Principal component for metabolic syndrome risk maps to chromosome 4p in Mexican Americans: the San Antonio Family Heart Study

Metabolic syndrome refers to the clustering of disease conditions such as insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and obesity. To explore the genetic predispositions of this complex syndrome, we conducted a principal components analysis using data on 14 phenotypes related to the risk of developing metabolic syndrome. The subjects were 566 nondiabetic Mexican Americans, distributed in 41 extended families from the San Antonio Family Heart Study. The factor scores obtained from these 14 phenotypes were used in multipoint linkage analysis using SOLAR. Factors were identified that accounted for 73% of the total variance of the original variables: body size-adiposity, insulin-glucose, blood pressure, and lipid levels. Each factor exhibited evidence for either significant or suggestive linkage involving four factor-specific chromosomal regions relating to chromosomes 1, 3, 4, and 6. Significant evidence for linkage of the lipid factor was found on chromosome 4 near marker D4S403 (LOD = 3.52), where the cholecystokinin A receptor (CCKAR) and ADP-ribosyl cyclase 1 (CD38) genes are located. Suggestive evidence for linkage of the body size-adiposity factor to chromosome 1 near marker D1S1597 (LOD = 2.53) in the region containing the nuclear receptor subfamily 0, group B, member 2 gene (NROB2) also was observed. The insulin-glucose and blood pressure factors were linked suggestively to regions on chromosome 3 near marker D3S1595 (LOD = 2.20) and on chromosome 6 near marker D6S 1031 (LOD = 2.08), respectively. In summary, our findings suggest that the factor structures for the risk of metabolic syndrome are influenced by multiple distinct genes across the genome.     

Global gene expression analysis of a rice high-tillering dwarf mutant

Plant height and tiller number are indispensible for the establishment of grain production in rice (Oryza sativa L.). A new rice mutant high-tillering dwarf 3 (htd3) exhibiting more tiller number and shorter culm length than the wild-type Guichao 2 (GC2, an indica cultivar) was used to investigate the global gene expression patterns at days after germination 25 (DAG25) and DAG60. In this study, we identified 305 and 987 genes with at least twofold change in gene expression level at DAG25 and DAG60 respectively using the rice microarray chip. Gene ontology enrichment analysis of these twofold change regulated genes revealed that large numbers of genes were involved in binding activity, catalytic activity and metabolic process. The chip results also showed that some of the regulated genes involved in diverse molecular pathways, including gibberellin pathway, brassinosteroid pathway and auxin signal, had significant differences in gene expression abundance at DAG60. This genome-wide gene expression analysis could provide a new opportunity to uncover the regulation mechanisms of the development of culm and tiller, two important components of yields in rice.     

Identification of gene expression profiles and key genes in subchondral bone of osteoarthritis using weighted gene coexpression network analysis

Osteoarthritis (OA) significantly influences the quality life of people around the world. It is urgent to find an effective way to understand the genetic etiology of OA. We used weighted gene coexpression network analysis (WGCNA) to explore the key genes involved in the subchondral bone pathological process of OA. Fifty gene expression profiles of GSE51588 were downloaded from the Gene Expression Omnibus database. The OA‐associated genes and gene ontologies were acquired from JuniorDoc. Weighted gene coexpression network analysis was used to find disease‐related networks based on 21756 gene expression correlation coefficients, hub‐genes with the highest connectivity in each module were selected, and the correlation between module eigengene and clinical traits was calculated. The genes in the traits‐related gene coexpression modules were subject to functional annotation and pathway enrichment analysis using ClusterProfiler. A total of 73 gene modules were identified, of which, 12 modules were found with high connectivity with clinical traits. Five modules were found with enriched OA‐associated genes. Moreover, 310 OA‐associated genes were found, and 34 of them were among hub‐genes in each module. Consequently, enrichment results indicated some key metabolic pathways, such as extracellular matrix (ECM)‐receptor interaction (hsa04512), focal adhesion (hsa04510), the phosphatidylinositol 3'‐kinase (PI3K)‐Akt signaling pathway (PI3K‐AKT) (hsa04151), transforming growth factor beta pathway, and Wnt pathway. We intended to identify some core genes, collagen (COL)6A3, COL6A1, ITGA11, BAMBI, and HCK, which could influence downstream signaling pathways once they were activated. In this study, we identified important genes within key coexpression modules, which associate with a pathological process of subchondral bone in OA. Functional analysis results could provide important information to understand the mechanism of OA.     

