scholarly journals Gene expression imputation across multiple brain regions reveals schizophrenia risk throughout development

2017 ◽  
Author(s):  
Laura M. Huckins ◽  
Amanda Dobbyn ◽  
Douglas M. Ruderfer ◽  
Gabriel Hoffman ◽  
Weiqing Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Patterns ◽  
Brain Regions ◽  
Developmental Expression ◽  
Genotype Data ◽  
Genome Wide ◽  
Hexosaminidase A ◽  
Gene Expression Levels

AbstractTranscriptomic imputation approaches offer an opportunity to test associations between disease and gene expression in otherwise inaccessible tissues, such as brain, by combining eQTL reference panels with large-scale genotype data. These genic associations could elucidate signals in complex GWAS loci and may disentangle the role of different tissues in disease development. Here, we use the largest eQTL reference panel for the dorso-lateral pre-frontal cortex (DLPFC), collected by the CommonMind Consortium, to create a set of gene expression predictors and demonstrate their utility. We applied these predictors to 40,299 schizophrenia cases and 65,264 matched controls, constituting the largest transcriptomic imputation study of schizophrenia to date. We also computed predicted gene expression levels for 12 additional brain regions, using publicly available predictor models from GTEx. We identified 413 genic associations across 13 brain regions. Stepwise conditioning across the genes and tissues identified 71 associated genes (67 outside the MHC), with the majority of associations found in the DLPFC, and of which 14/67 genes did not fall within previously genome-wide significant loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple pathways associated with porphyric disorders. We investigated developmental expression patterns for all 67 non-MHC associated genes using BRAINSPAN, and identified groups of genes expressed specifically pre-natally or post-natally.

scholarly journals Correlation between Bacillus subtilis scoC Phenotype and Gene Expression Determined Using Microarrays for Transcriptome Analysis

2001 ◽  
Vol 183 (24) ◽  
pp. 7329-7340 ◽  
Author(s):  
Robert Caldwell ◽  
Ron Sapolsky ◽  
Walter Weyler ◽  
Randal R. Maile ◽  
Stuart C. Causey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Expression Patterns ◽  
Global Scale ◽  
Complete Sequence ◽  
Dna Arrays ◽  
Genome Wide ◽  
Genes Encoding ◽  
Nucleoside Metabolism

ABSTRACT The availability of the complete sequence of the Bacillus subtilis chromosome (F. Kunst et al., Nature 390:249–256, 1997) makes possible the construction of genome-wide DNA arrays and the study of this organism on a global scale. Because we have a long-standing interest in the effects of scoC on late-stage developmental phenomena as they relate toaprE expression, we studied the genome-wide effects of ascoC null mutant with the goal of furthering the understanding of the role of scoC in growth and developmental processes. In the present work we compared the expression patterns of isogenic B. subtilis strains, one of which carries a null mutation in the scoC locus (scoC4). The results obtained indicate thatscoC regulates, either directly or indirectly, the expression of at least 560 genes in the B. subtilisgenome. ScoC appeared to repress as well as activate gene expression. Changes in expression were observed in genes encoding transport and binding proteins, those involved in amino acid, carbohydrate, and nucleotide and/or nucleoside metabolism, and those associated with motility, sporulation, and adaptation to atypical conditions. Changes in gene expression were also observed for transcriptional regulators, along with sigma factors, regulatory phosphatases and kinases, and members of sensor regulator systems. In this report, we discuss some of the phenotypes associated with the scoCmutant in light of the transcriptome changes observed.

scholarly journals The Potential Role of Genetic Assimilation during Maize Domestication

2017 ◽  
Author(s):  
Anne Lorant ◽  
Sarah Pedersen ◽  
Irene Holst ◽  
Matthew B. Hufford ◽  
Klaus Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zea Mays ◽  
Potential Role ◽  
Expression Patterns ◽  
Genetic Assimilation ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms ◽  
Maize Domestication

ABSTRACTDomestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. Recent research, in which maize and teosinte (i.e., wild maize) were exposed to environments similar to the time of domestication, resulted in a plastic induction of domesticated phenotypes in teosinte and little response to environment in maize. These results suggest that early agriculturalists may have selected for genetic mechanisms that cemented domestication phenotypes initially induced by a plastic response of teosinte to environment, a process known as genetic assimilation. To better understand this phenomenon and the potential role of environment in maize domestication, we examined differential gene expression in maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis) between past and present conditions. We identified a gene set of over 2000 loci showing a change in expression across environmental conditions in teosinte and invariance in maize. In fact, overall we observed both greater plasticity in gene expression and more substantial re-wiring of expression networks in teosinte across environments when compared to maize. While these results suggest genetic assimilation played at least some role in domestication, genes showing expression patterns consistent with assimilation are not significantly enriched for previously identified domestication candidates, indicating assimilation did not have a genome-wide effect.

scholarly journals Gene expression patterns are correlated with genomic and genic structure in soybean

Genome ◽  
2011 ◽  
Vol 54 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Jenna L. Woody ◽  
Andrew J. Severin ◽  
Yung-Tsi Bolon ◽  
Bindu Joseph ◽  
Brian W. Diers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sequence Data ◽  
Expression Patterns ◽  
Nucleotide Composition ◽  
Physical Parameters ◽  
Expression Levels ◽  
Noncoding Regions ◽  
Expression Breadth ◽  
Gene Expression Levels

Studies have indicated that exon and intron size and intergenic distance are correlated with gene expression levels and expression breadth. Previous reports on these correlations in plants and animals have been conflicting. In this study, next-generation sequence data, which has been shown to be more sensitive than previous expression profiling technologies, were generated and analyzed from 14 tissues. Our results revealed a novel dichotomy. At the low expression level, an increase in expression breadth correlated with an increase in transcript size because of an increase in the number of exons and introns. No significant changes in intron or exon sizes were noted. Conversely, genes expressed at the intermediate to high expression levels displayed a decrease in transcript size as their expression breadth increased. This was due to smaller exons, with no significant change in the number of exons. Taking advantage of the known gene space of soybean, we evaluated the positioning of genes and found significant clustering of similarly expressed genes. Identifying the correlations between the physical parameters of individual genes could lead to uncovering the role of regulation owing to nucleotide composition, which might have potential impacts in discerning the role of the noncoding regions.

scholarly journals Exogenous RNAi mechanisms contribute to transcriptome adaptation by phased siRNA clusters in Paramecium

2019 ◽  
Vol 47 (15) ◽  
pp. 8036-8049 ◽  
Author(s):  
Sivarajan Karunanithi ◽  
Vidya Oruganti ◽  
Simone Marker ◽  
Angela M Rodriguez-Viana ◽  
Franziska Drews ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Levels ◽  
Reading Frame ◽  
Transcriptome Regulation ◽  
Genome Wide ◽  
Exogenous Rna ◽  
Entire Open Reading Frame ◽  
Polymerase Mutants ◽  
Gene Expression Levels

Abstract Extensive research has characterized distinct exogenous RNAi pathways interfering in gene expression during vegetative growth of the unicellular model ciliate Paramecium. However, role of RNAi in endogenous transcriptome regulation, and environmental adaptation is unknown. Here, we describe the first genome-wide profiling of endogenous sRNAs in context of different transcriptomic states (serotypes). We developed a pipeline to identify, and characterize 2602 siRNA producing clusters (SRCs). Our data show no evidence that SRCs produce miRNAs, and in contrast to other species, no preference for strand specificity of siRNAs. Interestingly, most SRCs overlap coding genes and a separate group show siRNA phasing along the entire open reading frame, suggesting that the mRNA transcript serves as a source for siRNAs. Integrative analysis of siRNA abundance and gene expression levels revealed surprisingly that mRNA and siRNA show negative as well as positive associations. Two RNA-dependent RNA Polymerase mutants, RDR1 and RDR2, show a drastic loss of siRNAs especially in phased SRCs accompanied with increased mRNA levels. Importantly, most SRCs depend on both RDRs, reminiscent to primary siRNAs in the RNAi against exogenous RNA, indicating mechanistic overlaps between exogenous and endogenous RNAi contributing to flexible transcriptome adaptation.

