scholarly journals A target expression threshold dictates invader defense and autoimmunity by CRISPR-Cas13

2021 ◽  
Author(s):  
Elena Vialetto ◽  
Yanying Yu ◽  
Scott P. Collins ◽  
Katharina G. Wandera ◽  
Lars Barquist ◽  
...  
Keyword(s):  
Immune Activation ◽  
Rna Degradation ◽  
Lytic Bacteriophage ◽  
Immune Systems ◽  
Expression Levels ◽  
Additional Requirement ◽  
Genome Wide ◽  
A Genome ◽  
Rna Targeting ◽  
Target Transcript

Immune systems must recognize and clear foreign invaders without eliciting autoimmunity. CRISPR-Cas immune systems in prokaryotes manage this task by following two criteria: extensive guide:target complementarity and a defined target-flanking motif. Here we report an additional requirement for RNA-targeting CRISPR-Cas13 systems: expression of the target transcript exceeding a threshold. This finding is based on targeting endogenous non-essential transcripts, which rarely elicited dormancy through collateral RNA degradation. Instead, eliciting dormancy required over-expressing targeted transcripts above a threshold. A genome-wide screen confirmed target expression levels as the principal determinant of cytotoxic autoimmunity and revealed that the threshold shifts with the guide:target pair. This expression threshold ensured defense against a lytic bacteriophage yet allowed tolerance of a targeted beneficial gene expressed from an invading plasmid. These findings establish target expression levels as a third criterion for immune activation by RNA-targeting CRISPR-Cas systems, buffering against autoimmunity and distinguishing pathogenic and benign invaders.

scholarly journals A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues

PLoS Genetics ◽  
2011 ◽  
Vol 7 (2) ◽  
pp. e1001316 ◽  
Author(s):  
Athma A. Pai ◽  
Jordana T. Bell ◽  
John C. Marioni ◽  
Jonathan K. Pritchard ◽  
Yoav Gilad
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome ◽  
Methylation Patterns ◽  
Genome Wide Study ◽  
Gene Expression Levels

scholarly journals Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Vikas Duhan ◽  
Vishal Khairnar ◽  
Simo Kitanovski ◽  
Thamer A. Hamdan ◽  
Andrés D. Klein ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Vesicular Stomatitis Virus ◽  
Immune Activation ◽  
Genome Wide Association Study ◽  
Innate Immune ◽  
Akt Phosphorylation ◽  
Genome Wide ◽  
A Genome ◽  
Cell Type Specific ◽  
Vesicular Stomatitis

Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.

scholarly journals Genome-Wide Identification, Expression Profile, and Alternative Splicing Analysis of CAMTA Family Genes in Cucumber (Cucumis sativus L.)

Agronomy ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1827
Author(s):  
Rong Gao ◽  
Yanyan Luo ◽  
Fahong Yun ◽  
Xuetong Wu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Stress Response ◽  
Growth And Development ◽  
Chemical Properties ◽  
Pcr Analysis ◽  
Transcription Activator ◽  
Cucumis Sativus L ◽  
Expression Levels ◽  
Calmodulin Binding ◽  
Genome Wide ◽  
A Genome

The calmodulin-binding transcription activator (CAMTA), as one of the most distinctive families of transcription factors, plays an important role in plant growth and development and in the stress response. However, it is currently unknown whether CAMTA exists in cucumbers and what its function is. In this study, we first identified four CAMTA genes in the cucumber genome using a genome-wide search method. Subsequently, we analyzed their physical and chemical properties, gene structure, protein domains, and phylogenetic relationships. The results show that the structure of CsCAMTAs is similar to that of other plants, and a phylogenetic analysis divides them into three groups. The analysis of cis-acting elements shows that most CsCAMTAs contain a variety of hormones and stress-related elements. The RT-PCR analysis shows that CsCAMTAs have different expression levels in different tissues and can be induced by IAA, ABA, MeJA, NaCl, and PEG. Finally, we analyzed the expression pattern of CsCAMTAs’ alternative spliceosomes under salt and drought stress. The results show that the expression levels of the different spliceosomes are affected by the type of stress and the duration of stress. These data indicate that CsCAMTAs participate in growth and development and in the stress response in cucumbers, a finding which lays the foundation for future CsCAMTAs’ functional research.

scholarly journals Identification and Analysis of the AP2 Subfamily Transcription Factors in the Pecan (Carya illinoinensis)

