共查询到20条相似文献,搜索用时 15 毫秒
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Tova F. Fuller Anatole Ghazalpour Jason E. Aten Thomas A. Drake Aldons J. Lusis Steve Horvath 《Mammalian genome》2007,18(6-7):463-472
Systems-oriented genetic approaches that incorporate gene expression and genotype data are valuable in the quest for genetic
regulatory loci underlying complex traits. Gene coexpression network analysis lends itself to identification of entire groups
of differentially regulated genes—a highly relevant endeavor in finding the underpinnings of complex traits that are, by definition,
polygenic in nature. Here we describe one such approach based on liver gene expression and genotype data from an F2 mouse intercross utilizing weighted gene coexpression network analysis (WGCNA) of gene expression data to identify physiologically
relevant modules. We describe two strategies: single-network analysis and differential network analysis. Single-network analysis
reveals the presence of a physiologically interesting module that can be found in two distinct mouse crosses. Module quantitative
trait loci (mQTLs) that perturb this module were discovered. In addition, we report a list of genetic drivers for this module.
Differential network analysis reveals differences in connectivity and module structure between two networks based on the liver
expression data of lean and obese mice. Functional annotation of these genes suggests a biological pathway involving epidermal
growth factor (EGF). Our results demonstrate the utility of WGCNA in identifying genetic drivers and in finding genetic pathways
represented by gene modules. These examples provide evidence that integration of network properties may well help chart the
path across the gene–trait chasm.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.
Tova F. Fuller, Anatole Ghazalpour contributed equally to this work. 相似文献
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To understand the metabolic characteristics of Clostridium acetobutylicum and to examine the potential for enhanced butanol production, we reconstructed the genome-scale metabolic network from its
annotated genomic sequence and analyzed strategies to improve its butanol production. The generated reconstructed network
consists of 502 reactions and 479 metabolites and was used as the basis for an in silico model that could compute metabolic and growth performance for comparison with fermentation data. The in silico model successfully predicted metabolic fluxes during the acidogenic phase using classical flux balance analysis. Nonlinear
programming was used to predict metabolic fluxes during the solventogenic phase. In addition, essential genes were predicted
via single gene deletion studies. This genome-scale in silico metabolic model of C. acetobutylicum should be useful for genome-wide metabolic analysis as well as strain development for improving production of biochemicals,
including butanol.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
J. L. and H. Y. equally contributed to this work. 相似文献
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Histone acetylation is involved in the regulation of gene expression in plants and eukaryotes. Histone deacetylases (HDACs)
are enzymes that catalyze the removal of acetyl groups from histones, which is associated with the repression of gene expression.
To study the role of histone acetylation in the regulation of gene expression during seed germination, trichostatin A (TSA),
a specific inhibitor of histone deacetylase, was used to treat imbibing Arabidopsis thaliana seeds. GeneChip arrays were used to show that TSA induces up-regulation of 45 genes and down-regulation of 27 genes during
seed germination. Eight TSA-up-regulated genes were selected for further analysis – RAB18, RD29B, ATEM1, HSP70 and four late embryogenesis abundant protein genes (LEA). A gene expression time course shows that these eight genes are expressed at high levels in the dry seed and repressed upon
seed imbibition at an exponential rate. In the presence of TSA, the onset of repression of the eight genes is not affected
but the final level of repressed expression is elevated. Chromatin immunoprecipitation and HDAC assays show that there is
a transient histone deacetylation event during seed germination at 1 day after imbibition, which serves as a key developmental
signal that affects the repression of the eight genes.
Electronic supplementary material Electronic supplementary material is available for this article at
and accessible for authorised users. 相似文献
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?zgün Babur Mithat G?nen Bülent Arman Aksoy Nikolaus Schultz Giovanni Ciriello Chris Sander Emek Demir 《Genome biology》2015,16(1)
We present a novel method for the identification of sets of mutually exclusive gene alterations in a given set of genomic profiles. We scan the groups of genes with a common downstream effect on the signaling network, using a mutual exclusivity criterion that ensures that each gene in the group significantly contributes to the mutual exclusivity pattern. We test the method on all available TCGA cancer genomics datasets, and detect multiple previously unreported alterations that show significant mutual exclusivity and are likely to be driver events.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0612-6) contains supplementary material, which is available to authorized users. 相似文献6.