scholarly journals Recent progress towards understanding the role of DNA methylation in human placental development

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. R23-R30 ◽  
Author(s):  
Tina Bianco-Miotto ◽  
Benjamin T Mayne ◽  
Sam Buckberry ◽  
James Breen ◽  
Carlos M Rodriguez Lopez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Pregnancy Complications ◽  
Large Scale ◽  
Developmental Stages ◽  
Epigenetic Modifications ◽  
Placental Development ◽  
Functional Changes ◽  
Genome Wide

Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses.

scholarly journals Slide-seq: A Scalable Technology for Measuring Genome-Wide Expression at High Spatial Resolution

2019 ◽  
Author(s):  
Samuel G. Rodriques ◽  
Robert R. Stickels ◽  
Aleksandrina Goeva ◽  
Carly A. Martin ◽  
Evan Murray ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Resolution ◽  
Large Scale ◽  
Spatial Organization ◽  
Expression Patterns ◽  
Cell Types ◽  
Genome Wide ◽  
Biological Discovery ◽  
Spatial Locations ◽  
Genome Wide Expression

AbstractThe spatial organization of cells in tissue has a profound influence on their function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. Here, we introduce Slide-seq, a highly scalable method that enables facile generation of large volumes of unbiased spatial transcriptomes with 10 µm spatial resolution, comparable to the size of individual cells. In Slide-seq, RNA is transferred from freshly frozen tissue sections onto a surface covered in DNA-barcoded beads with known positions, allowing the spatial locations of the RNA to be inferred by sequencing. To demonstrate Slide-seq’s utility, we localized cell types identified by large-scale scRNA-seq datasets within the cerebellum and hippocampus. We next systematically characterized spatial gene expression patterns in the Purkinje layer of mouse cerebellum, identifying new axes of variation across Purkinje cell compartments. Finally, we used Slide-seq to define the temporal evolution of cell-type-specific responses in a mouse model of traumatic brain injury. Slide-seq will accelerate biological discovery by enabling routine, high-resolution spatial mapping of gene expression.One Sentence SummarySlide-seq measures genome-wide expression in complex tissues at 10-micron resolution.

scholarly journals Genome-Wide Identification and Analysis of Chitinase-Like Gene Family in Bemisia tabaci (Hemiptera: Aleyrodidae)

Insects ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 254
Author(s):  
Zhengke Peng ◽  
Jun Ren ◽  
Qi Su ◽  
Yang Zeng ◽  
Lixia Tian ◽  
...  
Keyword(s):  
Gene Family ◽  
Expression Patterns ◽  
Wide Distribution ◽  
Developmental Expression ◽  
Glycoside Hydrolase Family ◽  
Genome Wide ◽  
And Function ◽  
Disk Growth ◽  
Hydrolase Family

Chitinases are of great importance in chitin degradation and remodeling in insects. However, the genome-wide distribution of chitinase-like gene family in Bemsia tabaci, a destructive pest worldwide, is still elusive. With the help of bioinformatics, we annotated 14 genes that encode putative chitinase-like proteins, including ten chitinases (Cht), three imaginal disk growth factors (IDGF), and one endo-β-N-acetylglucosaminidase (ENGase) in the genome of the whitefly, B. tabaci. These genes were phylogenetically grouped into eight clades, among which 13 genes were classified in the glycoside hydrolase family 18 groups and one in the ENGase group. Afterwards, developmental expression analysis suggested that BtCht10, BtCht5, and BtCht7 were highly expressed in nymphal stages and exhibit similar expression patterns, implying their underlying role in nymph ecdysis. Notably, nymphs exhibited a lower rate of survival when challenged by dsRNA targeting these three genes via a nanomaterial-promoted RNAi method. In addition, silencing of BtCht10 significantly resulted in a longer duration of development compared to control nymphs. These results indicate a key role of BtCht10, BtCht5, and BtCht7 in B. tabaci nymph molting. Our research depicts the differences of chitinase-like family genes in structure and function and identified potential targets for RNAi-based whitefly management.

