Sample records for functionally related gene

  1. FSim: A Novel Functional Similarity Search Algorithm and Tool for Discovering Functionally Related Gene Products

    PubMed Central

    Hu, Qiang; Wang, ZhiGang; Zhang, ZhengGuo

    2014-01-01

    Background. During the analysis of genomics data, it is often required to quantify the functional similarity of genes and their products based on the annotation information from gene ontology (GO) with hierarchical structure. A flexible and user-friendly way to estimate the functional similarity of genes utilizing GO annotation is therefore highly desired. Results. We proposed a novel algorithm using a level coefficient-weighted model to measure the functional similarity of gene products based on multiple ontologies of hierarchical GO annotations. The performance of our algorithm was evaluated and found to be superior to the other tested methods. We implemented the proposed algorithm in a software package, FSim, based on R statistical and computing environment. It can be used to discover functionally related genes for a given gene, group of genes, or set of function terms. Conclusions. FSim is a flexible tool to analyze functional gene groups based on the GO annotation databases. PMID:25184141

  2. Molecular functions of genes related to grain shape in rice

    PubMed Central

    Zheng, Jia; Zhang, Yadong; Wang, Cailin

    2015-01-01

    Because grain shape is an important component of rice grain yield, the discovery of genes related to rice grain shape has attracted much attention of rice breeding programs. In recent years, some of these genes have been cloned and studied. They have been found not only regulate grain shape by changing the shape of the spikelet hull, but also regulate endosperm development through control of cell division using different molecular mechanisms. In this paper, we review the recent research on genes related to rice grain shape and their possible regulatory mechanisms.

  3. The clustering of functionally related genes contributes to CNV-mediated disease.

    PubMed

    Andrews, Tallulah; Honti, Frantisek; Pfundt, Rolph; de Leeuw, Nicole; Hehir-Kwa, Jayne; Vulto-van Silfhout, Anneke; de Vries, Bert; Webber, Caleb

    2015-06-01

    Clusters of functionally related genes can be disrupted by a single copy number variant (CNV). We demonstrate that the simultaneous disruption of multiple functionally related genes is a frequent and significant characteristic of de novo CNVs in patients with developmental disorders (P = 1 × 10(-3)). Using three different functional networks, we identified unexpectedly large numbers of functionally related genes within de novo CNVs from two large independent cohorts of individuals with developmental disorders. The presence of multiple functionally related genes was a significant predictor of a CNV's pathogenicity when compared to CNVs from apparently healthy individuals and a better predictor than the presence of known disease or haploinsufficient genes for larger CNVs. The functionally related genes found in the de novo CNVs belonged to 70% of all clusters of functionally related genes found across the genome. De novo CNVs were more likely to affect functional clusters and affect them to a greater extent than benign CNVs (P = 6 × 10(-4)). Furthermore, such clusters of functionally related genes are phenotypically informative: Different patients possessing CNVs that affect the same cluster of functionally related genes exhibit more similar phenotypes than expected (P < 0.05). The spanning of multiple functionally similar genes by single CNVs contributes substantially to how these variants exert their pathogenic effects. PMID:25887030

  4. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    MedlinePLUS

    ... factors for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... risk factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  5. The Function and Interaction of Genes Related to Esophageal Squamous Cell Cancer

    Microsoft Academic Search

    Yu Long Chen; Su Gai Yin; Yao Song Wu

    2011-01-01

    Objective: To study the function and interaction of genes related to esophageal squamous cell cancer and discuss esophageal cancer molecular mechanism.Methods: The gene microarray date set of esophageal was downloaded from the GEO BRB-ArrayTools and online tool was used to analysis the difference expression genes between esophageal squamous cell cancer and normal tissue, and analysis the functional and interaction of

  6. Identification of Three Related Human GRO Genes Encoding Cytokine Functions

    Microsoft Academic Search

    Stephen Haskill; Amy Peace; John Morris; Sarah A. Sporn; Anthony Anisowicz; Sam W. Lee; Temple Smith; George Martin; Peter Ralph; Ruth Sager

    1990-01-01

    The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRObeta and GROgamma, that share 90% and 86% identity at the deduced amino acid level with the original GROalpha isolate. One amino acid substitution of proline in GROalpha by leucine

  7. Calcitonin gene-related peptide: functional role in cerebrovascular regulation.

    PubMed Central

    McCulloch, J; Uddman, R; Kingman, T A; Edvinsson, L

    1986-01-01

    Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 +/- 1.5 mN; concentration eliciting half-maximal response, 9.6 +/- 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 +/- 5%; concentration eliciting half-maximal response, approximately equal to 3 nM). CGRP was significantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter. Images PMID:3488550

  8. Screening of osteoprotegerin-related feature genes in osteoporosis and functional analysis with DNA microarray

    PubMed Central

    2013-01-01

    Background Osteoporosis affects 200 million people worldwide and places an enormous economic burden on society. We aim to identify the feature genes that are related to osteoprotegerin in osteoporosis and to perform function analysis with DNA microarray from human bone marrow. Methods We downloaded the gene expression profile GSE35957 from Gene Expression Omnibus database including nine gene chips from bone marrow mesenchymal stem cells of five osteoporotic and four non-osteoporotic subjects. The differentially expressed genes between normal and disease samples were identified by LIMMA package in R language. The interactions among the osteoprotegerin gene (OPG) and differentially expressed genes were searched and visualized by Cytoscape. MCODE and Bingo were used to perform module analysis. Finally, GENECODIS was used to obtain enriched pathways of genes in an interaction network. Results A total of 656 genes were identified as differentially expressed genes between osteoporotic and non-osteoporotic samples. IL17RC, COL1A1, and ESR1 were identified to interact with OPG directly from the protein-protein interaction network. A module containing ERS1 was screened out, and this module was most significantly enriched in organ development. Pathway enrichment analysis suggested genes in the interaction network were related to focal adhesion. Conclusions The expression pattern of IL17RC, COL1A1, and ESR1 can be useful in osteoporosis detection, which may help in identifying those populations at high risk for osteoporosis, and in directing treatment of osteoporosis. PMID:23731710

  9. Possible functional links among brain- and skull-related genes selected in modern humans

    PubMed Central

    Benítez-Burraco, Antonio; Boeckx, Cedric

    2015-01-01

    The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language.

  10. Identification of minimum Rpn4-responsive elements in genes related to proteasome functions.

    PubMed

    Shirozu, Ryohei; Yashiroda, Hideki; Murata, Shigeo

    2015-04-01

    The proteasome is an essential, 66-subunit protease that mediates ubiquitin-dependent proteolysis. The transcription factor Rpn4 regulates concerted expression of proteasome subunits to increase the proteasome by recognizing nonamer proteasome-associated control element (PACE) elements on the promoter regions. However, the genes for proteasome assembly chaperones and some of the subunits have no PACEs. Here we identified a minimal hexamer "PACE-core" sequence that responds to Rpn4. PACE-cores are found in many genes related to proteasome function including the assembly chaperones, but cannot substitute for PACE of the subunits. Our results add a new layer of complexity in transcriptional regulation of genes involved in protein degradation. PMID:25747386

  11. An algorithm for identifying clusters of functionally related genes in genomes 

    E-print Network

    Yi, Gang Man

    2009-05-15

    as in properties of gene clusters, including size distribution and functional annotation. These properties may be diagnostic of the evolutionary forces that lead to the formation of gene clusters. The approach finds all gene clusters in the data set and ranks them...

  12. Definition of Historical Models of Gene Function and Their Relation to Students' Understanding of Genetics

    ERIC Educational Resources Information Center

    Gericke, Niklas Markus; Hagberg, Mariana

    2007-01-01

    Models are often used when teaching science. In this paper historical models and students' ideas about genetics are compared. The historical development of the scientific idea of the gene and its function is described and categorized into five historical models of gene function. Differences and similarities between these historical models are made…

  13. Virus-aided gene expression and silencing using TRV for functional analysis of floral scent-related genes.

    PubMed

    Spitzer-Rimon, Ben; Cna'ani, Alon; Vainstein, Alexander

    2013-01-01

    Flower scent is a composite character determined by a complex mixture of low-molecular-weight volatile molecules. Despite the importance of floral fragrance, our knowledge on factors regulating these pathways remains sketchy. Virus-induced gene silencing (VIGS) and virus-aided gene expression (VAGE) are characterized by a simple inoculation procedure and rapid results as compared to transgenesis, allowing screening and characterization of scent-related genes. Here, we describe methods using TRV as a VIGS/VAGE vector for the characterization of scent-related genes, protein compartmentalization studies, and protein subcellular targeting. PMID:23386300

  14. EvoCor: a platform for predicting functionally related genes using phylogenetic and expression profiles.

    PubMed

    Dittmar, W James; McIver, Lauren; Michalak, Pawel; Garner, Harold R; Valdez, Gregorio

    2014-07-01

    The wealth of publicly available gene expression and genomic data provides unique opportunities for computational inference to discover groups of genes that function to control specific cellular processes. Such genes are likely to have co-evolved and be expressed in the same tissues and cells. Unfortunately, the expertise and computational resources required to compare tens of genomes and gene expression data sets make this type of analysis difficult for the average end-user. Here, we describe the implementation of a web server that predicts genes involved in affecting specific cellular processes together with a gene of interest. We termed the server 'EvoCor', to denote that it detects functional relationships among genes through evolutionary analysis and gene expression correlation. This web server integrates profiles of sequence divergence derived by a Hidden Markov Model (HMM) and tissue-wide gene expression patterns to determine putative functional linkages between pairs of genes. This server is easy to use and freely available at http://pilot-hmm.vbi.vt.edu/. PMID:24848012

  15. Quantifying the sequence–function relation in gene silencing by bacterial small RNAs

    PubMed Central

    Hao, Yue; Zhang, Zhongge J.; Erickson, David W.; Huang, Min; Huang, Yingwu; Li, Junbai; Hwa, Terence; Shi, Hualin

    2011-01-01

    Sequence–function relations for small RNA (sRNA)-mediated gene silencing were quantified for the sRNA RyhB and some of its mRNA targets in Escherichia coli. Numerous mutants of RyhB and its targets were generated and their in vivo functions characterized at various levels of target and RyhB expression. Although a core complementary region is required for repression by RyhB, variations in the complementary sequences of the core region gave rise to a continuum of repression strengths, correlated exponentially with the computed free energy of RyhB-target duplex formation. Moreover, sequence variations in the linker region known to interact with the RNA chaperone Hfq also gave rise to a continuum of repression strengths, correlated exponentially with the computed energy cost of keeping the linker region open. These results support the applicability of the thermodynamic model in predicting sRNA–mRNA interaction and suggest that sequences at these locations may be used to fine-tune the degree of repression. Surprisingly, a truncated RyhB without the Hfq-binding region is found to repress multiple targets of the wild-type RyhB effectively, both in the presence and absence of Hfq, even though the former is required for the activity of wild-type RyhB itself. These findings challenge the commonly accepted model concerning the function of Hfq in gene silencing—both in providing stability to the sRNAs and in catalyzing the target mRNAs to take on active conformations—and raise the intriguing question of why many endogenous sRNAs subject their functions to Hfq-dependences. PMID:21742981

  16. Calcitonin gene-related peptide enhances experimental autoimmune encephalomyelitis by promoting Th17-cell functions.

    PubMed

    Mikami, Norihisa; Watanabe, Keiko; Hashimoto, Nagisa; Miyagi, Yayoi; Sueda, Kaori; Fukada, So-ichiro; Yamamoto, Hiroshi; Tsujikawa, Kazutake

    2012-11-01

    T(h)17 cells, an inflammatory T helper cell subset, are involved in the pathogenesis of various inflammatory, autoimmune and allergic diseases. Recent evidence supports the idea that immune cell functions and the inflammatory response are finely regulated by various physiological substances. Calcitonin gene-related peptide (CGRP), a neuropeptide released from the sensory nerve endings, is one of these mediators. By binding to its receptor composed of receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like receptor, CGRP modulates various immune cell functions, but the function of CGRP in T(h)17 cells is largely unknown. Here, we investigated the effect of CGRP signaling on T(h)17 cells and T(h)17 cell-mediated inflammation and observed that CGRP activates nuclear factor of activated T cells c2 through cAMP/PKA to increase IL-17 production in vitro. In vivo, IL-17 production is suppressed in RAMP1-deficient mice in the experimental autoimmune encephalomyelitis (EAE) model and RAMP1-deficient mice are completely resistant to EAE. Furthermore, T(h)17 cell function and EAE induction are also suppressed in T cell-specific RAMP1-deficient mice. Taken together, our findings indicate that CGRP promotes T(h)17 cell-mediated autoimmune inflammation through the regulation of IL-17 expression. PMID:22843730

  17. Expression of genes related to mitochondrial function in Nellore cattle divergently ranked on residual feed intake.

    PubMed

    Fonseca, Larissa Fernanda Simielli; Gimenez, Daniele Fernanda Jovino; Mercadante, Maria Eugęnia Zerlotti; Bonilha, Sarah Figueiredo Martins; Ferro, Jesus Aparecido; Baldi, Fernando; de Souza, Fábio Ricardo Pablos; de Albuquerque, Lucia Galvăo

    2015-02-01

    Several measures have been proposed to investigate and improve feed efficiency in cattle. One of the most commonly used measure of feed efficiency is residual feed intake (RFI), which is estimated as the difference between actual feed intake and expected feed intake based on the animal's average live weight. This measure permits to identify and select the most efficient animals without selecting for higher mature weight. Mitochondrial function has been indicated as a major factor that influences RFI. The analysis of genes involved in mitochondrial function is therefore an alternative to identify molecular markers associated with higher feed efficiency. This study analyzed the expression of PGC1?, TFAM, UCP2 and UCP3 genes by quantitative real-time PCR in liver and muscle tissues of two groups of Nellore cattle divergently ranked on RFI values in order to evaluate the relationship of these genes with RFI. In liver tissue, higher expression of TFAM and UCP2 genes was observed in the negative RFI group. Expression of PGC1? gene did not differ significantly between the two groups, whereas UCP3 gene was not expressed in liver tissue. In muscle tissue, higher expression of TFAM gene was observed in the positive RFI group. Expression of PGC1?, UCP2 and UCP3 genes did not differ significantly between the two groups. These results suggest the use of TFAM and UCP2 as possible candidate gene markers in breeding programs designed to increase the feed efficiency of Nellore cattle. PMID:25586767

  18. Functional Analysis of Bladder Cancer-Related Protein Gene: A Putative Cervical Cancer Tumor Suppressor Gene in Cervical Carcinoma

    Microsoft Academic Search

    Zehua Zuo; Min Zhao; Juan Liu; Guifang Gao; Xinxing Wu

    2006-01-01

    Our previous study has suggested thatthe bladder cancer-associated protein gene (BLCAP) was among the differentially expressed genes in cervical cancer. We confirm here that BLCAP is expressed in all noncancerous cervical tissues (10\\/10), but it is greatly lost in primary cervical cancer tissue (31\\/39). In order to further investigate the functional roles of BLCAP, we stably transfected BLCAP cDNA into

  19. Environmental survey for four pathogenic bacteria and closely related species using phylogenetic and functional genes.

    PubMed

    Kuske, Cheryl R; Barns, Susan M; Grow, Christy C; Merrill, Lori; Dunbar, John

    2006-05-01

    Bacterial species with high DNA sequence similarity to pathogens could affect the specificity of assays designed to detect biological threat agents in environmental samples. The natural presence of four pathogenic bacteria, Bacillus anthracis, Clostridium perfringens, Francisella tularensis, and Yersinia pestis and their closely related species, was determined for a large collection of soil and aerosol samples. Polymerase chain reaction (PCR) and gene sequencing were used using group-specific 16S rRNA primers to identify pathogens and related species, and pathogen-specific virulence genes. Close relatives of B. anthracis (B. cereus group species) were detected in 37% of the soils and 25% of the aerosol samples. The B. anthracis protective antigen (pag) gene or a close homolog was detected in 16 of these samples. For the other three pathogen groups, the frequency of detection was much lower, and none of the samples were positive with both the phylogenetic and virulence gene primer sets. PMID:16696701

  20. Functional Networks of Nucleocytoplasmic Transport-Related Genes Differentiate Ischemic and Dilated Cardiomyopathies. A New Therapeutic Opportunity

    PubMed Central

    Molina-Navarro, María Micaela; Trivińo, Juan Carlos; Martínez-Dolz, Luis; Lago, Francisca; González-Juanatey, Jose Ramón; Portolés, Manuel; Rivera, Miguel

    2014-01-01

    Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n?=?10; DCM, n?=?13) undergoing heart transplantation and control donors (CNT, n?=?8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed differentially regulated functional networks specific to ICM and DCM. In comparison with CNT, differential expression was seen in 9 and 12 nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively. DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3, NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU showing an identical trend in expression in both ICM and DCM. Notably, the core of the derived functional networks composed of nucleocytoplasmic transport-related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into several pathways with downregulated genes. Moreover, we identified genes whose expression levels correlated with left ventricular mass index and left ventricular function parameters in HF patients. Collectively, our study provides a clear distinction between the two pathologies at the transcriptome level and opens up new possibilities to search for appropriate therapeutic targets for ICM and DCM. PMID:25137373

  1. Pathophysiological function of endogenous calcitonin gene-related Peptide in ocular vascular diseases.

    PubMed

    Toriyama, Yuichi; Iesato, Yasuhiro; Imai, Akira; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Yamauchi, Akihiro; Igarashi, Kyoko; Tanaka, Megumu; Liu, Tian; Xian, Xian; Zhai, Liuyu; Owa, Shinji; Murata, Toshinori; Shindo, Takayuki

    2015-06-01

    Calcitonin gene-related peptide (CGRP; official name CALCA) has a variety of functions and exhibits both angiogenic and anti-inflammatory properties. We previously reported the angiogenic effects of the CGRP family peptide adrenomedullin in oxygen-induced retinopathy; however, the effects of CGRP on ocular angiogenesis remain unknown. Herein, we used CGRP knockout (CGRP(-/-)) mice to investigate the roles of CGRP in ocular vascular disease. Observation of pathological retinal angiogenesis in the oxygen-induced retinopathy model revealed no difference between CGRP(-/-) and wild-type mice. However, much higher levels of the CGRP receptor were present in the choroid than the retina. Laser-induced choroidal neovascularization (CNV), a model of exudative age-related macular degeneration, revealed more severe CNV lesions in CGRP(-/-) than wild-type mice, and fluorescein angiography showed greater leakage from CNV in CGRP(-/-). In addition, macrophage infiltration and tumor necrosis factor (TNF)-? production were enhanced within the CNV lesions in CGRP(-/-) mice, and the TNF-?, in turn, suppressed the barrier formation of retinal pigment epithelial cells. In vivo, CGRP administration suppressed CNV formation, and CGRP also dose dependently suppressed TNF-? production by isolated macrophages. From these data, we conclude that CGRP suppresses the development of leaky CNV through negative regulation of inflammation. CGRP may thus be a promising therapeutic agent for the treatment of ocular vascular diseases associated with inflammation. PMID:25857228

  2. Calcitonin receptor-stimulating peptide: Its evolutionary and functional relationship with calcitonin\\/calcitonin gene-related peptide based on gene structure

    Microsoft Academic Search

    Takeshi Katafuchi; Hiroshi Yasue; Tsukasa Osaki; Naoto Minamino

    2009-01-01

    This review focuses on the evolutionary and functional relationship of calcitonin receptor-stimulating peptide (CRSP) with calcitonin (CT)\\/calcitonin gene-related peptide (CGRP) in mammals. CRSP shows high sequence identity with CGRP, but distinct biological properties. CRSP genes (CRSPs) have been identified in mammals such as pigs and dogs of the Laurasiatheria, but not in primates and rodents of the Euarchontoglires or in

  3. Genes Related to Mitochondrial Functions, Protein Degradation, and Chromatin Folding Are Differentially Expressed in Lymphomonocytes of Rett Syndrome Patients

    PubMed Central

    Leoni, Guido; Cervellati, Franco; Canali, Raffaella; Cortelazzo, Alessio; De Felice, Claudio; Ciccoli, Lucia; Hayek, Joussef

    2013-01-01

    Rett syndrome (RTT) is mainly caused by mutations in the X-linked methyl-CpG binding protein (MeCP2) gene. By binding to methylated promoters on CpG islands, MeCP2 protein is able to modulate several genes and important cellular pathways. Therefore, mutations in MeCP2 can seriously affect the cellular phenotype. Today, the pathways that MeCP2 mutations are able to affect in RTT are not clear yet. The aim of our study was to investigate the gene expression profiles in peripheral blood lymphomonocytes (PBMC) isolated from RTT patients to try to evidence new genes and new pathways that are involved in RTT pathophysiology. LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of Microarrays) analyses on microarray data from 12 RTT patients and 7 control subjects identified 482 genes modulated in RTT, of which 430 were upregulated and 52 were downregulated. Functional clustering of a total of 146 genes in RTT identified key biological pathways related to mitochondrial function and organization, cellular ubiquitination and proteosome degradation, RNA processing, and chromatin folding. Our microarray data reveal an overexpression of genes involved in ATP synthesis suggesting altered energy requirement that parallels with increased activities of protein degradation. In conclusion, these findings suggest that mitochondrial-ATP-proteasome functions are likely to be involved in RTT clinical features. PMID:24453408

  4. Immune-Related Functions of the Hivep Gene Family in East African Cichlid Fishes

    PubMed Central

    Diepeveen, Eveline T.; Roth, Olivia; Salzburger, Walter

    2013-01-01

    Immune-related genes are often characterized by adaptive protein evolution. Selection on immune genes can be particularly strong when hosts encounter novel parasites, for instance, after the colonization of a new habitat or upon the exploitation of vacant ecological niches in an adaptive radiation. We examined a set of new candidate immune genes in East African cichlid fishes. More specifically, we studied the signatures of selection in five paralogs of the human immunodeficiency virus type I enhancer-binding protein (Hivep) gene family, tested their involvement in the immune defense, and related our results to explosive speciation and adaptive radiation events in cichlids. We found signatures of long-term positive selection in four Hivep paralogs and lineage-specific positive selection in Hivep3b in two radiating cichlid lineages. Exposure of the cichlid Astatotilapia burtoni to a vaccination with Vibrio anguillarum bacteria resulted in a positive correlation between immune response parameters and expression levels of three Hivep loci. This work provides the first evidence for a role of Hivep paralogs in teleost immune defense and links the signatures of positive selection to host–pathogen interactions within an adaptive radiation. PMID:24142922

  5. Genome-Wide Expression Analysis Reveals Diverse Effects of Acute Nicotine Exposure on Neuronal Function-Related Genes and Pathways

    PubMed Central

    Wang, Ju; Cui, Wenyan; Wei, Jinxue; Sun, Dongxiao; Gutala, Ramana; Gu, Jun; Li, Ming D.

    2011-01-01

    Previous human and animal studies demonstrate that acute nicotine exposure has complicated influences on the function of the nervous system, which may lead to long-lasting effects on the behavior and physiology of the subject. To determine the genes and pathways that might account for long-term changes after acute nicotine exposure, a pathway-focused oligoarray specifically designed for drug addiction research was used to assess acute nicotine effect on gene expression in the neuron-like SH-SY5Y cells. Our results showed that 295 genes involved in various biological functions were differentially regulated by 1?h of nicotine treatment. Among these genes, the expression changes of 221 were blocked by mecamylamine, indicating that the majority of nicotine-modulated genes were altered through the nicotinic acetylcholine receptors (nAChRs)-mediated signaling process. We further identified 14 biochemical pathways enriched among the nicotine-modulated genes, among which were those involved in neural development/synaptic plasticity, neuronal survival/death, immune response, or cellular metabolism. In the genes significantly regulated by nicotine but blocked by mecamylamine, 13 enriched pathways were detected. Nine of these pathways were shared with those enriched in the genes regulated by nicotine, including neuronal function-related pathways such as glucocorticoid receptor signaling, p38 MAPK signaling, PI3K/AKT signaling, and PTEN signaling, implying that nAChRs play important roles in the regulation of these biological processes. Together, our results not only provide insights into the mechanism underlying the acute response of neuronal cells to nicotine but also provide clues to how acute nicotine exposure exerts long-term effects on the nervous system. PMID:21556275

  6. Identification and functional clustering of global gene expression differences between human age-related cataract and clear lenses

    PubMed Central

    Hawse, John R.; Hejtmancik, James F.; Huang, Quingling; Sheets, Nancy L.; Hosack, Douglas A.; Lempicki, Richard A.; Horwitz, Joseph; Kantorow, Marc

    2010-01-01

    Purpose Age-related cataract is a multi-factorial disease with a poorly understood etiology. Numerous studies provide evidence that the human eye lens has evolved specific regulatory and protective systems to ameliorate lens damage associated with cataract. Other studies suggest that the presence of cataract is associated with the altered expression of specific genes including metallothionein IIa, osteonectin, transglutaminase 2, betaig-h3, multiple ribosomal proteins, ADAM9, and protein phosphatase 2A. Here, we sought to identify further gene expression changes that are associated with cataract and to cluster the identified genes into specific biological pathways. Methods Oligonucleotide microarray hybridization was used to analyze the full complement of gene expression differences between lens epithelia isolated from human age-related cataract relative to clear lenses. The expression levels of a subset of the identified genes were further evaluated by semi-quantitative RT-PCR. The identified genes were functionally clustered into specific categories and the probability of over-representation of each category was determined using the computer program EASE. Results 412 transcripts were observed to be increased and 919 transcripts were observed to be decreased by 2 fold or more in lens epithelia isolated from age-related cataract relative to clear lenses. Of these, 74 were increased and 241 were decreased at the 5 fold level or greater. Seventeen genes selected for further confirmation exhibited similar trends in expression when examined by RT-PCR using both the original and separately prepared clear and cataract RNA populations. Functional clustering of the identified genes using the EASE bioinformatics software package revealed that, among others, transcripts increased in cataract are associated with transcriptional control, chromosomal organization, ionic and cytoplasmic transport, and extracellular matrix components while transcripts decreased in cataract are associated with protein synthesis, defense against oxidative stress, heat-shock/chaperone activity, structural components of the lens, and cell cycle control. Conclusions These data suggest that cataract is associated with multiple previously identified and novel changes in lens epithelial gene expression and they point to numerous pathways likely to play important roles in lens protection, maintenance, and age-related cataract. PMID:14551530

  7. Gain and loss of multiple functionally related, horizontally transferred genes in the reduced genomes of two microsporidian parasites

    PubMed Central

    Pombert, Jean-François; Selman, Mohammed; Burki, Fabien; Bardell, Floyd T.; Farinelli, Laurent; Solter, Leellen F.; Whitman, Douglas W.; Weiss, Louis M.; Corradi, Nicolas; Keeling, Patrick J.

    2012-01-01

    Microsporidia of the genus Encephalitozoon are widespread pathogens of animals that harbor the smallest known nuclear genomes. Complete sequences from Encephalitozoon intestinalis (2.3 Mbp) and Encephalitozoon cuniculi (2.9 Mbp) revealed massive gene losses and reduction of intergenic regions as factors leading to their drastically reduced genome size. However, microsporidian genomes also have gained genes through horizontal gene transfers (HGT), a process that could allow the parasites to exploit their hosts more fully. Here, we describe the complete sequences of two intermediate-sized genomes (2.5 Mbp), from Encephalitozoon hellem and Encephalitozoon romaleae. Overall, the E. hellem and E. romaleae genomes are strikingly similar to those of Encephalitozoon cuniculi and Encephalitozoon intestinalis in both form and content. However, in addition to the expected expansions and contractions of known gene families in subtelomeric regions, both species also were found to harbor a number of protein-coding genes that are not found in any other microsporidian. All these genes are functionally related to the metabolism of folate and purines but appear to have originated by several independent HGT events from different eukaryotic and prokaryotic donors. Surprisingly, the genes are all intact in E. hellem, but in E. romaleae those involved in de novo synthesis of folate are all pseudogenes. Overall, these data suggest that a recent common ancestor of E. hellem and E. romaleae assembled a complete metabolic pathway from multiple independent HGT events and that one descendent already is dispensing with much of this new functionality, highlighting the transient nature of transferred genes. PMID:22802648

  8. Discovering molecular functions significantly related to phenotypes by combining gene expression data and biological information

    Microsoft Academic Search

    Fátima Al-shahrour; Ramón Díaz-uriarte; Joaquín Dopazo

    2005-01-01

    Motivation: The analysis of genome-scale data from differ- ent high throughput techniques can be used to obtain lists of genes ordered according their different behaviours under distinct experimental conditions corresponding to different phenotypes (e.g. differential gene expression between dis- eased samples and controls, different response to a drug, etc). The order the genes appear in the list is a consequence

  9. Gene function, gene networks and the fate of duplicated genes.

    PubMed

    Shimeld, S M

    1999-10-01

    For both copies of a duplicated gene to become fixed in a population and subsequently maintained, selection must favour individuals with both genes over individuals with one. Here I review and assess some of the proposed ways that gene structure and function might affect the likelihood of both copies acquiring distinct functions and therefore positive selection. In particular I focus on the interacting pathways of genes that make up gene networks, and how these may affect genes duplicated both singly and en masse. Using the Wnt and hedgehog pathways as examples and data from developmental and genome analyses, I show that, while some of these theories may genuinely reflect what has occurred in animal evolution, there are still insufficient data to rigorously assess their relative importance. This, however, is likely to change in the near future. PMID:10597639

  10. A common gene signature across multiple studies relate biomarkers and functional regulation in tolerance to renal allograft

    PubMed Central

    Baron, Daniel; Ramstein, Gérard; Chesneau, Mélanie; Echasseriau, Yann; Pallier, Annaick; Paul, Chloé; Degauque, Nicolas; Hernandez-Fuentes, Maria P; Sanchez-Fueyo, Alberto; Newell, Kenneth A; Giral, Magali; Soulillou, Jean-Paul; Houlgatte, Rémi; Brouard, Sophie

    2015-01-01

    Patients tolerant to a kidney graft display a specific blood cell transcriptional pattern but results from five different studies were inconsistent, raising the question of relevance for future clinical application. To resolve this, we sought to identify a common gene signature, specific functional and cellular components, and discriminating biomarkers for tolerance following kidney transplantation. A meta-analysis of studies identified a robust gene signature involving proliferation of B and CD4 T cells, and inhibition of CD14 monocyte related functions among 96 tolerant samples. This signature was further supported through a cross-validation approach, yielding 92.5% accuracy independent of the study of origin. Experimental validation, performed on new tolerant samples and using a selection of the top-20 biomarkers, returned 91.7% of good classification. Beyond the confirmation of B-cell involvement, our data also indicated participation of other cell subsets in tolerance. Thus, the use of the top 20 biomarkers, mostly centered on B cells, may provide a common and standardized tool towards personalized medicine for the monitoring of tolerant or low-risk patients among kidney allotransplant recipients. These data point to a global preservation of genes favoring the maintenance of a homeostatic and ‘healthy' environment in tolerant patients and may contribute to a better understanding of tolerance maintenance mechanisms. PMID:25629549

  11. Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function

    SciTech Connect

    Rangwala, Shamina M. [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States)]. E-mail: shamina.rangwala@novartis.com; Li, Xiaoyan [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Lindsley, Loren [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Wang, Xiaomei [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Shaughnessy, Stacey [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Daniels, Thomas G. [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Szustakowski, Joseph [Genome and Proteome Sciences, Novartis Institutes of BioMedical Research Institutes, 500 Technology Square, Cambridge, MA 02139 (United States); Nirmala, N.R. [Genome and Proteome Sciences, Novartis Institutes of BioMedical Research Institutes, 500 Technology Square, Cambridge, MA 02139 (United States); Wu, Zhidan [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Stevenson, Susan C. [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States)

    2007-05-25

    Estrogen-related receptor {alpha} (ERR{alpha}) is an important mediator of mitochondrial biogenesis and function. To investigate the transcriptional network controlling these phenomena, we investigated mitochondrial gene expression in embryonic fibroblasts isolated from ERR{alpha} null mice. Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) stimulated mitochondrial gene expression program in control cells, but not in the ERR{alpha} null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1{alpha} levels was dependent on ERR{alpha}. Furthermore, we found that the PGC-1{alpha}-mediated induction of estrogen-related receptor {gamma} and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERR{alpha}. Basal levels of NRF-2 were decreased in the absence of ERR{alpha}. The absence of ERR{alpha} resulted in a decrease in citrate synthase enzyme activity in response to PGC-1{alpha} overexpression. Our results indicate an essential role for ERR{alpha} as a key regulator of oxidative metabolism.

  12. Physiological Ageing as it is Related to Gene Function in the Lone Star Tick, Amblyomma americanum 

    E-print Network

    Catena, Amanda M.

    2010-07-14

    frequently been the center of research studies in ageing. Studies of Drosophila melanogaster, Caenorhabditis elegans, yeast, and mice have uncovered specific genes that up and down regulate with age and stress. Research has yet to produce, however, results...

  13. Dicer-related drh-3 gene functions in germ-line development by maintenance of chromosomal integrity in Caenorhabditis elegans

    Microsoft Academic Search

    Masaharu Nakamura; Rumi Ando; Taro Nakazawa; Takuro Yudazono; Naoko Tsutsumi; Naoki Hatanaka; Toshiyasu Ohgake; Fumio Hanaoka; Toshihiko Eki

    In the course of systematic RNA interference (RNAi)-based screens with helicase-like genes in Caenorhabditis elegans , we have identified the drh-3 ( D2005.5 ) gene as a candidate gene for protection against X-ray irradiation. This gene encodes a novel RNA helicase-like protein that is similar to two nematode Dicer-related helicases (DRH). Here, we have showed the increased expression of drh-3

  14. Structure and Expression Analyses of SVA Elements in Relation to Functional Genes

    PubMed Central

    Kwon, Yun-Jeong; Choi, Yuri; Eo, Jungwoo; Noh, Yu-Na; Gim, Jeong-An; Jung, Yi-Deun; Lee, Ja-Rang

    2013-01-01

    SINE-VNTR-Alu (SVA) elements are present in hominoid primates and are divided into 6 subfamilies (SVA-A to SVA-F) and active in the human population. Using a bioinformatic tool, 22 SVA element-associated genes are identified in the human genome. In an analysis of genomic structure, SVA elements are detected in the 5' untranslated region (UTR) of HGSNAT (SVA-B), MRGPRX3 (SVA-D), HYAL1 (SVA-F), TCHH (SVA-F), and ATXN2L (SVA-F) genes, while some elements are observed in the 3'UTR of SPICE1 (SVA-B), TDRKH (SVA-C), GOSR1 (SVA-D), BBS5 (SVA-D), NEK5 (SVA-D), ABHD2 (SVA-F), C1QTNF7 (SVA-F), ORC6L (SVA-F), TMEM69 (SVA-F), and CCDC137 (SVA-F) genes. They could contribute to exon extension or supplying poly A signals. LEPR (SVA-C), ALOX5 (SVA-D), PDS5B (SVA-D), and ABCA10 (SVA-F) genes also showed alternative transcripts by SVA exonization events. Dominant expression of HYAL1_SVA appeared in lung tissues, while HYAL1_noSVA showed ubiquitous expression in various human tissues. Expression of both transcripts (TDRKH_SVA and TDRKH_noSVA) of the TDRKH gene appeared to be ubiquitous. Taken together, these data suggest that SVA elements cause transcript isoforms that contribute to modulation of gene regulation in various human tissues. PMID:24124410

  15. Characterization of the Functionally Related Sites in the Neural Inducing Gene Noggin

    Microsoft Academic Search

    Weidong Liu; Caiping Ren; Jianling Shi; Xiangling Feng; Zhiwei He; Liangguo Xu; Ke Lan; Lu Xie; Ying Peng; Jing Fan; Hsiang-fu Kung; Kai-Tai Yao; Ren-He Xu

    2000-01-01

    Previously we have shown that blocking bone morphogenetic protein (BMP) receptor signaling by a dominant negative BMP receptor causes neurogenesis in Xenopus animal caps (ACs), whereas the physiological neural inducer noggin acts as a homodimer physically binding to BMP-4 and disrupting its signaling at the ligand level. The present study attempted to elucidate the relationship between the structure and function

  16. Loss-of-Function of Constitutive Expresser of Pathogenesis Related Genes5 Affects Potassium Homeostasis in Arabidopsis thaliana

    PubMed Central

    Borghi, Monica; Rus, Ana; Salt, David E.

    2011-01-01

    Here, we demonstrate that the reduction in leaf K+ observed in a mutant previously identified in an ionomic screen of fast neutron mutagenized Arabidopsis thaliana is caused by a loss-of-function allele of CPR5, which we name cpr5-3. This observation establishes low leaf K+ as a new phenotype for loss-of-function alleles of CPR5. We investigate the factors affecting this low leaf K+ in cpr5 using double mutants defective in salicylic acid (SA) and jasmonic acid (JA) signalling, and by gene expression analysis of various channels and transporters. Reciprocal grafting between cpr5 and Col-0 was used to determine the relative importance of the shoot and root in causing the low leaf K+ phenotype of cpr5. Our data show that loss-of-function of CPR5 in shoots primarily determines the low leaf K+ phenotype of cpr5, though the roots also contribute to a lesser degree. The low leaf K+ phenotype of cpr5 is independent of the elevated SA and JA known to occur in cpr5. In cpr5 expression of genes encoding various Cyclic Nucleotide Gated Channels (CNGCs) are uniquely elevated in leaves. Further, expression of HAK5, encoding the high affinity K+ uptake transporter, is reduced in roots of cpr5 grown with high or low K+ supply. We suggest a model in which low leaf K+ in cpr5 is driven primarily by enhanced shoot-to-root K+ export caused by a constitutive activation of the expression of various CNGCs. This activation may enhance K+ efflux, either indirectly via enhanced cytosolic Ca2+ and/or directly by increased K+ transport activity. Enhanced shoot-to-root K+ export may also cause the reduced expression of HAK5 observed in roots of cpr5, leading to a reduction in uptake of K+. All ionomic data presented is publically available at www.ionomicshub.org. PMID:22046278

  17. Evolutionary conservation of RecA genes in relation to protein structure and function.

    PubMed Central

    Karlin, S; Brocchieri, L

    1996-01-01

    Functional and structural regions inferred from the Escherichia coli R ecA protein crystal structure and mutation studies are evaluated in terms of evolutionary conservation across 63 RecA eubacterial sequences. Two paramount segments invariant in specific amino acids correspond to the ATP-binding A site and the functionally unassigned segment from residues 145 to 149 immediately carboxyl to the ATP hydrolysis B site. Not only are residues 145 to 149 conserved individually, but also all three-dimensional structural neighbors of these residues are invariant, strongly attesting to the functional or structural importance of this segment. The conservation of charged residues at the monomer-monomer interface, emphasizing basic residues on one surface and acidic residues on the other, suggests that RecA monomer polymerization is substantially mediated by electrostatic interactions. Different patterns of conservation also allow determination of regions proposed to interact with DNA, of LexA binding sites, and of filament-filament contact regions. Amino acid conservation is also compared with activities and properties of certain RecA protein mutants. Arginine 243 and its strongly cationic structural environment are proposed as the major site of competition for DNA and LexA binding to RecA. The conserved acidic and glycine residues of the disordered loop L1 and its proximity to the RecA acidic monomer interface suggest its involvement in monomer-monomer interactions rather than DNA binding. The conservation of various RecA positions and regions suggests a model for RecA-double-stranded DNA interaction and other functional and structural assignments. PMID:8606161

  18. Analysis of genes contributing to plant-beneficial functions in plant growth-promoting rhizobacteria and related Proteobacteria

    PubMed Central

    Bruto, Maxime; Prigent-Combaret, Claire; Muller, Daniel; Moënne-Loccoz, Yvan

    2014-01-01

    The positive effects of root-colonizing bacteria cooperating with plants lead to improved growth and/or health of their eukaryotic hosts. Some of these Plant Growth-Promoting Rhizobacteria (PGPR) display several plant-beneficial properties, suggesting that the accumulation of the corresponding genes could have been selected in these bacteria. Here, this issue was targeted using 23 genes contributing directly or indirectly to established PGPR effects, based on genome sequence analysis of 304 contrasted Alpha- Beta- and Gammaproteobacteria. Most of the 23 genes studied were also found in non-PGPR Proteobacteria and none of them were common to all 25 PGPR genomes studied. However, ancestral character reconstruction indicated that gene transfers -predominantly ancient- resulted in characteristic gene combinations according to taxonomic subgroups of PGPR strains. This suggests that the PGPR-plant cooperation could have established separately in various taxa, yielding PGPR strains that use different gene assortments. The number of genes contributing to plant-beneficial functions increased along the continuum -animal pathogens, phytopathogens, saprophytes, endophytes/symbionts, PGPR- indicating that the accumulation of these genes (and possibly of different plant-beneficial traits) might be an intrinsic PGPR feature. This work uncovered preferential associations occurring between certain genes contributing to phytobeneficial traits and provides new insights into the emergence of PGPR bacteria. PMID:25179219

  19. Analysis of genes contributing to plant-beneficial functions in Plant Growth-Promoting Rhizobacteria and related Proteobacteria.