Transcriptomic analysis of differentially expressed genes in flower-buds of genetic male sterile and wild type cucumber by RNA sequencing

Cucumber (Cucumis sativus L.) pollen development involves a diverse range of gene interactions between sporophytic and gametophytic tissues. Previous studies in our laboratory showed that male sterility was controlled by a single recessive nuclear gene, and occurred in pollen mother cell meiophase. To fully explore the global gene expression and identify genes related to male sterility, a RNA-seq analysis was adopted in this study. Young male flower-buds (1–2 mm in length) from genetic male sterility (GMS) mutant and homozygous fertile cucumber (WT) were collected for two sequencing libraries. Total 545 differentially expressed genes (DEGs), including 142 up-regulated DEGs and 403 down-regulated DEGs, were detected in two libraries (Fold Change ≥ 2, FDR < 0.01). These genes were involved in a variety of metabolic pathways, like ethylene-activated signaling pathway, sporopollenin biosynthetic pathway, cell cycle and DNA damage repair pathway. qRT-PCR analysis was performed and showed that the correlation between RNA-Seq and qRT-PCR was 0.876. These findings contribute to a better understanding of the mechanism that leads to GMS in cucumber.     

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC.     

A genome-wide survey of maize lipid-related genes: candidate genes mining,digital gene expression profiling and co-location with QTL for maize kernel oil

Lipids play an important role in plants due to their abundance and their extensive participation in many metabolic processes. Genes involved in lipid metabolism have been extensively studied in Arabidopsis and other plant species. In this study, a total of 1003 maize lipid-related genes were cloned and annotated, including 42 genes with experimental validation, 732 genes with full-length cDNA and protein sequences in public databases and 229 newly cloned genes. Ninety-seven maize lipid-related genes with tissue-preferential expression were discovered by in silico gene expression profiling based on 1984483 maize Expressed Sequence Tags collected from 182 cDNA libraries. Meanwhile, 70 QTL clusters for maize kernel oil were identified, covering 34.5% of the maize genome. Fifty-nine (84%) QTL clusters co-located with at least one lipid-related gene, and the total number of these genes amounted to 147. Interestingly, thirteen genes with kernel-preferential expression profiles fell within QTL clusters for maize kernel oil content. All the maize lipid-related genes identified here may provide good targets for maize kernel oil QTL cloning and thus help us to better understand the molecular mechanism of maize kernel oil accumulation.     

Down-regulation of RBP4 indicates a poor prognosis and correlates with immune cell infiltration in hepatocellular carcinoma

Recent research has indicated that metabolically related genes play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC). We evaluated the associations between novel biomarkers and retinol-binding protein 4 (RBP4) for predicting clinical HCC outcomes, hub-related genes, pathway regulation, and immune cells infiltration. Bioinformatic analyses based on data from The Cancer Genome Atlas were performed using online analysis tools. RBP4 expression was low in HCC and was also down-regulated in pan-cancers compared with normal tissues. RBP4 expression was also significantly different based on age (41–60 years old versus 61–80 years old), and low RBP4 expression levels were associated with advanced tumor stages and grades. Higher RBP4 expression was associated with better overall survival time in HCC patients, and we identified a deletion-mutation rate of 1.4% in RBP4. We also identified ten co-expressed genes most related to RBP4 and explored the relationships between six hub genes (APOB, FGA, FGG, SERPINC1, APOA1, and F2) involved in RBP4 regulation. A pathway enrichment analysis for RBP4 indicated complement and coagulation cascades, metabolic pathways, antibiotic biosynthesis pathways, peroxisome proliferator-activated receptor signaling pathways, and pyruvate metabolism pathways. These results suggest that RBP4 may be a novel biomarker for HCC prognosis, and an indicator of low immune response to the disease.     

