (CSSs) represent an alternate and powerful model for detecting epistasis given their limited allelic variation. Therefore, we utilized CSSs to identify and map both additive and epistatic loci that regulate a range of hematologic- and metabolism-related traits, as well as hepatic gene expression. Quantitative trait loci (QTLs) were identified using a modified backcross strategy involving the segregation of variants on the A/J-derived substituted chromosomes 4 and 6 on an otherwise C57BL/6J genetic background. By analyzing the transcriptomes of offspring from this cross, we identified and mapped additive QTLs regulating the expression of 768 genes, and epistatic QTLs for 519 genes. Similarly, we identified additive QTLs for fat pad weight, platelets, and percentage of granulocyte in the blood as well as epistatic QTLs controlling the percentage of lymphocytes in the blood and red cell distribution width. The variance attributed to the epistatic QTLs was approximately equal to that of the additive QTLs, demonstrating the importance of identifying genetic interactions to understand the genetic basis of complex traits. Of particular note, even the epistatic QTLs identified that accounted for the largest variances were undetected in our single loci GWAS-like association analyses, highlighting the need to account for epistasis in association studies.
2020-10-05 | GSE145607 | GEO
Project description:Ramie is an important industrial fiber crop, and the fiber yield and its related traits are the most valuable traits in ramie production. However, the genetic basis for these traits is still poorly understood. Herein, a high-density genetic map with 1085 markers spanning 2,118.8 cM was constructed using a population derived from two parents, cultivated ramie Zhongsizhu 1 (ZSZ1) and its wild progenitor B. nivea var. tenacissima (BNT). The fiber yield (FY) and its four related traits—stem diameter (SD) and length (SL), stem bark weight (BW) and thickness (BT)—were performed for quantitative trait locus (QTL) analysis, resulting in eight, six, six, three, and ten QTLs for SD, SL, BW, BD and FY traits, respectively. These 33 QTLs were mapped into 11 genomic regions, thus forming 11 QTL clusters; there were 11 QTLs identified their beneficial alleles from the wild species BNT. Interestingly, all QTLs in Cluster 8 and Cluster 10 displayed overdominance, indicating that these two regions were likely heterotic loci. In addition, there were five fiber yield-related genes identified to undergo positive selection in previous study, and they were found to locate into the genomic region near to the QTLs of this study. The genetic dissection for FY and its related traits improved our understanding to the genetic basis of these traits, as well to their domestication in ramie. The identification of many QTLs and the discovery of beneficial alleles from wild species provided a basis for the improvement of yield traits in ramie breeding.
2019-01-31 | GSE125891 | GEO
Project description:Genetic variants that impact gene regulation are important contributors to human phenotypic variation. For this reason, considerable efforts have been made to identify genetic associations with differences in mRNA levels of nearby genes, namely, cis expression quantitative trait loci (eQTLs). The phenotypic consequences of eQTLs are presumably due, in most cases, to their ultimate effects on protein expression levels. Yet, only few studies have quantified the impact of genetic variation on proteins levels directly. It remains unclear how faithfully eQTLs are reflected at the protein level, and whether there is a significant layer of cis regulatory variation acting primarily on translation or steady state protein levels. To address these questions, we measured ribosome occupancy by high-throughput sequencing, and relative protein levels by high-resolution quantitative mass spectrometry, in a panel of lymphoblastoid cell lines (LCLs) in which we had previously measured transcript expression using RNA sequencing. We then mapped genetic variants that are associated with changes in transcript expression (eQTLs), ribosome occupancy (rQTLs), or protein abundance (pQTLs). Most of the QTLs we detected are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, we found that eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we confirmed the presence of a class of cis QTLs that specifically affect protein abundance with little or no effect on mRNA levels; most of these QTLs have little effect on ribosome occupancy, and hence may arise from differences in post-translational regulation.
2014-12-19 | PXD001406 | Pride
Project description:These data are from the brains (amygdala and hippocampus) of mice originally derived from a cross between C57BL/6J and DBA/2J inbred strains. We used short-term selection to produce outbred mouse lines with differences in contextual fear conditioning, which is a measure of fear learning. We selected for a total of 4 generations. Fear learning differed in the selected lines and this difference was stronger with each successive generation of selection. These mice also showed differences for measures of anxiety-like behavior, but were not different for tests of non-fear motivated learning, suggesting that selection altered alleles that are specifically involved in emotional behaviors. We identified several QTLs for the selection response. We used Affymetrix microarrays to identify differentially expressed genes in the amygdala and hippocampus of mice from the final generation of selection. Amygdala and hippocampus samples were rapidly dissected out of experimentally naïve mice f rom each selected line. Three samples were pooled and hybridized to each array. Experimentally naïve mice were used because the behavior of the mice can be reliably anticipated due to their lineage. Thus, these gene expression differences are not due to the response to human handling, foot shock or fear-inducing conditioned stimuli. We have a second similar study that focuses on a different selected population that was based on C57BL/6J and A/J mice (see GES4034).
