scholarly journals Gene function contributes to gene expression levels inS. cerevisiae

2018 ◽  
Author(s):  
Mark J. Hickman ◽  
Andrea Jackson ◽  
Abigail Smith ◽  
Julianne Thornton ◽  
Amanda Tursi
Keyword(s):  
Gene Function ◽  
Expression Level ◽  
Rna Seq ◽  
Orthologous Genes ◽  
Specific Expression ◽  
Expression Levels ◽  
Protein Levels ◽  
Significant Expression ◽  
Gene Expression Levels

ABSTRACTIt is not understood what evolutionary factors drive some genes to be expressed at a higher level than others. Here, we hypothesized that a gene’s function plays an important role in setting expression level. First, we established that eachS. cerevisiaegene is maintained at a specific expression level by analyzing RNA-seq data from multiple studies. Next, we found that mRNA and protein levels were maintained for the orthologous genes inS. pombe, showing that gene function, conserved in orthologs, is important in setting expression level. To further explore the role of gene function in setting expression level, we analyzed mRNA and protein levels ofS. cerevisiaegenes within gene ontology (GO) categories. The GO framework systematically defines gene function based on experimental evidence. We found that several GO categories contain genes with statistically significant expression extremes; for example, genes involved in translation or energy production are highly expressed while genes involved in chromosomal activities, such as replication and transcription, are weakly expressed. Finally, we were able to predict expression levels using GO information alone. We created and optimized a linear equation that predicted a gene’s expression based on the gene’s membership in 161 GO categories. The greater number of GO categories with which a gene is associated, the more accurately expression could be predicted. Taken together, our analysis systematically demonstrates that gene function is an important determinant of expression level.

scholarly journals The genetic architecture of gene expression levels in wild baboons

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jenny Tung ◽  
Xiang Zhou ◽  
Susan C Alberts ◽  
Matthew Stephens ◽  
Yoav Gilad
Keyword(s):  
Gene Expression ◽  
Genetic Architecture ◽  
Eqtl Mapping ◽  
Rna Seq ◽  
Specific Expression ◽  
Data Set ◽  
Expression Levels ◽  
Trait Locus ◽  
Eqtl Data ◽  
Gene Expression Levels

Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates.

scholarly journals Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

2021 ◽  
Vol 11 (10) ◽  
pp. 976
Author(s):  
Alaa S. Wahba ◽  
Maha E. Ibrahim ◽  
Dina M. Abo-elmatty ◽  
Eman T. Mehanna
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Genetic Variants ◽  
Serum Levels ◽  
Expression Levels ◽  
Protein Levels ◽  
Egyptian Patients ◽  
Gene Expression Levels ◽  
Increased Susceptibility

Adipokines were shown to exert crucial roles in rheumatic diseases. This study aimed to assess the role of chemerin, apelin, vaspin, and omentin adipokines and their genetic variants rs17173608, rs2235306, rs2236242, and rs2274907, respectively, in rheumatoid arthritis (RA) pathogenesis in Egyptian patients. A total of 150 RA patients and 150 healthy individuals were recruited. Blood samples were collected and used for genotyping. Serum was separated and used for expression analysis by quantitative PCR, and various biochemical markers determination by ELISA. Serum protein levels of chemerin and vaspin, as well as their gene expression levels were higher, while those of apelin and omentin were lower in RA patients and were associated with most of RA clinical and laboratory characteristics. G allele of chemerin rs17173608, T allele of vaspin rs2236242, and T allele of omentin rs2274907 were more frequent in RA patients. Serum levels and gene expression levels of chemerin in GG genotype carriers and vaspin in TT genotype group were significantly higher, while those of omentin in TT genotype carriers were significantly lower than RA patients with other genotypes. There was no association between apelin rs2235306 and RA. Chemerin rs17173608, vaspin rs2236242, and omentin rs2274907 polymorphisms were associated with increased susceptibility to RA.

