scholarly journals Gene by environment interaction mouse model reveals a functional role for 5-hydroxymethylcytosine in neurodevelopmental disorders

2021 ◽  
pp. gr.276137.121
Author(s):  
Ligia A Papale ◽  
Andy Madrid ◽  
Qi Zhang ◽  
Kailei Chen ◽  
Lara Sak ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Chromatin Immunoprecipitation ◽  
High Throughput Sequencing ◽  
Repetitive Behaviors ◽  
Environment Interaction ◽  
Genome Wide ◽  
A Genome ◽  
Number Of Genes ◽  
Prenatally Stressed ◽  
Environmentally Sensitive

Mouse knockouts of Cntnap2 exhibit altered neurodevelopmental behavior, deficits in striatal GABAergic signaling and a genome-wide disruption of an environmentally sensitive DNA methylation modification (5-hydroxymethylcytosine, 5hmC) in the orthologs of a significant number of genes implicated in human neurodevelopmental disorders. We tested adult Cntnap2 heterozygous mice (Cntnap2+/-, lacking behavioral or neuropathological abnormalities) subjected to a prenatal stress and found that prenatally stressed Cntnap2+/- female mice showed repetitive behaviors and altered sociability, similar to the homozygote phenotype. Genomic profiling revealed disruptions in hippocampal and striatal 5hmC levels that were correlated to altered transcript levels of genes linked to these phenotypes (e.g., Reln, Dst, Trio, and Epha5). Chromatin-immunoprecipitation coupled with high-throughput sequencing and hippocampal nuclear lysate pull-down data indicated that 5hmC abundance alters the binding of the transcription factor CLOCK in the promoters of these genes (e.g., Palld, Gigyf1, and Fry), providing a mechanistic role for 5hmC in gene regulation. Together, these data support gene by environment hypotheses for the origins of mental illness and provide a means to identify the elusive factors contributing to complex human diseases.

scholarly journals Comparative ChIP-seq (Comp-ChIP-seq): a practical guideline for experimental design and a novel computational methodology

2019 ◽  
Author(s):  
Enrique Blanco ◽  
Luciano Di Croce ◽  
Sergi Aranda
Keyword(s):  
Chromatin Immunoprecipitation ◽  
High Throughput Sequencing ◽  
Confounding Factor ◽  
Decision Making Process ◽  
Local Regression ◽  
Binary Decision ◽  
Genome Wide ◽  
A Genome ◽  
Standard Chip ◽  
Multiple Conditions

ABSTRACTChromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is a pivotal technique for understanding the functionality of the chromatin-bound factors and for mapping the functional elements of the genome. In order to evaluate cell- and disease-specific changes in the interacting strength of chromatin targets, ChIP-seq signal across multiple conditions must undergo robust normalization. However, this is not possible using the standard ChIP-seq scheme, which lacks a reference for the control of biological and experimental variabilities. While several studies have recently proposed different solutions to circumvent this problem, substantial technical and analytical differences among methodologies could hamper the experimental reproducibility. Here we provide a practical binary decision-making process to experimentally implement a normalizing method for comparative ChIP-seq across different samples. In addition, we evaluate side-by-side the current computational approaches for normalizing using a reference internal genome. Finally, we propose a local regression strategy to accurately normalize ChIP-seq data in a genome-wide manner. Overall, our proposed experimental and computational standard for comparative ChIP-seq (Comp-ChIP-seq) will increase experimental reproducibility, thereby reducing this major confounding factor in interpreting ChIP-seq results.

scholarly journals Detection and application of genome-wide variations in peach for association and genetic relationship analysis

BMC Genetics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Liping Guan ◽  
Ke Cao ◽  
Yong Li ◽  
Jian Guo ◽  
Qiang Xu ◽  
...  
Keyword(s):  
Genetic Relationship ◽  
Dna Markers ◽  
High Throughput Sequencing ◽  
Prunus Persica ◽  
Genetic Research ◽  
Diploid Species ◽  
Sequencing Data ◽  
Relationship Analysis ◽  
Genome Wide ◽  
A Genome

Abstract Background Peach (Prunus persica L.) is a diploid species and model plant of the Rosaceae family. In the past decade, significant progress has been made in peach genetic research via DNA markers, but the number of these markers remains limited. Results In this study, we performed a genome-wide DNA markers detection based on sequencing data of six distantly related peach accessions. A total of 650,693~1,053,547 single nucleotide polymorphisms (SNPs), 114,227~178,968 small insertion/deletions (InDels), 8386~12,298 structure variants (SVs), 2111~2581 copy number variants (CNVs) and 229,357~346,940 simple sequence repeats (SSRs) were detected and annotated. To demonstrate the application of DNA markers, 944 SNPs were filtered for association study of fruit ripening time and 15 highly polymorphic SSRs were selected to analyze the genetic relationship among 221 accessions. Conclusions The results showed that the use of high-throughput sequencing to develop DNA markers is fast and effective. Comprehensive identification of DNA markers, including SVs and SSRs, would be of benefit to genetic diversity evaluation, genetic mapping, and molecular breeding of peach.