    PubMed

    Bruto, Maxime; Prigent-Combaret, Claire; Muller, Daniel; Moënne-Loccoz, Yvan

    2014-01-01

    The positive effects of root-colonizing bacteria cooperating with plants lead to improved growth and/or health of their eukaryotic hosts. Some of these Plant Growth-Promoting Rhizobacteria (PGPR) display several plant-beneficial properties, suggesting that the accumulation of the corresponding genes could have been selected in these bacteria. Here, this issue was targeted using 23 genes contributing directly or indirectly to established PGPR effects, based on genome sequence analysis of 304 contrasted Alpha- Beta- and Gammaproteobacteria. Most of the 23 genes studied were also found in non-PGPR Proteobacteria and none of them were common to all 25 PGPR genomes studied. However, ancestral character reconstruction indicated that gene transfers -predominantly ancient- resulted in characteristic gene combinations according to taxonomic subgroups of PGPR strains. This suggests that the PGPR-plant cooperation could have established separately in various taxa, yielding PGPR strains that use different gene assortments. The number of genes contributing to plant-beneficial functions increased along the continuum -animal pathogens, phytopathogens, saprophytes, endophytes/symbionts, PGPR- indicating that the accumulation of these genes (and possibly of different plant-beneficial traits) might be an intrinsic PGPR feature. This work uncovered preferential associations occurring between certain genes contributing to phytobeneficial traits and provides new insights into the emergence of PGPR bacteria. PMID:25179219

  20. Molecular Characterization and Functional Analysis of Three Pathogenesis-Related Cytochrome P450 Genes from Bursaphelenchus xylophilus (Tylenchida: Aphelenchoidoidea)

    PubMed Central

    Xu, Xiao-Lu; Wu, Xiao-Qin; Ye, Jian-Ren; Huang, Lin

    2015-01-01

    Bursaphelenchus xylophilus, the causal agent of pine wilt disease, causes huge economic losses in pine forests. The high expression of cytochrome P450 genes in B. xylophilus during infection in P. thunbergii indicated that these genes had a certain relationship with the pathogenic process of B. xylophilus. Thus, we attempted to identify the molecular characterization and functions of cytochrome P450 genes in B. xylophilus. In this study, full-length cDNA of three cytochrome P450 genes, BxCYP33C9, BxCYP33C4 and BxCYP33D3 were first cloned from B. xylophilus using 3' and 5' RACE PCR amplification. Sequence analysis showed that all of them contained a highly-conserved cytochrome P450 domain. The characteristics of the three putative proteins were analyzed with bioinformatic methods. RNA interference (RNAi) was used to assess the functions of BxCYP33C9, BxCYP33C4 and BxCYP33D3. The results revealed that these cytochrome P450 genes were likely to be associated with the vitality, dispersal ability, reproduction, pathogenicity and pesticide metabolism of B. xylophilus. This discovery confirmed the molecular characterization and functions of three cytochrome P450 genes from B. xylophilus and provided fundamental information in elucidating the molecular interaction mechanism between B. xylophilus and its host plant. PMID:25756378

  1. Functional analysis of four processing products from multiple precursors encoded by a lebocin-related gene from Manduca sexta

    PubMed Central

    Rayaprolu, Subrahmanyam; Wang, Yang; Kanost, Michael R.; Hartson, Steven; Jiang, Haobo

    2010-01-01

    Antimicrobial peptides (AMPs) are a crucial component of the natural immune system in insects. Five types of AMPs have been identified in the tobacco hornworm Manduca sexta, including attacin, cecropin, moricin, gloverin, and lebocin. Here we report the isolation of lebocin-related cDNA clones and antibacterial activity of their processed protein products. The seventeen cDNA sequences are composed of a constant 5? end and a variable 3? region containing 3?16 copies of an 81-nucleotide repeat. The sequence of the corresponding gene isolated from a M. sexta genomic library and Southern blotting results indicated that the gene lacks introns and exists as a single copy in the genome. The genomic sequence contained 13 complete and one partial copy of the 81-nucleotide repeat. Northern blot analysis revealed multiple transcripts with major size differences. The mRNA level of M. sexta lebocin increased substantially in fat body after larvae had been injected with bacteria. The RXXR motifs in the protein sequences led us to postulate that the precursors are processed by an intracellular convertase to form four bioactive peptides. To test this hypothesis, we chemically synthesized the peptides and examined their antibacterial activity. Peptide 1 killed Gram-positive and Gram-negative bacteria. Peptide 2, similar in sequence to a Galleria mellonella AMP, did not affect the bacterial growth. Peptide 3 was inactive but peptide 3 with an extra Arg at the carboxyl terminus was active against E. coli at a high minimum inhibitory concentration. Peptide 4, encoded by the 81-bp repeat, was inactive in the antibacterial tests. The hypothesis that posttranslational processing of the precursor proteins produces multiple bioactive peptides for defense purposes was validated by identification of peptides 1, 2, and 3 from larval hemolymph via liquid chromatography and tandem mass spectrometry. Comparison with the orthologs from other lepidopteran insects indicates that the same mechanism may be used to generate several functional products from a single precursor. PMID:20096726

  2. HA117 gene increased the multidrug resistance of K562 cells in vitro: an investigation to the function of a novel gene related to drug resistance

    Microsoft Academic Search

    Yuxia Guo; Gaihuan Zheng; Xianqing Jin; Youhua Xu; Qing Luo; Xiaomei Liu; Zhenzhen Zhao; Yong Chen

    2009-01-01

    OBJECTIVE: A novel multi-drug resistance gene named as HA117 has been screened and cloned in multidrug resisitant leukemia cell lines in our previous research, but its function is still unknown. In this study, HA117 gene was investigated whether it could increase the drug resistance in chronic myelogenous myeloid leukemia cell line K562. METHODS: HA117 was cloned and adenovirus vectors were

  3. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function

    PubMed Central

    Chasman, Daniel I.; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A.; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary F.; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Ĺsa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tőnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid B.; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Kao, W.H. Linda; Fox, Caroline S.; Köttgen, Anna

    2012-01-01

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10?9) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10?4–2.2 × 10?7. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general. PMID:22962313

  4. Using the Gene Ontology Hierarchy when Predicting Gene Function

    E-print Network

    Mostafavi, Sara

    2012-01-01

    The problem of multilabel classification when the labels are related through a hierarchical categorization scheme occurs in many application domains such as computational biology. For example, this problem arises naturally when trying to automatically assign gene function using a controlled vocabularies like Gene Ontology. However, most existing approaches for predicting gene functions solve independent classification problems to predict genes that are involved in a given function category, independently of the rest. Here, we propose two simple methods for incorporating information about the hierarchical nature of the categorization scheme. In the first method, we use information about a gene's previous annotation to set an initial prior on its label. In a second approach, we extend a graph-based semi-supervised learning algorithm for predicting gene function in a hierarchy. We show that we can efficiently solve this problem by solving a linear system of equations. We compare these approaches with a previous ...

  5. Neural networks approaches for discovering the learnable correlation between gene function and gene expression in mouse

    E-print Network

    Morris, Quaid

    Keywords: Gene function prediction Self organizing maps (SOM) Multilayer perceptrons (MLP) Gene expression function based on gene expression data is much easier in prokaryotes than eukaryotes due to the relatively between gene function and gene expression. In previous work, we presented novel clustering and neural

  6. Possible Regulatory Roles of Promoter G-Quadruplexes in Cardiac Function-Related Genes – Human TnIc as a Model

    PubMed Central

    Zhou, Wenhua; Suntharalingam, Kogularamanan; Brand, Nigel J.; Barton, Paul J. R.; Vilar, Ramon; Ying, Liming

    2013-01-01

    G-quadruplexes (G4s) are four-stranded DNA secondary structures, which are involved in a diverse range of biological processes. Although the anti-cancer potential of G4s in oncogene promoters has been thoroughly investigated, the functions of promoter G4s in non-cancer-related genes are not well understood. We have explored the possible regulatory roles of promoter G4s in cardiac function-related genes using both computational and a wide range of experimental approaches. According to our bioinformatics results, it was found that potential G4-forming sequences are particularly enriched in the transcription regulatory regions (TRRs) of cardiac function-related genes. Subsequently, the promoter of human cardiac troponin I (TnIc) was chosen as a model, and G4s found in this region were subjected to biophysical characterisations. The chromosome 19 specific minisatellite G4 sequence (MNSG4) and near transcription start site (TSS) G4 sequence (?80 G4) adopt anti-parallel and parallel structures respectively in 100 mM KCl, with stabilities comparable to those of oncogene G4s. It was also found that TnIc G4s act cooperatively as enhancers in gene expression regulation in HEK293 cells, when stabilised by a synthetic G4-binding ligand. This study provides the first evidence of the biological significance of promoter G4s in cardiac function-related genes. The feasibility of using a single ligand to target multiple G4s in a particular gene has also been discussed. PMID:23326389

  7. Differential Functional Variability of Serotonin Transporter and Monoamine Oxidase A Genes in Macaque Species Displaying Contrasting Levels of Aggression-Related Behavior

    Microsoft Academic Search

    Jens R. Wendland; Klaus-Peter Lesch; Timothy K. Newman; Angelika Timme; Hélčne Gachot-Neveu; Bernard Thierry; Stephen J. Suomi

    2006-01-01

    Functional allelic variation in the transcriptional control region of the serotonin transporter and monoamine oxidase A genes\\u000a has been associated with anxiety- and aggression-related behavior in humans and, more recently, in nonhuman primates. Here,\\u000a we have genotyped these polymorphic regions in seven species of the genus Macaca. Macaques exhibit exceptional inter-species variation in aggression-related social behavior as illustrated by recent

  8. Effect of Lead Ion on the Function of the Human Ether-Ŕ-Go-Go-Related Gene K + Channel

    Microsoft Academic Search

    Jiemin Zhou; Gang Hu

    Lead (Pb) is a trace metal element in the human body. In order to understand the hazard mechanism of the elevated blood lead\\u000a level on the human body, the effect of Pb2+ on the human ether-ŕ-go-go-related gene (hERG) K+ channel in the HEK 293 cell was investigated for the first time using whole-cell patch clamp technique, molecular dynamics\\u000a simulation, and

  9. Structural and functional characterization of microcystin detoxification-related liver genes in a phytoplanktivorous fish, Nile tilapia ( Oreochromis niloticus)

    Microsoft Academic Search

    Lin Wang; Xu-Fang Liang; Wan-Qin Liao; La-Mei Lei; Bo-Ping Han

    2006-01-01

    Liver genes related to phase I and phase II detoxification, as well as inhibition of reactive oxygen species (ROS) production, were cloned, and their response to microcystin-LR (MC-LR) and lipopolysaccharide (LPS) exposure via intraperitoneal injection, was determined in a phytoplanktivorous fish, Nile tilapia (Oreochromis niloticus). The cloned full-length cDNA of tilapia soluble glutathione S-transferase (sGST) was classified as alpha-class GST

  10. Loss-of-Function Mutations in a Human Gene Related to Chlamydomonas reinhardtii Dynein IC78 Result in Primary Ciliary Dyskinesia

    PubMed Central

    Pennarun, Gaëlle; Escudier, Estelle; Chapelin, Catherine; Bridoux, Anne-Marie; Cacheux, Valčre; Roger, Gilles; Clément, Annick; Goossens, Michel; Amselem, Serge; Duriez, Bénédicte

    1999-01-01

    Summary Primary ciliary dyskinesia (PCD) is a group of heterogeneous disorders of unknown origin, usually inherited as an autosomal recessive trait. Its phenotype is characterized by axonemal abnormalities of respiratory cilia and sperm tails leading to bronchiectasis and sinusitis, which are sometimes associated with situs inversus (Kartagener syndrome) and male sterility. The main ciliary defect in PCD is an absence of dynein arms. We have isolated the first gene involved in PCD, using a candidate-gene approach developed on the basis of documented abnormalities of immotile strains of Chlamydomonas reinhardtii, which carry axonemal ultrastructural defects reminiscent of PCD. Taking advantage of the evolutionary conservation of genes encoding axonemal proteins, we have isolated a human sequence (DNAI1) related to IC78, a C. reinhardtii gene encoding a dynein intermediate chain in which mutations are associated with the absence of outer dynein arms. DNAI1 is highly expressed in trachea and testis and is composed of 20 exons located at 9p13-p21. Two loss-of-function mutations of DNAI1 have been identified in a patient with PCD characterized by immotile respiratory cilia lacking outer dynein arms. In addition, we excluded linkage between this gene and similar PCD phenotypes in five other affected families, providing a clear demonstration of locus heterogeneity. These data reveal the critical role of DNAI1 in the development of human axonemal structures and open up new means for identification of additional genes involved in related developmental defects. PMID:10577904

  11. Mining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps

    E-print Network

    Obradovic, Zoran

    Mining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps Li An166522@temple.edu Abstract Association rules mining methods have been recently applied to gene expression, not much effort has focused on detecting the relation between gene expression maps and related gene

  12. Increased brain size in mammals is associated with size variations in gene families with cell signalling, chemotaxis and immune-related functions

    PubMed Central

    Castillo-Morales, Atahualpa; Monzón-Sandoval, Jimena; Urrutia, Araxi O.; Gutiérrez, Humberto

    2014-01-01

    Genomic determinants underlying increased encephalization across mammalian lineages are unknown. Whole genome comparisons have revealed large and frequent changes in the size of gene families, and it has been proposed that these variations could play a major role in shaping morphological and physiological differences among species. Using a genome-wide comparative approach, we examined changes in gene family size (GFS) and degree of encephalization in 39 fully sequenced mammalian species and found a significant over-representation of GFS variations in line with increased encephalization in mammals. We found that this relationship is not accounted for by known correlates of brain size such as maximum lifespan or body size and is not explained by phylogenetic relatedness. Genes involved in chemotaxis, immune regulation and cell signalling-related functions are significantly over-represented among those gene families most highly correlated with encephalization. Genes within these families are prominently expressed in the human brain, particularly the cortex, and organized in co-expression modules that display distinct temporal patterns of expression in the developing cortex. Our results suggest that changes in GFS associated with encephalization represent an evolutionary response to the specific functional requirements underlying increased brain size in mammals. PMID:24285197

  13. Functional genomics: Probing plant gene function and expression with transposons

    PubMed Central

    Martienssen, Robert A.

    1998-01-01

    Transposable elements provide a convenient and flexible means to disrupt plant genes, so allowing their function to be assessed. By engineering transposons to carry reporter genes and regulatory signals, the expression of target genes can be monitored and to some extent manipulated. Two strategies for using transposons to assess gene function are outlined here: First, the PCR can be used to identify plants that carry insertions into specific genes from among pools of heavily mutagenized individuals (site-selected transposon mutagenesis). This method requires that high copy transposons be used and that a relatively large number of reactions be performed to identify insertions into genes of interest. Second, a large library of plants, each carrying a unique insertion, can be generated. Each insertion site then can be amplified and sequenced systematically. These two methods have been demonstrated in maize, Arabidopsis, and other plant species, and the relative merits of each are discussed in the context of plant genome research. PMID:9482828

  14. Cost benefit theory and optimal design of gene regulation functions

    Microsoft Academic Search

    Tomer Kalisky; Erez Dekel; Uri Alon

    2007-01-01

    Cells respond to the environment by regulating the expression of genes according to environmental signals. The relation between the input signal level and the expression of the gene is called the gene regulation function. It is of interest to understand the shape of a gene regulation function in terms of the environment in which it has evolved and the basic

  15. GOToolBox: functional analysis of gene datasets based on Gene Ontology

    Microsoft Academic Search

    David Martin; Christine Brun; Elisabeth Remy; Pierre Mouren; Denis Thieffry; Bernard Jacq

    2004-01-01

    We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level

  16. ACE and UCP2 gene polymorphisms and their association with baseline and exercise-related changes in the functional performance of older adults

    PubMed Central

    Palmer, Barry R.; Taylor, Denise; Kilding, Andrew E.

    2015-01-01

    Maintaining high levels of physical function is an important aspect of successful ageing. While muscle mass and strength contribute to functional performance in older adults, little is known about the possible genetic basis for the heterogeneity of physical function in older adults and in how older adults respond to exercise. Two genes that have possible roles in determining levels of muscle mass, strength and function in young and older adults are angiotensin-converting enzyme (ACE) and mitochondrial uncoupling protein 2 (UCP2). This study examined whether polymorphisms in these two individual genes were associated with baseline functional performance levels and/or the training-related changes following exercise in previously untrained older adults. Five-eight Caucasian older adults (mean age 69.8 years) with no recent history of resistance training enrolled in a 12 week program of resistance, balance and cardiovascular exercises aimed at improving functional performance. Performance in 6 functional tasks was recorded at baseline and after 12 weeks. Genomic DNA was assayed for the ACE intron 16 insertion/deletion (I/D) and the UCP2 G-866A polymorphism. Baseline differences among genotype groups were tested using analysis of variance. Genotype differences in absolute and relative changes in physical function among the exercisers were tested using a general linear model, adjusting for age and gender. The genotype frequencies for each of the studied polymorphisms conformed to the Hardy-Weinberg equilibrium. The ACE I/D genotype was significantly associated with mean baseline measures of handgrip strength (II 30.9 ± 3.01 v. ID 31.7 ± 1.48 v. DD 29.3 ± 2.18 kg, p < 0.001), 8ft Up and Go time (II 6.45 ± 0.48 v. ID/DD 4.41 ± 0.19 s, p < 0.001) and 6 min walk distance (II 458 ± 28.7 v. ID/DD 546 ± 12.1m, p = 0.008). The UCP2 G-866A genotype was also associated with baseline 8ft Up and Go time (GG 5.45 ± 0.35 v. GA 4.47 ± 0.26 v. AA 3.89 ± 0.71 s, p = 0.045). After 12 weeks of training, a significant difference between UCP2 G-886A genotype groups for change in 8ft Up and Go time was detected (GG ?0.68 ± 0.17 v. GA ?0.10 ± 0.14 v. AA +0.05 ± 0.31 s, p = 0.023). While several interesting and possibly consistent associations with older adults’ baseline functional performance were found for the ACE and UCP2 polymorphisms, we found no strong evidence of genetic associations with exercise responses in this study. The relative equivalence of some of these training-response findings to the literature may have reflected the current study’s focus on physical function rather than just strength, the relatively high levels of baseline function for some genotype groups as well as the greater statistical power for detecting baseline differences than the training-related changes. PMID:26038734

  17. ACE and UCP2 gene polymorphisms and their association with baseline and exercise-related changes in the functional performance of older adults.

    PubMed

    Keogh, Justin W L; Palmer, Barry R; Taylor, Denise; Kilding, Andrew E

    2015-01-01

    Maintaining high levels of physical function is an important aspect of successful ageing. While muscle mass and strength contribute to functional performance in older adults, little is known about the possible genetic basis for the heterogeneity of physical function in older adults and in how older adults respond to exercise. Two genes that have possible roles in determining levels of muscle mass, strength and function in young and older adults are angiotensin-converting enzyme (ACE) and mitochondrial uncoupling protein 2 (UCP2). This study examined whether polymorphisms in these two individual genes were associated with baseline functional performance levels and/or the training-related changes following exercise in previously untrained older adults. Five-eight Caucasian older adults (mean age 69.8 years) with no recent history of resistance training enrolled in a 12 week program of resistance, balance and cardiovascular exercises aimed at improving functional performance. Performance in 6 functional tasks was recorded at baseline and after 12 weeks. Genomic DNA was assayed for the ACE intron 16 insertion/deletion (I/D) and the UCP2 G-866A polymorphism. Baseline differences among genotype groups were tested using analysis of variance. Genotype differences in absolute and relative changes in physical function among the exercisers were tested using a general linear model, adjusting for age and gender. The genotype frequencies for each of the studied polymorphisms conformed to the Hardy-Weinberg equilibrium. The ACE I/D genotype was significantly associated with mean baseline measures of handgrip strength (II 30.9 ± 3.01 v. ID 31.7 ± 1.48 v. DD 29.3 ± 2.18 kg, p < 0.001), 8ft Up and Go time (II 6.45 ± 0.48 v. ID/DD 4.41 ± 0.19 s, p < 0.001) and 6 min walk distance (II 458 ± 28.7 v. ID/DD 546 ± 12.1m, p = 0.008). The UCP2 G-866A genotype was also associated with baseline 8ft Up and Go time (GG 5.45 ± 0.35 v. GA 4.47 ± 0.26 v. AA 3.89 ± 0.71 s, p = 0.045). After 12 weeks of training, a significant difference between UCP2 G-886A genotype groups for change in 8ft Up and Go time was detected (GG -0.68 ± 0.17 v. GA -0.10 ± 0.14 v. AA +0.05 ± 0.31 s, p = 0.023). While several interesting and possibly consistent associations with older adults' baseline functional performance were found for the ACE and UCP2 polymorphisms, we found no strong evidence of genetic associations with exercise responses in this study. The relative equivalence of some of these training-response findings to the literature may have reflected the current study's focus on physical function rather than just strength, the relatively high levels of baseline function for some genotype groups as well as the greater statistical power for detecting baseline differences than the training-related changes. PMID:26038734

  18. Variation at FCGR2A and Functionally Related Genes Is Associated with the Response to Anti-TNF Therapy in Rheumatoid Arthritis

    PubMed Central

    Avila-Pedretti, Gabriela; Tornero, Jesús; Fernández-Nebro, Antonio; Blanco, Francisco; González-Alvaro, Isidoro; Cańete, Juan D.; Maymó, Joan; Alperiz, Mercedes; Fernández-Gutiérrez, Benjamín; Olivé, Alex; Corominas, Héctor; Erra, Alba; Aterido, Adriŕ; López Lasanta, María; Tortosa, Raül; Juliŕ, Antonio; Marsal, Sara

    2015-01-01

    Objective Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25–30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response. Methods A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy. Results We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042). Conclusions In the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA. PMID:25848939

  19. Comparison of Gene Coexpression Profiles and Construction of Conserved Gene Networks to Find Functional Modules

    PubMed Central

    Okamura, Yasunobu; Obayashi, Takeshi; Kinoshita, Kengo

    2015-01-01

    Background Computational approaches toward gene annotation are a formidable challenge, now that many genome sequences have been determined. Each gene has its own function, but complicated cellular functions are achieved by sets of genes. Therefore, sets of genes with strong functional relationships must be identified. For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution. Result & Discussion We propose a new method to find functional modules, by comparing gene coexpression profiles among species. A coexpression pattern is represented as a list of coexpressed genes with each guide gene. We compared two coexpression lists, one from a human guide gene and the other from a homologous mouse gene, and defined a measure to evaluate the similarity between the lists. Based on this coexpression similarity, we detected the highly conserved genes, and constructed human gene networks with conserved coexpression between human and mouse. Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge. We also found a few functional modules without any annotations, which may be good candidates for novel functional modules. All of the comparisons are available at the http://v1.coxsimdb.info web database. PMID:26147120

  20. Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats.

    PubMed

    Zhao, Xiaohong; Sun, Lei; Jia, Hongxiao; Meng, Qingxuan; Wu, Si; Li, Nanxin; He, Shuchang

    2009-10-01

    Isolation rearing induces various cognitive abnormalities such as reversal learning deficits and reduced prepulse inhibition in rats. However, there are few reports in the literature on its effects on social and emotional functions. In the current study we aimed to address these issues and demonstrated that isolation rearing induced aggression and impaired social recognition, produced moderate anxiogenic effects in the elevated-plus maze, and resulted in hyperactivity in a novel open field. We also found NR2A, NR2B, PSD-95 and SAP-102 mRNA expression were significantly up-regulated in the hippocampus while NR2B was down-regulated in prefrontal cortex in response to isolation rearing. This study advances the use of social isolation as an animal model for studying etiological mechanisms of various neuropsychiatric disorders. PMID:19563853

  1. GOToolBox: functional analysis of gene datasets based on Gene Ontology

    PubMed Central

    Martin, David; Brun, Christine; Remy, Elisabeth; Mouren, Pierre; Thieffry, Denis; Jacq, Bernard

    2004-01-01

    We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level of the ontology. The source codes are available upon request, and distributed under the GPL license. PMID:15575967

  2. Functional Analysis of the Molecular Interactions of TATA Box-Containing Genes and Essential Genes

    PubMed Central

    Moon, Jisook

    2015-01-01

    Genes can be divided into TATA-containing genes and TATA-less genes according to the presence of TATA box elements at promoter regions. TATA-containing genes tend to be stress-responsive, whereas many TATA-less genes are known to be related to cell growth or “housekeeping” functions. In a previous study, we demonstrated that there are striking differences among four gene sets defined by the presence of TATA box (TATA-containing) and essentiality (TATA-less) with respect to number of associated transcription factors, amino acid usage, and functional annotation. Extending this research in yeast, we identified KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways that are statistically enriched in TATA-containing or TATA-less genes and evaluated the possibility that the enriched pathways are related to stress or growth as reflected by the individual functions of the genes involved. According to their enrichment for either of these two gene sets, we sorted KEGG pathways into TATA-containing-gene-enriched pathways (TEPs) and essential-gene-enriched pathways (EEPs). As expected, genes in TEPs and EEPs exhibited opposite results in terms of functional category, transcriptional regulation, codon adaptation index, and network properties, suggesting the possibility that the bipolar patterns in these pathways also contribute to the regulation of the stress response and to cell survival. Our findings provide the novel insight that significant enrichment of TATA-binding or TATA-less genes defines pathways as stress-responsive or growth-related. PMID:25789484

  3. Combining Hierarchical and Associative Gene Ontology Relations with Textual Evidence in Estimating Gene and Gene Product Similarity

    SciTech Connect

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.; Tratz, Stephen C.; Gregory, Michelle L.

    2007-03-01

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the Gene Ontology, two complementary approaches have emerged where the similarity between two genes or gene products is obtained by comparing Gene Ontology (GO) annotations associated with the genes or gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene subontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene subontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy, and demonstrate that further improvements can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  4. Cross-Ontological Analytics: Combining Associative and Hierarchical Relations in the Gene Ontologies to Assess Gene Product Similarity

    SciTech Connect

    Posse, Christian; Sanfilippo, Antonio P.; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.

    2006-05-28

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the gene ontologies, two complementary approaches have emerged where the similarity between two genes/gene products is obtained by comparing gene ontology (GO) annotations associated with the gene/gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene ontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene ontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy.

  5. Function of the DISC1 Gene

    NSDL National Science Digital Library

    2009-04-14

    As a result of the human genome project, we now know largely where our genes are, and what structure they have. The search to uncover each gene's function, on the other hand, is only in its infancy. Functional genomics is an area of research dedicated to studying what protein is produced by a gene, and what happens in the body when it is activated. Understanding gene function is the next major hurdle in genomic research, which holds the key to developing revolutionary therapeutics.

  6. Relation between severity of coronary artery disease, left ventricular function, and myocardial infarction, and influence of the ACE I\\/D gene polymorphism

    Microsoft Academic Search

    François Ledru; Didier Blanchard; Salvatore Battaglia; Xavier Jeunemaitre; Dominique Courbon; Louis Guize; Jean-Léon Guermonprez; Pierre Ducimetičre; Benoit Diébold

    1998-01-01

    Left ventricular (LV) systolic function is partly determined by severity of coronary artery disease and is improved by angiotensin-converting enzyme (ACE) inhibition, at least in post-infarct patients. Because the ACE insertion\\/deletion (I\\/D) gene polymorphism is associated with circulating and tissue ACE activity, we sought to evaluate the role of this genetic variant on LV function in patients studied with coronary

  7. Mouse Genetics: Determining gene function

    E-print Network

    Goldschmidt, Christina

    mutagenesis Phenotype Driven Gene Driven · Gene traps · Gene targeting · Gene driven ENU · RNAi EUCOMM, Europe of offspring for transgenic DNA and expression in tissue X Construction of transgene driven by promoter X · Gene driven ENU · RNAi EUCOMM, Europe European Conditional Mouse Mutagenesis KOMP, US Knock-out Mouse

  8. Gene polymorphisms associated with functional dyspepsia

    PubMed Central

    Kourikou, Anastasia; Karamanolis, George P; Dimitriadis, George D; Triantafyllou, Konstantinos

    2015-01-01

    Functional dyspepsia (FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22PHOX, Toll like receptor 2, SCN10A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD. PMID:26167069

  9. In vivo effects of LCO soluble fraction on immune-related functions and gene transcription in the Pacific oyster, Crassostrea gigas (Thunberg).

    PubMed

    Bado-Nilles, Anne; Renault, Tristan; Faury, Nicole; Le Floch, Stéphane; Quentel, Claire; Auffret, Michel; Thomas-Guyon, Hélčne

    2010-05-01

    The effects of a soluble fraction of light cycle oil (LCO) on haemocyte parameters, phenoloxidase (PO) activity and mRNA expression of immune-related genes, in the Pacific oyster, Crassostrea gigas, were tested after seven days of exposure and two weeks of recovery period. Five polycyclic aromatic hydrocarbons (PAHs) out of ten detected in tank water had bioaccumulated at the end of the contamination period. The concentration of PAHs in oyster tissues decreased during the recovery period and 14 days after the exposure, 69% of bioaccumulated PAHs were detected in contaminated oysters. The exposure induced severe oyster mortality (21%), external and internal green colouration of the shell and a significant decrease of PO activity. The mRNA expression of several genes was altered. As a conclusion, a modulation of immune-related parameters was demonstrated using three different approaches, namely cellular (flow cytometry), biochemical (spectrophotometry) and genomics (gene transcription) in oysters after contact with soluble fraction of LCO. PMID:19800699

  10. Towards integrative gene functional similarity measurement

    PubMed Central

    2014-01-01

    Background In Gene Ontology, the "Molecular Function" (MF) categorization is a widely used knowledge framework for gene function comparison and prediction. Its structure and annotation provide a convenient way to compare gene functional similarities at the molecular level. The existing gene similarity measures, however, solely rely on one or few aspects of MF without utilizing all the rich information available including structure, annotation, common terms, lowest common parents. Results We introduce a rank-based gene semantic similarity measure called InteGO by synergistically integrating the state-of-the-art gene-to-gene similarity measures. By integrating three GO based seed measures, InteGO significantly improves the performance by about two-fold in all the three species studied (yeast, Arabidopsis and human). Conclusions InteGO is a systematic and novel method to study gene functional associations. The software and description are available at http://www.msu.edu/~jinchen/InteGO. PMID:24564710

  11. A Protein Required for RNA Processing and Splicing in Neurospora Mitochondria is Related to Gene Products Involved in Cell Cycle Protein Phosphatase Functions

    Microsoft Academic Search

    Beatrice Turcq; Katherine F. Dobinson; Nobufusa Serizawa; Alan M. Lambowitz

    1992-01-01

    The Neurospora crassa cyt-4 mutants have pleiotropic defects in mitochondrial RNA splicing, 5' and 3' end processing, and RNA turnover. Here, we show that the cyt-4^+ gene encodes a 120-kDa protein with significant similarity to the SSD1\\/SRK1 protein of Saccharomyces cerevisiae and the DIS3 protein of Schizosaccharomyces pombe, which have been implicated in protein phosphatase functions that regulate cell cycle

  12. Relation between severity of coronary artery disease, left ventricular function and myocardial infarction, and influence of the ACE I/D gene polymorphism.

    PubMed

    Ledru, F; Blanchard, D; Battaglia, S; Jeunemaitre, X; Courbon, D; Guize, L; Guermonprez, J L; Ducimetičre, P; Diébold, B

    1998-07-15

    Left ventricular (LV) systolic function is partly determined by severity of coronary artery disease and is improved by angiotensin-converting enzyme (ACE) inhibition, at least in post-infarct patients. Because the ACE insertion/deletion (I/D) gene polymorphism is associated with circulating and tissue ACE activity, we sought to evaluate the role of this genetic variant on LV function in patients studied with coronary angiography, taking into account coronary vessel anatomy and history of infarction. Coronary artery disease extent scores, coronary artery patency, and LV ejection fraction were assessed in 400 consecutive Caucasian patients referred for established or suspected ischemic heart disease. A previous infarction had occurred in 141 patients an average of 3.7 years before the study. The ACE DD genotype, compared with the ACE ID/II genotype, was associated with a 2.7% higher ejection fraction in noninfarct patients (p = 0.047) but a 5.0% lower ejection fraction in post-infarct patients (p = 0.047). An interaction effect between the ACE I/D gene polymorphism, the infarction status, and LV ejection fraction was observed in the whole population (p = 0.003), in patients with no disease and 1-, 2-, and 3-vessel diseases (p = 0.03 and p = 0.06, respectively), and in those with chronically occluded coronary vessels (p = 0.02). The influence of the ACE I/D gene polymorphism on LV function is modulated by infarction status and coronary anatomy. PMID:9678285

  13. A pharmacologically validated, high-capacity, functional thallium flux assay for the human Ether-ŕ-go-go related gene potassium channel.

    PubMed

    Schmalhofer, William A; Swensen, Andrew M; Thomas, Brande S; Felix, John P; Haedo, Rodolfo J; Solly, Kelli; Kiss, Laszlo; Kaczorowski, Gregory J; Garcia, Maria L

    2010-12-01

    The voltage-gated potassium channel, human Ether-ŕ-go-go related gene (hERG), represents the molecular component of IKr, one of the potassium currents involved in cardiac action potential repolarization. Inhibition of IKr increases the duration of the ventricular action potential, reflected as a prolongation of the QT interval in the electrocardiogram, and increases the risk for potentially fatal ventricular arrhythmias. Because hERG is an appropriate surrogate for IKr, hERG assays that can identify potential safety liabilities of compounds during lead identification and optimization have been implemented. Although the gold standard for hERG evaluation is electrophysiology, this technique, even with the medium capacity, automated instruments that are currently available, does not meet the throughput demands for supporting typical medicinal chemistry efforts in the pharmaceutical environment. Assays that could provide reliable molecular pharmacology data, while operating in high capacity mode, are therefore desirable. In the present study, we describe a high-capacity, 384- and 1,536-well plate, functional thallium flux assay for the hERG channel that fulfills these criteria. This assay was optimized and validated using different structural classes of hERG inhibitors. An excellent correlation was found between the potency of these agents in the thallium flux assay and in electrophysiological recordings of channel activity using the QPatch automated patch platform. Extension of this study to include 991 medicinal chemistry compounds from different internal drug development programs indicated that the thallium flux assay was a good predictor of in vitro hERG activity. These data suggest that the hERG thallium flux assay can play an important role in supporting drug development efforts. PMID:21158686

  14. Functional characterization of ether-a-go-go-related gene potassium channels in midbrain dopamine neurons: implications for a role in depolarization block

    PubMed Central

    Ji, Huifang; Tucker, Kristal R.; Putzier, Ilva; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.; Shepard, Paul D.

    2014-01-01

    Bursting activity by midbrain dopamine neurons reflects the complex interplay between their intrinsic pacemaker activity and synaptic inputs. Although the precise mechanism responsible for the generation and modulation of bursting in vivo has yet to be established, several ion channels have been implicated in the process. Previous studies with nonselective blockers suggested that ether-a-go-go-related gene (ERG) K+ channels are functionally significant. Here, electrophysiology with selective chemical and peptide ERG channel blockers (E-4031 and rBeKm-1) and computational methods were used to define the contribution made by ERG channels to the firing properties of midbrain dopamine neurons in vivo and in vitro. Selective ERG channel blockade increased the frequency of spontaneous activity as well as the response to depolarizing current pulses without altering spike frequency adaptation. ERG channel block also accelerated entry into depolarization inactivation during bursts elicited by virtual NMDA receptors generated with the dynamic clamp, and significantly prolonged the duration of the sustained depolarization inactivation that followed pharmacologically evoked bursts. In vivo, somatic ERG blockade was associated with an increase in bursting activity attributed to a reduction in doublet firing. Taken together, these results show that dopamine neuron ERG K+ channels play a prominent role in limiting excitability and in minimizing depolarization inactivation. As the therapeutic actions of antipsychotic drugs are associated with depolarization inactivation of dopamine neurons and blockade of cardiac ERG channels is a prominent side effect of these drugs, ERG channels in the central nervous system may represent a novel target for antipsychotic drug development. PMID:22780096

  15. Combining evidence, biomedical literature and statistical dependence: new insights for functional annotation of gene sets

    Microsoft Academic Search

    Marc Aubry; Annabelle Monnier; Celine Chicault; Marie De Tayrac; Marie-dominique Galibert; Anita Burgun; Jean Mosser

    2006-01-01

    BACKGROUND: Large-scale genomic studies based on transcriptome technologies provide clusters of genes that need to be functionally annotated. The Gene Ontology (GO) implements a controlled vocabulary organised into three hierarchies: cellular components, molecular functions and biological processes. This terminology allows a coherent and consistent description of the knowledge about gene functions. The GO terms related to genes come primarily from

  16. Discovery of Tumor Suppressor Gene Function.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.

    1995-01-01

    This is an update of a 1991 review on tumor suppressor genes written at a time when understanding of how the genes work was limited. A recent major breakthrough in the understanding of the function of tumor suppressor genes is discussed. (LZ)

  17. Transcriptional gene silencing as a tool for uncovering gene function in maize.

    PubMed

    Cigan, A Mark; Unger-Wallace, Erica; Haug-Collet, Kristin

    2005-09-01

    Transcriptional gene silencing has broad applications for studying gene function in planta. In maize, a large number of genes have been identified as tassel-preferred in their expression pattern, both by traditional genetic methods and by recent high-throughput expression profiling platforms. Approaches using RNA suppression may provide a rapid alternative means to identify genes directly related to pollen development in maize. The male fertility gene Ms45 and several anther-expressed genes of unknown function were used to evaluate the efficacy of generating male-sterile plants by transcriptional gene silencing. A high frequency of male-sterile plants was obtained by constitutively expressing inverted repeats (IR) of the Ms45 promoter. These sterile plants lacked MS45 mRNA due to transcriptional inactivity of the target promoter. Moreover, fertility was restored to these promoter IR-containing plants by expressing the Ms45 coding region using heterologous promoters. Transcriptional silencing of other anther-expressed genes also significantly affected male fertility phenotypes and led to increased methylation of the target promoter DNA sequences. These studies provide evidence of disruption of gene activity in monocots by RNA interference constructs directed against either native or transformed promoter regions. This approach not only enables the correlation of monocot anther-expressed genes with functions that are important for reproduction in maize, but may also provide a tool for studying gene function and identifying regulatory components unique to transcriptional gene control. PMID:16146530

  18. In Silico Functional Profiling of Individual Prostate Cancer Tumors: Many Genes, Few Functions

    PubMed Central

    Gorlov, Ivan P.; Byun, Jinyoung; Logothetis, Christopher J.