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

scholarly journals Association of intronic DNA methylation and hydroxymethylation alterations in the epigenetic etiology of dilated cardiomyopathy

2019 ◽  
Vol 317 (1) ◽  
pp. H168-H180 ◽  
Author(s):  
Ali M. Tabish ◽  
Mohammed Arif ◽  
Taejeong Song ◽  
Zaher Elbeck ◽  
Richard C. Becker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Rna Seq ◽  
Wild Type ◽  
Kegg Pathways ◽  
Wild Type Phenotype ◽  
Gene Expression Levels

In this study, we investigated the role of DNA methylation [5-methylcytosine (5mC)] and 5-hydroxymethylcytosine (5hmC), epigenetic modifications that regulate gene activity, in dilated cardiomyopathy (DCM). A MYBPC3 mutant mouse model of DCM was compared with wild type and used to profile genomic 5mC and 5hmC changes by Chip-seq, and gene expression levels were analyzed by RNA-seq. Both 5mC-altered genes (957) and 5hmC-altered genes (2,022) were identified in DCM hearts. Diverse gene ontology and KEGG pathways were enriched for DCM phenotypes, such as inflammation, tissue fibrosis, cell death, cardiac remodeling, cardiomyocyte growth, and differentiation, as well as sarcomere structure. Hierarchical clustering of mapped genes affected by 5mC and 5hmC clearly differentiated DCM from wild-type phenotype. Based on these data, we propose that genomewide 5mC and 5hmC contents may play a major role in DCM pathogenesis. NEW & NOTEWORTHY Our data demonstrate that development of dilated cardiomyopathy in mice is associated with significant epigenetic changes, specifically in intronic regions, which, when combined with gene expression profiling data, highlight key signaling pathways involved in pathological cardiac remodeling and heart contractile dysfunction.

scholarly journals Systems Metabolic Alteration in a Semi-Dwarf Rice Mutant Induced by OsCYP96B4 Gene Mutation

2020 ◽  
Vol 21 (6) ◽  
pp. 1924 ◽  
Author(s):  
Limiao Jiang ◽  
Rengasamy Ramamoorthy ◽  
Srinivasan Ramachandran ◽  
Prakash P. Kumar
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Secondary Metabolism ◽  
Gene Mutation ◽  
Gene Function ◽  
Nucleotide Metabolism ◽  
Expression Levels ◽  
Rice Mutant ◽  
Choline Metabolism ◽  
Gene Expression Levels

Dwarfism and semi-dwarfism are among the most valuable agronomic traits in crop breeding, which were adopted by the “Green Revolution”. Previously, we reported a novel semi-dwarf rice mutant (oscyp96b4) derived from the insertion of a single copy of Dissociator (Ds) transposon into the gene OsCYP96B4. However, the systems metabolic effect of the mutation is not well understood, which is important for understanding the gene function and developing new semi-dwarf mutants. Here, the metabolic phenotypes in the semi-dwarf mutant (M) and ectopic expression (ECE) rice line were compared to the wild-type (WT) rice, by using nuclear magnetic resonance (NMR) metabolomics and quantitative real-time polymerase chain reaction (qRT-PCR). Compared with WT, ECE of the OsCYP96B4 gene resulted in significant increase of γ-aminobutyrate (GABA), glutamine, and alanine, but significant decrease of glutamate, aromatic and branched-chain amino acids, and some other amino acids. The ECE caused significant increase of monosaccharides (glucose, fructose), but significant decrease of disaccharide (sucrose); induced significant changes of metabolites involved in choline metabolism (phosphocholine, ethanolamine) and nucleotide metabolism (adenosine, adenosine monophosphate, uridine). These metabolic profile alterations were accompanied with changes in the gene expression levels of some related enzymes, involved in GABA shunt, glutamate and glutamine metabolism, choline metabolism, sucrose metabolism, glycolysis/gluconeogenesis pathway, tricarboxylic acid (TCA) cycle, nucleotide metabolism, and shikimate-mediated secondary metabolism. The semi-dwarf mutant showed corresponding but less pronounced changes, especially in the gene expression levels. It indicates that OsCYP96B4 gene mutation in rice causes significant alteration in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism, and shikimate-mediated secondary metabolism. The present study will provide essential information for the OsCYP96B4 gene function analysis and may serve as valuable reference data for the development of new semi-dwarf mutants.