2021 ◽  
Vol 22 (24) ◽  
pp. 13568
Author(s):  
Zhengfu Yang ◽  
Hongmiao Jin ◽  
Junhao Chen ◽  
Caiyun Li ◽  
Jiani Wang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Expression Patterns ◽  
Carya Illinoinensis ◽  
Expression Levels ◽  
Cis Acting ◽  
Similar Expression ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Search ◽  
Ethylene Responsive Factor

The AP2 transcriptional factors (TFs) belong to the APETALA2/ ethylene-responsive factor (AP2/ERF) superfamily and regulate various biological processes of plant growth and development, as well as response to biotic and abiotic stresses. However, genome-wide research on the AP2 subfamily TFs in the pecan (Carya illinoinensis) is rarely reported. In this paper, we identify 30 AP2 subfamily genes from pecans through a genome-wide search, and they were unevenly distributed on the pecan chromosomes. Then, a phylogenetic tree, gene structure and conserved motifs were further analyzed. The 30 AP2 genes were divided into euAP2, euANT and basalANT three clades. Moreover, the cis-acting elements analysis showed many light responsive elements, plant hormone-responsive elements and abiotic stress responsive elements are found in CiAP2 promoters. Furthermore, a qPCR analysis showed that genes clustered together usually shared similar expression patterns in euAP2 and basalANT clades, while the expression pattern in the euANT clade varied greatly. In developing pecan fruits, CiAP2-5, CiANT1 and CiANT2 shared similar expression patterns, and their expression levels decreased with fruit development. CiANT5 displayed the highest expression levels in developing fruits. The subcellular localization and transcriptional activation activity assay demonstrated that CiANT5 is located in the nucleus and functions as a transcription factor with transcriptional activation activity. These results help to comprehensively understand the pecan AP2 subfamily TFs and lay the foundation for further functional research on pecan AP2 family genes.

scholarly journals Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

2018 ◽  
Author(s):  
Héléna A Gaspar ◽  
Zachary Gerring ◽  
Christopher Hübel ◽  
Christel M Middeldorp ◽  
Eske M Derks ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Drug Target ◽  
Model Systems ◽  
Genome Wide Association ◽  
Multiple Testing Correction ◽  
Major Depressive ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome

AbstractThe major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics and genetically predicted expression levels in different tissues, using our online tool Drug Targetor (drugtargetor.com). We also investigated drug-target relationships and drug effects on gene expression that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 25 druggable genes were significantly associated with MDD after multiple testing correction, and 19 were suggestively significant. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new – and better – treatment options.

scholarly journals CaSpER identifies and visualizes CNV events by integrative analysis of single-cell or bulk RNA-sequencing data

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Akdes Serin Harmanci ◽  
Arif O. Harmanci ◽  
Xiaobo Zhou
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Large Scale ◽  
Copy Number Variants ◽  
Complete Characterization ◽  
Integrative Analysis ◽  
Sequencing Data ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome

AbstractRNA sequencing experiments generate large amounts of information about expression levels of genes. Although they are mainly used for quantifying expression levels, they contain much more biologically important information such as copy number variants (CNVs). Here, we present CaSpER, a signal processing approach for identification, visualization, and integrative analysis of focal and large-scale CNV events in multiscale resolution using either bulk or single-cell RNA sequencing data. CaSpER integrates the multiscale smoothing of expression signal and allelic shift signals for CNV calling. The allelic shift signal measures the loss-of-heterozygosity (LOH) which is valuable for CNV identification. CaSpER employs an efficient methodology for the generation of a genome-wide B-allele frequency (BAF) signal profile from the reads and utilizes it for correction of CNVs calls. CaSpER increases the utility of RNA-sequencing datasets and complements other tools for complete characterization and visualization of the genomic and transcriptomic landscape of single cell and bulk RNA sequencing data.

scholarly journals TWAS results are complementary to and less affected by linkage disequilibrium than GWAS

2021 ◽  
Author(s):  
Delin Li ◽  
Qiang Liu ◽  
Patrick S Schnable
Keyword(s):  
Linkage Disequilibrium ◽  
Association Study ◽  
Phenotypic Variation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome ◽  
Gene Level ◽  
Gene Expression Levels