    2013-01-01

    Background Identification of genes that are differently expressed is a common approach used to analyze genetic mechanisms underlying cancer development. However, recent study results suggest that many such genes relate to a small number of biological functions. We hypothesized that analysis of these functions provides a better understanding of tumor biology than does actual identification of these genes does. Materials and Methods We re-analyzed publicly available gene expression data for paired samples of prostate tumor and adjacent normal tissue from the same patients to identify genes differently expressed in individual tumors and then used them to identify the functions. Results We found significant interindividual variation in the type and the number of functions. After adjusting for redundancy and nonspecificity of the functional terms, we identified seven functions. Several of them showed a strong association with clinical traits, e.g. age at diagnosis, preoperative prostate-specific antigen concentration, Gleason grade, and biochemical recurrence. Actin cytoskeleton was the function most frequently associated with clinical traits. Of note, the association between function and clinical traits was much stronger than that between the genes differently expressed and those traits. Conclusion Different prostate tumors differ in their functional profiles. Functions of differently expressed genes are strongly associated with clinical traits. This suggests that analysis of functions of differently expressed genes may provide a better description of tumor biology than does analysis of the respective genes. PMID:22593245

  19. From single-SNP to wide-locus: genome-wide association studies identifying functionally related genes and intragenic regions in small sample studies

    PubMed Central

    Wittkowski, Knut M; Sonakya, Vikas; Song, Tingting; Seybold, Martin P; Keddache, Mehdi; Durner, Martina

    2013-01-01

    Background Genome-wide association studies (GWAS) have had limited success when applied to complex diseases. Analyzing SNPs individually requires several large studies to integrate the often divergent results. In the presence of epistasis, multivariate approaches based on the linear model (including stepwise logistic regression) often have low sensitivity and generate an abundance of artifacts. Methods Recent advances in distributed and parallel processing spurred methodological advances in nonparametric statistics. U-statistics for structured multivariate data (?Stat) are not confounded by unrealistic assumptions (e.g., linearity, independence). Results By incorporating knowledge about relationships between SNPs, ?GWAS (GWAS based on ?Stat) can identify clusters of genes around biologically relevant pathways and pinpoint functionally relevant regions within these genes. Conclusion With this computational biostatistics approach increasing power and guarding against artifacts, personalized medicine and comparative effectiveness will advance while subgroup analyses of Phase III trials can now suggest risk factors for ad verse events and novel directions for drug development. PMID:23438886

  20. Gene Transfer Strategies for Augmenting Cardiac Function

    Microsoft Academic Search

    Karsten Peppel; Walter J Koch; Robert J Lefkowitz

    1997-01-01

    Recent transgenic as well as gene-targeted animal models have greatly increased our understanding of the molecular mechanisms of normal and compromised heart function. These studies have raised the possibility of using somatic gene transfer as a means for improving cardiac function. DNA transfer to a significant portion of the myocardium has thus far been difficult to accomplish. This review describes

  1. Integrating Gene Ontology and Blast to predict gene functions

    Microsoft Academic Search

    WANG Cheng-gang; MO Zhi-hong

    2007-01-01

    A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by

  2. Human Intellectual Disability Genes Form Conserved Functional Modules in Drosophila

    PubMed Central

    Oortveld, Merel A. W.; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G.; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A.; Schenck, Annette

    2013-01-01

    Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules. PMID:24204314

  3. Differential Gene Expression in Age-Related Macular Degeneration.

    PubMed

    Morgan, Denise J; DeAngelis, Margaret M

    2014-10-23

    Gene expression is the first step in ascribing function between an associated gene and disease. Understanding how variation in a gene influences expression, particularly in tissues affected by the disease, may help elucidate what influences the phenotypic outcome of that disease. Previous studies of the genetics of age-related macular degeneration (AMD) have identified several risk factors, but have not yet bridged the gap between gene association and identifying a specific mechanism or function that is involved in the pathogenesis of AMD. Advances in genomic technologies, such as RNA sequencing (RNA-seq), single cell RNA-seq, bilsulfite sequencing, and/or whole genome methylation, will be powerful tools for identifying genes/pathways that are differentially expressed in those with AMD versus those without AMD. These technologies should advance the field of AMD research so that appropriate preventive and therapeutic targets can be developed. PMID:25342062

  4. Neofunctionalization of Duplicated Tic40 Genes Caused a Gain-of-Function Variation Related to Male Fertility in Brassica oleracea Lineages1[W][OPEN

    PubMed Central

    Dun, Xiaoling; Shen, Wenhao; Hu, Kaining; Zhou, Zhengfu; Xia, Shengqian; Wen, Jing; Yi, Bin; Shen, Jinxiong; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Lagercrantz, Ulf

    2014-01-01

    Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp. homologs to Tic40 (for translocon at the inner membrane of chloroplasts with 40 kDa). Four Tic40 loci were identified in allotetraploid Brassica napus and two loci in each of three basic diploid Brassica spp. Although these Tic40 homologs share high sequence identities and similar expression patterns, they exhibit altered functional features. Complementation assays conducted on Arabidopsis thaliana tic40 and the B. napus male-sterile line 7365A suggested that all Brassica spp. Tic40 homologs retain an ancestral function similar to that of AtTic40, whereas BolC9.Tic40 in Brassica oleracea and its ortholog in B. napus, BnaC9.Tic40, in addition, evolved a novel function that can rescue the fertility of 7365A. A homologous chromosomal rearrangement placed bnac9.tic40 originating from the A genome (BraA10.Tic40) as an allele of BnaC9.Tic40 in the C genome, resulting in phenotypic variation for male sterility in the B. napus near-isogenic two-type line 7365AB. Assessment of the complementation activity of chimeric B. napus Tic40 domain-swapping constructs in 7365A suggested that amino acid replacements in the carboxyl terminus of BnaC9.Tic40 cause this functional divergence. The distribution of these amino acid replacements in 59 diverse Brassica spp. accessions demonstrated that the neofunctionalization of Tic40 is restricted to B. oleracea and its derivatives and thus occurred after the divergence of the Brassica spp. A, B, and C genomes. PMID:25185122

  5. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean) Cattle

    PubMed Central

    Lim, Dajeong; Lee, Seung-Hwan; Kim, Nam-Kuk; Cho, Yong-Min; Chai, Han-Ha; Seong, Hwan-Hoo; Kim, Heebal

    2013-01-01

    Marbling (intramuscular fat) is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the ‘marbling score’ trait and systemically analyzed the network topology in Hanwoo (Korean cattle). As a result, we determined 3 modules (gene groups) that showed statistically significant results for marbling score. In particular, one module (denoted as red) has a statistically significant result for marbling score (p = 0.008) and intramuscular fat (p = 0.02) and water capacity (p = 0.006). From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA) have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait. PMID:25049701

  6. RNA Interference for Wheat Functional Gene Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RNA interference (RNAi) refers to a common mechanism of RNA-based post-transcriptional gene silencing in eukaryotic cells. In model plant species such as Arabidopsis and rice, RNAi has been routinely used to characterize gene function and to engineer novel phenotypes. In polyploid species, this appr...

  7. Differentially-expressed genes in rice infected by Xanthomonas oryzae pv. oryzae relative to a flagellin-deficient mutant reveal potential functions of flagellin in host–pathogen interactions

    PubMed Central

    2014-01-01

    Background Plants have evolved a sensitive defense response system that detects and recognizes various pathogen-associated molecular patterns (PAMPs) (e.g. flagellin) and induces immune responses to protect against invasion. Transcriptional responses in rice to PAMPs produced by Xanthomonas oryzae pv. oryzae (Xoo), the bacterial blight pathogen, have not yet been defined. Results We characterized transcriptomic responses in rice inoculated with the wildtype (WT) Xoo and flagellin-deficient mutant ?fliC through RNA-seq analysis. Digital gene expression (DGE) analysis based on Solexa/Illumina sequencing was used to investigate transcriptomic responses in 30 day-old seedlings of rice (Oryza sativa L. cv. Nipponbare). 1,680 genes were differentially-expressed (DEGs) in rice inoculated with WT relative to ?fliC; among which 1,159 genes were up-regulated and 521 were down-regulated. Expression patterns of 12 randomly-selected DEGs assayed by quantitative real time PCR (qRT-PCR) were similar to those detected by DGE analyses, confirming reliability of the DGE data. Functional annotations revealed the up-regulated DEGs are involved in the cell wall, lipid and secondary metabolism, defense response and hormone signaling, whereas the down-regulated ones are associated with photosynthesis. Moreover, 57 and 21 specifically expressed genes were found after WT and ?fliC treatments, respectively. Conclusions DEGs were identified in rice inoculated with WT Xoo relative to ?fliC. These genes were predicted to function in multiple biological processes, including the defense response and photosynthesis in rice. This study provided additional insights into molecular basis of rice response to bacterial infection and revealed potential functions of bacterial flagellin in the rice-Xoo interactions. PMID:25187853

  8. Gene networks in Drosophila melanogaster: integrating experimental data to predict gene function

    PubMed Central

    Costello, James C; Dalkilic, Mehmet M; Beason, Scott M; Gehlhausen, Jeff R; Patwardhan, Rupali; Middha, Sumit; Eads, Brian D; Andrews, Justen R

    2009-01-01

    Background Discovering the functions of all genes is a central goal of contemporary biomedical research. Despite considerable effort, we are still far from achieving this goal in any metazoan organism. Collectively, the growing body of high-throughput functional genomics data provides evidence of gene function, but remains difficult to interpret. Results We constructed the first network of functional relationships for Drosophila melanogaster by integrating most of the available, comprehensive sets of genetic interaction, protein-protein interaction, and microarray expression data. The complete integrated network covers 85% of the currently known genes, which we refined to a high confidence network that includes 20,000 functional relationships among 5,021 genes. An analysis of the network revealed a remarkable concordance with prior knowledge. Using the network, we were able to infer a set of high-confidence Gene Ontology biological process annotations on 483 of the roughly 5,000 previously unannotated genes. We also show that this approach is a means of inferring annotations on a class of genes that cannot be annotated based solely on sequence similarity. Lastly, we demonstrate the utility of the network through reanalyzing gene expression data to both discover clusters of coregulated genes and compile a list of candidate genes related to specific biological processes. Conclusions Here we present the the first genome-wide functional gene network in D. melanogaster. The network enables the exploration, mining, and reanalysis of experimental data, as well as the interpretation of new data. The inferred annotations provide testable hypotheses of previously uncharacterized genes. PMID:19758432

  9. A protein required for RNA processing and splicing in Neurospora mitochondria is related to gene products involved in cell cycle protein phosphatase functions.

    PubMed

    Turcq, B; Dobinson, K F; Serizawa, N; Lambowitz, A M

    1992-03-01

    The Neurospora crassa cyt-4 mutants have pleiotropic defects in mitochondrial RNA splicing, 5' and 3' end processing, and RNA turnover. Here, we show that the cyt-4+ gene encodes a 120-kDa protein with significant similarity to the SSD1/SRK1 protein of Saccharomyces cerevisiae and the DIS3 protein of Schizosaccharomyces pombe, which have been implicated in protein phosphatase functions that regulate cell cycle and mitotic chromosome segregation. The CYT-4 protein is present in mitochondria and is truncated or deficient in two cyt-4 mutants. Assuming that the CYT-4 protein functions in a manner similar to the SSD1/SRK1 and DIS3 proteins, we infer that the mitochondrial RNA splicing and processing reactions defective in the cyt-4 mutants are regulated by protein phosphorylation and that the defects in the cyt-4 mutants result from failure to normally regulate this process. Our results provide evidence that RNA splicing and processing reactions may be regulated by protein phosphorylation. PMID:1311848

  10. Gene function prediction with gene interaction networks: a context graph kernel approach

    Microsoft Academic Search

    Xin Li; Hsinchun Chen; Jiexun Li; Zhu Zhang

    2010-01-01

    Predicting gene functions is a challenge for biologists in the postgenomic era. Interactions among genes and their products compose networks that can be used to infer gene functions. Most previous studies adopt a linkage assumption, i.e., they assume that gene interactions indicate functional similarities between connected genes. In this study, we propose to use a gene's context graph, i.e., the

  11. Empirical evidence of the applicability of functional clustering through gene expression classification.

    PubMed

    Krejník, Milos; Kléma, Jirí

    2012-01-01

    The availability of a great range of prior biological knowledge about the roles and functions of genes and gene-gene interactions allows us to simplify the analysis of gene expression data to make it more robust, compact, and interpretable. Here, we objectively analyze the applicability of functional clustering for the identification of groups of functionally related genes. The analysis is performed in terms of gene expression classification and uses predictive accuracy as an unbiased performance measure. Features of biological samples that originally corresponded to genes are replaced by features that correspond to the centroids of the gene clusters and are then used for classifier learning. Using 10 benchmark data sets, we demonstrate that functional clustering significantly outperforms random clustering without biological relevance. We also show that functional clustering performs comparably to gene expression clustering, which groups genes according to the similarity of their expression profiles. Finally, the suitability of functional clustering as a feature extraction technique is evaluated and discussed. PMID:22291159

  12. HLA Immune Function Genes in Autism

    PubMed Central

    Torres, Anthony R.; Westover, Jonna B.; Rosenspire, Allen J.

    2012-01-01

    The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects. PMID:22928105

  13. Analysis of intervertebral disc-related genes.

    PubMed

    Wu, D J; Chen, K; Wei, X Z; Ni, H J; Yu, S Z; Zhu, X D; Li, M

    2014-01-01

    Intervertebral disk disease is a common clinical disorder manifested by pain, ataxia, paresis, motor paralysis, and sensorimotor paralysis. The clinical features, diagnosis, and treatment of cervical and thoracolumbar disk disease have been unclear until now. In this study, some differentially expressed genes were identified, and a network was constructed based on these genes. Through the statistical analysis of nodes and the contrast of 2 more connectivity nodes, it was found that the nodes in the network are in an important position and play key roles. Several of these genes, including MAP2K6, MAP2K3, and MAPK14, belong to the MAP kinase family, and several genes, including RHOBTB2, RHOQ, and RHOH, belong to the RHO family. Therefore, we hypothesize that the development of intervertebral disk disease is related to MAP and RHO family proteins. PMID:24737428

  14. Fine-scale mergers of chloroplast and mitochondrial genes create functional, transcompartmentally chimeric mitochondrial genes

    PubMed Central

    Hao, Weilong; Palmer, Jeffrey D.

    2009-01-01

    The mitochondrial genomes of flowering plants possess a promiscuous proclivity for taking up sequences from the chloroplast genome. All characterized chloroplast integrants exist apart from native mitochondrial genes, and only a few, involving chloroplast tRNA genes that have functionally supplanted their mitochondrial counterparts, appear to be of functional consequence. We developed a novel computational approach to search for homologous recombination (gene conversion) in a large number of sequences and applied it to 22 mitochondrial and chloroplast gene pairs, which last shared common ancestry some 2 billion years ago. We found evidence of recurrent conversion of short patches of mitochondrial genes by chloroplast homologs during angiosperm evolution, but no evidence of gene conversion in the opposite direction. All 9 putative conversion events involve the atp1/atpA gene encoding the alpha subunit of ATP synthase, which is unusually well conserved between the 2 organelles and the only shared gene that is widely sequenced across plant mitochondria. Moreover, all conversions were limited to the 2 regions of greatest nucleotide and amino acid conservation of atp1/atpA. These observations probably reflect constraints operating on both the occurrence and fixation of recombination between ancient homologs. These findings indicate that recombination between anciently related sequences is more frequent than previously appreciated and creates functional mitochondrial genes of chimeric origin. These results also have implications for the widespread use of mitochondrial atp1 in phylogeny reconstruction. PMID:19805364

  15. Convergence in pigmentation at multiple levels: mutations, genes and function

    PubMed Central

    Manceau, Marie; Domingues, Vera S.; Linnen, Catherine R.; Rosenblum, Erica Bree; Hoekstra, Hopi E.

    2010-01-01

    Convergence—the independent evolution of the same trait by two or more taxa—has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels. PMID:20643733

  16. Integrator: surprisingly diverse functions in gene expression.

    PubMed

    Baillat, David; Wagner, Eric J

    2015-05-01

    The discovery of the metazoan-specific Integrator (INT) complex represented a breakthrough in our understanding of noncoding U-rich small nuclear RNA (UsnRNA) maturation and has triggered a reevaluation of their biosynthesis mechanism. In the decade since, significant progress has been made in understanding the details of its recruitment, specificity, and assembly. While some discrepancies remain on how it interacts with the C-terminal domain (CTD) of the RNA polymerase II (RNAPII) and the details of its recruitment to UsnRNA genes, preliminary models have emerged. Recent provocative studies now implicate INT in the regulation of protein-coding gene transcription initiation and RNAPII pause-release, thereby broadening the scope of INT functions in gene expression regulation. We discuss the implications of these findings while putting them into the context of what is understood about INT function at UsnRNA genes. PMID:25882383

  17. Genes for Chlorogenate and Hydroxycinnamate Catabolism (hca) Are Linked to Functionally Related Genes in the dca-pca-qui-pob-hca Chromosomal Cluster of Acinetobacter sp. Strain ADP1

    PubMed Central

    Smith, Michael A.; Weaver, Valerie B.; Young, David M.; Ornston, L. Nicholas

    2003-01-01

    Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca-qui-pob chromosomal cluster. In an appropriate genetic background, it was possible to select for an Acinetobacter strain that had lost the ability to grow with caffeate, a commonly occurring hydroxycinnamate. The newly identified mutation was shown to be a deletion in a gene designated hcaC and encoding a ligase required for conversion of commonly occurring hydroxycinnamates (caffeate, ferulate, coumarate, and 3,4-dihydroxyphenylpropionate) to thioesters. Linkage analysis showed that hcaC is linked to pobA. Downstream from hcaC and transcribed in the direction opposite the direction of pobA transcription are open reading frames designated hcaDEFG. Functions of these genes were inferred from sequence comparisons and from the properties of knockout mutants. HcaD corresponded to an acyl coenzyme A (acyl-CoA) dehydrogenase required for conversion of 3,4-dihydroxyphenylpropionyl-CoA to caffeoyl-CoA. HcaE appears to encode a member of a family of outer membrane proteins known as porins. Knockout mutations in hcaF confer no discernible phenotype. Knockout mutations in hcaG indicate that this gene encodes a membrane-associated esterase that hydrolyzes chlorogenate to quinate, which is metabolized in the periplasm, and caffeate, which is metabolized by intracellular enzymes. The chromosomal location of hcaG, between hcaC (required for growth with caffeate) and quiA (required for growth with quinate), provided the essential clue that led to the genetic test of HcaG as the esterase that produces caffeate and quinate from chlorogenate. Thus, in this study, organization within what is now established as the dca-pca-qui-pob-hca chromosomal cluster provided essential information about the function of genes in the environment. PMID:12514037

  18. Studying Functions of All Yeast Genes Simultaneously

    NASA Technical Reports Server (NTRS)

    Stolc, Viktor; Eason, Robert G.; Poumand, Nader; Herman, Zelek S.; Davis, Ronald W.; Anthony Kevin; Jejelowo, Olufisayo

    2006-01-01

    A method of studying the functions of all the genes of a given species of microorganism simultaneously has been developed in experiments on Saccharomyces cerevisiae (commonly known as baker's or brewer's yeast). It is already known that many yeast genes perform functions similar to those of corresponding human genes; therefore, by facilitating understanding of yeast genes, the method may ultimately also contribute to the knowledge needed to treat some diseases in humans. Because of the complexity of the method and the highly specialized nature of the underlying knowledge, it is possible to give only a brief and sketchy summary here. The method involves the use of unique synthetic deoxyribonucleic acid (DNA) sequences that are denoted as DNA bar codes because of their utility as molecular labels. The method also involves the disruption of gene functions through deletion of genes. Saccharomyces cerevisiae is a particularly powerful experimental system in that multiple deletion strains easily can be pooled for parallel growth assays. Individual deletion strains recently have been created for 5,918 open reading frames, representing nearly all of the estimated 6,000 genetic loci of Saccharomyces cerevisiae. Tagging of each deletion strain with one or two unique 20-nucleotide sequences enables identification of genes affected by specific growth conditions, without prior knowledge of gene functions. Hybridization of bar-code DNA to oligonucleotide arrays can be used to measure the growth rate of each strain over several cell-division generations. The growth rate thus measured serves as an index of the fitness of the strain.

  19. RNA interference for wheat functional gene analysis

    Microsoft Academic Search

    Daolin Fu; Cristobal Uauy; Ann Blechl; Jorge Dubcovsky

    2007-01-01

    RNA interference (RNAi) refers to a common mechanism of RNA-based post-transcriptional gene silencing in eukaryotic cells.\\u000a In model plant species such as Arabidopsis and rice, RNAi has been routinely used to characterize gene function and to engineer novel phenotypes. In polyploid species,\\u000a this approach is in its early stages, but has great potential since multiple homoeologous copies can be simultaneously

  20. Annotation of gene function in citrus using gene expression information and co-expression networks

    PubMed Central

    2014-01-01

    Background The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world’s most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a “guilt-by-association” principle whereby genes encoding proteins involved in similar and/or related biological processes may exhibit similar expression patterns across diverse sets of experimental conditions. While bioinformatics resources such as GCN analysis are widely available for efficient gene function prediction in model plant species including Arabidopsis, soybean and rice, in citrus these tools are not yet developed. Results We have constructed a comprehensive GCN for citrus inferred from 297 publicly available Affymetrix Genechip Citrus Genome microarray datasets, providing gene co-expression relationships at a genome-wide scale (33,000 transcripts). The comprehensive citrus GCN consists of a global GCN (condition-independent) and four condition-dependent GCNs that survey the sweet orange species only, all citrus fruit tissues, all citrus leaf tissues, or stress-exposed plants. All of these GCNs are clustered using genome-wide, gene-centric (guide) and graph clustering algorithms for flexibility of gene function prediction. For each putative cluster, gene ontology (GO) enrichment and gene expression specificity analyses were performed to enhance gene function, expression and regulation pattern prediction. The guide-gene approach was used to infer novel roles of genes involved in disease susceptibility and vitamin C metabolism, and graph-clustering approaches were used to investigate isoprenoid/phenylpropanoid metabolism in citrus peel, and citric acid catabolism via the GABA shunt in citrus fruit. Conclusions Integration of citrus gene co-expression networks, functional enrichment analysis and gene expression information provide opportunities to infer gene function in citrus. We present a publicly accessible tool, Network Inference for Citrus Co-Expression (NICCE, http://citrus.adelaide.edu.au/nicce/home.aspx), for the gene co-expression analysis in citrus. PMID:25023870

  1. Gene Transfers Between Distantly Related Organisms

    NASA Technical Reports Server (NTRS)

    Doolittle, Russell F.

    2003-01-01

    With the completion of numerous microbial genome sequences, reports of individual gene transfers between distantly related prokaryotes have become commonplace. On the other hand, transfers between prokaryotes and eukaryotes still excite the imagination. Many of these claims may be premature, but some are certainly valid. In this chapter, the kinds of supporting data needed to propose transfers between distantly related organisms and cite some interesting examples are considered.

  2. High presence/absence gene variability in defense-related gene clusters of Cucumis melo

    PubMed Central

    2013-01-01

    Background Changes in the copy number of DNA sequences are one of the main mechanisms generating genome variability in eukaryotes. These changes are often related to phenotypic effects such as genetic disorders or novel pathogen resistance. The increasing availability of genome sequences through the application of next-generation massive sequencing technologies has allowed the study of genomic polymorphisms at both the interspecific and intraspecific levels, thus helping to understand how species adapt to changing environments through genome variability. Results Data on gene presence/absence variation (PAV) in melon was obtained by resequencing a cultivated accession and an old-relative melon variety, and using previously obtained resequencing data from three other melon cultivars, among them DHL92, on which the current draft melon genome sequence is based. A total of 1,697 PAV events were detected, involving 4.4% of the predicted melon gene complement. In all, an average 1.5% of genes were absent from each analyzed cultivar as compared to the DHL92 reference genome. The most populated functional category among the 304 PAV genes of known function was that of stress response proteins (30% of all classified PAVs). Our results suggest that genes from multi-copy families are five times more likely to be affected by PAV than singleton genes. Also, the chance of genes present in the genome in tandem arrays being affected by PAV is double that of isolated genes, with PAV genes tending to be in longer clusters. The highest concentration of PAV events detected in the melon genome was found in a 1.1 Mb region of linkage group V, which also shows the highest density of melon stress-response genes. In particular, this region contains the longest continuous gene-containing PAV sequence so far identified in melon. Conclusions The first genome-wide report of PAV variation among several melon cultivars is presented here. Multi-copy and clustered genes, especially those with putative stress-response functions, were found to be particularly affected by PAV polymorphisms. As cucurbits are known to possess a significantly lower number of defense-related genes compared to other plant species, PAV variation may play an important role in generating new pathogen resistances at the subspecies level. In addition, these results show the limitations of single reference genome sequences as the only basis for characterization and cloning of resistance genes. PMID:24219589

  3. Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism

    PubMed Central

    Poot, Martin; Hochstenbach, Ron; Spierenburg, Henk A.; Vorstman, Jacob A. S.; van Daalen, Emma; de Jonge, Maretha V.; Verbeek, Nienke E.; Brilstra, Eva H.; van 't Slot, Ruben; Ophoff, Roel A.; van Es, Michael A.; Blauw, Hylke M.; Veldink, Jan H.; Buizer-Voskamp, Jacobine E.; Beemer, Frits A.; van den Berg, Leonard H.; Wijmenga, Cisca; van Amstel, Hans Kristian Ploos; van Engeland, Herman; Burbach, J. Peter H.; Staal, Wouter G.

    2009-01-01

    The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD. PMID:19492091

  4. A search for growth related genes in Kalanchoë blossfeldiana.

    PubMed

    Topp, Sine H; Rasmussen, Sřren K; Mibus, Heiko; Sander, Lilli

    2009-01-01

    Differential display of mRNA from four sets of contrasting phenotypes were carried out in order to identify and isolate genes associated with elongating growth of Kalanchoë blossfeldiana. A total of 17 unique differential expressed cDNA fragments were sequenced and 12 showed homology to genes in other plant species. Three genes were subsequently tested for growth related activity by Virus Induced Gene Silencing (VIGS) in Nicotiana benthamiana. One gene fragment (13C) resulted in plants with significantly reduced growth (N = 20, P = 0.05, one-tailed students t-test) from day 25 after virus infection. Full-length cDNA and genomic DNA sequences were obtained by inverse PCR and thermal asymmetric interlaced (TAIL) PCR and the gene was named KbORF1. The predicted gene is 2244 bp long with three exons of 411 bp in total encoding a protein of 137 amino acid residues with homologs widespread among plants. The protein has no known function, but its expression has been confirmed in a proteomic study of Arabidopsis. Southern blot analysis shows two hybridizing fragments in agreement with the tetraploid nature of K. blossfeldiana. Fragment 13C comprises 446 bp of the gene, and the portion of 13C conferring growth retardation by VIGS is located 10 bp into the second intron indicating a regulatory function of this part of the KbORF1 mRNA. Differential display in combination with VIGS as a screening method proved to be a good functional approach not only to search for genes of interest, but also to isolate expressed genetic regulatory domains. PMID:19819156

  5. Gene Function Prediction Based on the Gene Ontology Hierarchical Structure

    PubMed Central

    Cheng, Liangxi; Lin, Hongfei; Hu, Yuncui; Wang, Jian; Yang, Zhihao

    2014-01-01

    The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship. PMID:25192339

  6. Gene function prediction based on the Gene Ontology hierarchical structure.

    PubMed

    Cheng, Liangxi; Lin, Hongfei; Hu, Yuncui; Wang, Jian; Yang, Zhihao

    2014-01-01

    The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship. PMID:25192339

  7. Identification of Mycoparasitism-Related Genes in Trichoderma atroviride ? † ‡

    PubMed Central

    Reithner, Barbara; Ibarra-Laclette, Enrique; Mach, Robert L.; Herrera-Estrella, Alfredo

    2011-01-01

    A high-throughput sequencing approach was utilized to carry out a comparative transcriptome analysis of Trichoderma atroviride IMI206040 during mycoparasitic interactions with the plant-pathogenic fungus Rhizoctonia solani. In this study, transcript fragments of 7,797 Trichoderma genes were sequenced, 175 of which were host responsive. According to the functional annotation of these genes by KOG (eukaryotic orthologous groups), the most abundant group during direct contact was “metabolism.” Quantitative reverse transcription (RT)-PCR confirmed the differential transcription of 13 genes (including swo1, encoding an expansin-like protein; axe1, coding for an acetyl xylan esterase; and homologs of genes encoding the aspartyl protease papA and a trypsin-like protease, pra1) in the presence of R. solani. An additional relative gene expression analysis of these genes, conducted at different stages of mycoparasitism against Botrytis cinerea and Phytophthora capsici, revealed a synergistic transcription of various genes involved in cell wall degradation. The similarities in expression patterns and the occurrence of regulatory binding sites in the corresponding promoter regions suggest a possible analog regulation of these genes during the mycoparasitism of T. atroviride. Furthermore, a chitin- and distance-dependent induction of pra1 was demonstrated. PMID:21531825

  8. Evolutionary, Comparative and Functional Analyses of the Brassinosteroid Receptor Gene, BRI1, in Wheat and Its Relation to Other Plant Genomes

    PubMed Central

    Navarro, Christopher; Moore, Jerott; Ott, Alina; Baumert, Eric; Mohan, Amita; Gill, Kulvinder S.; Sandhu, Devinder

    2015-01-01

    Brassinosteroids (BRs) are plant hormones, fundamental for the growth and development of plants. A trans-membrane protein receptor kinase, Brassinosteroid-Insensitive 1 (BRI1), is known to interact with BRs and be directly involved in plant development. This study investigates the structural organization of BRI1 orthologs in several taxa, with a specific interest in Triticum aestivum. True orthologs of Arabidopsis thaliana BRI1 (AtBRI1) from seven-plant species showed sequence identity ranging from 54% to 95% at the protein level. All gene sequences lacked introns, leading to speculation that post-transcriptional processing in TaBRI1 is similar to AtBRI1. Based on in silico analysis, a single copy of BRI1 was present in each of the three wheat genomes on the long arm of chromosome 3. Domain structure of BRI1 orthologs among different taxa showed multiple leucine rich repeats (LRRs), an island domain (ID), a juxtamembrane/transmembrane domain (JTMD), a catalytic kinase domain (KD), C and N-Terminal domains. The KD showed the highest level of conservation while the LRRs and JTMD were most variable. Phosphorylation of residues in the juxtamembrane domain, known to be involved in the activation of the KD, is conserved in TaBRI1. While TaBRI1 has well-defined differences in the ID and LRR domains, many residues involved in ligand binding are conserved. The activation loop present in the KD showed 100% conservation in all taxa. Despite residue differences, hydrophobicity was conserved in the BR binding pocket across taxa, suggesting that function may not differ as drastically as residue identity may suggest. Predicted 3D structure of AtBRI1 and TaBRI1 showed a conserved super helical assembly, a feature essential in protein-protein interactions. An unrooted phylogram showed TaBRI1 in the monocot clade to be distinct from that of dicots. New insight in the structure and functions of BRI1 may help in targeting BR pathway for crop improvement. PMID:26020768

  9. Molecular and Functional Characterization of Broccoli EMBRYONIC FLOWER 2 Genes

    PubMed Central

    Chen, Long-Fang O.; Lin, Chun-Hung; Lai, Ying-Mi; Huang, Jia-Yuan; Sung, Zinmay Renee

    2012-01-01

    Polycomb group (PcG) proteins regulate major developmental processes in Arabidopsis. EMBRYONIC FLOWER 2 (EMF2), the VEFS domain-containing PcG gene, regulates diverse genetic pathways and is required for vegetative development and plant survival. Despite widespread EMF2-like sequences in plants, little is known about their function other than in Arabidopsis and rice. To study the role of EMF2 in broccoli (Brassica oleracea var. italica cv. Elegance) development, we identified two broccoli EMF2 (BoEMF2) genes with sequence homology to and a similar gene expression pattern to that in Arabidopsis (AtEMF2). Reducing their expression in broccoli resulted in aberrant phenotypes and gene expression patterns. BoEMF2 regulates genes involved in diverse developmental and stress programs similar to AtEMF2 in Arabidopsis. However, BoEMF2 differs from AtEMF2 in the regulation of flower organ identity, cell proliferation and elongation, and death-related genes, which may explain the distinct phenotypes. The expression of BoEMF2.1 in the Arabidopsis emf2 mutant (Rescued emf2) partially rescued the mutant phenotype and restored the gene expression pattern to that of the wild type. Many EMF2-mediated molecular and developmental functions are conserved in broccoli and Arabidopsis. Furthermore, the restored gene expression pattern in Rescued emf2 provides insights into the molecular basis of PcG-mediated growth and development. PMID:22537758

  10. Gene Ontology and KEGG Enrichment Analyses of Genes Related to Age-Related Macular Degeneration

    PubMed Central

    Zhang, Jian; Xing, ZhiHao; Ma, Mingming; Wang, Ning; Cai, Yu-Dong; Chen, Lei; Xu, Xun

    2014-01-01

    Identifying disease genes is one of the most important topics in biomedicine and may facilitate studies on the mechanisms underlying disease. Age-related macular degeneration (AMD) is a serious eye disease; it typically affects older adults and results in a loss of vision due to retina damage. In this study, we attempt to develop an effective method for distinguishing AMD-related genes. Gene ontology and KEGG enrichment analyses of known AMD-related genes were performed, and a classification system was established. In detail, each gene was encoded into a vector by extracting enrichment scores of the gene set, including it and its direct neighbors in STRING, and gene ontology terms or KEGG pathways. Then certain feature-selection methods, including minimum redundancy maximum relevance and incremental feature selection, were adopted to extract key features for the classification system. As a result, 720 GO terms and 11 KEGG pathways were deemed the most important factors for predicting AMD-related genes. PMID:25165703

  11. A global view of pleiotropy and phenotypically derived gene function in yeast

    Microsoft Academic Search

    Aimée Marie Dudley; Daniel Maarten Janse; Amos Tanay; Ron Shamir; George McDonald Church

    2005-01-01

    Pleiotropy, the ability of a single mutant gene to cause multiple mutant phenotypes, is a relatively common but poorly understood phenomenon in biology. Perhaps the greatest challenge in the analysis of pleiotropic genes is determining whether phenotypes associated with a mutation result from the loss of a single function or of multiple functions encoded by the same gene. Here we

  12. Association of Functional Polymorphisms from Brain-Derived Neurotrophic Factor and Serotonin-Related Genes with Depressive Symptoms after a Medical Stressor in Older Adults

    PubMed Central

    Rawson, Kerri S.; Dixon, David; Nowotny, Petra; Ricci, William M.; Binder, Ellen F.; Rodebaugh, Thomas L.; Wendleton, Leah; Doré, Peter; Lenze, Eric J.

    2015-01-01

    Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val) to methionine (Met) polymorphism in brain-derived neurotrophic factor (BDNF), serotonin 1A receptor (5HT1a-rs6295) polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR) interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531) as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012). BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37). Unlike prior studies of stressful life events, the S? 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006). No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor. PMID:25781924

  13. Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults.

    PubMed

    Rawson, Kerri S; Dixon, David; Nowotny, Petra; Ricci, William M; Binder, Ellen F; Rodebaugh, Thomas L; Wendleton, Leah; Doré, Peter; Lenze, Eric J

    2015-01-01

    Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val) to methionine (Met) polymorphism in brain-derived neurotrophic factor (BDNF), serotonin 1A receptor (5HT1a-rs6295) polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR) interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531) as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012). BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37). Unlike prior studies of stressful life events, the S' 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006). No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor. PMID:25781924

  14. Norrie disease gene: Characterization of deletions and possible function

    SciTech Connect

    Chen, Z.Y.; Battinelli, E.M.; Hendriks, R.W.; Craig, I.W. [Univ. of Oxford (United Kingdom)] [Univ. of Oxford (United Kingdom); Powell, J.F. [Institute of Psychiatry, London (United Kingdom)] [Institute of Psychiatry, London (United Kingdom); Middleton-Price, H. [Univ. of London (United Kingdom)] [Univ. of London (United Kingdom); Sims, K.B.; Breakefield, X.O. [Massachusetts General Hospital, Charlestown, MA (United States)] [Massachusetts General Hospital, Charlestown, MA (United States)

    1993-05-01

    Positional cloning experiments have resulted recently in the isolation of a candidate gene for Norrie disease (pseudoglioma; NDP), a severe X-linked neuro-developmental disorder. Here the authors report the isolation and analysis of human genomic DNA clones encompassing the NDP gene. The gene spans 28 kb and consists of 3 exons, the first of which is entirely contained within the 5{prime} untranslated region. Detailed analysis of genomic deletions in Norrie patients shows that they are heterogeneous, both in size and in position. By PCR analysis, they found that expression of the NDP gene was not confined to the eye or to the brain. An extensive DNA and protein sequence comparison between the human NDP gene and related genes from the database revealed homology with cysteine-rich protein-binding domains of immediate--early genes implicated in the regulation of cell proliferation. They propose that NDP is a molecule related in function to these genes and may be involved in a pathway that regulates neural cell differentiation and proliferation. 19 refs., 2 figs.

  15. Functionalization of a protosynaptic gene expression network.

    PubMed

    Conaco, Cecilia; Bassett, Danielle S; Zhou, Hongjun; Arcila, Mary Luz; Degnan, Sandie M; Degnan, Bernard M; Kosik, Kenneth S

    2012-06-26

    Assembly of a functioning neuronal synapse requires the precisely coordinated synthesis of many proteins. To understand the evolution of this complex cellular machine, we tracked the developmental expression patterns of a core set of conserved synaptic genes across a representative sampling of the animal kingdom. Coregulation, as measured by correlation of gene expression over development, showed a marked increase as functional nervous systems emerged. In the earliest branching animal phyla (Porifera), in which a nearly complete set of synaptic genes exists in the absence of morphological synapses, these "protosynaptic" genes displayed a lack of global coregulation although small modules of coexpressed genes are readily detectable by using network analysis techniques. These findings suggest that functional synapses evolved by exapting preexisting cellular machines, likely through some modification of regulatory circuitry. Evolutionarily ancient modules continue to operate seamlessly within the synapses of modern animals. This work shows that the application of network techniques to emerging genomic and expression data can provide insights into the evolution of complex cellular machines such as the synapse. PMID:22723359

  16. Functionalization of a protosynaptic gene expression network

    PubMed Central

    Conaco, Cecilia; Bassett, Danielle S.; Zhou, Hongjun; Arcila, Mary Luz; Degnan, Sandie M.; Degnan, Bernard M.; Kosik, Kenneth S.

    2012-01-01

    Assembly of a functioning neuronal synapse requires the precisely coordinated synthesis of many proteins. To understand the evolution of this complex cellular machine, we tracked the developmental expression patterns of a core set of conserved synaptic genes across a representative sampling of the animal kingdom. Coregulation, as measured by correlation of gene expression over development, showed a marked increase as functional nervous systems emerged. In the earliest branching animal phyla (Porifera), in which a nearly complete set of synaptic genes exists in the absence of morphological synapses, these “protosynaptic” genes displayed a lack of global coregulation although small modules of coexpressed genes are readily detectable by using network analysis techniques. These findings suggest that functional synapses evolved by exapting preexisting cellular machines, likely through some modification of regulatory circuitry. Evolutionarily ancient modules continue to operate seamlessly within the synapses of modern animals. This work shows that the application of network techniques to emerging genomic and expression data can provide insights into the evolution of complex cellular machines such as the synapse. PMID:22723359

  17. Gene expression module-based chemical function similarity search

    PubMed Central

    Li, Yun; Hao, Pei; Zheng, Siyuan; Tu, Kang; Fan, Haiwei; Zhu, Ruixin; Ding, Guohui; Dong, Changzheng; Wang, Chuan; Li, Xuan; Thiesen, H.-J.; Chen, Y. Eugene; Jiang, Hualiang; Li, Yixue

    2008-01-01

    Investigation of biological processes using selective chemical interventions is generally applied in biomedical research and drug discovery. Many studies of this kind make use of gene expression experiments to explore cellular responses to chemical interventions. Recently, some research groups constructed libraries of chemical related expression profiles, and introduced similarity comparison into chemical induced transcriptome analysis. Resembling sequence similarity alignment, expression pattern comparison among chemical intervention related expression profiles provides a new way for chemical function prediction and chemical–gene relation investigation. However, existing methods place more emphasis on comparing profile patterns globally, which ignore noises and marginal effects. At the same time, though the whole information of expression profiles has been used, it is difficult to uncover the underlying mechanisms that lead to the functional similarity between two molecules. Here a new approach is presented to perform biological effects similarity comparison within small biologically meaningful gene categories. Regarding gene categories as units, a reduced similarity matrix is generated for measuring the biological distances between query and profiles in library and pointing out in which modules do chemical pairs resemble. Through the modularization of expression patterns, this method reduces experimental noises and marginal effects and directly correlates chemical molecules with gene function modules. PMID:18842630

  18. Functional gene diversity of oolitic sands from Great Bahama Bank.

    PubMed

    Diaz, M R; Van Norstrand, J D; Eberli, G P; Piggot, A M; Zhou, J; Klaus, J S

    2014-05-01

    Despite the importance of oolitic depositional systems as indicators of climate and reservoirs of inorganic C, little is known about the microbial functional diversity, structure, composition, and potential metabolic processes leading to precipitation of carbonates. To fill this gap, we assess the metabolic gene carriage and extracellular polymeric substance (EPS) development in microbial communities associated with oolitic carbonate sediments from the Bahamas Archipelago. Oolitic sediments ranging from high-energy 'active' to lower energy 'non-active' and 'microbially stabilized' environments were examined as they represent contrasting depositional settings, mostly influenced by tidal flows and wave-generated currents. Functional gene analysis, which employed a microarray-based gene technology, detected a total of 12,432 of 95,847 distinct gene probes, including a large number of metabolic processes previously linked to mineral precipitation. Among these, gene-encoding enzymes for denitrification, sulfate reduction, ammonification, and oxygenic/anoxygenic photosynthesis were abundant. In addition, a broad diversity of genes was related to organic carbon degradation, and N2 fixation implying these communities has metabolic plasticity that enables survival under oligotrophic conditions. Differences in functional genes were detected among the environments, with higher diversity associated with non-active and microbially stabilized environments in comparison with the active environment. EPS showed a gradient increase from active to microbially stabilized communities, and when combined with functional gene analysis, which revealed genes encoding EPS-degrading enzymes (chitinases, glucoamylase, amylases), supports a putative role of EPS-mediated microbial calcium carbonate precipitation. We propose that carbonate precipitation in marine oolitic biofilms is spatially and temporally controlled by a complex consortium of microbes with diverse physiologies, including photosynthesizers, heterotrophs, denitrifiers, sulfate reducers, and ammonifiers. PMID:24612324

  19. Microbial functional gene diversity with a shift of subsurface redox conditions during In Situ uranium reduction.

    PubMed

    Liang, Yuting; Van Nostrand, Joy D; N'guessan, Lucie A; Peacock, Aaron D; Deng, Ye; Long, Philip E; Resch, C Tom; Wu, Liyou; He, Zhili; Li, Guanghe; Hazen, Terry C; Lovley, Derek R; Zhou, Jizhong

    2012-04-01

    To better understand the microbial functional diversity changes with subsurface redox conditions during in situ uranium bioremediation, key functional genes were studied with GeoChip, a comprehensive functional gene microarray, in field experiments at a uranium mill tailings remedial action (UMTRA) site (Rifle, CO). The results indicated that functional microbial communities altered with a shift in the dominant metabolic process, as documented by hierarchical cluster and ordination analyses of all detected functional genes. The abundance of dsrAB genes (dissimilatory sulfite reductase genes) and methane generation-related mcr genes (methyl coenzyme M reductase coding genes) increased when redox conditions shifted from Fe-reducing to sulfate-reducing conditions. The cytochrome genes detected were primarily from Geobacter sp. and decreased with lower subsurface redox conditions. Statistical analysis of environmental parameters and functional genes indicated that acetate, U(VI), and redox potential (E(h)) were the most significant geochemical variables linked to microbial functional gene structures, and changes in microbial functional diversity were strongly related to the dominant terminal electron-accepting process following acetate addition. The study indicates that the microbial functional genes clearly reflect the in situ redox conditions and the dominant microbial processes, which in turn influence uranium bioreduction. Microbial functional genes thus could be very useful for tracking microbial community structure and dynamics during bioremediation. PMID:22327592

  20. Rice functionality, starch structure and the genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Through collaborative efforts among USDA scientists at Beaumont, Texas, we have gained in-depth knowledge of how rice functionality, i.e. the texture of the cooked rice, rice processing properties, and starch gelatinization temperature, are associated with starch-synthesis genes and starch structure...