scholarly journals Support for the dominance theory in Drosophila transcriptomes

2018 ◽  
Author(s):  
Ana Llopart ◽  
Evgeny Brud ◽  
Nikale Pettie ◽  
Josep M. Comeron
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Transcriptional Networks ◽  
Expression Divergence ◽  
Gene Expression Divergence ◽  
Genome Wide ◽  
Regulatory Mutations ◽  
Opposite Sex ◽  
High Degree

ABSTRACTInteractions among divergent elements of transcriptional networks from different species can lead to misexpression in hybrids through regulatory incompatibilities, some with the potential to generate sterility. Genes with male-biased expression tend to be overrepresented among genes misexpressed in hybrid males. While the possible contribution of faster-male evolution to this misexpression has been explored, the role of the hemizygous X chromosome (i.e., the dominance theory for transcriptomes) remains yet to be determined. Here we study genome-wide patterns of gene expression in females and males of Drosophila yakuba and D. santomea and their hybrids. We used attached-X stocks to specifically test the dominance theory, and we uncovered a significant contribution of recessive alleles on the X chromosome to hybrid misexpression. Our analysis of gene expression patterns suggests that there is a contribution of weakly deleterious regulatory mutations to gene expression divergence in the sex towards which the expression is biased. In the opposite sex (e.g., genes with female-biased expression analyzed in male transcriptomes), we detect stronger selective constraints on gene expression divergence. Although genes with high degree of male-biased expression show a clear signal of faster-X evolution for gene expression divergence, we also detected slower-X evolution of gene expression in other gene classes (e.g. female-biased genes) that is mediated by significant decreases of cis- and trans-regulatory divergence. The distinct behavior of X-linked genes with high degree of male-biased expression is consistent with these genes experiencing a higher incidence of positively selected regulatory mutations than their autosomal counterparts. We propose that both dominance theory and faster-X evolution of gene expression may be major contributors to hybrid misexpression and possibly the large X-effect in these species.

scholarly journals Bile Acids in Dementia: Brain Amyloid, White Matter Lesions, and Atrophy

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 767-768
Author(s):  
Vijay Varma ◽  
Youjin Wang ◽  
Yang An ◽  
Sudhir Varma ◽  
Murat Bilgel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acids ◽  
White Matter Lesions ◽  
Pharmacological Modulation ◽  
Dementia Risk ◽  
The Brain ◽  
Step Study ◽  
Brain Amyloid Deposition ◽  
Gene Expression Levels

Abstract While Alzheimer’s disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association is unclear. Using a novel, 3-step study design we examined the role of cholesterol catabolism in dementia by testing whether 1) the synthesis of the primary cholesterol breakdown products (bile acids (BA)) were associated with neuroimaging markers of dementia; 2) pharmacological modulation of BAs alters dementia risk; and 3) brain BA concentrations and gene expression were associated with AD. We found that higher serum concentrations of BAs are associated with lower brain amyloid deposition, slower WML accumulation, and slower brain atrophy in males. Opposite effects were observed in females. Modulation of BA levels alters risk of incident VaD in males. Altered brain BA signaling at the metabolite and gene expression levels occurs in AD. Dysregulation of peripheral cholesterol catabolism and BA synthesis may impact dementia pathogenesis through signaling pathways in the brain.

Sign in / Sign up

Export Citation Format

Share Document