scholarly journals Specific chromatin changes mark lateral organ founder cells in the Arabidopsis inflorescence meristem

2019 ◽  
Vol 70 (15) ◽  
pp. 3867-3879 ◽  
Author(s):  
Anneke Frerichs ◽  
Julia Engelhorn ◽  
Janine Altmüller ◽  
Jose Gutierrez-Marcos ◽  
Wolfgang Werr
Keyword(s):  
Dna Sequences ◽  
High Throughput Sequencing ◽  
Gene Activation ◽  
Regulatory Elements ◽  
Inflorescence Meristem ◽  
Genome Wide ◽  
A Genome ◽  
Hypersensitive Sites ◽  
Lateral Organ ◽  
Founder Cells

Abstract Fluorescence-activated cell sorting (FACS) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were combined to analyse the chromatin state of lateral organ founder cells (LOFCs) in the peripheral zone of the Arabidopsis apetala1-1 cauliflower-1 double mutant inflorescence meristem. On a genome-wide level, we observed a striking correlation between transposase hypersensitive sites (THSs) detected by ATAC-seq and DNase I hypersensitive sites (DHSs). The mostly expanded DHSs were often substructured into several individual THSs, which correlated with phylogenetically conserved DNA sequences or enhancer elements. Comparing chromatin accessibility with available RNA-seq data, THS change configuration was reflected by gene activation or repression and chromatin regions acquired or lost transposase accessibility in direct correlation with gene expression levels in LOFCs. This was most pronounced immediately upstream of the transcription start, where genome-wide THSs were abundant in a complementary pattern to established H3K4me3 activation or H3K27me3 repression marks. At this resolution, the combined application of FACS/ATAC-seq is widely applicable to detect chromatin changes during cell-type specification and facilitates the detection of regulatory elements in plant promoters.

scholarly journals Genome-wide analysis of the H3K27me3 epigenome and transcriptome in Brassica rapa

GigaScience ◽  
2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Miriam Payá-Milans ◽  
Laura Poza-Viejo ◽  
Patxi San Martín-Uriz ◽  
David Lara-Astiaso ◽  
Mark D Wilkinson ◽  
...  
Keyword(s):  
Brassica Rapa ◽  
Chromatin Immunoprecipitation ◽  
High Throughput Sequencing ◽  
Model Systems ◽  
Epigenetic Mark ◽  
Protein Coding ◽  
Brassica Crops ◽  
Genome Wide ◽  
Floral Regulatory Genes ◽  
Complex Genome

Abstract Background Genome-wide maps of histone modifications have been obtained for several plant species. However, most studies focus on model systems and do not enforce FAIR data management principles. Here we study the H3K27me3 epigenome and associated transcriptome of Brassica rapa, an important vegetable cultivated worldwide. Findings We performed H3K27me3 chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis by 3′-end RNA sequencing from B. rapa leaves and inflorescences. To analyze these data we developed a Reproducible Epigenomic Analysis pipeline using Galaxy and Jupyter, packaged into Docker images to facilitate transparency and reuse. We found that H3K27me3 covers roughly one-third of all B. rapa protein-coding genes and its presence correlates with low transcript levels. The comparative analysis between leaves and inflorescences suggested that the expression of various floral regulatory genes during development depends on H3K27me3. To demonstrate the importance of H3K27me3 for B. rapa development, we characterized a mutant line deficient in the H3K27 methyltransferase activity. We found that braA.clf mutant plants presented pleiotropic alterations, e.g., curly leaves due to increased expression and reduced H3K27me3 levels at AGAMOUS-like loci. Conclusions We characterized the epigenetic mark H3K27me3 at genome-wide levels and provide genetic evidence for its relevance in B. rapa development. Our work reveals the epigenomic landscape of H3K27me3 in B. rapa and provides novel genomics datasets and bioinformatics analytical resources. We anticipate that this work will lead the way to further epigenomic studies in the complex genome of Brassica crops.

scholarly journals Re-analysis of a Genome-Wide Gene-By-Environment Interaction Study of Case Parent Trios, Adjusted for Population Stratification

2021 ◽  
Vol 11 ◽  
Author(s):  
Pulindu Ratnasekera ◽  
Brad McNeney
Keyword(s):  
East Asian ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Multivitamin Supplementation ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
The Impact ◽  
East Asian Ancestry