  1. Bayesian modelling of shared gene function

    Microsoft Academic Search

    P. Sykacek; R. Clarkson; C. Print; R. A. Furlong; Gos Micklem

    2007-01-01

    Motivation Biological assays are often carried out on tissues that contain many cell lineages and active pathways. Microarray data produced using such material therefore reflect superimpositions of biological processes. Analysing such data for shared gene function by means of well matched assays may help to provide a better focus on specific cell types and processes. The identification of ge nes

  2. Highlights of glycosylation and adhesion related genes involved in myogenesis

    PubMed Central

    2014-01-01

    Background Myogenesis is initiated by myoblast differentiation and fusion to form myotubes and muscle fibres. A population of myoblasts, known as satellite cells, is responsible for post-natal growth of muscle and for its regeneration. This differentiation requires many changes in cell behaviour and its surrounding environment. These modifications are tightly regulated over time and can be characterized through the study of changes in gene expression associated with this process. During the initial myogenesis steps, using the myoblast cell line C2C12 as a model, Janot et al. (2009) showed significant variations in expression for genes involved in pathways of glycolipid synthesis. In this study we used murine satellite cells (MSC) and their ability to differentiate into myotubes or early fat storage cells to select glycosylation related genes whose variation of expression is myogenesis specific. Results The comparison of variant genes in both MSC differentiation pathways identified 67 genes associated with myogenesis. Comparison with data obtained for C2C12 revealed that only 14 genes had similar expression profiles in both cell types and that 17 genes were specifically regulated in MSC. Results were validated statistically by without a priori clustering. Classification according to protein function encoded by these 31 genes showed that the main regulated cellular processes during this differentiation were (i) remodeling of the extracellular matrix, particularly, sulfated structures, (ii) down-regulation of O-mannosyl glycan biosynthesis, and (iii) an increase in adhesion protein expression. A functional study was performed on Itga11 and Chst5 encoding two highly up-regulated proteins. The inactivation of Chst5 by specific shRNA delayed the fusion of MSC. By contrast, the inactivation of Itga11 by specific shRNA dramatically decreased the fusion ability of MSC. This result was confirmed by neutralization of Itga11 product by specific antibodies. Conclusions Our screening method detected 31 genes specific for myogenic differentiation out of the 383 genes studied. According to their function, interaction networks of the products of these selected genes converged to cell fusion. Functional studies on Itga11 and Chst5 demonstrated the robustness of this screening. PMID:25051993

  3. ConceptGen: a gene set enrichment and gene set relation mapping tool

    PubMed Central

    Sartor, Maureen A.; Mahavisno, Vasudeva; Keshamouni, Venkateshwar G.; Cavalcoli, James; Wright, Zachary; Karnovsky, Alla; Kuick, Rork; Jagadish, H.V.; Mirel, Barbara; Weymouth, Terry; Athey, Brian; Omenn, Gilbert S.

    2010-01-01

    Motivation: The elucidation of biological concepts enriched with differentially expressed genes has become an integral part of the analysis and interpretation of genomic data. Of additional importance is the ability to explore networks of relationships among previously defined biological concepts from diverse information sources, and to explore results visually from multiple perspectives. Accomplishing these tasks requires a unified framework for agglomeration of data from various genomic resources, novel visualizations, and user functionality. Results: We have developed ConceptGen, a web-based gene set enrichment and gene set relation mapping tool that is streamlined and simple to use. ConceptGen offers over 20 000 concepts comprising 14 different types of biological knowledge, including data not currently available in any other gene set enrichment or gene set relation mapping tool. We demonstrate the functionalities of ConceptGen using gene expression data modeling TGF-beta-induced epithelial-mesenchymal transition and metabolomics data comparing metastatic versus localized prostate cancers. Availability: ConceptGen is part of the NIH's National Center for Integrative Biomedical Informatics (NCIBI) and is freely available at http://conceptgen.ncibi.org. For terms of use, visit http://portal.ncibi.org/gateway/pdf/Terms%20of%20use-web.pdf Contact: conceptgen@umich.edu; sartorma@umich.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20007254

  4. The mouse angiogenin gene family: Structures of an angiogenin-related protein gene and two pseudogenes

    SciTech Connect

    Brown, W.E.; Nobile, V.; Shapiro, R. [Harvard Medical School, Boston, MA (United States)] [and others] [Harvard Medical School, Boston, MA (United States); and others

    1995-09-01

    Angiogenin, a homologue of pancreatic ribonuclease, is a potent inducer of blood vessel formation. As an initial step toward investigating the in vivo functional role of this protein via gene disruption, we undertook the isolation of the angiogenin gene (Ang) from the 129 strain mouse, which will be used for generating targeting constructs. Unexpectedly, screening of a genomic library with an Ang gene probe obtained previously from the BALB/c strain yielded two new genes closely similar to Ang rather than Ang itself. One of these encodes a protein with 78% sequence identity to angiogenin and is designated {open_quotes}Angrp{close_quotes} for {open_quotes}angiogenin-related protein.{close_quotes} The ribonucleolytic active site of angiogenin, which is critical for angiogenic activity, is completely conserved in Angrp, whereas a second essential site, thought to bind cellular receptors, is considerably different. Thus, the Angrp product may have a function distinct from that of angiogenin. The second gene obtained by library screening is a pseudogene, designated {open_quotes}Ang-ps1,{close_quotes} that contains a frame shift mutation in the early part of the coding region. Although the Ang gene was not isolated from this library, it was possible to amplify this gene from 129 mouse genomic DNA by the polymerase chain reaction (PCR). Sequence analysis showed that the 129 strain Ang gene is identical to the BALB/c gene throughout the coding region. PCR cloning also yielded a second Ang-like pseudogene, designated {open_quotes}Ang-ps2.{close_quotes} Southern blotting of genomic DNA confirmed the presence of Ang, Angrp, and at least one of the pseudogenes in an individual mouse and suggested that the mouse Ang gene family may contain more than the four members identified here. 31 refs., 4 figs., 1 tab.

  5. Klotho, a Gene Related to a Syndrome Resembling Human Premature Aging, Functions in a Negative Regulatory Circuit of Vitamin D Endocrine System

    Microsoft Academic Search

    HIROSHI TSUJIKAWA; YOKO KUROTAKI; TOSHIHIKO FUJIMORI; KAZUHIKO FUKUDA; YO-ICHI NABESHIMA

    2003-01-01

    The klotho gene encodes a novel type I membrane protein of -glycosidase family and is expressed principally in distal tubule cells of the kidney and choroid plexus in the brain. These mutants dis- played abnormal calcium and phosphorus ho- meostasis together with increased serum 1,25- (OH)2D. In kl \\/ mice at the age of 3 wk, elevated levels of serum

  6. Transient transformation meets gene function discovery: the strawberry fruit case

    PubMed Central

    Guidarelli, Michela; Baraldi, Elena

    2015-01-01

    Beside the well known nutritional and health benefits, strawberry (Fragaria X ananassa) crop draws increasing attention as plant model system for the Rosaceae family, due to the short generation time, the rapid in vitro regeneration, and to the availability of the genome sequence of F. X ananassa and F. vesca species. In the last years, the use of high-throughput sequence technologies provided large amounts of molecular information on the genes possibly related to several biological processes of this crop. Nevertheless, the function of most genes or gene products is still poorly understood and needs investigation. Transient transformation technology provides a powerful tool to study gene function in vivo, avoiding difficult drawbacks that typically affect the stable transformation protocols, such as transformation efficiency, transformants selection, and regeneration. In this review we provide an overview of the use of transient expression in the investigation of the function of genes important for strawberry fruit development, defense and nutritional properties. The technical aspects related to an efficient use of this technique are described, and the possible impact and application in strawberry crop improvement are discussed. PMID:26124771

  7. Characterization of rainbow trout (Oncorhynchus mykiss) spleen transcriptome and identification of immune-related genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistance against specific diseases is affecting profitability in fish production systems including rainbow trout. Limited information is known about functions and mechanisms of the immune gene pathways in teleosts. Immunogenomics are powerful tools to determine immune-related genes/gene pathways a...

  8. Comparative Genomic Analysis of dha Regulon and Related Genes for Anaerobic Glycerol Metabolism in Bacteria

    Microsoft Academic Search

    Jibin Sun; Joop van den Heuvel; Philippe Soucaille; Yinbo Qu; An-Ping Zeng

    2003-01-01

    The dihydroxyacetone (dha) regulon of bacteria encodes genes for the anaerobic metabolism of glycerol. In this work, genomic data are used to analyze and compare the dha regulon and related genes in different organisms in silico with respect to gene organization, sequence similarity, and possible functions. Database searches showed that among the organisms, the genomes of which have been sequenced

  9. Genome-Wide Gene Expression in relation to Age in Large Laboratory Cohorts of Drosophila melanogaster

    PubMed Central

    Carlson, Kimberly A.; Gardner, Kylee; Pashaj, Anjeza; Carlson, Darby J.; Yu, Fang; Eudy, James D.; Zhang, Chi; Harshman, Lawrence G.

    2015-01-01

    Aging is a complex process characterized by a steady decline in an organism's ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age. PMID:26090231

  10. A weighted power framework for integrating multisource information: gene function prediction in yeast.

    PubMed

    Ray, Shubhra Sankar; Bandyopadhyay, Sanghamitra; Pal, Sankar K

    2012-04-01

    Predicting the functions of unannotated genes is one of the major challenges of biological investigation. In this study, we propose a weighted power scoring framework, called weighted power biological score (WPBS), for combining different biological data sources and predicting the function of some of the unclassified yeast Saccharomyces cerevisiae genes. The relative power and weight coefficients of different data sources, in the proposed score, are estimated systematically by utilizing functional annotations [yeast Gene Ontology (GO)-Slim: Process] of classified genes, available from Saccharomyces Genome Database. Genes are then clustered by applying k-medoids algorithm on WPBS, and functional categories of 334 unclassified genes are predicted using a P-value cutoff 1 ×10(-5). The WPBS is available online at http://www.isical.ac.in/~ shubhra/WPBS/WPBS.html, where one can download WPBS, related files, and a MATLAB code to predict functions of unclassified genes. PMID:22318478

  11. Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions

    PubMed Central

    Eswaran, Jeyanthy; Kumar, Rakesh

    2011-01-01

    Background Metastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1. Methods Gene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes. Significance/Conclusion This study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define “bona fide” Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions. PMID:21364872

  12. Cancer Proliferation Gene Discovery Through Functional Genomics

    PubMed Central

    Schlabach, Michael R.; Luo, Ji; Solimini, Nicole L.; Hu, Guang; Xu, Qikai; Li, Mamie Z.; Zhao, Zhenming; Smogorzewska, Agata; Sowa, Mathew E.; Ang, Xiaolu L.; Westbrook, Thomas F.; Liang, Anthony C.; Chang, Kenneth; Hackett, Jennifer A.; Harper, J. Wade; Hannon, Gregory J.; Elledge, Stephen J.

    2010-01-01

    Retroviral short hairpin RNA (shRNA)–mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology for screening large pools of shRNAs using half-hairpin barcodes for microarray deconvolution. We carried out dropout screens for shRNAs that affect cell proliferation and viability in cancer cells and normal cells. We identified many shRNAs to be antiproliferative that target core cellular processes, such as the cell cycle and protein translation, in all cells examined. Moreover, we identified genes that are selectively required for proliferation and survival in different cell lines. Our platform enables rapid and cost-effective genome-wide screens to identify cancer proliferation and survival genes for target discovery. Such efforts are complementary to the Cancer Genome Atlas and provide an alternative functional view of cancer cells. PMID:18239126

  13. Elucidating gene function and function evolution through comparison of co-expression networks of plants

    PubMed Central

    Hansen, Bjoern O.; Vaid, Neha; Musialak-Lange, Magdalena; Janowski, Marcin; Mutwil, Marek

    2014-01-01

    The analysis of gene expression data has shown that transcriptionally coordinated (co-expressed) genes are often functionally related, enabling scientists to use expression data in gene function prediction. This Focused Review discusses our original paper (Large-scale co-expression approach to dissect secondary cell wall formation across plant species, Frontiers in Plant Science 2:23). In this paper we applied cross-species analysis to co-expression networks of genes involved in cellulose biosynthesis. We showed that the co-expression networks from different species are highly similar, indicating that whole biological pathways are conserved across species. This finding has two important implications. First, the analysis can transfer gene function annotation from well-studied plants, such as Arabidopsis, to other, uncharacterized plant species. As the analysis finds genes that have similar sequence and similar expression pattern across different organisms, functionally equivalent genes can be identified. Second, since co-expression analyses are often noisy, a comparative analysis should have higher performance, as parts of co-expression networks that are conserved are more likely to be functionally relevant. In this Focused Review, we outline the comparative analysis done in the original paper and comment on the recent advances and approaches that allow comparative analyses of co-function networks. We hypothesize that in comparison to simple co-expression analysis, comparative analysis would yield more accurate gene function predictions. Finally, by combining comparative analysis with genomic information of green plants, we propose a possible composition of cellulose biosynthesis machinery during earlier stages of plant evolution. PMID:25191328

  14. Molecular cloning and functional analysis of three genes encoding polygalacturonase-inhibiting proteins from Capsicum annuum, and their relation to increased resistance to two fungal pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall glycoproteins that can inhibit fungal endopolygalacturonases (PGs). Inhibiting by PGIPs directly reduces potential PG activity in specific plant pathogenic fungi, reducing their aggressiveness. Here, we isolated and functionally chara...

  15. Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect.

    PubMed

    Bordner, Kelly A; George, Elizabeth D; Carlyle, Becky C; Duque, Alvaro; Kitchen, Robert R; Lam, Tukiet T; Colangelo, Christopher M; Stone, Kathryn L; Abbott, Thomas B; Mane, Shrikant M; Nairn, Angus C; Simen, Arthur A

    2011-01-01

    Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior. PMID:21629843

  16. Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

    PubMed Central

    Bordner, Kelly A.; George, Elizabeth D.; Carlyle, Becky C.; Duque, Alvaro; Kitchen, Robert R.; Lam, TuKiet T.; Colangelo, Christopher M.; Stone, Kathryn L.; Abbott, Thomas B.; Mane, Shrikant M.; Nairn, Angus C.; Simen, Arthur A.

    2011-01-01

    Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior. PMID:21629843

  17. A Resource of Quantitative Functional Annotation for Homo sapiens Genes

    PubMed Central

    Ta?an, Murat; Drabkin, Harold J.; Beaver, John E.; Chua, Hon Nian; Dunham, Julie; Tian, Weidong; Blake, Judith A.; Roth, Frederick P.

    2012-01-01

    The body of human genomic and proteomic evidence continues to grow at ever-increasing rates, while annotation efforts struggle to keep pace. A surprisingly small fraction of human genes have clear, documented associations with specific functions, and new functions continue to be found for characterized genes. Here we assembled an integrated collection of diverse genomic and proteomic data for 21,341 human genes and make quantitative associations of each to 4333 Gene Ontology terms. We combined guilt-by-profiling and guilt-by-association approaches to exploit features unique to the data types. Performance was evaluated by cross-validation, prospective validation, and by manual evaluation with the biological literature. Functional-linkage networks were also constructed, and their utility was demonstrated by identifying candidate genes related to a glioma FLN using a seed network from genome-wide association studies. Our annotations are presented—alongside existing validated annotations—in a publicly accessible and searchable web interface. PMID:22384401

  18. Transitive functional annotation by shortest-path analysis of gene expression data

    PubMed Central

    Zhou, Xianghong; Kao, Ming-Chih J.; Wong, Wing Hung

    2002-01-01

    Current methods for the functional analysis of microarray gene expression data make the implicit assumption that genes with similar expression profiles have similar functions in cells. However, among genes involved in the same biological pathway, not all gene pairs show high expression similarity. Here, we propose that transitive expression similarity among genes can be used as an important attribute to link genes of the same biological pathway. Based on large-scale yeast microarray expression data, we use the shortest-path analysis to identify transitive genes between two given genes from the same biological process. We find that not only functionally related genes with correlated expression profiles are identified but also those without. In the latter case, we compare our method to hierarchical clustering, and show that our method can reveal functional relationships among genes in a more precise manner. Finally, we show that our method can be used to reliably predict the function of unknown genes from known genes lying on the same shortest path. We assigned functions for 146 yeast genes that are considered as unknown by the Saccharomyces Genome Database and by the Yeast Proteome Database. These genes constitute around 5% of the unknown yeast ORFome. PMID:12196633

  19. Expression profiling with arrays of randomly disrupted genes in mouse embryonic stem cells leads to in vivo functional analysis

    Microsoft Academic Search

    Eishou Matsuda; Toshiaki Shigeoka; Ryuji Iida; Shinya Yamanaka; Masashi Kawaichi; Yasumasa Ishida

    2004-01-01

    DNA arrays are capable of profiling the expression patterns of many genes in a single experiment. After finding a gene of interest in a DNA array, however, labor-intensive gene-targeting experiments sometimes must be performed for the in vivo analysis of the gene function. With random gene trapping, on the other hand, it is relatively easy to disrupt and retrieve hundreds

  20. Influence of Rice Development on the Function of Bacterial Blight Resistance Genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disease resistance genes most commonly used in breeding programs are single, dominant, resistance (R) genes with relative effectiveness influenced by plant developmental stage. Knowing the developmental stages at which an R gene is functional is important for disease management. In rice, resistanc...

  1. Identifying pair-wise gene functional similarity by multiplex gene expression maps and supervised learning

    E-print Network

    Obradovic, Zoran

    Identifying pair-wise gene functional similarity by multiplex gene expression maps and supervised and gene expression profiles in the mammalian brain. However, little attention has been paid to the location information of a gene's expressions. Gene expression maps, which contain spatial information

  2. Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function

    Microsoft Academic Search

    Chao Di; Wenying Xu; Zhen Su; Joshua S Yuan

    2010-01-01

    BACKGROUND: PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence,

  3. Neural Networks Approaches for Discovering the Learnable Correlation between Gene Function and Gene

    E-print Network

    Bonner, Anthony

    Neural Networks Approaches for Discovering the Learnable Correlation between Gene Function and Gene novel clustering and Neural Network (NN) approaches for predicting mouse gene functions from gene. Our results show that neural networks can be extremely useful in this area. We present the improved

  4. Functional Analysis of Prognostic Gene Expression Network Genes in Metastatic Breast Cancer Models

    PubMed Central

    Geiger, Thomas R.; Ha, Ngoc-Han; Faraji, Farhoud; Michael, Helen T.; Rodriguez, Loren; Walker, Renard C.; Green, Jeffery E.; Simpson, R. Mark; Hunter, Kent W.

    2014-01-01

    Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+) breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease. PMID:25368990

  5. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

    PubMed Central

    2010-01-01

    Background Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. Results We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. Conclusion The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes. PMID:21172044

  6. On the relation between promoter divergence and gene expression evolution

    E-print Network

    Barkai, Naama

    On the relation between promoter divergence and gene expression evolution Itay Tirosh1 , Adina-regulatory sequences of related organisms, but the impact of these differences on gene expression remains largely)-binding sequences of yeasts and mammals have no detectable effect on gene expression, suggesting that compensatory

  7. Rabbit calcium-sensing receptor (CASR) gene: chromosome location and evidence for related genes

    Microsoft Academic Search

    P. A. Martin-DeLeon; L. Canaff; R. Korstanje; V. Bhide; M. Selkirk; G. N. Hendy

    1999-01-01

    Diverse cellular functions are regulated by the calcium-sensing receptor, encoded by the CASR gene, which plays an important role in calcium homeostasis. Here we provide the sequence for exon VII of the rabbit CASR gene and show that it is 91% identical to the human gene at the nucleotide level, and 95% identical at the amino acid level. The gene

  8. Phenotype-based clustering of glycosylation-related genes by RNAi-mediated gene silencing.

    PubMed

    Yamamoto-Hino, Miki; Yoshida, Hideki; Ichimiya, Tomomi; Sakamura, Sho; Maeda, Megumi; Kimura, Yoshinobu; Sasaki, Norihiko; Aoki-Kinoshita, Kiyoko F; Kinoshita-Toyoda, Akiko; Toyoda, Hidenao; Ueda, Ryu; Nishihara, Shoko; Goto, Satoshi

    2015-06-01

    Glycan structures are synthesized by a series of reactions conducted by glycosylation-related (GR) proteins such as glycosyltransferases, glycan-modifying enzymes, and nucleotide-sugar transporters. For example, the common core region of glycosaminoglycans (GAGs) is sequentially synthesized by peptide-O-xylosyltransferase, ?1,4-galactosyltransferase I, ?1,3-galactosyltransferase II, and ?1,3-glucuronyltransferase. This raises the possibility that functional impairment of GR proteins involved in synthesis of the same glycan might result in the same phenotypic abnormality. To examine this possibility, comprehensive silencing of genes encoding GR and proteoglycan core proteins was conducted in Drosophila. Drosophila GR candidate genes (125) were classified into five functional groups for synthesis of GAGs, N-linked, O-linked, Notch-related, and unknown glycans. Spatiotemporally regulated silencing caused a range of malformed phenotypes that fell into three types: extra veins, thick veins, and depigmentation. The clustered phenotypes reflected the biosynthetic pathways of GAGs, Fringe-dependent glycan on Notch, and glycans placed at or near nonreducing ends (herein termed terminal domains of glycans). Based on the phenotypic clustering, CG33145 was predicted to be involved in formation of terminal domains. Our further analysis showed that CG33145 exhibited galactosyltransferase activity in synthesis of terminal N-linked glycans. Phenotypic clustering, therefore, has potential for the functional prediction of novel GR genes. PMID:25940448

  9. Homeosis and beyond. What is the function of the Hox genes?

    PubMed

    Deutsch, Jean S

    2010-01-01

    What is the function of the Hox genes? At first glance, it is a curious question. Indeed, the answer seems so obvious that several authors have spoken of 'the Hox function' about some of the Hox genes, namely Hox3/zen and Hox6/ftz that seem to have lost it during the evolution of Arthropods. What these authors meant is that these genes have lost their 'homeotic' function. Indeed, 'homeotic' refers to a functional property that is so often associated with the Hox genes. However, the word 'Hox' should not be used to refer to a function, but to a group of genes. The above examples of Hox3/zen (see Schmitt-Ott's chapter, this book) and Hox6/ftz show that the homeotic function may be not so tightly linked to the Hox genes. Reversely, many genes, not belonging to the Hox group, do present a homeotic function. In the present chapter, I will first give a definition of the Hox genes. I will then ask what is the 'function' of a gene, examining its various meanings at different levels of biological organization. I will review and revisit the relation between the Hox genes and homeosis. I will suggest that their morphological homeotic function has been secondarily derived during the evolution of the Bilateria. PMID:20795330

  10. Functional Programming with Relations \\Lambda Graham Hutton

    E-print Network

    Hutton, Graham

    Functional Programming with Relations \\Lambda Graham Hutton Department of Computing Science Glasgow University, Scotland December 1990 Abstract While programming in a relational framework has much to offer over the functional style in terms of expressiveness, computing with relations is less efficient

  11. INVESTIGATION Gene Functional Trade-Offs and the Evolution

    E-print Network

    Otto, Sarah

    INVESTIGATION Gene Functional Trade-Offs and the Evolution of Pleiotropy Frédéric Guillaume*,1, Vancouver, British Columbia, Canada V6T 1Z4 ABSTRACT Pleiotropy is the property of genes affecting multiple functions or characters of an organism. Genes vary widely in their degree of pleiotropy, but this variation

  12. Gene function prediction from congruent synthetic lethal interactions in yeast

    Microsoft Academic Search

    Ping Ye; Brian D Peyser; Xuewen Pan; Jef D Boeke; Forrest A Spencer; Joel S Bader

    2005-01-01

    We predicted gene function using synthetic lethal genetic interactions between null alleles in Saccharomyces cerevisiae. Phenotypic and protein interaction data indicate that synthetic lethal gene pairs function in parallel or compensating pathways. Congruent gene pairs, defined as sharing synthetic lethal partners, are in single pathway branches. We predicted benomyl sensitivity and nuclear migration defects using congruence; these phenotypes were uncorrelated

  13. Genes for Chlorogenate and Hydroxycinnamate Catabolism (hca) Are Linked to Functionally Related Genes in the dca-pca-qui-pob-hca Chromosomal Cluster of Acinetobacter sp. Strain ADP1

    Microsoft Academic Search

    Michael A. Smith; Valerie B. Weaver; David M. Young; L. Nicholas Ornston

    2003-01-01

    Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca-qui-pob chromosomal cluster. In an appropriate genetic background, it was possible to select for an

  14. Inference of Gene Relations from Microarray Data by Abduction

    E-print Network

    Sergot, Marek

    Inference of Gene Relations from Microarray Data by Abduction Irene Papatheodorou, Antonis Kakas- iments. We develop an ALP theory that provides a simple and general model of how gene interactions can cause changes in observable expres- sion levels of genes. Input to the procedure are the observed

  15. Semantic Particularity Measure for Functional Characterization of Gene Sets Using Gene Ontology

    PubMed Central

    Bettembourg, Charles; Diot, Christian; Dameron, Olivier

    2014-01-01

    Background Genetic and genomic data analyses are outputting large sets of genes. Functional comparison of these gene sets is a key part of the analysis, as it identifies their shared functions, and the functions that distinguish each set. The Gene Ontology (GO) initiative provides a unified reference for analyzing the genes molecular functions, biological processes and cellular components. Numerous semantic similarity measures have been developed to systematically quantify the weight of the GO terms shared by two genes. We studied how gene set comparisons can be improved by considering gene set particularity in addition to gene set similarity. Results We propose a new approach to compute gene set particularities based on the information conveyed by GO terms. A GO term informativeness can be computed using either its information content based on the term frequency in a corpus, or a function of the term's distance to the root. We defined the semantic particularity of a set of GO terms Sg1 compared to another set of GO terms Sg2. We combined our particularity measure with a similarity measure to compare gene sets. We demonstrated that the combination of semantic similarity and semantic particularity measures was able to identify genes with particular functions from among similar genes. This differentiation was not recognized using only a semantic similarity measure. Conclusion Semantic particularity should be used in conjunction with semantic similarity to perform functional analysis of GO-annotated gene sets. The principle is generalizable to other ontologies. PMID:24489737

  16. Selecting Informative Genes from Microarray Dataset Using Fuzzy Relational Clustering

    NASA Astrophysics Data System (ADS)

    Kasiri-Bidhendi, Soudeh; Shiry Ghidary, Saeed

    Selecting informative genes from microarray experiments is one of the most important data analysis steps for deciphering biological information imbedded in such experiments. This paper presents a novel approach for selecting informative genes in two steps. First, fuzzy relational clustering is used to cluster co-expressed genes and select genes that express differently in distinct sample conditions. Second, Support Vector Machine Recursive Feature Elimination (SVM-RFE) method is applied to rank genes. The proposed method is tested on cancer datasets for cancer classification. The results show that the proposed feature selection method selects better subset of genes than the original SVM-RFE does and improves the classification accuracy.

  17. Transport of Magnesium by a Bacterial Nramp-Related Gene

    PubMed Central

    Rodionov, Dmitry A.; Freedman, Benjamin G.; Senger, Ryan S.; Winkler, Wade C.

    2014-01-01

    Magnesium is an essential divalent metal that serves many cellular functions. While most divalent cations are maintained at relatively low intracellular concentrations, magnesium is maintained at a higher level (?0.5–2.0 mM). Three families of transport proteins were previously identified for magnesium import: CorA, MgtE, and MgtA/MgtB P-type ATPases. In the current study, we find that expression of a bacterial protein unrelated to these transporters can fully restore growth to a bacterial mutant that lacks known magnesium transporters, suggesting it is a new importer for magnesium. We demonstrate that this transport activity is likely to be specific rather than resulting from substrate promiscuity because the proteins are incapable of manganese import. This magnesium transport protein is distantly related to the Nramp family of proteins, which have been shown to transport divalent cations but have never been shown to recognize magnesium. We also find gene expression of the new magnesium transporter to be controlled by a magnesium-sensing riboswitch. Importantly, we find additional examples of riboswitch-regulated homologues, suggesting that they are a frequent occurrence in bacteria. Therefore, our aggregate data discover a new and perhaps broadly important path for magnesium import and highlight how identification of riboswitch RNAs can help shed light on new, and sometimes unexpected, functions of their downstream genes. PMID:24968120

  18. Rationale for developing new virus vectors to analyze gene function in grasses through virus-induced gene silencing.

    PubMed

    Ramanna, Hema; Ding, Xin Shun; Nelson, Richard S

    2013-01-01

    The exploding availability of genome and EST-based sequences from grasses requires a technology that allows rapid functional analysis of the multitude of genes that these resources provide. There are several techniques available to determine a gene's function. For gene knockdown studies, silencing through RNAi is a powerful tool. Gene silencing can be accomplished through stable transformation or transient expression of a fragment of a target gene sequence. Stable transformation in rice, maize, and a few other species, although routine, remains a relatively low-throughput process. Transformation in other grass species is difficult and labor-intensive. Therefore, transient gene silencing methods including Agrobacterium-mediated and virus-induced gene silencing (VIGS) have great potential for researchers studying gene function in grasses. VIGS in grasses already has been used to determine the function of genes during pathogen challenge and plant development. It also can be used in moderate-throughput reverse genetics screens to determine gene function. However, the number of viruses modified to serve as silencing vectors in grasses is limited, and the silencing phenotype induced by these vectors is not optimal: the phenotype being transient and with moderate penetration throughout the tissue. Here, we review the most recent information available for VIGS in grasses and summarize the strengths and weaknesses in current virus-grass host systems. We describe ways to improve current virus vectors and the potential of other grass-infecting viruses for VIGS studies. This work is necessary because VIGS for the foreseeable future remains a higher throughput and more rapid system to evaluate gene function than stable transformation. PMID:23386292

  19. Selecting Informative Genes from Microarray Dataset Using Fuzzy Relational Clustering

    Microsoft Academic Search

    Soudeh Kasiri-Bidhendi; Saeed Shiry Ghidary

    2009-01-01

    Selecting informative genes from microarray experiments is one of the most important data analysis steps for deciphering biological\\u000a information imbedded in such experiments. This paper presents a novel approach for selecting informative genes in two steps.\\u000a First, fuzzy relational clustering is used to cluster co-expressed genes and select genes that express differently in distinct\\u000a sample conditions. Second, Support Vector Machine

  20. Land use change alters functional gene diversity, composition and abundance in Amazon forest soil microbial communities.

    PubMed

    Paula, Fabiana S; Rodrigues, Jorge L M; Zhou, Jizhong; Wu, Liyou; Mueller, Rebecca C; Mirza, Babur S; Bohannan, Brendan J M; Nüsslein, Klaus; Deng, Ye; Tiedje, James M; Pellizari, Vivian H

    2014-06-01

    Land use change in the Amazon rainforest alters the taxonomic structure of soil microbial communities, but whether it alters their functional gene composition is unknown. We used the highly parallel microarray technology GeoChip 4.0, which contains 83,992 probes specific for genes linked nutrient cycling and other processes, to evaluate how the diversity, abundance and similarity of the targeted genes responded to forest-to-pasture conversion. We also evaluated whether these parameters were reestablished with secondary forest growth. A spatially nested scheme was employed to sample a primary forest, two pastures (6 and 38 years old) and a secondary forest. Both pastures had significantly lower microbial functional genes richness and diversity when compared to the primary forest. Gene composition and turnover were also significantly modified with land use change. Edaphic traits associated with soil acidity, iron availability, soil texture and organic matter concentration were correlated with these gene changes. Although primary and secondary forests showed similar functional gene richness and diversity, there were differences in gene composition and turnover, suggesting that community recovery was not complete in the secondary forest. Gene association analysis revealed that response to ecosystem conversion varied significantly across functional gene groups, with genes linked to carbon and nitrogen cycling mostly altered. This study indicates that diversity and abundance of numerous environmentally important genes respond to forest-to-pasture conversion and hence have the potential to affect the related processes at an ecosystem scale. PMID:24806276

  1. Irf6-Related Gene Regulatory Network Involved in Palate and Lip Development.

    PubMed

    Dai, Jiewen; Yu, Hongbo; Si, Jiawen; Fang, Bing; Shen, Steve Guofang

    2015-07-01

    Numerous genes including Irf6 have been revealed to contribute to cleft lip with or without cleft palate (CL/P). In this study, we performed a systematic bioinformatics analysis of Irf6-related gene regulatory network involved in palate and lip development by using GeneDecks, DAVID, STRING, and GeneMANIA database. Our results showed that many CL/P candidate genes have relation with Irf6, and 9 of these genes, including Msx1, Pvrl1, Pax9, Jag2, Irf6, Tgfb3, Rara, Gli2, and Tgfb2, were enriched into the CL/P gene group. Some of these 9 genes also were commonly involved in different signaling pathways and different biological processes, and they also have protein-protein interactions with Irf6. These findings make us analyze the intricate function of Irf6 in a CL/P gene regulatory network, followed by guiding us to perform further functional studies on these genes in the future. This method also offers us a simple, cheap, but useful method to analyze the relationship with a gene regulatory network of a certain disease such as CL/P. PMID:26086926

  2. Isolation of tumor suppressor genes from MEN-1 related neoplasms

    SciTech Connect

    Yavari, R.; Kinder, B.; Bale, A.E. [Yale Univ. School of Medicine, New Haven, CT (United States)

    1994-09-01

    Multiple Endocrine Neoplasia type 1 (MEN 1) is a cancer predisposition syndrome marked by the development of tumors in specific endocrine tissues such as the pituitary, parathyroid and pancreatic islets. Genetic linkage studies have mapped the MEN 1 gene to 11q13, and allelic loss in related tumors suggests that the gene is a tumor suppressor. Because inactivation of tumor suppressors may be accompanied by underexpression, subtractive hybridization was used to isolate potential candidate genes underexpressed in MEN 1 tumors. cDNA was synthesized from tumor and normal parathyroid tissue by RT-PCR. Biotinylated tumor cDNA was used as a driver and normal cDNA as a tester in subtractive hybridization. Following annealing of the driver and tester amplicons, the biotinylated strands were removed with streptavidin. The subtracted material was then used as a probe to isolate clones from a normal pancreatic islet library. Screening 2 x 10{sup 5} plaques yielded 14 positive clones. Of 6 clones analyzed, 3 were confirmed to be underexpressed in parathyroid tumors. Sequence analysis identified 2 clones as human ribosomal protein S10 (RPS10, chromosome 6) and 1 as the islet amyloid polypeptide (1AP, chromosome 12). The precise function of human RPS10 is not known but the related RPS6 functions as a tumor suppressor in Drosophila. 1AP has been implicated in modulation of G protein activity. The remaining positive clones will be mapped to determine if any fall on chromosome 11q13, and additional subtractions with parathyroid and pancreatic islet neoplasms are underway.

  3. Functional Identification of a Putative ?-Galactosidase Gene in the Special lac Gene Cluster of Lactobacillus   acidophilus

    Microsoft Academic Search

    Qu Pan; Junmin Zhu; Lina Liu; Yanguang Cong; Fuquan Hu; Jinchuan Li; Xiaoping Yu

    2010-01-01

    The putative ?-galactosidase gene (lacZ) of Lactobacillus acidophilus has a very low degree of homology to the Escherichia coli ?-galactosidase gene (lacZ) and locates in a special lac gene cluster which contains two ?-galactosidase genes. No functional characteristic of the putative ?-galactosidase has been\\u000a described so far. In this study, the lacZ gene of L. acidophilus was hetero-expressed in E. coli and the recombinant

  4. Reconstruction of a Functional Human Gene Network, with an Application for Prioritizing Positional Candidate Genes

    PubMed Central

    Franke, Lude; Bakel, Harm van; Fokkens, Like; de Jong, Edwin D.; Egmont-Petersen, Michael; Wijmenga, Cisca

    2006-01-01

    Most common genetic disorders have a complex inheritance and may result from variants in many genes, each contributing only weak effects to the disease. Pinpointing these disease genes within the myriad of susceptibility loci identified in linkage studies is difficult because these loci may contain hundreds of genes. However, in any disorder, most of the disease genes will be involved in only a few different molecular pathways. If we know something about the relationships between the genes, we can assess whether some genes (which may reside in different loci) functionally interact with each other, indicating a joint basis for the disease etiology. There are various repositories of information on pathway relationships. To consolidate this information, we developed a functional human gene network that integrates information on genes and the functional relationships between genes, based on data from the Kyoto Encyclopedia of Genes and Genomes, the Biomolecular Interaction Network Database, Reactome, the Human Protein Reference Database, the Gene Ontology database, predicted protein-protein interactions, human yeast two-hybrid interactions, and microarray coexpressions. We applied this network to interrelate positional candidate genes from different disease loci and then tested 96 heritable disorders for which the Online Mendelian Inheritance in Man database reported at least three disease genes. Artificial susceptibility loci, each containing 100 genes, were constructed around each disease gene, and we used the network to rank these genes on the basis of their functional interactions. By following up the top five genes per artificial locus, we were able to detect at least one known disease gene in 54% of the loci studied, representing a 2.8-fold increase over random selection. This suggests that our method can significantly reduce the cost and effort of pinpointing true disease genes in analyses of disorders for which numerous loci have been reported but for which most of the genes are unknown. PMID:16685651

  5. Discovery of New Candidate Genes Related to Brain Development Using Protein Interaction Information

    PubMed Central

    Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2015-01-01

    Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development. PMID:25635857

  6. Discovery of new candidate genes related to brain development using protein interaction information.

    PubMed

    Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2015-01-01

    Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development. PMID:25635857

  7. Soybean kinome: functional classification and gene expression patterns

    PubMed Central

    Liu, Jinyi; Chen, Nana; Grant, Joshua N.; Cheng, Zong-Ming (Max); Stewart, C. Neal; Hewezi, Tarek

    2015-01-01

    The protein kinase (PK) gene family is one of the largest and most highly conserved gene families in plants and plays a role in nearly all biological functions. While a large number of genes have been predicted to encode PKs in soybean, a comprehensive functional classification and global analysis of expression patterns of this large gene family is lacking. In this study, we identified the entire soybean PK repertoire or kinome, which comprised 2166 putative PK genes, representing 4.67% of all soybean protein-coding genes. The soybean kinome was classified into 19 groups, 81 families, and 122 subfamilies. The receptor-like kinase (RLK) group was remarkably large, containing 1418 genes. Collinearity analysis indicated that whole-genome segmental duplication events may have played a key role in the expansion of the soybean kinome, whereas tandem duplications might have contributed to the expansion of specific subfamilies. Gene structure, subcellular localization prediction, and gene expression patterns indicated extensive functional divergence of PK subfamilies. Global gene expression analysis of soybean PK subfamilies revealed tissue- and stress-specific expression patterns, implying regulatory functions over a wide range of developmental and physiological processes. In addition, tissue and stress co-expression network analysis uncovered specific subfamilies with narrow or wide interconnected relationships, indicative of their association with particular or broad signalling pathways, respectively. Taken together, our analyses provide a foundation for further functional studies to reveal the biological and molecular functions of PKs in soybean. PMID:25614662

  8. Tmc gene therapy restores auditory function in deaf mice.

    PubMed

    Askew, Charles; Rochat, Cylia; Pan, Bifeng; Asai, Yukako; Ahmed, Hena; Child, Erin; Schneider, Bernard L; Aebischer, Patrick; Holt, Jeffrey R

    2015-07-01

    Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken ?-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations. PMID:26157030

  9. Geochip-Based Functional Gene Analysis of Anodophilic

    E-print Network

    Geochip-Based Functional Gene Analysis of Anodophilic Communities in Microbial Electrolysis Cells. A microbial electrolysis cell (MEC) is a bioelectrochemical the microbial community functional structure in MECs initially operated under different conditions. We found

  10. Identification of immunity related genes to study the Physalis peruviana--Fusarium oxysporum pathosystem.

    PubMed

    Enciso-Rodríguez, Felix E; González, Carolina; Rodríguez, Edwin A; López, Camilo E; Landsman, David; Barrero, Luz Stella; Marińo-Ramírez, Leonardo

    2013-01-01

    The Cape gooseberry (Physalisperuviana L) is an Andean exotic fruit with high nutritional value and appealing medicinal properties. However, its cultivation faces important phytosanitary problems mainly due to pathogens like Fusarium oxysporum, Cercosporaphysalidis and Alternaria spp. Here we used the Cape gooseberry foliar transcriptome to search for proteins that encode conserved domains related to plant immunity including: NBS (Nucleotide Binding Site), CC (Coiled-Coil), TIR (Toll/Interleukin-1 Receptor). We identified 74 immunity related gene candidates in P. peruviana which have the typical resistance gene (R-gene) architecture, 17 Receptor like kinase (RLKs) candidates related to PAMP-Triggered Immunity (PTI), eight (TIR-NBS-LRR, or TNL) and nine (CC-NBS-LRR, or CNL) candidates related to Effector-Triggered Immunity (ETI) genes among others. These candidate genes were categorized by molecular function (98%), biological process (85%) and cellular component (79%) using gene ontology. Some of the most interesting predicted roles were those associated with binding and transferase activity. We designed 94 primers pairs from the 74 immunity-related genes (IRGs) to amplify the corresponding genomic regions on six genotypes that included resistant and susceptible materials. From these, we selected 17 single band amplicons and sequenced them in 14 F. oxysporum resistant and susceptible genotypes. Sequence polymorphisms were analyzed through preliminary candidate gene association, which allowed the detection of one SNP at the PpIRG-63 marker revealing a nonsynonymous mutation in the predicted LRR domain suggesting functional roles for resistance. PMID:23844210

  11. Gene expression profile analysis of testis and ovary of oriental river prawn, Macrobrachium nipponense, reveals candidate reproduction-related genes.