The MYB Transcription Factor Superfamily of Arabidopsis: Expression Analysis and Phylogenetic Comparison with the Rice MYB Family 总被引:15,自引:0,他引:15
Yanhui C Xiaoyuan Y Kun H Meihua L Jigang L Zhaofeng G Zhiqiang L Yunfei Z Xiaoxiao W Xiaoming Q Yunping S Li Z Xiaohui D Jingchu L Xing-Wang D Zhangliang C Hongya G Li-Jia Q 《Plant molecular biology》2006,60(1):107-124
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Edwin C. M. Mariman Radek Szklarczyk Freek G. Bouwman Erik E. J. G. Aller Marleen A. van Baak Ping Wang 《Genes & nutrition》2015,10(4)
Worldwide, the incidence of obesity has increased dramatically over the past decades. More knowledge about the complex etiology of obesity is needed in order to find additional approaches for treatment and prevention. Investigating the exome sequencing data of 30 extremely obese subjects (BMI 45–65 kg/m2) shows that predicted damaging missense variants in olfactory receptor genes on chromosome 1q and rare predicted damaging variants in the protocadherin (PCDH) beta-cluster genes on chromosome 5q31, reported in our previous work, co-localize in subjects with extreme obesity. This implies a synergistic effect between genetic variation in these gene clusters in the predisposition to extreme obesity. Evidence for a general involvement of the olfactory transduction pathway on itself could not be found. Bioinformatic analysis indicates a specific involvement of the PCDH beta-cluster genes in controlling tissue development. Further mechanistic insight needs to await the identification of the ligands of the 1q olfactory receptors. Eventually, this may provide the possibility to manipulate food flavor in a way to reduce the risk of overeating and of extreme obesity in genetically predisposed subjects.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-015-0465-3) contains supplementary material, which is available to authorized users. 相似文献10.
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The centromere protein A (CENP-A), a histone H3-like protein, provides an essential role for chromosomal segregation during
mitosis and meiosis. In this study we identified ten new CENP-A-like genes (excluding the original CENP-A gene) in cow by
searching its genome database, while all other examined mammals contained only a single copy of the CENP-A gene. Phylogenetic
analysis shows that the expansion of these genes occurred before the divergence of cow and sheep but after the artiodactyls
diverged from other mammals. Our analyses also indicate that multiple gene duplication and intron loss events have occurred
during the formation of this gene family, and the high similarity in intron sequences between the new genes and the old one
suggests very recent gene expansion events. Furthermore, evidence from the comparisons of the synonymous and nonsynonymous
substitutions and the distributions of the mutation sites suggested that the CENP-A-L-1 gene, a potentially functional member
of cow CENP-A gene family, evolved under positive selection.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Calcium serves as a second messenger in various signal transduction pathways in plants. CBL-interacting protein kinases (CIPKs),
which have a variety of functions, are involved in calcium signal transduction. Previous, the studies on CIPK family members
focused on Arabidopsis and rice. Here, we present a comparative genomic analysis of the CIPK gene family in Arabidopsis and poplar, a model tree species. Twenty-seven potential CIPKs were identified from poplar using genome-wide analysis. Like
the CIPK gene family from Arabidopsis, CIPK genes from poplar were also divided into intron-free and intron-harboring groups. In the intron-harboring group, the
intron distribution of CIPKs is rather conserved during the genome evolutionary process. Many homologous gene pairs were found
in the CIPK gene family, indicating duplication events might contribute to the amplification of this gene family. The phylogenetic
comparison of CIPKs in combination with intron distribution analysis revealed that CIPK genes from both Arabidopsis and poplar might have an ancient origin, which formed earlier than the separation of these two eudicot species. Our genomic
and bioinformatic analysis will provide an important foundation for further functional dissection of the CBL-CIPK signaling
network in poplars.
Electronic Supplementary Material
The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Previous studies have shown widespread conservation of gene expression levels between species of the Drosophila melanogaster subgroup as well as a positive correlation between coding sequence divergence and expression level divergence between species.