Expression profiles of metamorphosis-related genes during natural transformations in tadpoles of wild Wood Frogs (Lithobates sylvaticus)

2012 ◽  
Vol 90 (9) ◽  
pp. 1059-1071 ◽  
Author(s):  
Laia Navarro-Martín ◽  
Chantal Lanctôt ◽  
Christopher Edge ◽  
Jeff Houlahan ◽  
Vance L. Trudeau
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Rana Sylvatica ◽  
Fold Increase ◽  
Gonadal Development ◽  
Specific Expression ◽  
Wood Frogs ◽  
Lithobates Sylvaticus ◽  
Expression Levels ◽  
Gene Expression Levels

Numerous studies using laboratory-reared tadpoles have shown the importance of thyroid hormones (TH), thyroid receptors (TR), and deiodinase (Dio) enzymes during anuran metamorphosis. Our study focuses on the analysis of thyroid-related genes in tadpoles of wild Wood Frogs ( Lithobates sylvaticus (LeConte, 1825); also known as Rana sylvatica (Cope, 1889)) during metamorphosis. Results showed that, in concordance with laboratory-reared studies, thyroid receptor beta (trb) gene expression profiles presented the most marked changes. At climax and compared with premetamorphic stages, brains, tails, and gonad–mesonephros complex (GMC) tissues increased trb expression levels 5-, 21-, and 41-fold, respectively (p < 0.05). In addition, gene expression levels of brain deiodinase type II and III showed opposite trends, where 3-fold decrease and 10-fold increase were, respectively, found. This finding supports the idea that thyroid hormone, as it has been demonstrated in laboratory-reared tadpoles, is also involved in natural metamorphosis in wild tadpoles. Interestingly, and contrary to our predictions, we observed that whole brain corticotropin-releasing factor (crf) and crf receptor 1 (crfr1) gene expression levels significantly decrease through metamorphosis in wild L. sylvaticus tadpoles. Further analyses are required to determine if a role of TH in the timing of anuran gonadal development exists, as well as the importance of cell-specific and tissue-specific expression of crf and crfr1 to metamorphosis.

Effect of Resistance Training with Palm Pollen and Testosterone on Runx2 Protein and Gene Expression Levels in Bone Tissue of Adult Male Rats

2020 ◽  
Vol 24 (3) ◽  
Author(s):  
Nazila Payandeh ◽  
Maghsoud Peeri ◽  
Mohammad Ali Azarbayjani ◽  
Seyed Ali Hosseini
Keyword(s):  
Gene Expression ◽  
Resistance Training ◽  
Bone Tissue ◽  
Healthy Lifestyle ◽  
Male Rats ◽  
Expression Levels ◽  
Protein Levels ◽  
Related Transcription Factor ◽  
And Training ◽  
Gene Expression Levels

Background: A healthy lifestyle, nutrition, and exercise can improve bone mass via several mechanisms. Objectives: This study assessed the effects of four weeks of palm pollen consumption along with resistance training on protein and gene expression levels of Runt-related transcription factor 2 (Runx2) in bone tissue of rats. Methods: Thirty-six rats were selected and assigned into six groups, including (1) training + testosterone, (2) training + palm pollen, (3) testosterone, (4) palm pollen, (5) training and (6) sham. Then, 100 mg/kg of palm pollen was prescribed five days per week. Resistance training was performed five sessions per week, and 2 mg/kg of testosterone propionate was prescribed peritoneally. Gene expression and protein levels of Runx2 were measured via the real-time PCR and Western blot methods. Results: Training had a significant effect on the increase in Runx2 protein levels (P ≤ 0.05). Training + testosterone, training + palm pollen, testosterone, and palm pollen had significant effects on gene expression and protein levels of Runx2 (P ≤ 0.05). Training + testosterone and training + palm pollen had more favorable effects on the increase of gene expression and protein levels of Runx2 than had testosterone, palm pollen, and training (P ≤ 0.05). Conclusions: Although training, palm pollen, and testosterone alone could increase the Runx2 protein levels in the bone tissue of rats, training with palm pollen and training with testosterone appeared to have more favorable effects on the increase of gene expression and protein levels of Runx2 than either alone.

Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3977-3977
Author(s):  
Ida Bruun Kristensen ◽  
Jacob Haaber ◽  
Maria B Lyng ◽  
Lise Pedersen ◽  
Lars Melholt Rasmussen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Level ◽  
Expression Levels ◽  
Protein Levels ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Osteolytic Bone Disease ◽  
Gene Expression Studies ◽  
Novel Strategy ◽  
Gene Expression Levels

Abstract Abstract 3977 Osteolytic bone disease (OBD) in multiple myeloma (MM) is known to be caused by a combination of osteoclast hyperactivation and osteoblast inhibition. One of the pathways known to be involved in osteoblast inhibition from in vitro studies is the HGF pathway consisting of HGF, its receptor MET, the co-receptor Syndecan-1 (SDC-1), the partial MET antagonist Decorin and HGF activator responsible for HGF processing to its active form. So far, gene expression studies in MM have been performed on isolated MM plasma cells or bone marrow (BM) aspirates, which are not completely representative of the cell composition in the BM micro-environment. We used a novel strategy, whereby gene expression of factors associated with the HGF pathway was evaluated in snap-frozen BM biopsies, and moreover we determined the protein levels in matched BM plasma samples. An additional BM core biopsy obtained during the diagnostic procedure of MM patients was snap-frozen. Biopsies were cut, homogenized and RNA was purified and analyzed by qRT-PCR using low density arrays (Applied Biosystems). The relative quantitative gene expression was calculated using 3 internal reference genes (ABL, GAPDH and GUS). OBD was evaluated using standard radiographs. All patients were untreated and did not receive medicine that could influence bone remodeling. We examined 10 healthy volunteers (HV), 35 monoclonal gammopathy of unknown significance (MGUS) and 65 untreated MM patients, which according to radiographic findings were divided into NO/LOW and advanced OBD, i.e. OBD in ≥2 regions. ELISA was performed on a total of 31 matched BM plasma samples of HV, MGUS and MM obtained at the same time point as the biopsies. In addition, extra samples without gene data (N=52) were analyzed. Commercial kits for SDC-1 (Diaclone), HGF (RnD, Quantikine) and Decorin (RnD, Duoset) were run in duplicates according to manufacturer's instructions. Gene expression of HGF, SDC1, and MET were significantly different comparing HV, MGUS, no/low and advanced OBD (p<0.05) (For HGF, see figure 1). Decorin was not associated to OBD. HGF activator was not expressed in any of our samples, but only in the positive control. A significant correlation between gene and protein expression levels measured by ELISA was found for SDC-1 (Spearman's rho= 0.463, p=0.0058) and HGF (Spearman's rho=0.45, p=0.01). No correlation was found between Decorin gene levels and BM plasma levels (Spearman's rho =-0.24, p=0.22). The protein level of SDC-1 and HGF in BM plasma were both upregulated in MM and associated significantly to OBD level (p<0.05), while Decorin were significantly downregulated in MGUS and MM samples compared to HVs (p<0.05). A significant difference in HGF BM plasma levels were found between patients with no/limited OBD (median: 1.7ng/mL) and advanced OBD (median: 6.2ng/mL) in BM plasma. In our expression study reflecting the in vivo situation in MM patients, genes in the HGF pathway and proteins were significantly associated to OBD. The use of whole snap-frozen BM biopsies is a novel strategy for evaluation of gene expression in MM making it possible to investigate patients independent of degree of MM plasma cell infiltration. In addition to the dys-regulated gene expression levels alteration of SDC-1 and HGF was also observed at protein level, supporting the gene expression findings, and underscoring the usefulness of BM biopsies for gene expression studies in MM. Furthermore, our study for the first time shows up regulation of HGF in association with OBD at both gene and protein level in a large clinical material. Figure 1A. HGF Gene Expression levels in whole snap-frozen BM biopsies. Figure 1B. HGF protein levels in BM plasma (pg/mL). 1 = HV, 2 = MGUS, 3 = no/low OBD MM, 4 = advanced OBD MM. Figure 1A. HGF Gene Expression levels in whole snap-frozen BM biopsies. Figure 1B. HGF protein levels in BM plasma (pg/mL). 1 = HV, 2 = MGUS, 3 = no/low OBD MM, 4 = advanced OBD MM. Disclosures: No relevant conflicts of interest to declare.

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