    PubMed

    Qiao, H; Xiong, Y W; Jiang, S F; Fu, H T; Sun, S M; Jin, S B; Gong, Y S; Zhang, W Y

    2015-01-01

    This study utilized high-throughput RNA sequencing technology to identify reproduction- and development-related genes of Macrobrachium nipponense by analyzing gene expression profiles of testis and ovary. More than 20 million 1 x 51-bp reads were obtained by Illumina sequencing, generating more than 7.7 and 11.7 million clean reads in the testis and ovary library, respectively. As a result, 10,018 unitags were supposed to be differentially expressed genes (DEGs) between ovary and testis. Compared to the ovary library, 4563 (45.5%) of these DEGs exhibited at least 6-fold upregulated expression, while 5455 (54.5%) DEGs exhibited at least 2-fold downregulated expression in the testis. The Gene Ontology (GO) enrichment analysis showed that 113 GO terms had potential molecular functions in reproduction. The Kyoto Encyclopedia of Genes and Genomes results revealed that the most important pathways may be relevant to reproduction and included 7 pathways. Forty-two genes were identified as reproduction-, development-, and sex-related genes based on GO classification and sequence comparison with other publications, including male reproductive-related LIM protein, spermatogenesis-associated protein, gametocyte-specific factor 1, VASA-like protein, vitellogenin, sex-determining protein fem-1, and other potential candidates. These results will advance research in the field of molecular genetics in M. nipponense and offer a valuable resource for further research related to reproduction in crustaceans. PMID:25867350

  12. Reproduction-related genes in the pearl oyster genome.

    PubMed

    Matsumoto, Toshie; Masaoka, Tetsuji; Fujiwara, Atsushi; Nakamura, Yoji; Satoh, Nori; Awaji, Masahiko

    2013-10-01

    Molluscan reproduction has been a target of biological research because of the various reproductive strategies that have evolved in this phylum. It has also been studied for the development of fisheries technologies, particularly aquaculture. Although fundamental processes of reproduction in other phyla, such as vertebrates and arthropods, have been well studied, information on the molecular mechanisms of molluscan reproduction remains limited. The recently released draft genome of the pearl oyster Pinctada fucata provides a novel and powerful platform for obtaining structural information on the genes and proteins involved in bivalve reproduction. In the present study, we analyzed the pearl oyster draft genome to screen reproduction-related genes. Analysis was mainly conducted for genes reported from other molluscs for encoding orthologs of reproduction-related proteins in other phyla. The gene search in the P. fucata gene models (version 1.1) and genome assembly (version 1.0) were performed using Genome Browser and BLAST software. The obtained gene models were then BLASTP searched against a public database to confirm the best-hit sequences. As a result, more than 40 gene models were identified with high accuracy to encode reproduction-related genes reported for P. fucata and other molluscs. These include vasa, nanos, doublesex- and mab-3-related transcription factor, 5-hydroxytryptamine (5-HT) receptors, vitellogenin, estrogen receptor, and others. The set of reproduction-related genes of P. fucata identified in the present study constitute a new tool for research on bivalve reproduction at the molecular level. PMID:24125647

  13. The expression of two engrailed -related genes in an apterygote insect and a phylogenetic analysis of insect engrailed -related genes

    Microsoft Academic Search

    Michael D. Peterson; Aleksandar Popadi?; T. C. Kaufman

    1998-01-01

    Homologues of the Drosophila segment polarity gene engrailed have been cloned from many insect species, as well as other arthropods and non-arthropods. We have cloned partial cDNAs of\\u000a two engrailed homologues, which we call engrailed-related genes, from the phylogenetically basal insect, Thermobia domestica (Order Thysanura) and possibly as many as four engrailed-related genes from the phylogenetically intermediate insect, Oncopeltus fasciatus

  14. GEO: the Gene Expression Omnibus A family of databases for gene expression related data

    E-print Network

    Levin, Judith G.

    GEO: the Gene Expression Omnibus A family of databases for gene expression related data http://www.ncbi.nlm.nih.gov Contact: info@ncbi.nlm.nih.gov Scope and access The Gene Expression Omnibus (GEO) is a public repository for searching and browsing high-throughput array data: www.ncbi.nlm.nih.gov/geo/. GEO accepts many categories

  15. Recent Achievement in Gene Cloning and Functional Genomics in Soybean

    PubMed Central

    Zhai, Hong; Lü, Shixiang; Wu, Hongyan; Zhang, Yupeng

    2013-01-01

    Soybean is a model plant for photoperiodism as well as for symbiotic nitrogen fixation. However, a rather low efficiency in soybean transformation hampers functional analysis of genes isolated from soybean. In comparison, rapid development and progress in flowering time and photoperiodic response have been achieved in Arabidopsis and rice. As the soybean genomic information has been released since 2008, gene cloning and functional genomic studies have been revived as indicated by successfully characterizing genes involved in maturity and nematode resistance. Here, we review some major achievements in the cloning of some important genes and some specific features at genetic or genomic levels revealed by the analysis of functional genomics of soybean. PMID:24311973

  16. Multifunction of autophagy-related genes in filamentous fungi.

    PubMed

    Khan, Irshad Ali; Lu, Jian-Ping; Liu, Xiao-Hong; Rehman, Abdur; Lin, Fu-Cheng

    2012-06-20

    Autophagy (macroautophagy), a highly conserved eukaryotic mechanism, is a non-selective degradation process, helping to maintain a balance between the synthesis, degradation and subsequent recycling of macromolecules to overcome various stress conditions. The term autophagy denotes any cellular process which involves the delivery of cytoplasmic material to the lysosome for degradation. Autophagy, in filamentous fungi plays a critical role during cellular development and pathogenicity. Autophagy, like the mitogen-activated protein (MAP) kinase cascade and nutrient-sensing cyclic AMP (cAMP) pathway, is also an important process for appressorium turgor accumulation in order to penetrate the leaf surface of host plant and destroy the plant defense. Yeast, an autophagy model, has been used to compare the multi-valued functions of ATG (autophagy-related genes) in different filamentous fungi. The autophagy machinery in both yeast and filamentous fungi is controlled by Tor kinase and both contain two distinct phosphatidylinositol 3-kinase complexes. In this review, we focus on the functions of ATG genes during pathogenic development in filamentous fungi. PMID:22554685

  17. Concerted down-regulation of immune-system related genes predicts metastasis in colorectal carcinoma

    PubMed Central

    2014-01-01

    Background This study aimed at the identification of prognostic gene expression markers in early primary colorectal carcinomas without metastasis at the time point of surgery by analyzing genome-wide gene expression profiles using oligonucleotide microarrays. Methods Cryo-conserved tumor specimens from 45 patients with early colorectal cancers were examined, with the majority of them being UICC stage II or earlier and with a follow-up time of 41–115 months. Gene expression profiling was performed using Whole Human Genome 4x44K Oligonucleotide Microarrays. Validation of microarray data was performed on five of the genes in a smaller cohort. Results Using a novel algorithm based on the recursive application of support vector machines (SVMs), we selected a signature of 44 probes that discriminated between patients developing later metastasis and patients with a good prognosis. Interestingly, almost half of the genes was related to the patients’ immune response and showed reduced expression in the metastatic cases. Conclusions Whereas up to now gene signatures containing genes with various biological functions have been described for prediction of metastasis in CRC, in this study metastasis could be well predicted by a set of gene expression markers consisting exclusively of genes related to the MHC class II complex involved in immune response. Thus, our data emphasize that the proper function of a comprehensive network of immune response genes is of vital importance for the survival of colorectal cancer patients. PMID:24495478

  18. Relative Transfer Function Identification Using Convolutive Transfer Function Approximation

    Microsoft Academic Search

    Ronen Talmon; Israel Cohen; Sharon Gannot

    2009-01-01

    In this paper, we present a relative transfer function (RTF) identification method for speech sources in reverberant environments. The proposed method is based on the convolutive transfer function (CTF) approximation, which enables to represent a linear convolution in the time domain as a linear convolution in the short-time Fourier transform (STFT) domain. Unlike the restrictive and commonly used multiplicative transfer

  19. DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3?-end GC density

    PubMed Central

    Yu, Bo; Russanova, Valya R.; Gravina, Silvia; Hartley, Stephen; Mullikin, James C.; Ignezweski, Alice; Graham, James; Segars, James H.; DeCherney, Alan H.; Howard, Bruce H.

    2015-01-01

    Diminished ovarian function occurs early and is a primary cause for age-related decline in female fertility; however, its underlying mechanism remains unclear. This study investigated the roles that genome and epigenome structure play in age-related changes in gene expression and ovarian function, using human ovarian granulosa cells as an experimental system. DNA methylomes were compared between two groups of women with distinct age-related differences in ovarian functions, using both Methylated DNA Capture followed by Next Generation Sequencing (MethylCap-seq) and Reduced Representation Bisulfite Sequencing (RRBS); their transcriptomes were investigated using mRNA-seq. Significant, non-random changes in transcriptome and DNA methylome features are observed in human ovarian granulosa cells as women age and their ovarian functions deteriorate. The strongest correlations between methylation and the age-related changes in gene expression are not confined to the promoter region; rather, high densities of hypomethylated CpG-rich regions spanning the gene body are preferentially associated with gene down-regulation. This association is further enhanced where CpG regions are localized near the 3?-end of the gene. Such features characterize several genes crucial in age-related decline in ovarian function, most notably the AMH (Anti-Müllerian Hormone) gene. The genome-wide correlation between the density of hypomethylated intragenic and 3?-end regions and gene expression suggests previously unexplored mechanisms linking epigenome structure to age-related physiology and pathology. PMID:25682867

  20. Identification of Development and Pathogenicity Related Gene in Botrytis cinerea via Digital Gene Expression Profile

    PubMed Central

    Zhao, Bin; Si, He Long; Sun, Zhi Ying; Xu, Zheng; Chen, Zhan; Zhang, Jin lin; Xing, Ji Hong; Dong, Jin Gao

    2015-01-01

    Background: Botrytis cinerea, a haploid Euascomycete fungus that infects numerous crops, has been used as a model system for studying molecular phytopathology. Botrytis cinerea adopts various modes of infection, which are mediated by a number of pathogenicity and virulence-related genes. Many of these genes have not been reported previously. Objectives: This study aimed to investigate development and pathogenicity-related genes between a novel nonpathogenic mutant and the Wild Type (WT) in B. cinerea. Materials and Methods: Digital Gene Expression (DGE) tag profiling can reveal novel genes that may be involved in development and pathogenicity of plant pathogen. A large volume of B. cinerea tag-seq was generated to identify differential expressed genes by the Illumina DGE tag pro?ling technology. Results: A total of 4,182,944 and 4,182,021 clean tags were obtained from the WT and a nonpathogenic mutant stain (BCt89), respectively, and 10,410 differentially expressed genes were identified. In addition, 84 genes were expressed in the WT only while 34 genes were expressed in the mutant only. A total of 664 differentially expressed genes were involved in 91 Kyoto Encyclopedia of Genes and Genome pathways, including signaling and metabolic pathways. Conclusions: Expression levels of 1,426 genes were significantly up-regulated in the mutant compared to WT. Furthermore, 301 genes were down-regulated with False Discovery Rates (FDR) of < 0.001 and absolute value of log2 Ratio of ? 1. PMID:26034553

  1. Phylogenetic and functional analysis of Arabidopsis RCI2 genes

    Microsoft Academic Search

    Joaquin Medina; Maria Luisa Ballesteros; Julio Salinas

    2007-01-01

    Six new Arabidopsis thaliana genes (AtRCI2C-H) have been identified that show high homology to AtRCI2A and AtRCI2B. Sequence comparisons revealed that AtRCI2-related genes are widely spread among very different organisms, including other plant species, prokaryotes, fungi, and simply organized animals, and are also organized in gene families. Most RCI2 genes show a similar exon-intron organization, which indi- cates that they

  2. The function and evolution of Msx genes: pointers and paradoxes

    Microsoft Academic Search

    Duncan Davidson

    1995-01-01

    The Msx genes of vertebrates comprise a small family of chromosomally unlinked homeobox-containing genes related to the Drosophila gene muscle-segment homeobox (msb). Despite their ancient pedigree, the Msx genes are expressed in a range of vertebrate-specific tissues, including neural crest, cranial sensory placodes, bone and teeth. They are active in numerous systems, which have been used as models to study

  3. Predicting function: from genes to genomes and back1

    Microsoft Academic Search

    Peer Bork; Thomas Dandekar; Yolande Diaz-Lazcoz; Frank Eisenhaber; Martijn Huynen; Yanping Yuan

    1998-01-01

    Predicting function from sequence using computational tools is a highly complicated procedure that is generally done for each gene individually. This review focuses on the added value that is provided by completely sequenced genomes in function prediction. Various levels of sequence annotation and function prediction are discussed, ranging from genomic sequence to that of complex cellular processes. Protein function is

  4. Distinct Functions of Egr Gene Family Members in Cognitive Processes

    PubMed Central

    Poirier, Roseline; Cheval, Hélčne; Mailhes, Caroline; Garel, Sonia; Charnay, Patrick; Davis, Sabrina; Laroche, Serge

    2008-01-01

    The different gene members of the Egr family of transcriptional regulators have often been considered to have related functions in brain, based on their co-expression in many cell-types and structures, the relatively high homology of the translated proteins and their ability to bind to the same consensus DNA binding sequence. Recent research, however, suggest this might not be the case. In this review, we focus on the current understanding of the functional roles of the different Egr family members in learning and memory. We briefly outline evidence from mutant mice that Egr1 is required specifically for the consolidation of long-term memory, while Egr3 is primarily essential for short-term memory. We also review our own recent findings from newly generated forebrain-specific conditional Egr2 mutant mice, which revealed that Egr2, as opposed to Egr1 and Egr3, is dispensable for several forms of learning and memory and on the contrary can act as an inhibitory constraint for certain cognitive functions. The studies reviewed here highlight the fact that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain. PMID:18982106

  5. Role of G-protein-coupled receptor-related genes in insecticide resistance of the mosquito, Culex quinquefasciatus.

    PubMed

    Li, Ting; Liu, Lena; Zhang, Lee; Liu, Nannan

    2014-01-01

    G-protein-coupled receptors regulate signal transduction pathways and play diverse and pivotal roles in the physiology of insects, however, the precise function of GPCRs in insecticide resistance remains unclear. Using quantitative RT-PCR and functional genomic methods, we, for the first time, explored the function of GPCRs and GPCR-related genes in insecticide resistance of mosquitoes, Culex quinquefasciatus. A comparison of the expression of 115 GPCR-related genes at a whole genome level between resistant and susceptible Culex mosquitoes identified one and three GPCR-related genes that were up-regulated in highly resistant Culex mosquito strains, HAmCq(G8) and MAmCq(G6), respectively. To characterize the function of these up-regulated GPCR-related genes in resistance, the up-regulated GPCR-related genes were knockdown in HAmCq(G8) and MAmCq(G6) using RNAi technique. Knockdown of these four GPCR-related genes not only decreased resistance of the mosquitoes to permethrin but also repressed the expression of four insecticide resistance-related P450 genes, suggesting the role of GPCR-related genes in resistance is involved in the regulation of resistance P450 gene expression. This results help in understanding of molecular regulation of resistance development in Cx. quinquefasciatus. PMID:25262705

  6. Combining many interaction networks to predict gene function and analyze gene lists.

    PubMed

    Mostafavi, Sara; Morris, Quaid

    2012-05-01

    In this article, we review how interaction networks can be used alone or in combination in an automated fashion to provide insight into gene and protein function. We describe the concept of a "gene-recommender system" that can be applied to any large collection of interaction networks to make predictions about gene or protein function based on a query list of proteins that share a function of interest. We discuss these systems in general and focus on one specific system, GeneMANIA, that has unique features and uses different algorithms from the majority of other systems. PMID:22589215

  7. Family business: the multidrug-resistance related protein (MRP) ABC transporter genes in Arabidopsis thaliana.

    PubMed

    Kolukisaoglu, H Uner; Bovet, Lucien; Klein, Markus; Eggmann, Thomas; Geisler, Markus; Wanke, Dierk; Martinoia, Enrico; Schulz, Burkhard

    2002-11-01

    Despite the completion of the sequencing of the entire genome of Arabidopsis thaliana (L.) Heynh., the exact determination of each single gene and its function remains an open question. This is especially true for multigene families. An approach that combines analysis of genomic structure, expression data and functional genomics to ascertain the role of the members of the multidrug-resistance-related protein ( MRP) gene family, a subfamily of the ATP-binding cassette (ABC) transporters from Arabidopsis is presented. We used cDNA sequencing and alignment-based re-annotation of genomic sequences to define the exact genic structure of all known AtMRP genes. Analysis of promoter regions suggested different induction conditions even for closely related genes. Expression analysis for the entire gene family confirmed these assumptions. Phylogenetic analysis and determination of segmental duplication in the regions of AtMRP genes revealed that the evolution of the extraordinarily high number of ABC transporter genes in plants cannot solely be explained by polyploidisation during the evolution of the Arabidopsis genome. Interestingly MRP genes from Oryza sativa L. (rice; OsMRP) show very similar genomic structures to those from Arabidopsis. Screening of large populations of T-DNA-mutagenised lines of A. thaliana resulted in the isolation of AtMRP insertion mutants. This work opens the way for the defined analysis of a multigene family of important membrane transporters whose broad variety of functions expands their traditional role as cellular detoxifiers. PMID:12430019

  8. Combining evidence, biomedical literature and statistical dependence: new insights for functional annotation of gene sets

    PubMed Central

    Aubry, Marc; Monnier, Annabelle; Chicault, Celine; de Tayrac, Marie; Galibert, Marie-Dominique; Burgun, Anita; Mosser, Jean

    2006-01-01

    Background Large-scale genomic studies based on transcriptome technologies provide clusters of genes that need to be functionally annotated. The Gene Ontology (GO) implements a controlled vocabulary organised into three hierarchies: cellular components, molecular functions and biological processes. This terminology allows a coherent and consistent description of the knowledge about gene functions. The GO terms related to genes come primarily from semi-automatic annotations made by trained biologists (annotation based on evidence) or text-mining of the published scientific literature (literature profiling). Results We report an original functional annotation method based on a combination of evidence and literature that overcomes the weaknesses and the limitations of each approach. It relies on the Gene Ontology Annotation database (GOA Human) and the PubGene biomedical literature index. We support these annotations with statistically associated GO terms and retrieve associative relations across the three GO hierarchies to emphasise the major pathways involved by a gene cluster. Both annotation methods and associative relations were quantitatively evaluated with a reference set of 7397 genes and a multi-cluster study of 14 clusters. We also validated the biological appropriateness of our hybrid method with the annotation of a single gene (cdc2) and that of a down-regulated cluster of 37 genes identified by a transcriptome study of an in vitro enterocyte differentiation model (CaCo-2 cells). Conclusion The combination of both approaches is more informative than either separate approach: literature mining can enrich an annotation based only on evidence. Text-mining of the literature can also find valuable associated MEDLINE references that confirm the relevance of the annotation. Eventually, GO terms networks can be built with associative relations in order to highlight cooperative and competitive pathways and their connected molecular functions. PMID:16674810

  9. Evolutionary Persistence of Functional Compensation by Duplicate Genes in Arabidopsis

    PubMed Central

    Kuromori, Takashi; Myouga, Fumiyoshi; Toyoda, Tetsuro; Shinozaki, Kazuo

    2009-01-01

    Knocking out a gene from a genome often causes no phenotypic effect. This phenomenon has been explained in part by the existence of duplicate genes. However, it was found that in mouse knockout data duplicate genes are as essential as singleton genes. Here, we study whether it is also true for the knockout data in Arabidopsis. From the knockout data in Arabidopsis thaliana obtained in our study and in the literature, we find that duplicate genes show a significantly lower proportion of knockout effects than singleton genes. Because the persistence of duplicate genes in evolution tends to be dependent on their phenotypic effect, we compared the ages of duplicate genes whose knockout mutants showed less severe phenotypic effects with those with more severe effects. Interestingly, the latter group of genes tends to be more anciently duplicated than the former group of genes. Moreover, using multiple-gene knockout data, we find that functional compensation by duplicate genes for a more severe phenotypic effect tends to be preserved by natural selection for a longer time than that for a less severe effect. Taken together, we conclude that duplicate genes contribute to genetic robustness mainly by preserving compensation for severe phenotypic effects in A. thaliana. PMID:20333209

  10. Saliva Microbiota Carry Caries-Specific Functional Gene Signatures

    PubMed Central

    Chang, Xingzhi; Yuan, Xiao; Tu, Qichao; Yuan, Tong; Deng, Ye; Hemme, Christopher L.; Van Nostrand, Joy; Cui, Xinping; He, Zhili; Chen, Zhenggang; Guo, Dawei; Yu, Jiangbo; Zhang, Yue; Zhou, Jizhong; Xu, Jian

    2014-01-01

    Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis. PMID:24533043

  11. Targeting Fungal Genes by Diced siRNAs: A Rapid Tool to Decipher Gene Function in Aspergillus nidulans

    PubMed Central

    Kalleda, Natarajaswamy; Naorem, Aruna; Manchikatla, Rajam V.

    2013-01-01

    Background Gene silencing triggered by chemically synthesized small interfering RNAs (siRNAs) has become a powerful tool for deciphering gene function in many eukaryotes. However, prediction and validation of a single siRNA duplex specific to a target gene is often ineffective. RNA interference (RNAi) with synthetic siRNA suffers from lower silencing efficacy, off-target effects and is cost-intensive, especially for functional genomic studies. With the explosion of fungal genomic information, there is an increasing need to analyze gene function in a rapid manner. Therefore, studies were performed in order to investigate the efficacy of gene silencing induced by RNase III-diced-siRNAs (d-siRNA) in model filamentous fungus, Aspergillus nidulans. Methodology/Principal Findings Stable expression of heterologous reporter gene in A. nidulans eases the examination of a new RNAi-induction route. Hence, we have optimized Agrobacterium tumefaciens-mediated transformation (AMT) of A. nidulans for stable expression of sGFP gene. This study demonstrates that the reporter GFP gene stably introduced into A. nidulans can be effectively silenced by treatment of GFP-d-siRNAs. We have shown the down-regulation of two endogenous genes, AnrasA and AnrasB of A. nidulans by d-siRNAs. We have also elucidated the function of an uncharacterized Ras homolog, rasB gene, which was found to be involved in hyphal growth and development. Further, silencing potency of d-siRNA was higher as compared to synthetic siRNA duplex, targeting AnrasA. Silencing was shown to be sequence-specific, since expression profiles of other closely related Ras family genes in d-siRNA treated AnrasA and AnrasB silenced lines exhibited no change in gene expression. Conclusions/Significance We have developed and applied a fast, specific and efficient gene silencing approach for elucidating gene function in A. nidulans using d-siRNAs. We have also optimized an efficient AMT in A. nidulans, which is useful for stable integration of transgenes. PMID:24130711

  12. Functional microarray analysis of nitrogen and carbon cycling genes across an Antarctic latitudinal transect.

    PubMed

    Yergeau, Etienne; Kang, Sanghoon; He, Zhili; Zhou, Jizhong; Kowalchuk, George A

    2007-06-01

    Soil-borne microbial communities were examined via a functional gene microarray approach across a southern polar latitudinal gradient to gain insight into the environmental factors steering soil N- and C-cycling in terrestrial Antarctic ecosystems. The abundance and diversity of functional gene families were studied for soil-borne microbial communities inhabiting a range of environments from 51 degrees S (cool temperate-Falkland Islands) to 72 degrees S (cold rock desert-Coal Nunatak). The recently designed functional gene array used contains 24,243 oligonucleotide probes and covers >10,000 genes in >150 functional groups involved in nitrogen, carbon, sulfur and phosphorus cycling, metal reduction and resistance and organic contaminant degradation (He et al. 2007). The detected N- and C-cycle genes were significantly different across different sampling locations and vegetation types. A number of significant trends were observed regarding the distribution of key gene families across the environments examined. For example, the relative detection of cellulose degradation genes was correlated with temperature, and microbial C-fixation genes were more present in plots principally lacking vegetation. With respect to the N-cycle, denitrification genes were linked to higher soil temperatures, and N2-fixation genes were linked to plots mainly vegetated by lichens. These microarray-based results were confirmed for a number of gene families using specific real-time PCR, enzymatic assays and process rate measurements. The results presented demonstrate the utility of an integrated functional gene microarray approach in detecting shifts in functional community properties in environmental samples and provide insight into the forces driving important processes of terrestrial Antarctic nutrient cycling. PMID:18043626

  13. In silico prioritisation of candidate genes for prokaryotic gene function discovery: an application of phylogenetic profiles

    PubMed Central

    Lin, Frank PY; Coiera, Enrico; Lan, Ruiting; Sintchenko, Vitali

    2009-01-01

    Background In silico candidate gene prioritisation (CGP) aids the discovery of gene functions by ranking genes according to an objective relevance score. While several CGP methods have been described for identifying human disease genes, corresponding methods for prokaryotic gene function discovery are lacking. Here we present two prokaryotic CGP methods, based on phylogenetic profiles, to assist with this task. Results Using gene occurrence patterns in sample genomes, we developed two CGP methods (statistical and inductive CGP) to assist with the discovery of bacterial gene functions. Statistical CGP exploits the differences in gene frequency against phenotypic groups, while inductive CGP applies supervised machine learning to identify gene occurrence pattern across genomes. Three rediscovery experiments were designed to evaluate the CGP frameworks. The first experiment attempted to rediscover peptidoglycan genes with 417 published genome sequences. Both CGP methods achieved best areas under receiver operating characteristic curve (AUC) of 0.911 in Escherichia coli K-12 (EC-K12) and 0.978 Streptococcus agalactiae 2603 (SA-2603) genomes, with an average improvement in precision of >3.2-fold and a maximum of >27-fold using statistical CGP. A median AUC of >0.95 could still be achieved with as few as 10 genome examples in each group of genome examples in the rediscovery of the peptidoglycan metabolism genes. In the second experiment, a maximum of 109-fold improvement in precision was achieved in the rediscovery of anaerobic fermentation genes in EC-K12. The last experiment attempted to rediscover genes from 31 metabolic pathways in SA-2603, where 14 pathways achieved AUC >0.9 and 28 pathways achieved AUC >0.8 with the best inductive CGP algorithms. Conclusion Our results demonstrate that the two CGP methods can assist with the study of functionally uncategorised genomic regions and discovery of bacterial gene-function relationships. Our rediscovery experiments also provide a set of standard tasks against which future methods may be compared. PMID:19292914

  14. Incorporating Functional Gene Quantification into Traditional Decomposition Models

    NASA Astrophysics Data System (ADS)

    Todd-Brown, K. E.; Zhou, J.; Yin, H.; Wu, L.; Tiedje, J. M.; Schuur, E. A. G.; Konstantinidis, K.; Luo, Y.

    2014-12-01

    Incorporating new genetic quantification measurements into traditional substrate pool models represents a substantial challenge. These decomposition models are built around the idea that substrate availablity, with environmental drivers, limit carbon dioxide respiration rates. In this paradigm, microbial communities optimally adapt to a given substrate and environment on much shorter time scales then the carbon flux of interest. By characterizing the relative shift in biomass of these microbial communities, we informed previously poorly constrained parameters in traditional decomposition models. In this study we coupled a 9 month laboratory incubation study with quantitative gene measurements with traditional CO2 flux measurements plus initial soil organic carbon quantification. GeoChip 5.0 was used to quantify the functional genes associated with carbon cycling at 2 weeks, 3 months and 9 months. We then combined the genes which 'collapsed' over the experiment and assumed that this tracked the relative change in the biomass associated with the 'fast' pool. We further assumed that this biomass was proportional to the 'fast' SOC pool and thus were able to constrain the relative change in the fast SOC pool in our 3-pool decomposition model. We found that biomass quantification described above, combined with traditional CO2 flux and SOC measurements, improve the transfer coefficient estimation in traditional decomposition models. Transfer coefficients are very difficult to characterized using traditional CO2 flux measurements, thus DNA quantification provides new and significant information about the system. Over a 100 year simulation, these new biologically informed parameters resulted in an additional 10% of SOC loss over the traditionally informed parameters.

  15. ICan: An Integrated Co-Alteration Network to Identify Ovarian Cancer-Related Genes

    PubMed Central

    Zhou, Yuanshuai; Liu, Yongjing; Li, Kening; Zhang, Rui; Qiu, Fujun; Zhao, Ning; Xu, Yan

    2015-01-01

    Background Over the last decade, an increasing number of integrative studies on cancer-related genes have been published. Integrative analyses aim to overcome the limitation of a single data type, and provide a more complete view of carcinogenesis. The vast majority of these studies used sample-matched data of gene expression and copy number to investigate the impact of copy number alteration on gene expression, and to predict and prioritize candidate oncogenes and tumor suppressor genes. However, correlations between genes were neglected in these studies. Our work aimed to evaluate the co-alteration of copy number, methylation and expression, allowing us to identify cancer-related genes and essential functional modules in cancer. Results We built the Integrated Co-alteration network (ICan) based on multi-omics data, and analyzed the network to uncover cancer-related genes. After comparison with random networks, we identified 155 ovarian cancer-related genes, including well-known (TP53, BRCA1, RB1 and PTEN) and also novel cancer-related genes, such as PDPN and EphA2. We compared the results with a conventional method: CNAmet, and obtained a significantly better area under the curve value (ICan: 0.8179, CNAmet: 0.5183). Conclusion In this paper, we describe a framework to find cancer-related genes based on an Integrated Co-alteration network. Our results proved that ICan could precisely identify candidate cancer genes and provide increased mechanistic understanding of carcinogenesis. This work suggested a new research direction for biological network analyses involving multi-omics data. PMID:25803614

  16. Pan-metazoan phylogeny of the DMRT gene family: a framework for functional studies.

    PubMed

    Wexler, Judith R; Plachetzki, David C; Kopp, Artyom

    2014-06-01

    The family of Doublesex-Mab-3 Related Transcription factors (DMRTs) includes key regulators of sexual differentiation and neurogenesis. To help understand the functional diversification of this gene family, we examined DMRT gene complements from the whole genome sequences and predicted gene models of 32 animal species representing 12 different phyla and from several non-metazoan outgroups. DMRTs are present in all animals except the sponge Amphimedon queenslandica, but are not found in any of the outgroups, indicating that this gene family is specific to animals and has an ancient pre-eumetazoan origin. Our analyses suggest that DMRT genes diversified independently in bilaterian and non-bilaterian animals. Most clades in the DMRT gene tree, including those containing the well-characterized DMRT1 and doublesex genes, have phylogenetically limited distributions. PMID:24903586

  17. Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

    PubMed Central

    Pandey, Ashutosh K.; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W.

    2014-01-01

    What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes. PMID:24523945

  18. NHR-23 dependent collagen and hedgehog-related genes required for molting

    PubMed Central

    Kouns, Nathaniel A.; Nakielna, Johana; Behensky, Frantisek; Krause, Michael W.; Kostrouch, Zdenek; Kostrouchova, Marta

    2011-01-01

    NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in C. elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa. PMID:21910973

  19. The Structure of a Gene Co-Expression Network Reveals Biological Functions Underlying eQTLs

    PubMed Central

    Villa-Vialaneix, Nathalie; Liaubet, Laurence; Laurent, Thibault; Cherel, Pierre; Gamot, Adrien; SanCristobal, Magali

    2013-01-01

    What are the commonalities between genes, whose expression level is partially controlled by eQTL, especially with regard to biological functions? Moreover, how are these genes related to a phenotype of interest? These issues are particularly difficult to address when the genome annotation is incomplete, as is the case for mammalian species. Moreover, the direct link between gene expression and a phenotype of interest may be weak, and thus difficult to handle. In this framework, the use of a co-expression network has proven useful: it is a robust approach for modeling a complex system of genetic regulations, and to infer knowledge for yet unknown genes. In this article, a case study was conducted with a mammalian species. It showed that the use of a co-expression network based on partial correlation, combined with a relevant clustering of nodes, leads to an enrichment of biological functions of around 83%. Moreover, the use of a spatial statistics approach allowed us to superimpose additional information related to a phenotype; this lead to highlighting specific genes or gene clusters that are related to the network structure and the phenotype. Three main results are worth noting: first, key genes were highlighted as a potential focus for forthcoming biological experiments; second, a set of biological functions, which support a list of genes under partial eQTL control, was set up by an overview of the global structure of the gene expression network; third, pH was found correlated with gene clusters, and then with related biological functions, as a result of a spatial analysis of the network topology. PMID:23577081

  20. Spaceflight effects on T lymphocyte distribution, function and gene expression.

    PubMed

    Gridley, Daila S; Slater, James M; Luo-Owen, Xian; Rizvi, Asma; Chapes, Stephen K; Stodieck, Louis S; Ferguson, Virginia L; Pecaut, Michael J

    2009-01-01

    The immune system is highly sensitive to stressors present during spaceflight. The major emphasis of this study was on the T lymphocytes in C57BL/6NTac mice after return from a 13-day space shuttle mission (STS-118). Spleens and thymuses from flight animals (FLT) and ground controls similarly housed in animal enclosure modules (AEM) were evaluated within 3-6 h after landing. Phytohemagglutinin-induced splenocyte DNA synthesis was significantly reduced in FLT mice when based on both counts per minute and stimulation indexes (P < 0.05). Flow cytometry showed that CD3(+) T and CD19(+) B cell counts were low in spleens from the FLT group, whereas the number of NK1.1(+) natural killer (NK) cells was increased (P < 0.01 for all three populations vs. AEM). The numerical changes resulted in a low percentage of T cells and high percentage of NK cells in FLT animals (P < 0.05). After activation of spleen cells with anti-CD3 monoclonal antibody, interleukin-2 (IL-2) was decreased, but IL-10, interferon-gamma, and macrophage inflammatory protein-1alpha were increased in FLT mice (P < 0.05). Analysis of cancer-related genes in the thymus showed that the expression of 30 of 84 genes was significantly affected by flight (P < 0.05). Genes that differed from AEM controls by at least 1.5-fold were Birc5, Figf, Grb2, and Tert (upregulated) and Fos, Ifnb1, Itgb3, Mmp9, Myc, Pdgfb, S100a4, Thbs, and Tnf (downregulated). Collectively, the data show that T cell distribution, function, and gene expression are significantly modified shortly after return from the spaceflight environment. PMID:18988762

  1. Exploration of Essential Gene Functions via Titratable Promoter Alleles

    Microsoft Academic Search

    Sanie Mnaimneh; Armaity P Davierwala; Jennifer Haynes; Jason Moffat; Wen-Tao Peng; Wen Zhang; Xueqi Yang; Jeff Pootoolal; Gordon Chua; Andres Lopez; Miles Trochesset; Darcy Morse; Nevan J Krogan; Shawna L Hiley; Zhijian Li; Quaid Morris; Jörg Grigull; Nicholas Mitsakakis; Christopher J Roberts; Jack F Greenblatt; Charles Boone; Chris A Kaiser; Brenda J Andrews; Timothy R Hughes

    2004-01-01

    Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these

  2. Complexity of gene circuits, Pfaan functions and morphogenesis problem

    E-print Network

    Grigoriev, Dima

    with special circuits of the neural type playing a key role in biology [3, 4, 5]. These circuits are dynamicalComplexity of gene circuits, PfaĆan functions and morphogenesis problem Sergey VAKULENKO 1 , Dmitry Rennes, Beaulieu, 35042, Rennes, France Abstract. We consider a model of gene circuits. We show

  3. Genotype and Gene Expression Associations with Immune Function in Drosophila

    E-print Network

    Nachman, Michael

    in genes near the top of the immune system signaling cascade can have a disproportionate effect response to combat pathogens. Unlike vertebrates, the insect immune response consists solely of an innateGenotype and Gene Expression Associations with Immune Function in Drosophila Timothy B. Sackton1

  4. Measuring semantic similarities by combining gene ontology annotations and gene co-function networks

    DOE PAGESBeta

    Peng, Jiajie; Uygun, Sahra; Kim, Taehyong; Wang, Yadong; Rhee, Seung Y; Chen, Jin

    2015-12-01

    Background: Gene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms. Results: We introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstratemore »that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families. Conclusions: Using NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited.« less

  5. Cloning and functional analysis of three genes encoding polygalacturonase-inhibiting proteins from Capsicum annuum and transgenic CaPGIP1 in tobacco in relation to increased resistance to two fungal pathogens.

    PubMed

    Wang, Xiuju; Zhu, Xiaoping; Tooley, Paul; Zhang, Xiuguo

    2013-03-01

    Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall glycoproteins that can inhibit fungal endopolygalacturonases (PGs). The PGIPs directly reduce the aggressive potential of PGs. Here, we isolated and functionally characterized three members of the pepper (Capsicum annuum) PGIP gene family. Each was up-regulated at a different time following stimulation of the pepper leaves by Phytophthora capcisi and abiotic stresses including salicylic acid, methyl jasmonate, abscisic acid, wounding and cold treatment. Purified recombinant proteins individually inhibited activity of PGs produced by Alternaria alternata and Colletotrichum nicotianae, respectively, and virus-induced gene silencing in pepper conferred enhanced susceptibility to P. capsici. Because three PGIP genes acted similarily in conferring resistance to infection by P. capsici, and because individually purified proteins showed consistent inhibition against PG activity of both pathogens, CaPGIP1 was selected for manipulating transgenic tobacco. The crude proteins from transgenic tobacco exhibited distinct enhanced resistance to PG activity of both fungi. Moreover, the transgenic tobacco showed effective resistance to infection and a significant reduction in the number of infection sites, number of lesions and average size of lesions in the leaves. All results suggest that CaPGIPs may be involved in plant defense response and play an important role in a plant's resistance to disease. PMID:23334855

  6. Identification of developmental competence-related genes in mature porcine oocytes

    PubMed Central

    Yuan, Ye; Ida, Jennifer M.; Paczkowski, Melissa; Krisher, Rebecca L.

    2011-01-01

    Oocyte competence is a key factor limiting female fertility, yet the underlying molecular mechanisms that contribute to oocyte competence remain unclear. The objective of this study was to elucidate specific genes whose function contributes to oocyte competence. We observed that 6 of 20 target genes examined were differentially expressed between adult (more competent) and prepubertal (less competent) porcine in vitro matured (IVM) oocytes. These genes were the cholesterol synthesis related gene HMG-CoA reductase (HMGCR), fatty acid oxidation genes acyl-CoA synthetase long-chain family member 3 (ACSL3) and long-chain acyl-CoA dehydrogenase (ACADL), glycolytic genes fructose 1,6 bisphosphate aldolase (ALDOA) and lactate dehydrogenase C (LDHC), and tumor necrosis factor-? (TNF). These 6 genes, as well as 3 other genes (porcine endogenous retrovirus (PERV), transcribed loci 10 (TL10), serine/arginine-rich splicing factor 1 (SRSF1)), were further analyzed by comparing transcript abundance in IVM and in vivo matured (VVM) prepubertal and adult porcine oocytes. Among these 9 target genes, five were differentially expressed between IVM and VVM prepubertal oocytes, while eight genes were differentially expressed between IVM and VVM adult oocytes. None was differentially expressed between VVM prepubertal and adult oocytes. A functional study of TNF demonstrated that depletion of endogenous TNF decreased oocyte competence and TNFAIP6 expression in cumulus cells, while TNF in IVM medium regulated TNFAIP6 expression in cumulus cells. Differential expression of the genes identified in this study suggests that these genes may be functionally relevant to oocyte competence. PMID:21774025

  7. NHR-23 dependent collagen and hedgehog-related genes required for molting

    SciTech Connect

    Kouns, Nathaniel A.; Nakielna, Johana; Behensky, Frantisek [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic)] [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic); Krause, Michael W. [Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)] [Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Kostrouch, Zdenek [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic)] [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic); Kostrouchova, Marta, E-mail: marta.kostrouchova@lf1.cuni.cz [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic)] [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic)

    2011-10-07

    Highlights: {yields} NHR-23 is a critical regulator of nematode development and molting. {yields} The manuscript characterizes the loss-of-function phenotype of an nhr-23 mutant. {yields} Whole genome expression analysis identifies new potential targets of NHR-23. {yields} Hedgehog-related genes are identified as NHR-23 dependent genes. {yields} New link between sterol mediated signaling and regulation by NHR-23 is found. -- Abstract: NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in Caenorhabditis elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.