We investigate the impact of confounding on the results of a genome-wide association analysis by Beaty et al., which identified multiple single nucleotide polymorphisms that appeared to modify the effect of maternal smoking, alcohol consumption, or multivitamin supplementation on risk of cleft palate. The study sample of case-parent trios was primarily of European and East Asian ancestry, and the distribution of all three exposures differed by ancestral group. Such differences raise the possibility that confounders, rather than the exposures, are the risk modifiers and hence that the inference of gene-environment (G×E) interaction may be spurious. Our analyses generally confirmed the result of Beaty et al. and suggest the interaction G×E is driven by the European trios, whereas the East Asian trios were less informative.

scholarly journals Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)

2020 ◽  
Author(s):  
Xiaofei Yu ◽  
Hendrik-Jan Megens ◽  
Samuel B. Mengistu ◽  
John W.M. Bastiaansen ◽  
Han A. Mulder ◽  
...  
Keyword(s):  
Body Weight ◽  
Growth Stage ◽  
Early Stage ◽  
Nervous System Development ◽  
Genome Wide Association ◽  
Environment Interaction ◽  
Genome Wide ◽  
Hypoxic Environment ◽  
A Genome ◽  
Vegf Signalling

Abstract Background: Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 17th generation of a Genetically Improved Farmed tilapia population. Results: In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage.Conclusions: There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.

scholarly journals Analysis of genotype by environment interactions in a maize mapping population

2021 ◽  
Author(s):  
Asher I Hudson ◽  
Sarah G Odell ◽  
Pierre Dubreuil ◽  
Marie-Helene Tixier ◽  
Sebastien Praud ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genotype By Environment Interaction ◽  
Environment Interaction ◽  
Crop Breeding ◽  
Genotype By Environment Interactions ◽  
Genotype By Environment ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Covariances

Genotype by environment interactions are a significant challenge for crop breeding as well as being important for understanding the genetic basis of environmental adaptation. In this study, we analyzed genotype by environment interaction in a maize multi-parent advanced generation intercross population grown across five environments. We found that genotype by environment interactions contributed as much as genotypic effects to the variation in some agronomically important traits. In order to understand how genetic correlations between traits change across environments, we estimated the genetic variance-covariance matrix in each environment. Changes in genetic covariances between traits across environments were common, even among traits that show low genotype by environment variance. We also performed a genome-wide association study to identify markers associated with genotype by environment interactions but found only a small number of significantly associated markers, possibly due to the highly polygenic nature of genotype by environment interactions in this population.

scholarly journals Genome-wide dysregulation of histone acetylation in the Parkinson’s disease brain

2019 ◽  
Author(s):  
Lilah Toker ◽  
Gia T Tran ◽  
Janani Sundaresan ◽  
Ole-Bjørn Tysnes ◽  
Guido Alves ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
Genetic Risk ◽  
Neurodegenerative Disorder ◽  
Unknown Etiology ◽  
Transcriptomic Data ◽  
Genome Wide ◽  
A Genome ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Epigenetic Signatures

AbstractParkinson disease (PD) is a complex neurodegenerative disorder of largely unknown etiology. While several genetic risk factors have been identified, the involvement of epigenetics in the pathophysiology of PD is mostly unaccounted for. We conducted a histone acetylome-wide association study in PD, using brain tissue from two independent cohorts of cases and controls. Immunoblotting revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. Chromatin immunoprecipitation sequencing (ChIP-seq) further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon, with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Our findings strongly suggest that dysregulation of histone acetylation plays an important role in the pathophysiology of PD and identify novel epigenetic signatures associated with the disease.

scholarly journals Characterization of the radiation desiccation response regulon of the radioresistant bacterium Deinococcus radiodurans by integrative genomic analyses.

2021 ◽  
Author(s):  
Nicolas Eugenie ◽  
Yvan Zivanovic ◽  
Gaelle Lelandais ◽  
Genevieve Coste ◽  
Claire Bouthier de la Tour ◽  
...  
Keyword(s):  
Deinococcus Radiodurans ◽  
Normal Growth ◽  
Growth Conditions ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Analyses ◽  
Number Of Genes ◽  
Wide Scale

Numerous genes are overexpressed in the radioresistant bacterium Deinococcus radiodurans after exposure to radiation or prolonged desiccation. The DdrO and IrrE proteins play a major role in regulating the expression of approximately predicted twenty of these genes. The transcriptional repressor DdrO blocks the expression of these genes under normal growth conditions. After exposure to genotoxic agents, the IrrE metalloprotease cleaves DdrO and relieves gene repression. Bioinformatic analyzes showed that this mechanism seems to be conserved in several species of Deinococcus, but many questions remain as such the number of genes regulated by DdrO. Here, by RNA-seq and CHiP-seq assays performed at a genome-wide scale coupled with bioinformatic analyses, we show that, the DdrO regulon in D. radiodurans includes many other genes than those previously described. These results thus pave the way to better understand the radioresistance mechanisms encoded by this bacterium.

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