Meanwhile, large-scale misregulation of gene expression level has been described in interspecific sterile hybrids between
D. melanogaster, D. simulans, D. mauritiana, and D. sechellia. Using data from gene expression analysis involving D. simulans, D. melanogaster, and their hybrids, we observed a significant positive correlation between protein sequence divergence and gene expression
differences between hybrids and their parental species. Furthermore, we demonstrate that underexpressed misregulated genes in hybrids are evolving more rapidly at the protein sequence
level than nonmisregulated genes or overexpressed misregulated genes, highlighting the possible effects of sexual and natural
selection as male-biased genes and nonessential genes are the principal gene categories affected by interspecific hybrid misregulation.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Carlo G. Artieri and Wilfried Haerty contributed equally to this publication. 相似文献
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Verica JA Maximova SN Strem MD Carlson JE Bailey BA Guiltinan MJ 《Plant cell reports》2004,23(6):404-413
Pathogenic diseases represent a major constraint to the growth and yield of cacao (Theobroma cacao L.). Ongoing research on model plant systems has revealed that defense responses are activated via signaling pathways mediated by endogenous signaling molecules such as salicylic acid, jasmonic acid and ethylene. Activation of plant defenses is associated with changes in the expression of large numbers of genes. To gain a better understanding of defense responses in cacao, we have employed suppressive subtractive hybridization (SSH) cDNA libraries, macroarray hybridization analysis, high throughput DNA sequencing and bioinformatics to identify cacao genes induced by these signaling molecules. Additionally, we investigated gene activation by a phytotoxic elicitor-like protein, Nep1. We have identified a unigene set of 1,256 members, including 330 members representing genes induced during the defense response.Electronic Supplementary Material Electronic supplementary material is available in the online version of this article at Sequences presented here are deposited with GenBank under accession numbers CF972636–CF974749 相似文献
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Haritz Irizar Maider Mu?oz-Culla Matías Sáenz-Cuesta I?aki Osorio-Querejeta Lucía Sepúlveda Tamara Castillo-Trivi?o Alvaro Prada Adolfo Lopez de Munain Javier Olascoaga David Otaegui 《BMC genomics》2015,16(1)
Background
Several studies have revealed a potential role for both small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs) in the physiopathology of relapsing-remitting multiple sclerosis (RRMS). This potential implication has been mainly described through differential expression studies. However, it has been suggested that, in order to extract additional information from large-scale expression experiments, differential expression studies must be complemented with differential network studies. Thus, the present work is aimed at the identification of potential therapeutic ncRNA targets for RRMS through differential network analysis of ncRNA – mRNA coexpression networks. ncRNA – mRNA coexpression networks have been constructed from both selected ncRNA (specifically miRNAs, snoRNAs and sdRNAs) and mRNA large-scale expression data obtained from 22 patients in relapse, the same 22 patients in remission and 22 healthy controls. Condition-specific (relapse, remission and healthy) networks have been built and compared to identify the parts of the system most affected by perturbation and aid the identification of potential therapeutic targets among the ncRNAs.Results
All the coexpression networks we built present a scale-free topology and many snoRNAs are shown to have a prominent role in their architecture. The differential network analysis (relapse vs. remission vs. controls’ networks) has revealed that, although both network topology and the majority of the genes are maintained, few ncRNA – mRNA links appear in more than one network. We have selected as potential therapeutic targets the ncRNAs that appear in the disease-specific network and were found to be differentially expressed in a previous study.Conclusions
Our results suggest that the diseased state of RRMS has a strong impact on the ncRNA – mRNA network of peripheral blood leukocytes, as a massive rewiring of the network happens between conditions. Our findings also indicate that the role snoRNAs have in targeted gene silencing is a widespread phenomenon. Finally, among the potential therapeutic target ncRNAs, SNORA40 seems to be the most promising candidate.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1396-5) contains supplementary material, which is available to authorized users. 相似文献18.
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Linkage Disequilibrium Mapping of Morphological, Resistance, and Other Agronomically Relevant Traits in Modern Spring Barley Cultivars 总被引:6,自引:0,他引:6
A. T. W. Kraakman F. Martínez B. Mussiraliev F. A. van Eeuwijk R. E. Niks 《Molecular breeding : new strategies in plant improvement》2006,17(1):41-58
A set of 148 modern spring barley cultivars was explored for the extent of linkage disequilibrium (LD) between genes governing
traits and nearby marker alleles. Associations of agronomically relevant traits (days to heading, plant height), resistance
traits (leaf rust, barley yellow dwarf virus (BYD)), and morphological traits (rachilla hair length, lodicule size) with AFLP
markers and SSR markers were found. Known major genes and QTLs were confirmed, but also new putative QTLs were found. The
LD mapping clearly indicated the common occurrence of Rph3, a gene for hypersensitivity resistance against Puccinia hordei, and also confirmed the QTL Rphq2 for prolonging latency period of P. hordei in seedlings. We also found strong indication for a hitherto not reported gene for resistance or tolerance to BYD on chromosome
2, linked to SSR marker HVM054. Our conclusion is that LD mapping is a valuable additional tool in the search for applicable
marker associations with major genes and QTLs.
Electronic supplementary material Electronic supplementary material is available for this article at
and accessible for authorised users. 相似文献