  8. Islet cell hyperplasia in transgenic mice overexpressing EAT\\/mcl-1, a bcl-2 related gene

    Microsoft Academic Search

    Kenichi Matsushita; Hajime Okita; Atsushi Suzuki; Kouji Shimoda; Mariko Fukuma; Taketo Yamada; Fumihiko Urano; Takahiro Honda; Makoto Sano; Shiro Iwanaga; Satoshi Ogawa; Jun-ichi Hata; Akihiro Umezawa

    2003-01-01

    EAT\\/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1? promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet

  9. Relating Perturbation Magnitude to Temporal Gene Expression in Biological Systems

    SciTech Connect

    Callister, Stephen J.; Parnell, John J.; Pfrender, Michael E.; Hashsham, Syed

    2009-03-19

    A method to quantitatively relate stress to response at the level of gene expression is described using Saccharomyces cerevisiae as a model organism. Stress was defined as the magnitude of perturbation and strain was defined as the magnitude of cumulative response in terms of gene expression. Expression patterns of sixty genes previously reported to be significantly impacted by osmotic shock or belonging to the high-osmotic glycerol, glycerolipid metabolism, and glycolysis pathways were determined following perturbations of increasing sodium chloride concentrations (0, 0.5, 0.7, 1.0, 1.5, and 1.4 M). Expression of these genes was quantified temporally using reverse transcriptase real time polymerase chain reaction. The magnitude of cumulative response was obtained by calculating the total moment of area of the temporal response envelope for all the 60 genes, either together or for the set of genes related to each pathway. A non-linear relationship between stress and response was observed for the range of stress studied. This study examines a quantitative approach to quantify the strain at the level of gene expression to relate stress to strain in biological systems. The approach should be generally applicable to quantitatively evaluate the response of organisms to environmental change.

  10. Functional and structural diversity of the human Dickkopf gene family.

    PubMed

    Krupnik, V E; Sharp, J D; Jiang, C; Robison, K; Chickering, T W; Amaravadi, L; Brown, D E; Guyot, D; Mays, G; Leiby, K; Chang, B; Duong, T; Goodearl, A D; Gearing, D P; Sokol, S Y; McCarthy, S A

    1999-10-01

    Wnt proteins influence many aspects of embryonic development, and their activity is regulated by several secreted antagonists, including the Xenopus Dickkopf-1 (xDkk-1) protein. xDkk-1 inhibits Wnt activities in Xenopus embryos and may play a role in induction of head structures. Here, we characterize a family of human Dkk-related genes composed of Dkk-1, Dkk-2, Dkk-3, and Dkk-4, together with a unique Dkk-3 related protein termed Soggy (Sgy). hDkks 1-4 contain two distinct cysteine-rich domains in which the positions of 10 cysteine residues are highly conserved between family members. Sgy is a novel secreted protein related to Dkk-3 but which lacks the cysteine-rich domains. Members of the Dkk-related family display unique patterns of mRNA expression in human and mouse tissues, and are secreted when expressed in 293T cells. Furthermore, secreted hDkk-2 and hDkk-4 undergo proteolytic processing which results in cleavage of the second cysteine-rich domain from the full-length protein. Members of the human Dkk-related family differ not only in their structures and expression patterns, but also in their abilities to inhibit Wnt signaling. hDkk-1 and hDkk-4, but not hDkk-2, hDkk-3 or Sgy, suppress Wnt-induced secondary axis induction in Xenopus embryos. hDkk-1 and hDkk-4 do not block axis induction triggered either by Xenopus Dishevelled (Xdsh) or Xenopus Frizzled-8 (Xfz8), both of which function to transduce signals from Wnt ligands. Thus, hDkks 1 and 4 may inhibit Wnt activity by a mechanism upstream of Frizzled. Our findings highlight the structural and functional heterogeneity of human Dkk-related proteins. PMID:10570958

  11. Multivariate gene expression analysis reveals functional connectivity changes between normal/tumoral prostates

    PubMed Central

    Fujita, André; Gomes, Luciana Rodrigues; Sato, Joăo Ricardo; Yamaguchi, Rui; Thomaz, Carlos Eduardo; Sogayar, Mari Cleide; Miyano, Satoru

    2008-01-01

    Background Prostate cancer is a leading cause of death in the male population, therefore, a comprehensive study about the genes and the molecular networks involved in the tumoral prostate process becomes necessary. In order to understand the biological process behind potential biomarkers, we have analyzed a set of 57 cDNA microarrays containing ~25,000 genes. Results Principal Component Analysis (PCA) combined with the Maximum-entropy Linear Discriminant Analysis (MLDA) were applied in order to identify genes with the most discriminative information between normal and tumoral prostatic tissues. Data analysis was carried out using three different approaches, namely: (i) differences in gene expression levels between normal and tumoral conditions from an univariate point of view; (ii) in a multivariate fashion using MLDA; and (iii) with a dependence network approach. Our results show that malignant transformation in the prostatic tissue is more related to functional connectivity changes in their dependence networks than to differential gene expression. The MYLK, KLK2, KLK3, HAN11, LTF, CSRP1 and TGM4 genes presented significant changes in their functional connectivity between normal and tumoral conditions and were also classified as the top seven most informative genes for the prostate cancer genesis process by our discriminant analysis. Moreover, among the identified genes we found classically known biomarkers and genes which are closely related to tumoral prostate, such as KLK3 and KLK2 and several other potential ones. Conclusion We have demonstrated that changes in functional connectivity may be implicit in the biological process which renders some genes more informative to discriminate between normal and tumoral conditions. Using the proposed method, namely, MLDA, in order to analyze the multivariate characteristic of genes, it was possible to capture the changes in dependence networks which are related to cell transformation. PMID:19055846

  12. Functional characterization of Nicotiana benthamiana homologs of peanut water deficit-induced genes by virus-induced gene silencing.

    PubMed

    Senthil-Kumar, M; Govind, Geetha; Kang, Li; Mysore, Kirankumar S; Udayakumar, M

    2007-02-01

    Determining the functional role of genes that are differentially regulated during a stress response is challenging. In this study, few water deficit-induced genes from peanut were characterized in Nicotiana benthamiana using virus-induced gene silencing (VIGS) and their relevance for stress adaptation was validated. Twenty-five cDNA clones from peanut water deficit stress-induced cDNA library that had more than 50% nucleotide similarity with N. benthamiana or tomato homologs were selected. VIGS in peanut is not yet feasible and therefore we characterized these 25 genes in N. benthamiana. Increased membrane damage was seen under water deficit stress in most of the silenced plants signifying that many of these stress-induced genes are important to confer drought tolerance. Among the genes tested, silencing by homolog of flavonol 3-O-glucosyltransferase (F3OGT), homolog of alcohol dehydrogenase, homologous to salt inducible protein, and homolog of heat shock protein 70 showed more visible wilting symptoms compared with the control plants during water deficit stress. Interestingly, down-regulation of two genes, homologous to aspartic proteinase 2, and homolog of Jumonji class of transcription factor showed relative drought tolerant phenotypes. F3OGT silenced plants showed more wilting symptoms, membrane damage and chlorophyll degradation than any other silenced plants during water deficit. Our results demonstrate that VIGS approach can be used to characterize and assess the functional relevance of water deficit stress-induced cDNAs in a heterologous species. PMID:16924536

  13. Evolution of Floral Meristem Identity Genes. Analysis of Lolium temulentum Genes Related to APETALA1 and

    E-print Network

    Weigel, Detlef

    Evolution of Floral Meristem Identity Genes. Analysis of Lolium temulentum Genes Related to APETALA formation) of the grass Lolium temulentum is strictly regulated, occurring rapidly on exposure to a single long day (LD). During floral induction, L. temulentum differs significantly from dicot species

  14. Functions of the gene products of Escherichia coli.

    PubMed Central

    Riley, M

    1993-01-01

    A list of currently identified gene products of Escherichia coli is given, together with a bibliography that provides pointers to the literature on each gene product. A scheme to categorize cellular functions is used to classify the gene products of E. coli so far identified. A count shows that the numbers of genes concerned with small-molecule metabolism are on the same order as the numbers concerned with macromolecule biosynthesis and degradation. One large category is the category of tRNAs and their synthetases. Another is the category of transport elements. The categories of cell structure and cellular processes other than metabolism are smaller. Other subjects discussed are the occurrence in the E. coli genome of redundant pairs and groups of genes of identical or closely similar function, as well as variation in the degree of density of genetic information in different parts of the genome. PMID:7508076

  15. Selection and Validation of Reference Genes for Functional Studies in the Calliphoridae Family

    PubMed Central

    Cardoso, Gisele Antoniazzi; Matiolli, Cleverson Carlos; de Azeredo-Espin, Ana Maria Lima; Torres, Tatiana Teixeira

    2014-01-01

    The genera Cochliomyia and Chrysomya contain both obligate and saprophagous flies, which allows the comparison of different feeding habits between closely related species. Among the different strategies for comparing these habits is the use of qPCR to investigate the expression levels of candidate genes involved in feeding behavior. To ensure an accurate measure of the levels of gene expression, it is necessary to normalize the amount of the target gene with the amount of a reference gene having a stable expression across the compared species. Since there is no universal gene that can be used as a reference in functional studies, candidate genes for qPCR data normalization were selected and validated in three Calliphoridae (Diptera) species, Cochliomyia hominivorax Coquerel, Cochliomyia macellaria Fabricius, and Chrysomya albiceps Wiedemann. The expression stability of six genes (Actin, Gapdh, Rp49, Rps17, ?-tubulin, and GstD1) was evaluated among species within the same life stage and between life stages within each species. The expression levels of Actin, Gapdh, and Rp49 were the most stable among the selected genes. These genes can be used as reliable reference genes for functional studies in Calliphoridae using similar experimental settings. PMID:25373149

  16. History of a prolific family: the Hes/Hey-related genes of the annelid Platynereis

    PubMed Central

    2014-01-01

    Background The Hes superfamily or Hes/Hey-related genes encompass a variety of metazoan-specific bHLH genes, with somewhat fuzzy phylogenetic relationships. Hes superfamily members are involved in a variety of major developmental mechanisms in metazoans, notably in neurogenesis and segmentation processes, in which they often act as direct effector genes of the Notch signaling pathway. Results We have investigated the molecular and functional evolution of the Hes superfamily in metazoans using the lophotrochozoan Platynereis dumerilii as model. Our phylogenetic analyses of more than 200 Metazoan Hes/Hey-related genes revealed the presence of five families, three of them (Hes, Hey and Helt) being pan-metazoan. Those families were likely composed of a unique representative in the last common metazoan ancestor. The evolution of the Hes family was shaped by many independent lineage specific tandem duplication events. The expression patterns of 13 of the 15 Hes/Hey-related genes in Platynereis indicate a broad functional diversification. Nevertheless, a majority of these genes are involved in two crucial developmental processes in annelids: neurogenesis and segmentation, resembling functions highlighted in other animal models. Conclusions Combining phylogenetic and expression data, our study suggests an unusual evolutionary history for the Hes superfamily. An ancestral multifunctional annelid Hes gene may have undergone multiples rounds of duplication-degeneration-complementation processes in the lineage leading to Platynereis, each gene copies ensuring their maintenance in the genome by subfunctionalisation. Similar but independent waves of duplications are at the origin of the multiplicity of Hes genes in other metazoan lineages. PMID:25250171

  17. Mining Disease-Resistance Genes in Roses: Functional and Molecular Characterization of the Rdr1 Locus

    PubMed Central

    Terefe-Ayana, Diro; Yasmin, Aneela; Le, Thanh Loan; Kaufmann, Helgard; Biber, Anja; Kühr, Astrid; Linde, Marcus; Debener, Thomas

    2011-01-01

    The interaction of roses with the leaf spot pathogen Diplocarpon rosae (the cause of black spot on roses) is an interesting pathosystem because it involves a long-lived woody perennial, with life history traits very different from most model plants, and a hemibiotrophic pathogen with moderate levels of gene flow. Here we present data on the molecular structure of the first monogenic dominant resistance gene from roses, Rdr1, directed against one isolate of D. rosae. Complete sequencing of the locus carrying the Rdr1 gene resulted in a sequence of 265,477?bp with a cluster of nine highly related TIR–NBS–LRR (TNL) candidate genes. After sequencing revealed candidate genes for Rdr1, we implemented a gene expression analysis and selected five genes out of the nine TNLs. We then silenced the whole TNL gene family using RNAi (Rdr1–RNAi) constructed from the most conserved sequence region and demonstrated a loss of resistance in the normally resistant genotype. To identify the functional TNL gene, we further screened the five TNL candidate genes with a transient leaf infiltration assay. The transient expression assay indicated a single TNL gene (muRdr1H), partially restoring resistance in the susceptible genotype. Rdr1 was found to localize within the muRdr1 gene family; the genes within this locus contain characteristic motifs of active TNL genes and belong to a young cluster of R genes. The transient leaf assay can be used to further analyze the rose black spot interaction and its evolution, extending the analyses to additional R genes and to additional pathogenic types of the pathogen. PMID:22639591

  18. Characterization of transformation related genes in oral cancer cells

    Microsoft Academic Search

    David D Chang; No-Hee Park; Christopher T Denny; Stanley F Nelson; Mark Pe

    1998-01-01

    A cDNA representational difference analysis (cDNA-RDA) and an arrayed filter technique were used to characterize transformation-related genes in oral cancer. From an initial comparison of normal oral epithelial cells and a human papilloma virus (HPV)-immortalized oral epithelial cell line, we obtained 384 differentially expressed gene fragments and arrayed them on a filter. Two hundred and twelve redundant clones were identified

  19. Consequences of recurrent gene flow from crops to wild relatives.

    PubMed

    Haygood, Ralph; Ives, Anthony R; Andow, David A

    2003-09-22

    Concern about gene flow from crops to wild relatives has become widespread with the increasing cultivation of transgenic crops. Possible consequences of such gene flow include genetic assimilation, wherein crop genes replace wild ones, and demographic swamping, wherein hybrids are less fertile than their wild parents, and wild populations shrink. Using mathematical models of a wild population recurrently receiving pollen from a genetically fixed crop, we find that the conditions for genetic assimilation are not stringent, and progress towards replacement can be fast, even for disfavoured crop genes. Demographic swamping and genetic drift relax the conditions for genetic assimilation and speed progress towards replacement. Genetic assimilation can involve thresholds and hysteresis, such that a small increase in immigration can lead to fixation of a disfavoured crop gene that had been maintained at a moderate frequency, even if the increase in immigration is cancelled before the gene fixes. Demographic swamping can give rise to 'migrational meltdown', such that a small increase in immigration can lead to not only fixation of a disfavoured crop gene but also drastic shrinkage of the wild population. These findings suggest that the spread of crop genes in wild populations should be monitored more closely. PMID:14561300

  20. A graphic method for identification of novel glioma related genes.

    PubMed

    Gao, Yu-Fei; Shu, Yang; Yang, Lei; He, Yi-Chun; Li, Li-Peng; Huang, GuaHua; Li, Hai-Peng; Jiang, Yang

    2014-01-01

    Glioma, as the most common and lethal intracranial tumor, is a serious disease that causes many deaths every year. Good comprehension of the mechanism underlying this disease is very helpful to design effective treatments. However, up to now, the knowledge of this disease is still limited. It is an important step to understand the mechanism underlying this disease by uncovering its related genes. In this study, a graphic method was proposed to identify novel glioma related genes based on known glioma related genes. A weighted graph was constructed according to the protein-protein interaction information retrieved from STRING and the well-known shortest path algorithm was employed to discover novel genes. The following analysis suggests that some of them are related to the biological process of glioma, proving that our method was effective in identifying novel glioma related genes. We hope that the proposed method would be applied to study other diseases and provide useful information to medical workers, thereby designing effective treatments of different diseases. PMID:25050377

  1. Age and Gender Related Differences in Human Parotid Gland Gene Expression

    PubMed Central

    Srivastava, Alaka; Wang, Jianghua; Zhou, Hui; Melvin, James E.; Wong, David T.

    2008-01-01

    Objective The present study evaluated differences in gene expression associated with age and gender in the human parotid gland. Design Parotid gland tissue was analyzed using the Affymetrix® GeneChip® HGU133plus2.0 array. Results Differential gene expression, defined as a statistically significant difference with a 1.5 fold or greater change, was detected in 787 gene probe sets; 467 (~59%) showed higher expression in females. Several genes associated with saliva secretion were differentially expressed in male and female parotid glands including vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated protein SNAP23, RAS oncogene family member RAB1A and the syntaxin binding protein STXBP1. Evaluation of gene expression in the youngest and the oldest female subjects revealed that the expression of 228 probe sets were altered during aging; 155 genes were up-regulated in the aged female parotid gland. However, of the genes that were altered during aging, 22 of the 30 probes (73%) classified as being associated with immune responses were down-regulated in the aged parotid gland. A panel of differentially expressed, age- and gender-related genes was selected for validation by quantitative, real-time RT-PCR. Comparable differences in gene expression were detected by both Affymetrix array and quantitative, real-time RT-PCR methods. Conclusions Our data suggest that salivary gland function may be adversely affected in the aged population due, at least in part, to the altered regulation of several categories of genes. Moreover, the gender specific differences in gene expression identified in the present study correlate with the previously observed sexual dimorphism in salivary gland function. PMID:18571147

  2. Rapid Determination of Gene Function by Virus-induced Gene Silencing in Wheat and Barley

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cereal crops are essential components to the human and animal food supply. Solutions to many of the problems challenging cereal production will require identification of genes responsible for particular traits. Unfortunately, the process of identifying gene function is very slow and complex in...

  3. Differential Selection on Carotenoid Biosynthesis Genes as a Function of Gene Position in the Metabolic Pathway

    E-print Network

    Paris-Sud XI, Université de

    Differential Selection on Carotenoid Biosynthesis Genes as a Function of Gene Position in controlling metabolic fluxes. This hypothesis was tested in the carotenoid biosynthesis pathway using distributed along the carotenoid biosynthesis pathway, IPI, PDS, CRTISO, LCYB, LCYE, CHXE and ZEP, were

  4. Predicting Gene-Regulation Functions: Lessons from Temperate Bacteriophages

    PubMed Central

    Teif, Vladimir B.

    2010-01-01

    Gene-regulation functions (GRF) provide a unique characteristic of a cis-regulatory module (CRM), relating the concentrations of transcription factors (input) to the promoter activities (output). The challenge is to predict GRFs from the sequence. Here we systematically consider the lysogeny-lysis CRMs of different temperate bacteriophages such as the Lactobacillus casei phage A2, Escherichia coli phages ?, and 186 and Lactococcal phage TP901-1. This study allowed explaining a recent experimental puzzle on the role of Cro protein in the lambda switch. Several general conclusions have been drawn: 1), long-range interactions, multilayer assembly and DNA looping may lead to complex GRFs that cannot be described by linear functions of binding site occupancies; 2), in general, GRFs cannot be described by the Boolean logic, whereas a three-state non-Boolean logic suffices for the studied examples; 3), studied CRMs of the intact phages seemed to have a similar GRF topology (the number of plateaus and peaks corresponding to different expression regimes); we hypothesize that functionally equivalent CRMs might have topologically equivalent GRFs for a larger class of genetic systems; and 4) within a given GRF class, a set of mechanistic-to-mathematical transformations has been identified, which allows shaping the GRF before carrying out a system-level analysis. PMID:20371324

  5. Mapping of a family of heterogeneous nuclear ribonucleoprotein [hnRNP] genes related to the fragile X gene - fmr1

    SciTech Connect

    Srinivasan, S.; Siomi, M.; Siomi, H. [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

    1994-09-01

    RNA binding proteins are involved in a wide range of cellular processes in the nucleus and cytoplasm including regulation of pre-mRNA splicing, mRNA stability, translation efficiency and the transport of RNAs between the nucleus and the cytoplasm. The gene involved in the Fragile X syndrome encodes a protein that contains two types of sequence motifs found in RNA binding proteins: an RGG box as seen in hnRNP U and two KH (hnRNP K homology) domains. The FMR1 gene product binds RNA in vitro and a missense mutation in a highly conserved isoleucine residue in the KH domain of fmr1 impairs RNA binding, demonstrating the importance of the KH domain in the RNA binding ability of FMR1. We have identified a new gene, fxr1 (fmr1 cross-hybridizing related), that bears striking homology to the fmr1 gene. The two genes are highly homologous at the amino acid level. Fxr1 has two KH domains, as does fmr1. This suggests that fmr1 may be only one of a family of RNA binding proteins that have yet to be characterized, but are potentially important for normal cellular function. We are systematically mapping hnRNP genes related to fmrl as a first step towards investigating the role of these proteins in human disease states. We have mapped fxr1 to chromosome 12 using a somatic cell hybrid panel and are currently using YACs containing fxr1 to perform FISH to further pinpoint the exact location of fxr1. HnRNP K and U share common sequence motifs with fmr1 and fxr1 that seem to be important for RNA binding function. We are also mapping these genes by both somatic cell hybrid panels and by FISH with the corresponding YACs.

  6. Rapid evolution of sex-related genes in?Chlamydomonas

    PubMed Central

    Ferris, Patrick J.; Pavlovic, Christopher; Fabry, Stefan; Goodenough, Ursula W.

    1997-01-01

    Biological speciation ultimately results in prezygotic isolation—the inability of incipient species to mate with one another–but little is understood about the selection pressures and genetic changes that generate this outcome. The genus Chlamydomonas comprises numerous species of unicellular green algae, including numerous geographic isolates of the species C. reinhardtii. This diverse collection has allowed us to analyze the evolution of two sex-related genes: the mid gene of C. reinhardtii, which determines whether a gamete is mating-type plus or minus, and the fus1 gene, which dictates a cell surface glycoprotein utilized by C. reinhardtii plus gametes to recognize minus gametes. Low stringency Southern analyses failed to detect any fus1 homologs in other Chlamydomonas species and detected only one mid homolog, documenting that both genes have diverged extensively during the evolution of the lineage. The one mid homolog was found in C. incerta, the species in culture that is most closely related to C. reinhardtii. Its mid gene carries numerous nonsynonymous and synonymous codon changes compared with the C. reinhardtii mid gene. In contrast, very high sequence conservation of both the mid and fus1 sequences is found in natural isolates of C. reinhardtii, indicating that the genes are not free to drift within a species but do diverge dramatically between species. Striking divergence of sex determination and mate recognition genes also has been encountered in a number of other eukaryotic phyla, suggesting that unique, and as yet unidentified, selection pressures act on these classes of genes during the speciation process. PMID:9238029

  7. Duplication and relocation of the functional DPY19L2 gene within low copy repeats

    Microsoft Academic Search

    Andrew R Carson; Joseph Cheung; Stephen W Scherer

    2006-01-01

    BACKGROUND: Low copy repeats (LCRs) are thought to play an important role in recent gene evolution, especially when they facilitate gene duplications. Duplicate genes are fundamental to adaptive evolution, providing substrates for the development of new or shared gene functions. Moreover, silencing of duplicate genes can have an indirect effect on adaptive evolution by causing genomic relocation of functional genes.

  8. Complex genomic rearrangements lead to novel primate gene function

    PubMed Central

    Ciccarelli, Francesca D.; von Mering, Christian; Suyama, Mikita; Harrington, Eoghan D.; Izaurralde, Elisa; Bork, Peer

    2005-01-01

    Orthologous genes that maintain a single-copy status in a broad range of species may indicate a selection against gene duplication. If this is the case, then duplicates of such genes that do survive may have escaped the dosage control by rapid and sizable changes in their function. To test this hypothesis and to develop a strategy for the identification of novel gene functions, we have analyzed 22 primate-specific intrachromosomal duplications of genes with a single-copy ortholog in all other completely sequenced metazoans. When comparing this set to genes not exposed to the single-copy status constraint, we observed a higher tendency of the former to modify their gene structure, often through complex genomic rearrangements. The analysis of the most dramatic of these duplications, affecting ?10% of human Chromosome 2, enabled a detailed reconstruction of the events leading to the appearance of a novel gene family. The eight members of this family originated from the highly conserved nucleoporin RanBP2 by several genetic rearrangements such as segmental duplications, inversions, translocations, exon loss, and domain accretion. We have experimentally verified that at least one of the newly formed proteins has a cellular localization different from RanBP2's, and we show that positive selection did act on specific domains during evolution. PMID:15710750

  9. Functional Characterization of the dRYBP Gene in Drosophila

    PubMed Central

    González, Inma; Aparicio, Ricardo; Busturia, Ana

    2008-01-01

    The Drosophila dRYBP gene has been described to function as a Polycomb-dependent transcriptional repressor. To determine the in vivo function of the dRYBP gene, we have generated mutations and analyzed the associated phenotypes. Homozygous null mutants die progressively throughout development and present phenotypes variable both in their penetrance and in their expressivity, including disrupted oogenesis, a disorganized pattern of the syncytial nuclear divisions, defects in pattern formation, and decreased wing size. Although dRYBP mutations do not show the homeotic-like phenotypes typical of mutations in the PcG and trxG genes, they enhance the phenotypes of mutations of either the Sex comb extra gene (PcG) or the trithorax gene (trxG). Finally, the dRYBP protein interacts physically with the Sex comb extra and the Pleiohomeotic proteins, and the homeotic-like phenotypes produced by the high levels of the dRYBP protein are mediated through its C-terminal domain. Our results indicate that the dRYBP gene functions in the control of cell identity together with the PcG/trxG proteins. Furthermore, they also indicate that dRYBP participates in the control of cell proliferation and cell differentiation and we propose that its functional requirement may well depend on the robustness of the animal. PMID:18562658

  10. COMT but not serotonin-related genes modulates the influence of childhood abuse on anger traits

    PubMed Central

    Perroud, Nader; Jaussent, Isabelle; Guillaume, Sébastien; Bellivier, Frank; Baud, Patrick; Jollant, Fabrice; Leboyer, Marion; Lewis, Cathryn; Malafosse, Alain; Courtet, Philippe

    2010-01-01

    Anger-related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger-related traits in 875 adult suicide attempters. The State-Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences respectively. The functional polymorphism of the catecholamine-O-methyl-transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger-trait level (p=0.001). In the presence of sexual abuse, individuals carrying the Val high-activity allele displayed greater disposition towards anger than individuals homozygous for the Met allele (p=0.0003). Notably, none of the serotonin-related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger-trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition towards anger, and replication in healthy subjects is needed. PMID:20002200

  11. Identification of oxysterol 7alpha-hydroxylase (Cyp7b1) as a novel retinoid-related orphan receptor alpha (RORalpha) (NR1F1) target gene and a functional cross-talk between RORalpha and liver X receptor (NR1H3).

    PubMed

    Wada, Taira; Kang, Hong Soon; Angers, Martin; Gong, Haibiao; Bhatia, Shikha; Khadem, Shaheen; Ren, Songrong; Ellis, Ewa; Strom, Stephen C; Jetten, Anton M; Xie, Wen

    2008-03-01

    The retinoid-related orphan receptors (RORs) and liver X receptors (LXRs) were postulated to have distinct functions. RORs play a role in tissue development and circadian rhythm, whereas LXRs are sterol sensors that affect lipid homeostasis. In this study, we revealed a novel function of RORalpha (NR1F1) in regulating the oxysterol 7alpha-hydroxylase (Cyp7b1), an enzyme critical for the homeostasis of cholesterol, bile acids, and oxysterols. The expression of Cyp7b1 gene was suppressed in the RORalpha null (RORalpha(sg/sg)) mice, suggesting RORalpha as a positive regulator of Cyp7b1. Promoter analysis established Cyp7b1 as a transcriptional target of RORalpha, and transfection of RORalpha induced the expression of endogenous Cyp7b1 in the liver. Interestingly, Cyp7b1 regulation seemed to be RORalpha-specific, because RORgamma had little effect. Reporter gene analysis showed that the activation of Cyp7b1 gene promoter by RORalpha was suppressed by LXRalpha (NR1H3), whereas RORalpha inhibited both the constitutive and ligand-dependent activities of LXRalpha. The mutual suppression between RORalpha and LXR was supported by the in vivo observation that loss of RORalpha increased the expression of selected LXR target genes, leading to hepatic triglyceride accumulation. Likewise, mice deficient of LXR alpha and beta isoforms showed activation of selected RORalpha target genes. Our results have revealed a novel role for RORalpha and a functional interplay between RORalpha and LXR in regulating endo- and xenobiotic genes, which may have broad implications in metabolic homeostasis. PMID:18055760

  12. Age-related gene expression in Tourette syndrome.

    PubMed

    Lit, Lisa; Enstrom, Amanda; Sharp, Frank R; Gilbert, Donald L

    2009-01-01

    Because infection and immune responses have been implicated in the pathogenesis of Tourette syndrome (TS), we hypothesized that children with TS would have altered gene expression in blood compared to controls. In addition, because TS symptoms in childhood vary with age, we tested whether gene expression changes that occur with age in TS differ from normal control children. Whole blood was obtained from 30 children and adolescents with TS and 28 healthy children and adolescents matched for age, race, and gender. Gene expression (RNA) was assessed using whole genome Affymetrix microarrays. Age was analyzed as a continuous covariate and also stratified into three groups: 5-9 (common age for tic onset), 10-12 (when tics often peak), and 13-16 (tics may begin to wane). No global differences were found between TS and controls. However, expression of many genes and multiple pathways differed between TS and controls within each age group (5-9, 10-12, and 13-16), including genes involved in the immune-synapse, and proteasome- and ubiquitin-mediated proteolysis pathways. Notably, across age strata, expression of interferon response, viral processing, natural killer and cytotoxic T-lymphocyte cell genes differed. Our findings suggest age-related interferon, immune and protein degradation gene expression differences between TS and controls. PMID:18485367

  13. Additive functions in boolean models of gene regulatory network modules.

    PubMed

    Darabos, Christian; Di Cunto, Ferdinando; Tomassini, Marco; Moore, Jason H; Provero, Paolo; Giacobini, Mario

    2011-01-01

    Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome's evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a boolean model. We use two sub-networks of biological organisms, the yeast cell-cycle and the mouse embryonic stem cell, as topological support for our system. On these structures, we substitute the original random update functions by a novel threshold-based dynamic function in which the promoting and repressing effect of each interaction is considered. We use a third real-life regulatory network, along with its inferred boolean update functions to validate the proposed update function. Results of this validation hint to increased biological plausibility of the threshold-based function. To investigate the dynamical behavior of this new model, we visualized the phase transition between order and chaos into the critical regime using Derrida plots. We complement the qualitative nature of Derrida plots with an alternative measure, the criticality distance, that also allows to discriminate between regimes in a quantitative way. Simulation on both real-life genetic regulatory networks show that there exists a set of parameters that allows the systems to operate in the critical region. This new model includes experimentally derived biological information and recent discoveries, which makes it potentially useful to guide experimental research. The update function confers additional realism to the model, while reducing the complexity and solution space, thus making it easier to investigate. PMID:22132067

  14. Identification of genes related to beak deformity of chickens using digital gene expression profiling.

    PubMed

    Bai, Hao; Zhu, Jing; Sun, Yanyan; Liu, Ranran; Liu, Nian; Li, Dongli; Wen, Jie; Chen, Jilan

    2014-01-01

    Frequencies of up to 3% of beak deformity (normally a crossed beak) occur in some indigenous chickens in China, such as and Beijing-You. Chickens with deformed beaks have reduced feed intake, growth rate, and abnormal behaviors. Beak deformity represents an economic as well as an animal welfare problem in the poultry industry. Because the genetic basis of beak deformity remains incompletely understood, the present study sought to identify important genes and metabolic pathways involved in this phenotype. Digital gene expression analysis was performed on deformed and normal beaks collected from Beijing-You chickens to detect global gene expression differences. A total of >11 million cDNA tags were sequenced, and 5,864,499 and 5,648,877 clean tags were obtained in the libraries of deformed and normal beaks, respectively. In total, 1,156 differentially expressed genes (DEG) were identified in the deformed beak with 409 being up-regulated and 747 down-regulated in the deformed beaks. qRT-PCR using eight genes was performed to verify the results of DGE profiling. Gene ontology (GO) analysis highlighted that genes of the keratin family on GGA25 were abundant among the DEGs. Pathway analysis showed that many DEGs were linked to the biosynthesis of unsaturated fatty acids and glycerolipid metabolism. Combining the analyses, 11 genes (MUC, LOC426217, BMP4, ACAA1, LPL, ALDH7A1, GLA, RETSAT, SDR16C5, WWOX, and MOGAT1) were highlighted as potential candidate genes for beak deformity in chickens. Some of these genes have been identified previously, while others have unknown function with respect to thus phenotype. To the best of our knowledge, this is the first genome-wide study to investigate the transcriptome differences in the deformed and normal beaks of chickens. The DEGs identified here are worthy of further functional characterization. PMID:25198128

  15. Stochastic gene expression modeling with Hill function for switch-like gene responses.

    PubMed

    Kim, Haseong; Gelenbe, Erol

    2012-01-01

    Gene expression models play a key role to understand the mechanisms of gene regulation whose aspects are grade and switch-like responses. Though many stochastic approaches attempt to explain the gene expression mechanisms, the Gillespie algorithm which is commonly used to simulate the stochastic models requires additional gene cascade to explain the switch-like behaviors of gene responses. In this study, we propose a stochastic gene expression model describing the switch-like behaviors of a gene by employing Hill functions to the conventional Gillespie algorithm. We assume eight processes of gene expression and their biologically appropriate reaction rates are estimated based on published literatures. We observed that the state of the system of the toggled switch model is rarely changed since the Hill function prevents the activation of involved proteins when their concentrations stay below a criterion. In ScbA-ScbR system, which can control the antibiotic metabolite production of microorganisms, our modified Gillespie algorithm successfully describes the switch-like behaviors of gene responses and oscillatory expressions which are consistent with the published experimental study. PMID:22144531

  16. Tributyltin increases the expression of apoptosis- and adipogenesis-related genes in rat ovaries

    PubMed Central

    Lee, Hyojin; Lim, Sojeong; Yun, Sujin; Yoon, Ayoung; Park, Gayoung

    2012-01-01

    Objective Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease ovarian function by causing apoptosis in the ovary, but the mechanism is not fully understood. Therefore, we examined whether TBT increases the expression of adipogenesis-related genes in the ovary and the increased expression of these genes is associated with apoptosis induction. Methods Three-week-old Sprague-Dawley rats were orally administered TBT (1 or 10 mg/kg body weight) or sesame oil as a control for 7 days. The ovaries were obtained and weighed on day 8, and then they were fixed for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or frozen for RNA extraction. Using the total RNA of the ovaries, adipogenesis- and apoptosis-related genes were analyzed by real-time polymerase chain reaction (PCR). Results The ovarian weight was significantly decreased in rats administered 10 mg/kg TBT compared to that in control rats. As determined by the TUNEL assay, the number of apoptotic follicles in ovary was significantly increased in rats administered 10 mg/kg TBT. The real-time PCR results showed that the expression of adipogenesis-related genes such as PPAR?, aP2, CD36, and PEPCK was increased after TBT administration. In addition, apoptosis-related genes such as TNF? and TNFR1 were expressed more in the TBT-administered rats compared with the control rats. Conclusion The present study demonstrates that TBT induces the expression of adipogenesis- and apoptosis-related genes in the ovary leading to apoptosis in the ovarian follicles. These results suggest that the increased expression of adipogenesis-related genes in the ovary by TBT exposure might induce apoptosis resulting in a loss of ovarian function. PMID:22563546

  17. EpilepsyGene: a genetic resource for genes and mutations related to epilepsy

    PubMed Central

    Ran, Xia; Li, Jinchen; Shao, Qianzhi; Chen, Huiqian; Lin, Zhongdong; Sun, Zhong Sheng; Wu, Jinyu

    2015-01-01

    Epilepsy is one of the most prevalent chronic neurological disorders, afflicting about 3.5–6.5 per 1000 children and 10.8 per 1000 elderly people. With intensive effort made during the last two decades, numerous genes and mutations have been published to be associated with the disease. An organized resource integrating and annotating the ever-increasing genetic data will be imperative to acquire a global view of the cutting-edge in epilepsy research. Herein, we developed EpilepsyGene (http://61.152.91.49/EpilepsyGene). It contains cumulative to date 499 genes and 3931 variants associated with 331 clinical phenotypes collected from 818 publications. Furthermore, in-depth data mining was performed to gain insights into the understanding of the data, including functional annotation, gene prioritization, functional analysis of prioritized genes and overlap analysis focusing on the comorbidity. An intuitive web interface to search and browse the diversified genetic data was also developed to facilitate access to the data of interest. In general, EpilepsyGene is designed to be a central genetic database to provide the research community substantial convenience to uncover the genetic basis of epilepsy. PMID:25324312

  18. Drosha Regulates Gene Expression Independently of RNA Cleavage Function

    PubMed Central

    Gromak, Natalia; Dienstbier, Martin; Macias, Sara; Plass, Mireya; Eyras, Eduardo; Cáceres, Javier F.; Proudfoot, Nicholas J.

    2013-01-01

    Summary Drosha is the main RNase III-like enzyme involved in the process of microRNA (miRNA) biogenesis in the nucleus. Using whole-genome ChIP-on-chip analysis, we demonstrate that, in addition to miRNA sequences, Drosha specifically binds promoter-proximal regions of many human genes in a transcription-dependent manner. This binding is not associated with miRNA production or RNA cleavage. Drosha knockdown in HeLa cells downregulated nascent gene transcription, resulting in a reduction of polyadenylated mRNA produced from these gene regions. Furthermore, we show that this function of Drosha is dependent on its N-terminal protein-interaction domain, which associates with the RNA-binding protein CBP80 and RNA Polymerase II. Consequently, we uncover a previously unsuspected RNA cleavage-independent function of Drosha in the regulation of human gene expression. PMID:24360955

  19. proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS PFP: Automated prediction of gene ontology

    E-print Network

    Kihara, Daisuke

    proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS PFP: Automated prediction of gene ontology functional introduced PFP (Protein Function Prediction) as our sequence-based predictor of Gene Ontology (GO) functional

  20. Common polymorphisms in dopamine-related genes combine to produce a ‘schizophrenia-like' prefrontal hypoactivity

    PubMed Central

    Vercammen, A; Weickert, C S; Skilleter, A J; Lenroot, R; Schofield, P R; Weickert, T W

    2014-01-01

    Individual changes in dopamine-related genes influence prefrontal activity during cognitive-affective processes; however, the extent to which common genetic variations combine to influence prefrontal activity is unknown. We assessed catechol-O-methyltransferase (COMT) Val108/158Met (rs4680) and dopamine D2 receptor (DRD2) G-T (rs2283265) single nucleotide polymorphisms and functional magnetic resonance imaging during an emotional response inhibition test in 43 healthy adults and 27 people with schizophrenia to determine the extent to which COMT Val108/158Met and DRD2 G-T polymorphisms combine to influence prefrontal response to cognitive-affective challenges. We found an increased number of cognitive-deficit risk alleles in these two dopamine-regulating genes predict reduced prefrontal activation during response inhibition in healthy adults, mimicking schizophrenia-like prefrontal hypoactivity. Our study provides evidence that functionally related genes can combine to produce a disease-like endophenotype. PMID:24495967

  1. Dynamic nature of a wheat centromere with a functional gene

    Microsoft Academic Search

    Jasdeep S. Mutti; Devinder Sandhu; Deepak Sidhu; Kulvinder S. Gill

    2010-01-01

    Centromeric regions of higher eukaryotes are comprised mainly of tandem and non-tandem repeat sequences with variable copy\\u000a number, spacing, order and orientation; are heterochromatic in nature, and are believed to be devoid of actively transcribing\\u000a genes. Here, we report an actively transcribing wheat homolog of HSP70 gene that maps in the functional wheat centromere, and copy number of which seems

  2. Functions of rol genes in plant secondary metabolism

    Microsoft Academic Search

    Victor P. Bulgakov

    2008-01-01

    For a long time, the Agrobacterium rhizogenes rolA, rolB and rolC oncogenes have been considered to be modulators of plant growth and cell differentiation. A new function of the rol genes in plant–Agrobacterium interaction became apparent with the discovery that these genes are potential activators of secondary metabolism in transformed cells from the Solanaceae, Araliaceae, Rubiaceae, Vitaceae and Rosaceae families.