基于转录组分析铜绿假单胞菌DN1降解荧蒽特性

[背景]铜绿假单胞菌DN1是一株从石油污染土壤中分离筛选到的具有广谱降解功能的菌株。[目的]深入了解荧蒽胁迫条件下铜绿假单胞菌DN1降解污染物过程中重要的降解相关基因信息。[方法]通过高通量测序技术对铜绿假单胞菌DN1进行转录组测序,对其所有的转录本进行KEGG (kyoto encyclopedia of genes and genomes)分类和Pathway注释、GO (gene ontology)分类和富集分析。[结果]转录组测序显示:与对照组相比,荧蒽诱导组检测到6 189个基因,其中1 919个基因上调表达,1 603个基因下调表达。KEGG注释分析显示差异上调表达基因匹配到了112个KEGG代谢途径,注释到"代谢途径"的1 408个基因(约占总差异基因的73.4%)中有317个基因参与了碳氢化合物代谢及含有苯环结构的异源生物质的生物降解,占"代谢途径"的16.53%,暗示了菌株DN1降解荧蒽可能与这些途径有密切关系。另外,主要代谢途径中的差异表达基因主要集中在ABC转运系统、氨基酸生物合成、双组分系统及碳代谢,这些途径大多数参与了底物的识别转运、信号转导及基因表达调控。[结论]进一步拓展了铜绿假单胞菌DN1在荧蒽胁迫条件下的代谢途径和逆境反应,也为微生物修复环境污染物研究夯实了理论基础。     

Bioinformatics analysis reveals disturbance mechanism of MAPK signaling pathway and cell cycle in Glioblastoma multiforme

Background & objectives

To analyze the reversal gene pairs and identify featured reversal genes related to mitogen-activated protein kinases (MAPK) signaling pathway and cell cycle in Glioblastoma multiforme (GBM) to reveal its pathogenetic mechanism.

Methods

We downloaded the gene expression profile GSE4290 from the Gene Expression Omnibus database, including 81 gene chips of GBM and 23 gene chips of controls. The t test was used to analyze the DEGs (differentially expressed genes) between 23 normal and 81 GBM samples. Then some perturbing metabolic pathways, including MAPK (mitogen-activated protein kinases) and cell cycle signaling pathway, were extracted from KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database. Cancer genes were obtained from the database of Cancer Gene Census. The reversal gene pairs between DEGs and cancer genes were further analyzed in MAPK and cell cycle signaling pathway.

Results

A total 8523 DEGs were obtained including 4090 up-regulated and 4433 down-regulated genes. Among them, ras-related protein rab-13(RAB13), neuroblastoma breakpoint family member 10 (NBPF10) and disks large homologue 4 (DLG4) were found to be involved in GBM for the first time. We obtained MAPK and cell cycle signaling pathways from KEGG database. By analyzing perturbing mechanism in these two pathways, we identified several reversal gene pairs, including NRAS (neuroblastoma RAS) and CDK2 (cyclin-dependent kinase 2), CCND1 (cyclin D1) and FGFR (fibroblast growth factor receptor). Further analysis showed that NRAS and CDK2 were positively related with GBM. However, FGFR2 and CCND1 were negatively related with GBM.

Interpretation & conclusions

These findings suggest that newly identified DEGs and featured reversal gene pairs participated in MAPK and cell cycle signaling pathway may provide a new therapeutic line of approach to GBM.     

Transcriptome analysis alk-SMase knockout mice reveals the effect of alkaline sphingomyelinase on liver

Alkaline sphingomyelinase (alk-SMase) is phospholipase that creates ceramides and inactivates platelet activating factors during metabolism, and is linked to digestion and cancer prevention. There have been few studies that completely investigate the linked function and identify the genes related to alk-SMase. In this work, RNA sequencing was performed to investigate the function of alk-SMase. Using RNA-seq data, we discovered 95 differentially expressed genes in the liver of wild type (WT) mice and alk-SMase (gene NPP7) knockout (KO) mice. Differentially expressed genes were functionally associated with the inflammatory response, steroid metabolic process and TNF signaling pathway related terms, regulation of carbohydrate biosynthetic process, and Cytochrome P450-arranged by substrate type using Metascape, according to the results of gene ontology functional enrichment analysis. In addition, an integrated PPI and KEGG network was used to investigate the relationship of differentially expressed genes, It was discovered that one module, which contained 21 nodes and 23 interactions, was significantly related to Cytochrome P450 family, which as mediator of phospholipase. To corroborate the RNAseq results, we identified 12 important genes with high expression levels and significant differences in RNAseq for quantitative real-time polymerase chain reaction (qPCR) verification; 7 genes showed difference significantly (P < 0.05). Our research is the first to conduct a comprehensive genome-wide analysis of the alk-SMase knockout model. Alk-SMase is involved in sphingomyelin hydrolysis. In liver tissues lacking alk-SMase expression, the expression levels of seven genes, including Cyp4a14 and Cyp4a10, were altered.