2006-01-13 | GSE4035 | GEO
Project description:Analyses of QTLs for expression levels (eQTLs) of the genes reveal genetic relationship between expression variation and the regulator, thus unlocking the information for identifying the regulatory network. Oligo-nucleotide expression microarrays hybridized with RNA can simultaneously provide data for molecular markers and transcript abundance. In this study, we used Affymetrix GeneChip Rice Genome Array to analyze eQTLs in rice shoots at 72 h after germination from 110 recombinant inbred lines (RILs) derived from a cross between Zhenshan 97 and Minghui 63. Totally 1,632 single feature polymorphisms (SFPs) plus 23 PCR markers were identified and placed into 601 recombinant bins, spanning 1,459 cM in length, which were used as markers to genotype the RILs. We obtained 16,372 expression traits (e-traits) each with at least one eQTL, resulting in 26,051 eQTLs in total, including both cis- and trans-eQTLs. We also identified 171 eQTL hotspots among rice genome, each of which controls transcript variations of many e-traits. Gene Ontology analysis revealed enrichment of certain functional categories of genes in some of the eQTL hotspots. In particular, eQTLs for e-traits involving DNA metabolic process was significantly enriched in several eQTL hotspots on chromosomes 3, 5 and 10. Several transcription factors colocalizing with cis-eQTLs showed significant correlations with hundreds of e-traits, indicating possible co-regulation. We also detected correlations between the QTLs for shoot dry weight and eQTLs, revealing possible candidate genes for the trait. These results provided the clues for identification and characterization of regulatory network in the whole genome at the transcriptional level. To dissect the genetic variation between the two rice indica varieties Minghui 63 and Zhenshan 97, a total of 110 RILs from Minghui 63 and Zhenshan 97 and parents were sampled. And the Affymetrix Genechip rice Genome Array was used to investigate their dynamic transcript levels. Two independent biological replicates were sampled from each RIL, and three replicates for each parent.resulting in a dataset of 226 microarrays.
2011-06-24 | E-GEOD-22564 | biostudies-arrayexpress
Project description:The mechanistic basis for how genetic variants cause differences in phenotypic traits is often elusive. We identified a quantitative trait locus in C. elegans that affects three seemingly unrelated phenotypic traits: lifetime fecundity, adult body size, and susceptibility to the human pathogen Staphyloccus aureus. We found a QTL for all three traits arises from variation in the neuropeptide receptor gene npr-1. Moreover, we found that variation in npr-1 is also responsive for differences in 247 gene expression traits. Variation in npr-1 is known to determine whether animals disperse throughout a bacterial lawn or aggregate at the edges of the lawn. We found that the allele that leads to aggregation is associated with reduced growth and reproductive output. The altered gene expression pattern caused by this allele suggests that the aggregation behavior might cause a weak starvation state, which is known to reduce growth rate and fecundity. Importantly, we show that variation in npr-1 causes each of these phenotypic differences through behavioral avoidance of ambient oxygen concentrations. These results suggest that variation in npr-1 has broad pleiotropic effects mediated by altered exposure to bacterial food. Two-channel experiment comparing mixed stage sample to mixed stage mixed 50:50 N2,CB4856 common reference
2013-07-30 | E-GEOD-49307 | biostudies-arrayexpress
Project description:A proportion of the genetic variants underlying complex phenotypes do so through their effects on gene expression, so an important challenge in complex trait analysis is to discover the genetic basis for the variation in transcript abundance. So far, the potential of mapping both quantitative trait loci (QTLs) and expression quantitative trait loci (eQTLs) in rodents has been limited by the low mapping resolution inherent in crosses between inbred strains. We provide a megabase resolution map of thousands of eQTLs in hippocampus, lung, and liver samples from heterogeneous stock (HS) mice in which 843 QTLs have also been mapped at megabase resolution. We exploit dense mouse SNP data to show that artifacts due to allele-specific hybridization occur in _30% of the cis-acting eQTLs and, by comparison with exon expression data, we show that alternative splicing of the 3_ end of the genes accounts for <1% of cis-acting eQTLs. Approximately one third of cis-acting eQTLs and one half of trans-acting eQTLs are tissue specific. We have created an important systems biology resource for the genetic analysis of complex traits in a key model organism.
2009-10-22 | E-MTAB-88 | biostudies-arrayexpress
Project description:The suppression of fear memory in the absence of danger (fear extinction) requires coordinated neural activity within the amygdala and medial prefrontal (prelimbic and infralimbic) cortex. Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear memory and extinction. In the present study, we investigated the effects of optogenetic manipulations of prelimbic pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in fear extinction. To this aim, transgenic mice (Thy1-COP4) having cortical and amygdala pyramidal neurons optogenetically excitable were (or not) fear-conditioned. During the extinction phase, the mice received optogenetic (or sham) stimulations to maintain the activation of the prelimbic pyramidal neurons and impair fear extinction. At the end of behavioral testing, electrophysiological (Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the pyramidal neurons of prelimbic cortex. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Results demonstrate that pyramidal neurons of prelimbic cortex are involved in modulation of the fear responses during extinction phase and their optogenetic stimulation in fear-conditioned mice results in strong modifications of the amygdala transcriptome. Understanding the transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.
2021-01-14 | GSE162417 | GEO
Project description:Domestication of animals causes large phenotypic alterations during a brief evolutionary window of time. These alterations are caused by genomic variation, yet the prevalence of modified traits is larger than expected if caused only by classical genetics and mutations. Two selection lines of Red Junglefowl (ancestors of modern chickens), bred for either high or low fear of human for five generations, were used to study the differences in hypothalamic DNA methylation between the two populations.
2018-05-29 | E-MTAB-6407 | biostudies-arrayexpress