  3. The Innate Immune-Related Genes in Catfish

    PubMed Central

    Gao, Lei; He, Chongbo; Liu, Xueguang; Su, Hao; Gao, Xianggang; Li, Yunfeng; Liu, Weidong

    2012-01-01

    Catfish is one of the most important aquaculture species in America (as well as in Asia and Africa). In recent years, the production of catfish has suffered massive financial losses due to pathogen spread and breakouts. Innate immunity plays a crucial role in increasing resistance to pathogenic organisms and has generated increasing interest in the past few years. This review summarizes the current understanding of innate immune-related genes in catfish, including pattern recognition receptors, antimicrobial peptides, complements, lectins, cytokines, transferrin and gene expression profiling using microarrays and next generation sequencing technologies. This review will benefit the understanding of innate immune system in catfish and further efforts in studying the innate immune-related genes in fish. PMID:23203058

  4. The innate immune-related genes in catfish.

    PubMed

    Gao, Lei; He, Chongbo; Liu, Xueguang; Su, Hao; Gao, Xianggang; Li, Yunfeng; Liu, Weidong

    2012-01-01

    Catfish is one of the most important aquaculture species in America (as well as in Asia and Africa). In recent years, the production of catfish has suffered massive financial losses due to pathogen spread and breakouts. Innate immunity plays a crucial role in increasing resistance to pathogenic organisms and has generated increasing interest in the past few years. This review summarizes the current understanding of innate immune-related genes in catfish, including pattern recognition receptors, antimicrobial peptides, complements, lectins, cytokines, transferrin and gene expression profiling using microarrays and next generation sequencing technologies. This review will benefit the understanding of innate immune system in catfish and further efforts in studying the innate immune-related genes in fish. PMID:23203058

  5. Immune- and ribosome-related genes were associated with systemic vasculitis.

    PubMed

    Gan, S J; Ye, B; Qian, S X; Zhang, C; Mao, J Q; Li, K; Tang, J D

    2015-02-01

    This study aimed to investigate the molecular mechanism of systemic vasculitis via bioinformatics analysis. Gene express profile of E-GEOD-16945 (13 Takayasu arteritis samples and 13 control samples) was downloaded from European Bioinformatics Institute (EBI) database. Differentially expressed genes (DEGs) were screened between Takayasu arteritis and normal controls (|log FC| > 1). Basic local alignment search tool (BLASTX) was used for the Clusters of Orthologous Groups (COG) classification of DEGs. Gene ontology analysis was performed for the DEGs (P < 0.05). A gene expression network was built with DEGs. Mcode in Cytoscape software was used to extract modules from the network (degree ? 2, K-core ? 2 and adjusted P-value < 0.05) followed by pathway analysis using GenMAPP (false discovery rate < 0.05). A total of 747 DEGs were identified. There were 16 significant GO function terms enriched with DEGs, of which immune and defence response was the most significant GO term. Totally, three modules were extracted from gene expression network, including one module constituted with upregulated genes and two modules constituted with downregulated genes. Furthermore, human leucocyte antigen (HLA)-DRB1, HLA-DPA1, HLA-DPB1, HLA-DOA and HLA-DRA in the downregulated modules were significantly linked to immune-related pathways (intestinal immune network for IgA production and systemic lupus erythematosus pathways), while ribosomal protein L 31 (RPL31), RPS3A and RPL9 in the upregulated module were enriched in ribosome pathway. The immune-related pathways, ribosome pathway, immune-related genes including (HLA-DRB1, HLA-DPA1, HLA-DPB1, HLA-DOA and HLA-DRA) and ribosome-related genes (RPL31, RPS3A and RPL9) might be involved in systemic vasculitis. PMID:25410188

  6. RNAi-Mediated Gene Function Analysis in Skin

    PubMed Central

    Beronja, Slobodan; Fuchs, Elaine

    2014-01-01

    We have recently developed a method for RNAi-mediated gene function analysis in skin (Beronja et al., Nat Med 16:821–827, 2010). It employs ultrasound-guided in utero microinjections of lentivirus into the amniotic cavity of embryonic day 9 mice, which result in rapid, efficient, and stable transduction into mouse skin. Our technique greatly extends the available molecular and genetic toolbox for comprehensive functional examination of outstanding problems in epidermal biology. In its simplest form, as a single-gene function analysis via shRNA-mediated gene knockdown, our technique requires no animal mating and may need as little as only a few days between manipulation and phenotypic analysis. PMID:23325656

  7. APOLIPOPROTEIN E GENE AND EARLY AGE-RELATED MACULOPATHY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants from the Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 ye...

  8. Searching for functional gene modules with interaction component models

    PubMed Central

    2010-01-01

    Background Functional gene modules and protein complexes are being sought from combinations of gene expression and protein-protein interaction data with various clustering-type methods. Central features missing from most of these methods are handling of uncertainty in both protein interaction and gene expression measurements, and in particular capability of modeling overlapping clusters. It would make sense to assume that proteins may play different roles in different functional modules, and the roles are evidenced in their interactions. Results We formulate a generative probabilistic model for protein-protein interaction links and introduce two ways for including gene expression data into the model. The model finds interaction components, which can be interpreted as overlapping clusters or functional modules. We demonstrate the performance on two data sets of yeast Saccharomyces cerevisiae. Our methods outperform a representative set of earlier models in the task of finding biologically relevant modules having enriched functional classes. Conclusions Combining protein interaction and gene expression data with a probabilistic generative model improves discovery of modules compared to approaches based on either data source alone. With a fairly simple model we can find biologically relevant modules better than with alternative methods, and in addition the modules may be inherently overlapping in the sense that different interactions may belong to different modules. PMID:20100324

  9. Functional analysis of fungal polyketide biosynthesis genes

    Microsoft Academic Search

    Isao Fujii

    2010-01-01

    Fungal polyketides have huge structural diversity from simple aromatics to highly modified complex reduced-type compounds. Despite such diversty, single modular iterative type I polyketide synthases (iPKSs) are responsible for their carbon skeleton construction. Using heterologous expression systems, we have studied on ATX, a 6-methylsalicylic acid synthase from Aspergillus terreus as a model iPKS. In addition, iPKS functions involved in fungal

  10. Core Promoter Functions in the Regulation of Gene Expression of Drosophila Dorsal Target Genes*

    PubMed Central

    Zehavi, Yonathan; Kuznetsov, Olga; Ovadia-Shochat, Avital; Juven-Gershon, Tamar

    2014-01-01

    Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters consist of core promoter motifs, e.g. the initiator, TATA box, and the downstream core promoter element (DPE), which confer specific properties to the core promoter. Here, we explored the importance of core promoter functions in the dorsal-ventral developmental gene regulatory network. This network includes multiple genes that are activated by different nuclear concentrations of Dorsal, an NF?B homolog transcription factor, along the dorsal-ventral axis. We show that over two-thirds of Dorsal target genes contain DPE sequence motifs, which is significantly higher than the proportion of DPE-containing promoters in Drosophila genes. We demonstrate that multiple Dorsal target genes are evolutionarily conserved and functionally dependent on the DPE. Furthermore, we have analyzed the activation of key Dorsal target genes by Dorsal, as well as by another Rel family transcription factor, Relish, and the dependence of their activation on the DPE motif. Using hybrid enhancer-promoter constructs in Drosophila cells and embryo extracts, we have demonstrated that the core promoter composition is an important determinant of transcriptional activity of Dorsal target genes. Taken together, our results provide evidence for the importance of core promoter composition in the regulation of Dorsal target genes. PMID:24634215

  11. PHYLOGENOMICS - GUIDED VALIDATION OF FUNCTION FOR CONSERVED UNKNOWN GENES

    SciTech Connect

    V, DE CRECY-LAGARD; D, HANSON A

    2012-01-03

    Identifying functions for all gene products in all sequenced organisms is a central challenge of the post-genomic era. However, at least 30-50% of the proteins encoded by any given genome are of unknown function, or wrongly or vaguely annotated. Many of these 'unknown' proteins are common to prokaryotes and plants. We accordingly set out to predict and experimentally test the functions of such proteins. Our approach to functional prediction is integrative, coupling the extensive post-genomic resources available for plants with comparative genomics based on hundreds of microbial genomes, and functional genomic datasets from model microorganisms. The early phase is computer-assisted; later phases incorporate intellectual input from expert plant and microbial biochemists. The approach thus bridges the gap between automated homology-based annotations and the classical gene discovery efforts of experimentalists, and is much more powerful than purely computational approaches to identifying gene-function associations. Among Arabidopsis genes, we focused on those (2,325 in total) that (i) are unique or belong to families with no more than three members, (ii) are conserved between plants and prokaryotes, and (iii) have unknown or poorly known functions. Computer-assisted selection of promising targets for deeper analysis was based on homology .. independent characteristics associated in the SEED database with the prokaryotic members of each family, specifically gene clustering and phyletic spread, as well as availability of functional genomics data, and publications that could link candidate families to general metabolic areas, or to specific functions. In-depth comparative genomic analysis was then performed for about 500 top candidate families, which connected ~55 of them to general areas of metabolism and led to specific functional predictions for a subset of ~25 more. Twenty predicted functions were experimentally tested in at least one prokaryotic organism via reverse genetics, metabolic profiling, functional complementation, and recombinant protein biochemistry. Our approach predicted and validated functions for 10 formerly uncharacterized protein families common to plants and prokaryotes; none of these functions had previously been correctly predicted by computational methods. The functions of five more are currently being validated. Experimental testing of diverse representatives of these families combined with in silica analysis allowed accurate projection of the annotations to hundreds more sequenced genomes.

  12. Gene-Gene Interaction and Functional Impact of Polymorphisms on Innate Immune Genes in Controlling Plasmodium falciparum Blood Infection Level

    PubMed Central

    Basu, Madhumita; Das, Tania; Ghosh, Alip; Majumder, Subhadipa; Maji, Ardhendu Kumar; Kanjilal, Sumana Datta; Mukhopadhyay, Indranil; Roychowdhury, Susanta; Banerjee, Soma; Sengupta, Sanghamitra

    2012-01-01

    Genetic variations in toll-like receptors and cytokine genes of the innate immune pathways have been implicated in controlling parasite growth and the pathogenesis of Plasmodium falciparum mediated malaria. We previously published genetic association of TLR4 non-synonymous and TNF-? promoter polymorphisms with P.falciparum blood infection level and here we extend the study considerably by (i) investigating genetic dependence of parasite-load on interleukin-12B polymorphisms, (ii) reconstructing gene-gene interactions among candidate TLRs and cytokine loci, (iii) exploring genetic and functional impact of epistatic models and (iv) providing mechanistic insights into functionality of disease-associated regulatory polymorphisms. Our data revealed that carriage of AA (P?=?0.0001) and AC (P?=?0.01) genotypes of IL12B 3?UTR polymorphism was associated with a significant increase of mean log-parasitemia relative to rare homozygous genotype CC. Presence of IL12B+1188 polymorphism in five of six multifactor models reinforced its strong genetic impact on malaria phenotype. Elevation of genetic risk in two-component models compared to the corresponding single locus and reduction of IL12B (2.2 fold) and lymphotoxin-? (1.7 fold) expressions in patients'peripheral-blood-mononuclear-cells under TLR4Thr399Ile risk genotype background substantiated the role of Multifactor Dimensionality Reduction derived models. Marked reduction of promoter activity of TNF-? risk haplotype (C-C-G-G) compared to wild-type haplotype (T-C-G-G) with (84%) and without (78%) LPS stimulation and the loss of binding of transcription factors detected in-silico supported a causal role of TNF-1031. Significantly lower expression of IL12B+1188 AA (5 fold) and AC (9 fold) genotypes compared to CC and under-representation (P?=?0.0048) of allele A in transcripts of patients' PBMCs suggested an Allele-Expression-Imbalance. Allele (A+1188C) dependent differential stability (2 fold) of IL12B-transcripts upon actinomycin-D treatment and observed structural modulation (P?=?0.013) of RNA-ensemble were the plausible explanations for AEI. In conclusion, our data provides functional support to the hypothesis that de-regulated receptor-cytokine axis of innate immune pathway influences blood infection level in P. falciparum malaria. PMID:23071570

  13. Hmx homeobox gene function in inner ear and nervous system cell-type specification and development.

    PubMed

    Wang, Weidong; Lufkin, Thomas

    2005-06-10

    The Hmx homeobox gene family is comprised of three members in mammals, Hmx1, Hmx2, and Hmx3, which are conserved across the animal kingdom and are part of the larger NKL clustered family of homeobox genes. Expression domains of Hmx genes in distantly related species such as Drosophila and mouse suggest an ancestral function in rostral central nervous system development. During vertebrate evolution, the Hmx genes appear to have been recruited into additional roles in inner ear morphogenesis and specification of vestibular inner ear sensory and supporting cell types. Being derived from a common ancestor, the vertebrate Hmx gene family is thus a strong candidate to investigate functional overlap versus the unique roles played by multiple genes belonging to the same family. The functions of Hmx2 and Hmx3 were investigated via directed gene mutagenesis and the primary regions where Hmx2 and Hmx3 exert their individual functions are consistent with their expression domains, such as the vestibule and uterus. Meanwhile, it is notable that some tissues where both Hmx2 and Hmx3 are extensively expressed were not severely affected in either of the Hmx2 or Hmx3 single mutant mice, suggesting a possible functional overlap existing between these two genes. Compound Hmx2 and Hmx3 double mutant mice showed more severe defects in the inner ear than those displayed by either single knockout. Furthermore, novel abnormalities in the hypothalamic-neuroendocrine system, which were never observed in either of the single mutant mice, confirmed a hypothesis that Hmx2 and Hmx3 also function redundantly to control embryonic development of the central nervous system. PMID:15925593

  14. Association of genes with physiological functions by comparative analysis of pooled expression microarray data

    PubMed Central

    Chen, Iuan-bor D.; Rathi, Vinay K.; DeAndrade, Diana S.

    2013-01-01

    The physiological functions of a tissue in the body are carried out by its complement of expressed genes. Genes that execute a particular function should be more specifically expressed in tissues that perform the function. Given this premise, we mined public microarray expression data to build a database of genes ranked by their specificity of expression in multiple organs. The database permitted the accurate identification of genes and functions known to be specific to individual organs. Next, we used the database to predict transcriptional regulators of brown adipose tissue (BAT) and validated two candidate genes. Based upon hypotheses regarding pathways shared between combinations of BAT or white adipose tissue (WAT) and other organs, we identified genes that met threshold criteria for specific or counterspecific expression in each tissue. By contrasting WAT to the heart and BAT, the two most mitochondria-rich tissues in the body, we discovered a novel function for the transcription factor ESRRG in the induction of BAT genes in white adipocytes. Because the heart and other estrogen-related receptor gamma (ESRRG)-rich tissues do not express BAT markers, we hypothesized that an adipocyte co-regulator acts with ESRRG. By comparing WAT and BAT to the heart, brain, kidney and skeletal muscle, we discovered that an isoform of the transcription factor sterol regulatory element binding transcription factor 1 (SREBF1) induces BAT markers in C2C12 myocytes in the presence of ESRRG. The results demonstrate a straightforward bioinformatic strategy to associate genes with functions. The database upon which the strategy is based is provided so that investigators can perform their own screens. PMID:23170034

  15. Molecular evolution of the Cecropin multigene family in Drosophila. functional genes vs. pseudogenes.

    PubMed Central

    Ramos-Onsins, S; Aguadé, M

    1998-01-01

    Approximately 4 kb of the Cecropin cluster region have been sequenced in nine lines of Drosophila melanogaster and one line of the sibling species D. simulans, D. mauritiana, and D. sechellia. This region includes three functional genes (CecA1, CecA2, and CecB), which are involved in the insect immune response, and two pseudogenes (CecPsi1 and CecPsi2). The level of silent polymorphism in the three Cec genes is rather high (0.028), and there is no excess of nonsynonymous polymorphism. There is no evidence of gene conversion in the history of these genes. The interspecific comparison has revealed that in the three species of the simulans cluster the CecA2 gene is partially deleted and has therefore lost its function and become a pseudogene; in each of the species, subsequent deletions have accumulated. Divergence estimates indicate that the CecPsi1 and CecPsi2 pseudogenes are highly diverged, both between themselves and relative to the other three Cec genes. However, both CecPsi1 and CecPsi2 have conserved transcriptional signals and splice sites, and they present an open reading frame; also, correctly spliced transcripts have been detected for both CecPsi1 and CecPsi2. The data support that these genes are either active genes with some null alleles or young pseudogenes. PMID:9725836

  16. The maize brown midrib4 (bm4) gene encodes a functional folylpolyglutamate synthase

    PubMed Central

    Li, Li; Hill-Skinner, Sarah; Liu, Sanzhen; Beuchle, Danielle; Tang, Ho Man; Yeh, Cheng-Ting; Nettleton, Dan; Schnable, Patrick S

    2015-01-01

    Mutations in the brown midrib4 (bm4) gene affect the accumulation and composition of lignin in maize. Fine-mapping analysis of bm4 narrowed the candidate region to an approximately 105 kb interval on chromosome 9 containing six genes. Only one of these six genes, GRMZM2G393334, showed decreased expression in mutants. At least four of 10 Mu-induced bm4 mutant alleles contain a Mu insertion in the GRMZM2G393334 gene. Based on these results, we concluded that GRMZM2G393334 is the bm4 gene. GRMZM2G393334 encodes a putative folylpolyglutamate synthase (FPGS), which functions in one-carbon (C1) metabolism to polyglutamylate substrates of folate-dependent enzymes. Yeast complementation experiments demonstrated that expression of the maize bm4 gene in FPGS-deficient met7 yeast is able to rescue the yeast mutant phenotype, thus demonstrating that bm4 encodes a functional FPGS. Consistent with earlier studies, bm4 mutants exhibit a modest decrease in lignin concentration and an overall increase in the S:G lignin ratio relative to wild-type. Orthologs of bm4 include at least one paralogous gene in maize and various homologs in other grasses and dicots. Discovery of the gene underlying the bm4 maize phenotype illustrates a role for FPGS in lignin biosynthesis. PMID:25495051

  17. Computational prediction of SEG (single exon gene) function in humans.

    PubMed

    Sakharkar, Meena K; Chow, Vincent T K; Ghosh, Kingshuk; Chaturvedi, Iti; Lee, Pern Chern; Bagavathi, Sundara Perumal; Shapshak, Paul; Subbiah, Subramanian; Kangueane, Pandjassarame

    2005-01-01

    Human genes are often interrupted by non-coding, intragenic sequences called introns. Hence, the gene sequence is divided into exons (coding segments) and introns (non-coding segments). Consequently, a majority of them are multi exon genes (MEG). However, a considerable amount of single exon genes (SEG) are present in the human genome (approximately 12%). This amount is sizeable and it is important to probe their molecular function and cellular role. Hence, we performed a genome wide functional assignment to 3750 SEG sequences using PFAM (protein family database), PROSITE (database of biologically meaningful signatures or motifs) and SUPERFAMILY (a library covering all proteins of known 3 dimensional structure). PFAM assigned 13% SEG to trans-membrane receptor genes of the G-protein coupled receptor (GPCR) family and showed that a majority of SEG proteins have DNA binding function. PROSITE identified 336 unique motif types in them and this accounts for 25% of all known patterns, with a majority having PHOSPHORYLATION and ACETYLATION signals. SUPERFAMILY assigned 33% SEG to the membrane all alpha (proteins containing alpha helix structural elements according to SCOP (structural classification of proteins) definition). Functional assignment of SEG proteins at multiple levels (sequence signals, sequence families, 3D structures) using PFAM, PROSITE and SUPERFAMILY is envisioned to suggest their selective and predominant molecular function in cellular systems. Their function as DNA binding, phosphorylating, acetylating and house-keeping agents is intriguing. The analysis also showed evidence of SEG expression and retro-transposition. However, this information is inadequate to draw concerted conclusion on the prevalent role played by these proteins in cellular biology. A complete understanding of SEG function will help to explore their role in cellular environment. The derived datasets from these analyses are available at http://sege.ntu.edu.sg/wester/intronless/human/. PMID:15769633

  18. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development.

    PubMed

    Liu, Leah Y; Fox, Caroline S; North, Trista E; Goessling, Wolfram

    2013-09-01

    Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf) and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10) decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50) decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes. PMID:23813869

  19. Titanium nanotubes activate genes related to bone formation in vitro

    PubMed Central

    Pozio, Alfonso; Palmieri, Annalisa; Girardi, Ambra; Cura, Francesca; Carinci, Francesco

    2012-01-01

    Background: Titanium is used worldwide to make osseointegrable devices, thanks to its favorable characteristics as mechanical proprieties and biocompatibility, demonstrated by in vivo studies with animal models and clinical trials over a forty-year period. However, the exact genetic effect of the titanium layer on cells is still not well characterized. Materials and Methods: To investigate how titanium nanotubes stimulate osteoblasts differentiation and proliferation, some osteoblast genes (SP7, RUNX2, COL3A1, COL1A1, ALPL, SPP1 and FOSL1) were analyzed by quantitative Real Time RT- PCR. Results: After 15 days, osteoblasts cultivated on titanium naotube showed the up-regulation of bone related genes SP7, ENG, FOSL1 and SPP1 and the down-regulation of RUNX2, COL3A1, COL1A1, and ALPL. After 30 days of treatment, the bone related genes SP7, ENG, FOSL1 and RUNX2 were up-regulated while COL3A1, COL1A1, ALPL and SPP1 were down-regulated. Conclusions: Our results, demonstrates that titanium nanotubes can lead to osteoblast differentiation and extracellular matrix deposition and mineralization in dental pulp stem cells by the activation of osteoblast related genes SPP1, FOSL1 and RUNX2. PMID:23814577

  20. A functional gene array for detection of bacterial virulence elements.

    PubMed

    Jaing, Crystal; Gardner, Shea; McLoughlin, Kevin; Mulakken, Nisha; Alegria-Hartman, Michelle; Banda, Phillip; Williams, Peter; Gu, Pauline; Wagner, Mark; Manohar, Chitra; Slezak, Tom

    2008-01-01

    Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples. PMID:18478124

  1. Identifying gene-independent noncoding functional elements in the yeast ribosomal DNA by phylogenetic footprinting

    PubMed Central

    Ganley, Austen R. D.; Hayashi, Kouji; Horiuchi, Takashi; Kobayashi, Takehiko

    2005-01-01

    Sequences involved in the regulation of genetic and genomic processes are primarily located in noncoding regions. Identifying such cis-acting sequences from sequence data is difficult because their patterns are not readily apparent, and, to date, identification has concentrated on regions associated with gene-coding functions. Here, we used phylogenetic footprinting to look for gene-independent noncoding elements in the ribosomal RNA gene repeats from several Saccharomyces species. Similarity plots of ribosomal intergenic spacer alignments from six closely related Saccharomyces species allowed the identification of previously characterized functional elements, such as the origin-of-replication and replication-fork barrier sites, demonstrating that this method is a powerful predictor of noncoding functional elements. Seventeen previously uncharacterized elements, showing high levels of conservation, were also discovered. The conservation of these elements suggests that they are functional, and we demonstrate the functionality of two classes of these elements, a putative bidirectional noncoding promoter and a series of conserved peaks with matches to the origin-of-replication core consensus. Our results paint a comprehensive picture of the functionality of the Saccharomyces ribosomal intergenic region and demonstrate that functional elements not involved in gene-coding function can be identified by using comparative genomics based on sequence conservation. PMID:16081534

  2. The Caenorhabditis elegans APC-related gene apr-1 is required for epithelial cell migration and Hox gene expression.

    PubMed

    Hoier, E F; Mohler, W A; Kim, S K; Hajnal, A

    2000-04-01

    Inactivation of the Caenorhabditis elegans APC-related gene (apr-1) has pointed at two separate functions of apr-1. First, apr-1 is required for the migration of epithelial cells during morphogenesis of the embryo. In this process, APR-1 may act in a Cadherin/alpha-Catenin/beta-Catenin complex as a component of adherens junctions. Second, apr-1 is required for Hox gene expression, most likely by positively regulating the activity of the Wingless signaling pathway. During embryogenesis, apr-1 is required for the expression of ceh-13 labial in anterior seam and muscle cells and during larval development, apr-1 is necessary for the expression of lin-39 deformed in the vulval precursor cells. Thus, APR-1 may positively regulate the activity of the beta-Catenin/Armadillo-related proteins HMP-2 in migrating epithelial cells and BAR-1 in the vulval precursor cells. PMID:10766743

  3. The Caenorhabditis elegans APC-related gene apr-1 is required for epithelial cell migration and Hox gene expression

    PubMed Central

    Hoier, Erika Fröhli; Mohler, William A.; Kim, Stuart K.; Hajnal, Alex

    2000-01-01

    Inactivation of the Caenorhabditis elegans APC-related gene (apr-1) has pointed at two separate functions of apr-1. First, apr-1 is required for the migration of epithelial cells during morphogenesis of the embryo. In this process, APR-1 may act in a Cadherin/?-Catenin/?-Catenin complex as a component of adherens junctions. Second, apr-1 is required for Hox gene expression, most likely by positively regulating the activity of the Wingless signaling pathway. During embryogenesis, apr-1 is required for the expression of ceh-13 labial in anterior seam and muscle cells and during larval development, apr-1 is necessary for the expression of lin-39 deformed in the vulval precursor cells. Thus, APR-1 may positively regulate the activity of the ?-Catenin/Armadillo-related proteins HMP-2 in migrating epithelial cells and BAR-1 in the vulval precursor cells. PMID:10766743

  4. New gene functions in megakaryopoiesis and platelet formation

    PubMed Central

    Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, Tőnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C.; Cucca, Francesco; D’Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Völker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

    2012-01-01

    Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. PMID:22139419

  5. Developmental and functional analysis of Jonah gene expression.

    PubMed

    Carlson, J R; Hogness, D S

    1985-04-01

    The Jonah genes are expressed twice in development: Jonah RNA is detected during all larval stages, disappears at the end of the third larval instar, and then reappears shortly after eclosion, in the adult midgut. Construction and analysis of Jonah cDNA clones reveals that multiple Jonah genes are transcribed; cDNA clones deriving from at least four different clusters of Jonah genes have been identified. In at least one case, multiple genes in a cluster are transcribed, and one cluster is found to be transcribed both in larvae and adults. Evidence that different Jonah genes are under different control with respect to both spatial and temporal patterns of expression has been provided. Jonah RNA encodes a 28-kDa translation product or products for which we consider a possible function. Jonah RNA of constant length is found to be conserved in all strains of Drosophila melanogaster examined, Jonah genes are found at a minimum of three common chromosomal sites in all of seven D. melanogaster strains examined, and multiple Jonah genes are found in other Drosophila species. PMID:2416611

  6. Functional Genomic Analysis of Cotton Genes with Agrobacterium-Mediated Virus-Induced Gene Silencing

    PubMed Central

    Gao, Xiquan; Shan, Libo

    2015-01-01

    Cotton (Gossypium spp.) is one of the most agronomically important crops worldwide for its unique textile fiber production and serving as food and feed stock. Molecular breeding and genetic engineering of useful genes into cotton have emerged as advanced approaches to improve cotton yield, fiber quality, and resistance to various stresses. However, the understanding of gene functions and regulations in cotton is largely hindered by the limited molecular and biochemical tools. Here, we describe the method of an Agrobacterium infiltration-based virus-induced gene silencing (VIGS) assay to transiently silence endogenous genes in cotton at 2-week-old seedling stage. The genes of interest could be readily silenced with a consistently high efficiency. To monitor gene silencing efficiency, we have cloned cotton GrCla1 from G. raimondii, a homolog gene of Arabidopsis Cloroplastos alterados 1 (AtCla1) involved in chloroplast development, and inserted into a tobacco rattle virus (TRV) binary vector pYL156. Silencing of GrCla1 results in albino phenotype on the newly emerging leaves, serving as a visual marker for silencing efficiency. To further explore the possibility of using VIGS assay to reveal the essential genes mediating disease resistance to Verticillium dahliae, a fungal pathogen causing severe Verticillium wilt in cotton, we developed a seedling infection assay to inoculate cotton seedlings when the genes of interest are silenced by VIGS. The method we describe here could be further explored for functional genomic analysis of cotton genes involved in development and various biotic and abiotic stresses. PMID:23386302

  7. Interorganellar gene transfer in bryophytes: the functional nad7 gene is nuclear encoded in Marchantia polymorpha

    Microsoft Academic Search

    Y. Kobayashi; V. Knoop; H. Fukuzawa; A. Brennicke; K. Ohyama

    1997-01-01

    The nad7 gene, encoding subunit 7 of NADH dehydrogenase, is mitochondrially encoded in seed plants. In the liverwort, Marchantia polymorpha, only a pseudogene is located in the mitochondrial genome. We have now identified the functional nad7 gene copy in the nuclear genome of Marchantia, coding for a polypeptide of 468 amino acids. The nuclear-encoded nad7 has lost the two group

  8. Functional Overlap Between the mec-8 Gene and Five sym Genes in Caenorhabditis elegans

    Microsoft Academic Search

    Andrew G. Davies; Caroline A. Spike; Jocelyn E. Shaw; Robert K. Herman

    Earlier work showed that the Caenorhabditis elegans gene mec-8 encodes a regulator of alternative RNA splicing and that mec-8 null mutants have defects in sensory neurons and body muscle attachment but are generally viable and fertile. We have used a genetic screen to identify five mutations in four genes, sym- 1-sym-4, that are synthetically lethal with mec-8 loss-of-function mutations. The

  9. Functions of mammalian Smad genes as revealed by targeted gene disruption in mice

    Microsoft Academic Search

    Michael Weinstein; Xiao Yang; Chu-Xia Deng

    2000-01-01

    The Smad genes are the intracellular mediators of TGF-beta signals. Targeted mutagenesis in mice has yielded valuable new insights into the functions of this important gene family. These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the skeleton. In addition, these

  10. HuMiChip: Development of a Functional Gene Array for the Study of Human Microbiomes

    SciTech Connect

    Tu, Q.; Deng, Ye; Lin, Lu; Hemme, Chris L.; He, Zhili; Zhou, Jizhong

    2010-05-17

    Microbiomes play very important roles in terms of nutrition, health and disease by interacting with their hosts. Based on sequence data currently available in public domains, we have developed a functional gene array to monitor both organismal and functional gene profiles of normal microbiota in human and mouse hosts, and such an array is called human and mouse microbiota array, HMM-Chip. First, seed sequences were identified from KEGG databases, and used to construct a seed database (seedDB) containing 136 gene families in 19 metabolic pathways closely related to human and mouse microbiomes. Second, a mother database (motherDB) was constructed with 81 genomes of bacterial strains with 54 from gut and 27 from oral environments, and 16 metagenomes, and used for selection of genes and probe design. Gene prediction was performed by Glimmer3 for bacterial genomes, and by the Metagene program for metagenomes. In total, 228,240 and 801,599 genes were identified for bacterial genomes and metagenomes, respectively. Then the motherDB was searched against the seedDB using the HMMer program, and gene sequences in the motherDB that were highly homologous with seed sequences in the seedDB were used for probe design by the CommOligo software. Different degrees of specific probes, including gene-specific, inclusive and exclusive group-specific probes were selected. All candidate probes were checked against the motherDB and NCBI databases for specificity. Finally, 7,763 probes covering 91.2percent (12,601 out of 13,814) HMMer confirmed sequences from 75 bacterial genomes and 16 metagenomes were selected. This developed HMM-Chip is able to detect the diversity and abundance of functional genes, the gene expression of microbial communities, and potentially, the interactions of microorganisms and their hosts.

  11. Endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(A) tracts.

    PubMed

    Tamas, Ivica; Wernegreen, Jennifer J; Nystedt, Björn; Kauppinen, Seth N; Darby, Alistair C; Gomez-Valero, Laura; Lundin, Daniel; Poole, Anthony M; Andersson, Siv G E

    2008-09-30

    Among host-dependent bacteria that have evolved by extreme reductive genome evolution, long-term bacterial endosymbionts of insects have the smallest (160-790 kb) and most A + T-rich (>70%) bacterial genomes known to date. These genomes are riddled with poly(A) tracts, and 5-50% of genes contain tracts of 10 As or more. Here, we demonstrate transcriptional slippage at poly(A) tracts within genes of Buchnera aphidicola associated with aphids and Blochmannia pennsylvanicus associated with ants. Several tracts contain single frameshift deletions; these apparent pseudogenes showed patterns of constraint consistent with purifying selection on the encoded proteins. Transcriptional slippage yielded a heterogeneous population of transcripts with variable numbers of As in the tract. Across several frameshifted genes, including B. aphidicola cell wall biosynthesis genes and a B. pennsylvanicus histidine biosynthesis gene, 12-50% of transcripts contained corrected reading frames that could potentially yield full-length proteins. In situ immunostaining confirmed the production of the cell wall biosynthetic enzyme UDP-N-acetylmuramyl pentapeptide synthase encoded by the frameshifted murF gene. Simulation studies indicated an overrepresentation of poly(A) tracts in endosymbiont genomes relative to other A + T-rich bacterial genomes. Polymerase infidelity at poly(A) tracts rescues the functionality of genes with frameshift mutations and, conversely, reduces the efficiency of expression for in-frame genes carrying poly(A) regions. These features of homopolymeric tracts could be exploited to manipulate gene expression in small synthetic genomes. PMID:18815381

  12. Ascorbate peroxidase-related (APx-R) is not a duplicable gene

    PubMed Central

    Dunand, Christophe; Mathé, Catherine; Lazzarotto, Fernanda; Margis, Rogério; Margis-Pinheiro, Marcia

    2011-01-01

    Phylogenetic, genomic and functional analyses have allowed the identification of a new class of putative heme peroxidases, so called APx-R (APx-Related). These new class, mainly present in the green lineage (including green algae and land plants), can also be detected in other unicellular chloroplastic organisms. Except for recent polyploid organisms, only single-copy of APx-R gene was detected in each genome, suggesting that the majority of the APx-R extra-copies were lost after chromosomal or segmental duplications. In a similar way, most APx-R co-expressed genes in Arabidopsis genome do not have conserved extra-copies after chromosomal duplications and are predicted to be localized in organelles, as are the APx-R. The member of this gene network can be considered as unique gene, well conserved through the evolution due to a strong negative selection pressure and a low evolution rate. PMID:22231200

  13. Male- and Female-Biased Gene Expression of Olfactory-Related Genes in the Antennae of Asian Corn Borer, Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae)

    PubMed Central

    Zhang, Tiantao; Coates, Brad S.; Ge, Xing; Bai, Shuxiong; He, Kanglai; Wang, Zhenying

    2015-01-01

    The Asian corn borer (ACB), Ostrinia furnacalis (Guenée), is a destructive pest insect of cultivated corn crops, for which antennal-expressed receptors are important to detect olfactory cues for mate attraction and oviposition. Few olfactory related genes were reported in ACB, so we sequenced and characterized the transcriptome of male and female O. furnacalis antennae. Non-normalized male and female O. furnacalis antennal cDNA libraries were sequenced on the Illumina HiSeq 2000 and assembled into a reference transcriptome. Functional gene annotations identified putative olfactory-related genes; 56 odorant receptors (ORs), 23 odorant binding proteins (OBPs), and 10 CSPs. RNA-seq estimates of gene expression respectively showed up- and down-regulation of 79 and 30 genes in female compared to male antennae, which included up-regulation of 8 ORs and 1 PBP gene in male antennae as well as 3 ORs in female antennae. Quantitative real-time RT-PCR analyses validated strong male antennal-biased expression of OfurOR3, 4, 6, 7, 8, 11, 12, 13 and 14 transcripts, whereas OfurOR17 and 18 were specially expressed in female antennae. Sex-biases gene expression described here provides important insight in gene functionalization, and provides candidate genes putatively involved in environmental perception, host plant attraction, and mate recognition. PMID:26062030

  14. The PMP22 Gene and Its Related Diseases

    PubMed Central

    Li, Jun; Parker, Brett; Martyn, Colin; Natarajan, Chandramohan; Guo, Jiasong

    2012-01-01

    Peripheral myelin protein-22 (PMP22) is primarily expressed in the compact myelin of the peripheral nervous system. Levels of PMP22 have to be tightly regulated since alterations of PMP22 levels by mutations of the PMP22 gene are responsible for >50% of all patients with inherited peripheral neuropathies, including Charcot-Marie-Tooth type-1A (CMT1A) with trisomy of PMP22, hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of PMP22, and CMT1E with point mutations of PMP22. While over-expression and point-mutations of the PMP22 gene may produce gain-of-function phenotypes, deletion of PMP22 results in a loss-of-function phenotype that reveals the normal physiological functions of the PMP22 protein. In this article, we will review the basic genetics, biochemistry and molecular structure of PMP22, followed by discussion of the current understanding of pathogenic mechanisms involving in the inherited neuropathies with mutations in PMP22 gene. PMID:23224996

  15. Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia

    PubMed Central

    Janssen, Sarah F.; Gorgels, Theo G. M. F.; Bossers, Koen; ten Brink, Jacoline B.; Essing, Anke H. W.; Nagtegaal, Martijn; van der Spek, Peter J.; Jansonius, Nomdo M.; Bergen, Arthur A. B.

    2012-01-01

    Purpose The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. Methods We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. Results The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma. Conclusion Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma. PMID:23028713

  16. Identification of apoptosis-related PLZF target genes

    SciTech Connect

    Bernardo, Maria Victoria [Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia (Spain); Yelo, Estefania [Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia (Spain); Gimeno, Lourdes [Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia (Spain); Campillo, Jose Antonio [Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia (Spain); Parrado, Antonio [Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia (Spain)]. E-mail: antonio.parrado@carm.es

    2007-07-27

    The PLZF gene encodes a BTB/POZ-zinc finger-type transcription factor, involved in physiological development, proliferation, differentiation, and apoptosis. In this paper, we investigate proliferation, survival, and gene expression regulation in stable clones from the human haematopoietic K562, DG75, and Jurkat cell lines with inducible expression of PLZF. In Jurkat cells, but not in K562 and DG75 cells, PLZF induced growth suppression and apoptosis in a cell density-dependent manner. Deletion of the BTB/POZ domain of PLZF abrogated growth suppression and apoptosis. PLZF was expressed with a nuclear speckled pattern distinctively in the full-length PLZF-expressing Jurkat clones, suggesting that the nuclear speckled localization is required for PLZF-induced apoptosis. By microarray analysis, we identified that the apoptosis-inducer TP53INP1, ID1, and ID3 genes were upregulated, and the apoptosis-inhibitor TERT gene was downregulated. The identification of apoptosis-related PLZF target genes may have biological and clinical relevance in cancer typified by altered PLZF expression.

  17. Influence of CHIEF pathway genes on gene expression: a pathway approach to functionality

    PubMed Central

    Slattery, Martha L; Lundgreen, Abbie; Mullany, Lila E; Penney, Rosalind B; Wolff, Roger K

    2014-01-01

    Background: Candidate pathway approaches in disease association studies often utilize a tagSNP approach to capture genetic variation. In this paper we assess gene expression patterns with SNPs in genes in the CHIEF pathway to help determine their potential functionality. Methods: Quantitative real-time RT-PCR was run to determine gene expression of 13 genes in normal colon tissue samples from 82 individuals. TagSNP genotype data were obtained from a GoldenGate Illumina multiplex bead array platform. Age, sex, and genetic ancestry adjusted general linear models were used to estimate beta coefficients and p values. Results: Genetic variation in mTOR (1 SNP), NFKB1 (4 SNPs), PRKAG2 (3 SNPs), and TSC2 (1 SNP) significantly influenced their expression. After adjustment for multiple comparisons several associations between pathway genes and expression of other genes were significant. These included AKT1 rs1130214 associated with expression of PDK1; NF?B1 rs13117745 and rs4648110 with STK11 expression; PRKAG2 rs6965771 with expression of NF?B1, PIK3CA, and RPS6KB2; RPS6KB1 rs80711475 with STK11 expression; STK11 rs741765 with PIK3CA and PRKAG2 expression; and TSC2 rs3087631 with AKT1, IkB?B, NF?B1, PDK1, PIK3CA, PRKAG2, and PTEN expression. The higher levels of differential expression were noted for TSC2 rs3087631 (percent difference ranges from 108% to 198% across genes). Many of these SNPs and genes also were associated with colon and rectal cancer risk. Conclusions: Our results suggest that pathway genes may regulate expression of other genes in the pathway. The convergence of these genes in several biological pathways involved in cancer further supports their importance to the carcinogenic process. PMID:24959314

  18. Baculoviruses deficient in ie1 gene function abrogate viral gene expression in transduced mammalian cells

    SciTech Connect

    Efrose, Rodica; Swevers, Luc; Iatrou, Kostas, E-mail: iatrou@bio.demokritos.g

    2010-10-25

    One of the newest niches for baculoviruses-based technologies is their use as vectors for mammalian cell transduction and gene therapy applications. However, an outstanding safety issue related to such use is the residual expression of viral genes in infected mammalian cells. Here we show that infectious baculoviruses lacking the major transcriptional regulator, IE1, can be produced in insect host cells stably transformed with IE1 expression constructs lacking targets of homologous recombination that could promote the generation of wt-like revertants. Such ie1-deficient baculoviruses are unable to direct viral gene transcription to any appreciable degree and do not replicate in normal insect host cells. Most importantly, the residual viral gene expression, which occurs in mammalian cells infected with wt baculoviruses is reduced 10 to 100 fold in cells infected with ie1-deficient baculoviruses. Thus, ie1-deficient baculoviruses offer enhanced safety features to baculovirus-based vector systems destined for use in gene therapy applications.