Abstract A genome-wide association study (GWAS) is used to identify genetic markers associated with phenotypic variation. In contrast, a transcriptome-wide association study (TWAS) detects associations between gene expression levels and phenotypic variation. It has previously been shown that in the cross-pollinated species, maize (Zea mays), GWAS and TWAS identify complementary sets of trait-associated genes, many of which exhibit characteristics of true positives. Here, we extend this conclusion to the self-pollinated species, Arabidopsis thaliana and soybean (Glycine max). Linkage disequilibrium (LD) can result in the identification, via GWAS, of false-positive associations. In all three analyzed plant species, most trait-associated genes identified via TWAS are well separated physically from other candidate genes. Hence, TWAS is less affected by LD than is GWAS, demonstrating that TWAS is particularly well suited for association studies in genomes with slow rates of LD decay, such as soybean. TWAS is reasonably robust to the plant organs/tissues used to determine expression levels. In summary, this study confirms that TWAS is a promising approach for accurate gene-level association mapping in plants that is complementary to GWAS, and established that TWAS can exhibit substantial advantages relative to GWAS in species with slow rates of LD decay.

scholarly journals Characterization of MATE Gene Family And Its Role In Drought, Heat, And Salt Tolerance In Wheat (Triticum Aestivum L.)

2021 ◽  
Author(s):  
Joseph Noble Amoah ◽  
Yong Weon Seo
Keyword(s):  
Salt Stress ◽  
Expression Patterns ◽  
Triticum Aestivum L ◽  
Stress Conditions ◽  
Crop Species ◽  
Expression Levels ◽  
Cis Acting ◽  
Genome Wide ◽  
A Genome

Abstract To explore the response of multidrug and toxic compound extrusion (MATE) proteins to drought, heat, and salt stress in wheat, a genome-wide identification and expression study was performed. 20 MATE genes located on 4 of the 12 chromosomes were identified and categorized into four (I-1V) subfamilies, based on phylogenetic analysis. Wheat MATE family expansion was primarily driven by whole-genome duplication (WGD) and tandem events. In the same subfamily, gene exon-intron structures and motif composition are more similar. TaMATE genes had cis-acting elements that were implicated in stress and defense response. Tae-miR5175e was identified as the highly expressed miRNA that targets TaMATEs by miRNA prediction. When compared to controls, the relative expression patterns of seven TaMATE genes were substantially elevated during drought stress. TaMATE2, 10, 13, and 14 expression levels considerably elevated after 15 days (d) of heat stress, whereas TaMATE2, 14, 18, and 20 expression levels were highly upregulated following 15 d of salt stress treatment, indicating the crucial role of TaMATEs under these abiotic stress conditions. Furthermore, drought, heat, and salt stress decreased wheat water content, but increased malondialdehyde (MDA), electrolyte leakage (EL), and proline content, whereas the expression of the 7 putative MATE genes was correlated with physio-biochemical indicators of these stress conditions. The findings contribute to a better understanding of the complexities of MATEs and present a theoretical base for future MATE gene discovery and application in wheat and other crop species.

scholarly journals Genome-Wide Identification and Analysis of HAK/KUP/KT Potassium Transporters Gene Family in Wheat (Triticum aestivum L.)

2018 ◽  
Vol 19 (12) ◽  
pp. 3969 ◽  
Author(s):  
Xiyong Cheng ◽  
Xiaodan Liu ◽  
Weiwei Mao ◽  
Xurui Zhang ◽  
Shulin Chen ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Triticum Aestivum L ◽  
Pcr Analysis ◽  
Chromosomal Distribution ◽  
Wheat Seedlings ◽  
Expression Levels ◽  
Transporter Family ◽  
Genome Wide ◽  
A Genome ◽  
Potassium Transporters

In plants, the HAK (high-affinity K+)/KUP (K+ uptake)/KT (K+ transporter) family represents a large group of potassium transporters that play important roles in plant growth and environmental adaptation. Although HAK/KUP/KT genes have been extensively investigated in many plant species, they remain uncharacterized in wheat, especially those involved in the response to environmental stresses. In this study, 56 wheat HAK/KUP/KT (hereafter called TaHAKs) genes were identified by a genome-wide search using recently released wheat genomic data. Phylogenetic analysis grouped these genes into four clusters (Ι, II, III, IV), containing 22, 19, 7 and 8 genes, respectively. Chromosomal distribution, gene structure, and conserved motif analyses of the 56 TaHAK genes were subsequently performed. In silico RNA-seq data analysis revealed that TaHAKs from clusters II and III are constitutively expressed in various wheat tissues, while most genes from clusters I and IV have very low expression levels in the examined tissues at different developmental stages. qRT-PCR analysis showed that expression levels of TaHAK genes in wheat seedlings were significantly up- or downregulated when seedlings were exposed to K+ deficiency, high salinity, or dehydration. Furthermore, we functionally characterized TaHAK1b-2BL and showed that it facilitates K+ transport in yeast. Collectively, these results provide valuable information for further functional studies of TaHAKs, and contribute to a better understanding of the molecular basis of wheat development and stress tolerance.

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