  19. Ontology-based functional classification of genes: Evaluation with reference sets and overlap analysis

    Microsoft Academic Search

    Sidahmed Benabderrahmane; Marie Dominique Devignes; Malika Smail Tabbone; Amedeo Napoli; Olivier Poch

    2011-01-01

    Functional classification involves grouping genes according to their molecular functions or the biological processes they participate in. This unsupervised classification task is essential for interpreting gene datasets produced by post-genomic experiments. As the functional annotation of genes is mostly based on the Gene Ontology (GO), many similarity measures using the GO have been described, but few of them have been

  20. Gene Perturbation Atlas (GPA): a single-gene perturbation repository for characterizing functional mechanisms of coding and non-coding genes.

    PubMed

    Xiao, Yun; Gong, Yonghui; Lv, Yanling; Lan, Yujia; Hu, Jing; Li, Feng; Xu, Jinyuan; Bai, Jing; Deng, Yulan; Liu, Ling; Zhang, Guanxiong; Yu, Fulong; Li, Xia

    2015-01-01

    Genome-wide transcriptome profiling after gene perturbation is a powerful means of elucidating gene functional mechanisms in diverse contexts. The comprehensive collection and analysis of the resulting transcriptome profiles would help to systematically characterize context-dependent gene functional mechanisms and conduct experiments in biomedical research. To this end, we collected and curated over 3000 transcriptome profiles in human and mouse from diverse gene perturbation experiments, which involved 1585 different perturbed genes (microRNAs, lncRNAs and protein-coding genes) across 1170 different cell lines/tissues. For each profile, we identified differential genes and their associated functions and pathways, constructed perturbation networks, predicted transcription regulation and cancer/drug associations, and assessed cooperative perturbed genes. Based on these transcriptome analyses, the Gene Perturbation Atlas (GPA) can be used to detect (i) novel or cell-specific functions and pathways affected by perturbed genes, (ii) protein interactions and regulatory cascades affected by perturbed genes, and (iii) perturbed gene-mediated cooperative effects. The GPA is a user-friendly database to support the rapid searching and exploration of gene perturbations. Particularly, we visualized functional effects of perturbed genes from multiple perspectives. In summary, the GPA is a valuable resource for characterizing gene functions and regulatory mechanisms after single-gene perturbations. The GPA is freely accessible at http://biocc.hrbmu.edu.cn/GPA/. PMID:26039571

  1. Inference of gene function based on gene fusion events: the rosetta-stone method.

    PubMed

    Suhre, Karsten

    2007-01-01

    The method described in this chapter can be used to infer putative functional links between two proteins. The basic idea is based on the principle of "guilt by association." It is assumed that two proteins, which are found to be transcribed by a single transcript in one (or several) genomes are likely to be functionally linked, for example by acting in a same metabolic pathway or by forming a multiprotein complex. This method is of particular interest for studying genes that exhibit no, or only remote, homologies with already well-characterized proteins. Combined with other non-homology based methods, gene fusion events may yield valuable information for hypothesis building on protein function, and may guide experimental characterization of the target protein, for example by suggesting potential ligands or binding partners. This chapter uses the FusionDB database (http://www.igs.cnrs-mrs.fr/FusionDB/) as source of information. FusionDB provides a characterization of a large number of gene fusion events at hand of multiple sequence alignments. Orthologous genes are included to yield a comprehensive view of the structure of a gene fusion event. Phylogenetic tree reconstruction is provided to evaluate the history of a gene fusion event, and three-dimensional protein structure information is used, where available, to further characterize the nature of the gene fusion. For genes that are not comprised in FusionDB, some instructions are given as how to generate a similar type of information, based solely on publicly available web tools that are listed here. PMID:18025684

  2. Structural, Functional, and Evolutionary Analysis of the Unusually Large Stilbene Synthase Gene Family in Grapevine1[W

    PubMed Central

    Parage, Claire; Tavares, Raquel; Réty, Stéphane; Baltenweck-Guyot, Raymonde; Poutaraud, Anne; Renault, Lauriane; Heintz, Dimitri; Lugan, Raphaël; Marais, Gabriel A.B.; Aubourg, Sébastien; Hugueney, Philippe

    2012-01-01

    Stilbenes are a small family of phenylpropanoids produced in a number of unrelated plant species, including grapevine (Vitis vinifera). In addition to their participation in defense mechanisms in plants, stilbenes, such as resveratrol, display important pharmacological properties and are postulated to be involved in the health benefits associated with a moderate consumption of red wine. Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene backbone, seem to have evolved from chalcone synthases (CHSs) several times independently in stilbene-producing plants. STS genes usually form small families of two to five closely related paralogs. By contrast, the sequence of grapevine reference genome (cv PN40024) has revealed an unusually large STS gene family. Here, we combine molecular evolution and structural and functional analyses to investigate further the high number of STS genes in grapevine. Our reannotation of the STS and CHS gene families yielded 48 STS genes, including at least 32 potentially functional ones. Functional characterization of nine genes representing most of the STS gene family diversity clearly indicated that these genes do encode for proteins with STS activity. Evolutionary analysis of the STS gene family revealed that both STS and CHS evolution are dominated by purifying selection, with no evidence for strong selection for new functions among STS genes. However, we found a few sites under different selection pressures in CHS and STS sequences, whose potential functional consequences are discussed using a structural model of a typical STS from grapevine that we developed. PMID:22961129

  3. Functional analysis of yersiniabactin transport genes of Yersinia enterocolitica.

    PubMed

    Brem, D; Pelludat, C; Rakin, A; Jacobi, C A; Heesemann, J

    2001-05-01

    Yersinia enterocolitica O:8, biogroup (BG) IB, strain WA-C carries a high-pathogenicity island (HPI) including iron-repressible genes (irp1-9, fyuA) for biosynthesis and uptake of the siderophore yersiniabactin (Ybt). The authors report the functional analysis of irp6,7,8, which show 98-99% similarity to the corresponding genes ybtP,Q,X on the HPI of Yersinia pestis. It was demonstrated that irp6,7 are involved in ferric (Fe)-Ybt utilization and mouse virulence of Y. enterocolitica, thus confirming corresponding results for Y. pestis. Additionally it was shown that inactivation of the ampG-like gene irp8 did not affect either Fe-Ybt utilization or mouse virulence. To determine whether irp6, irp7 and fyuA (encoding the outer-membrane Fe-Ybt/pesticin receptor FyuA) are sufficient to mediate Fe-Ybt transport/utilization, these genes were transferred into Escherichia coli entD,F and into non-pathogenic Y. enterocolitica, BG IA, strain NF-O. Surprisingly, E. coli entD,F but not Y. enterocolitica NF-O gained the capability to utilize exogenous Fe-Ybt as a result of this gene transfer, although both strains expressed functional FyuA (pesticin sensitivity). These results suggest that besides irp6, irp7 and fyuA, additional genes are required for sufficient Fe-Ybt transport/utilization. Finally, it was shown that irp6, irp7 and fyuA but not irp8 are involved in controlling Ybt biosynthesis and fyuA gene expression: irp6 and/or irp7 mutation leads to upregulation whereas fyuA mutation leads to downregulation. However, fyuA-dependent control of Ybt biosynthesis could be bypassed in a fyuA mutant by ingredients of chrome azurol S (CAS) siderophore indicator agar. PMID:11320115

  4. Functional optimization of gene clusters by combinatorial design and assembly.

    PubMed

    Smanski, Michael J; Bhatia, Swapnil; Zhao, Dehua; Park, YongJin; B A Woodruff, Lauren; Giannoukos, Georgia; Ciulla, Dawn; Busby, Michele; Calderon, Johnathan; Nicol, Robert; Gordon, D Benjamin; Densmore, Douglas; Voigt, Christopher A

    2014-12-01

    Large microbial gene clusters encode useful functions, including energy utilization and natural product biosynthesis, but genetic manipulation of such systems is slow, difficult and complicated by complex regulation. We exploit the modularity of a refactored Klebsiella oxytoca nitrogen fixation (nif) gene cluster (16 genes, 103 parts) to build genetic permutations that could not be achieved by starting from the wild-type cluster. Constraint-based combinatorial design and DNA assembly are used to build libraries of radically different cluster architectures by varying part choice, gene order, gene orientation and operon occupancy. We construct 84 variants of the nifUSVWZM operon, 145 variants of the nifHDKY operon, 155 variants of the nifHDKYENJ operon and 122 variants of the complete 16-gene pathway. The performance and behavior of these variants are characterized by nitrogenase assay and strand-specific RNA sequencing (RNA-seq), and the results are incorporated into subsequent design cycles. We have produced a fully synthetic cluster that recovers 57% of wild-type activity. Our approach allows the performance of genetic parts to be quantified simultaneously in hundreds of genetic contexts. This parallelized design-build-test-learn cycle, which can access previously unattainable regions of genetic space, should provide a useful, fast tool for genetic optimization and hypothesis testing. PMID:25419741

  5. Gene-function studies in systemic lupus erythematosus.

    PubMed

    Crispín, José C; Hedrich, Christian M; Tsokos, George C

    2013-08-01

    The aetiology of systemic lupus erythematosus (SLE) is complex and is known to involve both genetic and environmental factors. In a small number of patients, single-gene defects can lead to the development of SLE. Such genes include those encoding early components of the complement cascade and the 3'-5' DNA exonuclease TREX1. In addition, genome-wide association studies have identified single-nucleotide polymorphisms that confer some susceptibility to SLE. In this Review, we discuss selected examples of genes whose products have distinctly altered function in SLE and contribute to the pathogenic process. Specifically, we focus on the genes encoding integrin ?M (ITGAM), IgG Fc receptors, sialic acid O-acetyl esterase (SIAE), the catalytic subunit of protein phosphatase PP2A (PPP2CA) and signalling lymphocytic activation molecule (SLAM) family members. Moreover, we highlight the changes in epigenetic signatures that occur in SLE. Such epigenetic modifications, which are abundantly present and might alter gene expression in the presence or absence of susceptibility variants, should be carefully considered when deconstructing the contribution of individual genes to the complex pathogenesis of SLE. PMID:23732569

  6. Common variants in Mendelian kidney disease genes and their association with renal function.

    PubMed

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tőnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  7. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

    PubMed Central

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Ĺsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tőnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

    2013-01-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  8. Nucleotide substitutions revealing specific functions of Polycomb group genes.

    PubMed

    Bajusz, Izabella; Sipos, László; Pirity, Melinda K

    2015-04-01

    POLYCOMB group (PCG) proteins belong to the family of epigenetic regulators of genes playing important roles in differentiation and development. Mutants of PcG genes were isolated first in the fruit fly, Drosophila melanogaster, resulting in spectacular segmental transformations due to the ectopic expression of homeotic genes. Homologs of Drosophila PcG genes were also identified in plants and in vertebrates and subsequent experiments revealed the general role of PCG proteins in the maintenance of the repressed state of chromatin through cell divisions. The past decades of gene targeting experiments have allowed us to make significant strides towards understanding how the network of PCG proteins influences multiple aspects of cellular fate determination during development. Being involved in the transmission of specific expression profiles of different cell lineages, PCG proteins were found to control wide spectra of unrelated epigenetic processes in vertebrates, such as stem cell plasticity and renewal, genomic imprinting and inactivation of X-chromosome. PCG proteins also affect regulation of metabolic genes being important for switching programs between pluripotency and differentiation. Insight into the precise roles of PCG proteins in normal physiological processes has emerged from studies employing cell culture-based systems and genetically modified animals. Here we summarize the findings obtained from PcG mutant fruit flies and mice generated to date with a focus on PRC1 and PRC2 members altered by nucleotide substitutions resulting in specific alleles. We also include a compilation of lessons learned from these models about the in vivo functions of this complex protein family. With multiple knockout lines, sophisticated approaches to study the consequences of peculiar missense point mutations, and insights from complementary gain-of-function systems in hand, we are now in a unique position to significantly advance our understanding of the molecular basis of in vivo functions of PcG proteins. PMID:25669595

  9. Transcriptome analysis revealed positive selection of immune-related genes in tilapia.

    PubMed

    Xiao, Jun; Zhong, Huan; Liu, Zhen; Yu, Fan; Luo, Yongju; Gan, Xi; Zhou, Yi

    2015-05-01

    High-throughput sequencing of transcriptome promises a new approach for detecting evolutionary divergence among species. Up to now, the information about evolution of immune genes in cultured fish, especially in tilapias which would aid to understand the molecular basis of immune phenotypic differentiation is still lack. Thus, in the present study, we used high-throughput sequencing to obtain large amount of gene sequences in blue tilapia and characterized the diversity of orthologs among Nile tilapia, blue tilapia and zebrafish. A total of 52,424,506 raw reads, representing 31,404 unigenes were obtained from blue tilapia cDNA library of mixed tissues, including brain, pituitary, gill, heart, liver, spleen, kidney, intestine, muscle, testis and ovary. Based on Ks value, we calculated that the divergence time between Nile tilapia and blue tilapia is 2.93 million years ago. And the tilapias are both apart from zebrafish in 197 million years ago. Furthermore, the positive selected genes were identified by calculating of Ka/Ks ratio. Several immune-related genes were identified as positively selected genes, such as Notch2 and nfatc3b. Considering that these genes play crucial role in immune regulating function, the immune system genes met a great variation under environment selection in tilapias which suggests fast evolution in immune system of cultured tilapias. PMID:25659230

  10. Towards revealing the functions of all genes in plants.

    PubMed

    Rhee, Seung Yon; Mutwil, Marek

    2014-04-01

    The great recent progress made in identifying the molecular parts lists of organisms revealed the paucity of our understanding of what most of the parts do. In this review, we introduce computational and statistical approaches and omics data used for inferring gene function in plants, with an emphasis on network-based inference. We also discuss caveats associated with network-based function predictions such as performance assessment, annotation propagation, the guilt-by-association concept, and the meaning of hubs. Finally, we note the current limitations and possible future directions such as the need for gold standard data from several species, unified access to data and tools, quantitative comparison of data and tool quality, and high-throughput experimental validation platforms for systematic gene function elucidation in plants. PMID:24231067

  11. Identification of Age-Related Macular Degeneration Related Genes by Applying Shortest Path Algorithm in Protein-Protein Interaction Network

    PubMed Central

    Zhang, Jian; Jiang, Min; Yuan, Fei; Feng, Kai-Yan; Cai, Yu-Dong; Xu, Xun; Chen, Lei

    2013-01-01

    This study attempted to find novel age-related macular degeneration (AMD) related genes based on 36 known AMD genes. The well-known shortest path algorithm, Dijkstra's algorithm, was applied to find the shortest path connecting each pair of known AMD related genes in protein-protein interaction (PPI) network. The genes occurring in any shortest path were considered as candidate AMD related genes. As a result, 125 novel AMD genes were predicted. The further analysis based on betweenness and permutation test indicates that there are 10 genes involved in the formation or development of AMD and may be the actual AMD related genes with high probability. We hope that this contribution would promote the study of age-related macular degeneration and discovery of novel effective treatments. PMID:24455700

  12. Transposing Relations: From Maybe Functions to Hash Tables

    Microsoft Academic Search

    José Fonseca de Oliveira; César De Jesus Pereira Cunha Rodrigues

    2004-01-01

    Functional transposition is a technique for converting relations into functions aimed at developing the relational algebra via the algebra of functions. This paper attempts to develop a basis for generic transposition. Two instances of this construction are considered, one applicable to any relation and the other applicable to simple relations only. Our illustration of the usefulness of the generic transpose

  13. Altered expression of immune-related genes in children with Down syndrome.

    PubMed

    Zampieri, Bruna Lancia; Biselli-Périco, Joice Matos; de Souza, Jorge Estefano Santana; Bürger, Matheus Carvalho; Silva Júnior, Wilson Araújo; Goloni-Bertollo, Eny Maria; Pavarino, Erika Cristina

    2014-01-01

    Individuals with Down syndrome (DS) have a high incidence of immunological alterations with increased susceptibility to bacterial and viral infections and high frequency of different types of hematologic malignancies and autoimmune disorders. In the current study, we profiled the expression pattern of 92 immune-related genes in peripheral blood mononuclear cells (PBMCs) of two different groups, children with DS and control children, to identify differentially expressed genes that might be of pathogenetic importance for the development and phenotype of the immunological alterations observed in individuals with DS. PBMCs samples were obtained from six DS individuals with karyotypically confirmed full trisomy 21 and six healthy control individuals (ages 2-6 years). Gene expression was profiled in duplicate according to the manufacturer's instructions provided by commercially available TaqMan Human Immune Array representing 92 immune function genes and four reference genes on a 96-plex gene card. A set of 17 differentially expressed genes, not located on chromosome 21 (HSA21), involved in immune and inflammatory pathways was identified including 13 genes (BCL2, CCL3, CCR7, CD19, CD28, CD40, CD40LG, CD80, EDN1, IKBKB, IL6, NOS2 and SKI) significantly down-regulated and four genes (BCL2L1, CCR2, CCR5 and IL10) significantly up-regulated in children with DS. These findings highlight a list of candidate genes for further investigation into the molecular mechanism underlying DS pathology and reinforce the secondary effects of the presence of a third copy of HSA21. PMID:25222269

  14. Use of functional gene arrays for elucidating in situ biodegradation

    PubMed Central

    Nostrand, Joy D. Van; He, Zhili; Zhou, Jizhong

    2012-01-01

    Microarrays have revolutionized the study of microbiology by providing a high-throughput method for examining thousands of genes with a single test and overcome the limitations of many culture-independent approaches. Functional gene arrays (FGA) probe a wide range of genes involved in a variety of functions of interest to microbial ecology (e.g., carbon degradation, N fixation, metal resistance) from many different microorganisms, cultured and uncultured. The most comprehensive FGA to date is the GeoChip array, which targets tens of thousands of genes involved in the geochemical cycling of carbon, nitrogen, phosphorus, and sulfur, metal resistance and reduction, energy processing, antibiotic resistance and contaminant degradation as well as phylogenetic information (gyrB). Since the development of GeoChips, many studies have been performed using this FGA and have shown it to be a powerful tool for rapid, sensitive, and specific examination of microbial communities in a high-throughput manner. As such, the GeoChip is well-suited for linking geochemical processes with microbial community function and structure. This technology has been used successfully to examine microbial communities before, during, and after in situ bioremediation at a variety of contaminated sites. These studies have expanded our understanding of biodegradation and bioremediation processes and the associated microorganisms and environmental conditions responsible. This review provides an overview of FGA development with a focus on the GeoChip and highlights specific GeoChip studies involving in situ bioremediation. PMID:23049526

  15. Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge

    PubMed Central

    Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben

    2013-01-01

    We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems. PMID:24155925

  16. Widespread Decreased Expression of Immune Function Genes in Human Peripheral Blood Following Radiation Exposure

    PubMed Central

    Paul, Sunirmal; Smilenov, Lubomir B.; Amundson, Sally A.

    2014-01-01

    We report a large-scale reduced expression of genes in pathways related to cell-type specific immunity functions that emerges from microarray analysis 48 h after ex vivo ?-ray irradiation (0, 0.5, 2, 5, 8 Gy) of human peripheral blood from five donors. This response is similar to that seen in patients at 24 h after the start of total-body irradiation and strengthens the rationale for the ex vivo model as an adjunct to human in vivo studies. The most marked response was in genes associated with natural killer (NK) cell immune functions, reflecting a relative loss of NK cells from the population. T- and B-cell mediated immunity genes were also significantly represented in the radiation response. Combined with our previous studies, a single gene expression signature was able to predict radiation dose range with 97% accuracy at times from 6–48 h after exposure. Gene expression signatures that may report on the loss or functional deactivation of blood cell subpopulations after radiation exposure may be particularly useful both for triage biodosimetry and for monitoring the effect of radiation mitigating treatments. PMID:24168352

  17. The ERCC6 Gene and Age-Related Macular Degeneration

    PubMed Central

    Bergeron-Sawitzke, Julie; Uitterlinden, André G.; Hofman, Albert; van Duijn, Cornelia M.; Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C. W.; Allikmets, Rando; Dean, Michael; Bergen, Arthur A. B.

    2010-01-01

    Background Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. Methodology/Principal Findings Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P?=?0.018). Conclusions/Significance Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants. PMID:21072178

  18. The human glioma pathogenesis-related protein is structurally related to plant pathogenesis-related proteins and its gene is expressed specifically in brain tumors.

    PubMed

    Murphy, E V; Zhang, Y; Zhu, W; Biggs, J

    1995-06-14

    We report the cloning of a cDNA encoding GliPR (glioma pathogenesis-related protein), a protein that is structurally similar to plant pathogenesis-related proteins. The GLIPR gene is highly expressed in the human brain tumor, glioblastoma multiforme/astrocytoma, but neither in normal fetal or adult brain tissue, nor in other nervous system tumors. GliPR shares up to 50% amino acid (aa) homology with plant pathogenesis-related proteins, group 1, over a region that comprises almost two thirds of the protein. We speculate that there may be functional similarities between the human and plant proteins as well. PMID:7607567

  19. FUNCTIONAL ANALYSIS OF THE DOMESTICATION GENE Q IN WHEAT.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Q gene confers the free-threshing character of wheat and pleiotropically influences other domestication-related traits. In previous work, we showed that; Q is a member of the APETALA2 (AP2) family of transcription factors, the Q allele is more abundantly transcribed than q, and Q and q alleles d...

  20. Function of the aux and rol genes of the Ri plasmid in plant cell division in vitro.

    PubMed

    Nemoto, Keiichirou; Hara, Masamitsu; Suzuki, Masashi; Seki, Hikaru; Oka, Atsuhiro; Muranaka, Toshiya; Mano, Yoshihiro

    2009-12-01

    Auxin-autonomous growth in vitro may be related to the integration and expression of the aux and rol genes from the root-inducing (Ri) plasmid in plant cells infected by agropine-type Agrobacterium rhizogenes. To elucidate the functions of the aux and rol genes in plant cell division, plant cell lines transformed with the aux1 and aux2 genes or with the rolABCD genes were established using tobacco (Nicotiana tabacum) Bright Yellow-2 (BY-2) cells. The introduction of the aux1 and aux2 genes enabled the auxin-autonomous growth of BY-2 cells, but the introduction of the rolABCD genes did not affect the auxin requirement of the BY-2 cells. The results clearly show that the aux genes are necessary for auxinautotrophic cell division, and that the rolABCD genes are irrelevant in auxin autotrophy. PMID:20514230

  1. Function of the aux and rol genes of the Ri plasmid in plant cell division in vitro

    PubMed Central

    Nemoto, Keiichirou; Hara, Masamitsu; Suzuki, Masashi; Seki, Hikaru; Oka, Atsuhiro; Muranaka, Toshiya

    2009-01-01

    Auxin-autonomous growth in vitro may be related to the integration and expression of the aux and rol genes from the root-inducing (Ri) plasmid in plant cells infected by agropine-type Agrobacterium rhizogenes. To elucidate the functions of the aux and rol genes in plant cell division, plant cell lines transformed with the aux1 and aux2 genes or with the rolABCD genes were established using tobacco (Nicotiana tabacum) Bright Yellow-2 (BY-2) cells. The introduction of the aux1 and aux2 genes enabled the auxin-autonomous growth of BY-2 cells, but the introduction of the rolABCD genes did not affect the auxin requirement of the BY-2 cells. The results clearly show that the aux genes are necessary for auxinautotrophic cell division, and that the rolABCD genes are irrelevant in auxin autotrophy. PMID:20514230

  2. Effects of soil type and farm management on soil ecological functional genes and microbial activities

    SciTech Connect

    Reeve, Jennifer [Washington State University; Schadt, Christopher Warren [ORNL; Carpenter-Boggs, Lynne [Washington State University; Kang, S. [University of Oklahoma; Zhou, Jizhong [University of Oklahoma, Norman; Reganold, John P. [Washington State University

    2010-01-01

    Relationships between soil microbial diversity and soil function are the subject of much debate. Process-level analyses have shown that microbial function varies with soil type and responds to soil management. However, such measurements cannot determine the role of community structure and diversity in soil function. The goal of this study was to investigate the role of gene frequency and diversity, measured by microarray analysis, on soil processes. The study was conducted in an agro-ecosystem characterized by contrasting management practices and soil types. Eight pairs of adjacent commercial organic and conventional strawberry fields were matched for soil type, strawberry variety, and all other environmental conditions. Soil physical, chemical and biological analyses were conducted including functional gene microarrays (FGA). Soil physical and chemical characteristics were primarily determined by soil textural type (coarse vs fine-textured), but biological and FGA measures were more influenced by management (organic vs conventional). Organically managed soils consistently showed greater functional activity as well as FGA signal intensity (SI) and diversity. Overall FGA SI and diversity were correlated to total soil microbial biomass. Functional gene group SI and/or diversity were correlated to related soil chemical and biological measures such as microbial biomass, cellulose, dehydrogenase, ammonium and sulfur. Management was the dominant determinant of soil biology as measured by microbial gene frequency and diversity, which paralleled measured microbial processes.

  3. Transglutaminase regulates immune-related genes in shrimp.

    PubMed

    Fagutao, Fernand F; Maningas, Mary Beth B; Kondo, Hidehiro; Aoki, Takashi; Hirono, Ikuo

    2012-05-01

    Transglutaminase (TGase) is known to be involved in blood coagulation, a conserved defence mechanism among invertebrates. Gene silencing of TGase was previously shown to render shrimp susceptible to both bacterial and viral infections suggesting that TGase is an essential component of the shrimp immune system. Here, we examine the effects of the absence of TGase on the transcriptomic profile of kuruma shrimp by microarray analysis, focussing on genes that are involved in shrimp immunity. Total RNAs from shrimp haemocytes injected with dsRNA specific for TGase and control samples were isolated at 3 and 7 days p.i. and analyzed by microarray. Results revealed that TGase silencing affects the expression of genes in shrimp and caused significant down-regulation of the expressions of crustin and lysozyme. Furthermore, TGase-depleted samples were found to have lower haemocyte counts and higher total bacterial counts in their haemolymph. These results suggest that TGase is an important component of the shrimp immune response and is involved in the regulation of some immune-related genes particularly antimicrobial peptides. PMID:22306779

  4. Relating protein adduction to gene expression changes: a systems approach

    PubMed Central

    Zhang, Bing; Shi, Zhiao; Duncan, Dexter T; Prodduturi, Naresh; Marnett, Lawrence J; Liebler, Daniel C

    2013-01-01

    Modification of proteins by reactive electrophiles such as the 4-hydroxy-2-nonenal (HNE) plays a critical role in oxidant-associated human diseases. However, little is known about protein adduction and the mechanism by which protein damage elicits adaptive effects and toxicity. We developed a systems approach for relating protein adduction to gene expression changes through the integration of protein adduction, gene expression, protein-DNA interaction, and protein-protein interaction data. Using a random walk strategy, we expanded a list of responsive transcription factors inferred from gene expression studies to upstream signaling networks, which in turn allowed overlaying protein adduction data on the network for the prediction of stress sensors and their associated regulatory mechanisms. We demonstrated the general applicability of transcription factor-based signaling network inference using 103 known pathways. Applying our workflow on gene expression and protein adduction data from HNE-treatment not only rediscovered known mechanisms of electrophile stress but also generated novel hypotheses regarding protein damage sensors. Although developed for analyzing protein adduction data, the framework can be easily adapted for phosphoproteomics and other types of protein modification data. PMID:21594272

  5. Experimental evidence validating the computational inference of functional associations from gene fusion events: a critical survey

    PubMed Central

    Promponas, Vasilis J.; Ouzounis, Christos A.; Iliopoulos, Ioannis

    2014-01-01

    More than a decade ago, a number of methods were proposed for the inference of protein interactions, using whole-genome information from gene clusters, gene fusions and phylogenetic profiles. This structural and evolutionary view of entire genomes has provided a valuable approach for the functional characterization of proteins, especially those without sequence similarity to proteins of known function. Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence. Yet, despite these exciting developments, there have been relatively few cases of real use of these methods outside the computational biology field, as reflected from citation analysis. These methods have the potential to be used in high-throughput experimental settings in functional genomics and proteomics to validate results with very high accuracy and good coverage. In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations. Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology. PMID:23220349

  6. Experimental evidence validating the computational inference of functional associations from gene fusion events: a critical survey.

    PubMed

    Promponas, Vasilis J; Ouzounis, Christos A; Iliopoulos, Ioannis

    2014-05-01

    More than a decade ago, a number of methods were proposed for the inference of protein interactions, using whole-genome information from gene clusters, gene fusions and phylogenetic profiles. This structural and evolutionary view of entire genomes has provided a valuable approach for the functional characterization of proteins, especially those without sequence similarity to proteins of known function. Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence. Yet, despite these exciting developments, there have been relatively few cases of real use of these methods outside the computational biology field, as reflected from citation analysis. These methods have the potential to be used in high-throughput experimental settings in functional genomics and proteomics to validate results with very high accuracy and good coverage. In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations. Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology. PMID:23220349

  7. HD CAG-correlated gene expression changes support a simple dominant gain of function

    PubMed Central

    Jacobsen, Jessie C.; Gregory, Gillian C.; Woda, Juliana M.; Thompson, Morgan N.; Coser, Kathryn R.; Murthy, Vidya; Kohane, Isaac S.; Gusella, James F.; Seong, Ihn Sik; MacDonald, Marcy E.; Shioda, Toshi; Lee, Jong-Min

    2011-01-01

    Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (HdhQ20/7, HdhQ50/7, HdhQ91/7, HdhQ111/7), to genes differentially expressed between Hdhex4/5/ex4/5 huntingtin null and wild-type (HdhQ7/7) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

  8. HD CAG-correlated gene expression changes support a simple dominant gain of function.

    PubMed

    Jacobsen, Jessie C; Gregory, Gillian C; Woda, Juliana M; Thompson, Morgan N; Coser, Kathryn R; Murthy, Vidya; Kohane, Isaac S; Gusella, James F; Seong, Ihn Sik; MacDonald, Marcy E; Shioda, Toshi; Lee, Jong-Min

    2011-07-15

    Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (Hdh(Q20/7), Hdh(Q50/7), Hdh(Q91/7), Hdh(Q111/7)), to genes differentially expressed between Hdh(ex4/5/ex4/5) huntingtin null and wild-type (Hdh(Q7/7)) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

  9. Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice

    PubMed Central

    Jellen, Leslie C.; Lu, Lu; Wang, Xusheng; Unger, Erica L.; Earley, Christopher J.; Allen, Richard P.; Williams, Robert W.; Jones, Byron C.

    2013-01-01

    A clear link exists between iron deficiency (ID) and nigrostriatal dopamine malfunction. This link appears to play an important role in at least restless legs syndrome (RLS) if not several other neurological diseases. Yet, the underlying mechanisms remain unclear. The effects of ID on gene expression in the brain have not been studied extensively. Here, to better understand how exactly ID alters dopamine functioning, we investigated the effects of ID on gene expression in the brain, seeking to identify any potential transcription-based mechanisms. We used six strains of recombinant inbred mice (BXD type) known to differ in susceptibility to ID in the brain. Upon weaning, we subjected mice from each strain to either an iron-deficient or iron-adequate diet. After 100 days of dietary treatment, we measured the effects of ID on gene expression in the ventral midbrain (VMB), a region containing the substantia nigra. The substantia nigra is the base of the nigrostriatal dopamine pathway and a region particularly affected by iron loss in RLS. We screened for ID-induced changes in expression, including changes in that of both iron-regulating and dopamine-related genes. Results revealed a number of expression changes occurring in ID, with large strain-based differences in the genes involved and number of expression changes occurring. In terms of dopamine-related genes, results revealed ID-induced expression changes in three genes with direct ties to nigrostriatal dopamine functioning, two of which have never before been implicated in an iron-dopamine pathway. These were stromal cell-derived factor 1 (Cxcl12, or SDF-1), a ferritin regulator and potent dopamine neuromodulator, and hemoglobin, beta adult chain 1 (Hbb-b1), a gene recently shown to play a functional role in dopaminergic neurons. The extent of up-regulation of these genes varied by strain. This work not only demonstrates wide genetic variation in the transcriptional response to ID in the brain, but also reveals two novel biochemical pathways by which iron may potentially alter dopamine function. PMID:23911809

  10. Applying Support Vector Machines for Gene ontology based gene function prediction

    Microsoft Academic Search

    Arunachalam Vinayagam; Rainer König; Jutta Moormann; Falk Schubert; Roland Eils; Karl-heinz Glatting; Sándor Suhai

    2004-01-01

    BACKGROUND: The current progress in sequencing projects calls for rapid, reliable and accurate function assignments of gene products. A variety of methods has been designed to annotate sequences on a large scale. However, these methods can either only be applied for specific subsets, or their results are not formalised, or they do not provide precise confidence estimates for their predictions.

  11. Molecular cloning and functional analysis of the goose FSH? gene.

    PubMed

    Huang, Z; Li, X; Li, Y; Liu, R; Chen, Y; Wu, N; Wang, M; Song, Y; Yuan, X; Lan, L; Xu, Q; Chen, G; Zhao, W

    2015-06-01

    The objective of this investigation was to clone goose FSH?-subunit cDNA and to construct a FSH fusion gene to identify the function of FSH? mRNA during stages of the breeding cycle. The FSH? gene was obtained by reverse transcription-PCR, and the full-length FSH? mRNA sequence was amplified by rapid-amplification of cDNA ends. FSH? mRNA expression was detected in reproductive tissues at different stages (pre-laying, laying period, and broody period). Additionally, the expression of 4 genes known to be involved in reproduction (FSH?, GnRH, GH, and BMP) were evaluated in COS-7 cells expressing the fusion gene (pVITRO2-FSH??-CTP). The results show that the FSH? gene consists of a 16 base pair (bp) 5'-untranslated region (UTR), 396 bp open reading frame, and alternative 3'-UTRs at 518 bp and 780 bp, respectively. qPCR analyses revealed that FSH? mRNA is highly transcribed in reproductive tissues, including the pituitary, hypothalamus, ovaries, and oviduct. FSH? mRNA expression increased and subsequently decreased in the pituitary, ovaries, and oviduct during the reproductive stages. Stable FSH expression was confirmed using enzyme-linked immunosorbent assays after transfection with the pVITRO2-FSH??-CTP plasmid. FSH?, GnRH, and BMP expression increased significantly 36 h and 48 h after transfection with the fusion gene in COS-7 cells. The results demonstrate that the FSH? subunit functions in the goose reproductive cycle and provides a theoretical basis for future breeding work. PMID:25719958

  12. Genetic variants in microRNA genes: impact on microRNA expression, function, and disease

    PubMed Central

    Cammaerts, Sophia; Strazisar, Mojca; De Rijk, Peter; Del Favero, Jurgen

    2015-01-01

    MicroRNAs (miRNAs) are important regulators of gene expression and like any other gene, their coding sequences are subject to genetic variation. Variants in miRNA genes can have profound effects on miRNA functionality at all levels, including miRNA transcription, maturation, and target specificity, and as such they can also contribute to disease. The impact of variants in miRNA genes is the focus of the present review. To put these effects into context, we first discuss the requirements of miRNA transcripts for maturation. In the last part an overview of available databases and tools and experimental approaches to investigate miRNA variants related to human disease is presented.

  13. Predicting Gene Function from Uncontrolled Expression Variation among Individual Wild-Type Arabidopsis Plants[W

    PubMed Central

    Bhosale, Rahul; Jewell, Jeremy B.; Hollunder, Jens; Koo, Abraham J.K.; Vuylsteke, Marnik; Michoel, Tom; Hilson, Pierre; Goossens, Alain; Howe, Gregg A.; Browse, John; Maere, Steven

    2013-01-01

    Gene expression profiling studies are usually performed on pooled samples grown under tightly controlled experimental conditions to suppress variability among individuals and increase experimental reproducibility. In addition, to mask unwanted residual effects, the samples are often subjected to relatively harsh treatments that are unrealistic in a natural context. Here, we show that expression variations among individual wild-type Arabidopsis thaliana plants grown under the same macroscopic growth conditions contain as much information on the underlying gene network structure as expression profiles of pooled plant samples under controlled experimental perturbations. We advocate the use of subtle uncontrolled variations in gene expression between individuals to uncover functional links between genes and unravel regulatory influences. As a case study, we use this approach to identify ILL6 as a new regulatory component of the jasmonate response pathway. PMID:23943861

  14. Functional Analysis of the Validamycin Biosynthetic Gene Cluster and Engineered Production of Validoxylamine A

    PubMed Central

    Bai, Linquan; Li, Lei; Xu, Hui; Minagawa, Kazuyuki; Yu, Yi; Zhang, Yirong; Zhou, Xiufen; Floss, Heinz G.; Mahmud, Taifo; Deng, Zixin

    2006-01-01

    Summary A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VAL-A) biosynthesis revealed 16 structural, 2 regulatory, and 5 genes related to transport, transposition/integration, tellurium resistance, and another 4 genes with no obvious identity. The VAL-A biosynthetic pathway was proposed, with assignment of the required genetic functions confined in the sequenced region. A cluster of eight reassembled genes was found to support the VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo inactivation of the putative glycosyltransferase gene (valG) abolished the final attachment of glucose for VAL production, and resulted in the accumulation of the VAL-A precursor, validoxylamine, while the normal production of VAL-A could be restored by complementation with valG. The role of ValG in the glycosylation of validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay. PMID:16632251

  15. Functional annotation of human cytomegalovirus gene products: an update

    PubMed Central

    Van Damme, Ellen; Van Loock, Marnix

    2014-01-01

    Human cytomegalovirus is an opportunistic double-stranded DNA virus with one of the largest viral genomes known. The 235 kB genome is divided in a unique long (UL) and a unique short (US) region which are flanked by terminal and internal repeats. The expression of HCMV genes is highly complex and involves the production of protein coding transcripts, polyadenylated long non-coding RNAs, polyadenylated anti-sense transcripts and a variety of non-polyadenylated RNAs such as microRNAs. Although the function of many of these transcripts is unknown, they are suggested to play a direct or regulatory role in the delicately orchestrated processes that ensure HCMV replication and life-long persistence. This review focuses on annotating the complete viral genome based on three sources of information. First, previous reviews were used as a template for the functional keywords to ensure continuity; second, the Uniprot database was used to further enrich the functional database; and finally, the literature was manually curated for novel functions of HCMV gene products. Novel discoveries were discussed in light of the viral life cycle. This functional annotation highlights still poorly understood regions of the genome but more importantly it can give insight in functional clusters and/or may be helpful in the analysis of future transcriptomics and proteomics studies. PMID:24904534

  16. Identification of functional apple scab resistance gene promoters.

    PubMed

    Silfverberg-Dilworth, E; Besse, S; Paris, R; Belfanti, E; Tartarini, S; Sansavini, S; Patocchi, A; Gessler, C

    2005-04-01

    Apple scab (Venturia inaequalis) is one of the most damaging diseases affecting commercial apple production. Some wild Malus species possess resistance against apple scab. One gene, HcrVf2, from a cluster of three genes derived from the wild apple Malus floribunda clone 821, has recently been shown to confer resistance to apple scab when transferred into a scab-susceptible apple variety. For this proof-of-function experiment, the use of the 35S promoter from Cauliflower mosaic virus was reliable and appropriate. However, in order to reduce the amount of non-plant DNA in genetically modified apple to a minimum, with the aim of increasing genetically modified organism acceptability, these genes would ideally be regulated by their own promoters. In this study, sequences from the promoter region of the three members of the HcrVf gene family were compared. Promoter constructs containing progressive 5' deletions were prepared and used for functional analyses. Qualitative assessment confirmed promoter activity in apple. Quantitative promoter comparison was carried out in tobacco (Nicotiana glutinosa) and led to the identification of several promoter regions with different strengths from a basal level to half the strength of the 35S promoter from Cauliflower mosaic virus. PMID:15726316

  17. Tenm, a Drosophila gene related to tenascin, is a new pair-rule gene.

    PubMed

    Baumgartner, S; Martin, D; Hagios, C; Chiquet-Ehrismann, R

    1994-08-15

    We describe the molecular characterization of the Drosophila gene tenm, a large transcription unit spanning > 110 kb of DNA. tenm encodes a large extracellular protein of 2515 amino acids related to the extracellular matrix molecule tenascin. The Tenm protein is found in seven stripes during the blastoderm stage, and each stripe overlaps with the even-skipped stripes. tenm mutants show a phenotype resembling that of odd-paired (opa), a member of the pair-rule class of segmentation genes. Thus, Tenm is the first example of a pair-rule gene product acting from outside the cell. While the Tenm protein is under the control of fushi tarazu and even-skipped, but not of opa, at least two pair-rule genes, paired (prd) and sloppy paired (slp), and all segment-polarity genes analysed to date are under the control of tenm. Our data suggest that Tenm initiates a signal transduction cascade which acts, via or in concert with opa, on downstream targets such as prd, slp, gooseberry, engrailed and wingless, leading to an opa-like phenotype. PMID:8070401

  18. Differential Expression of Granulopoiesis Related Genes in Neutrophil Subsets Distinguished by Membrane Expression of CD177

    PubMed Central

    Hu, Nan; Mora-Jensen, Helena; Theilgaard-Mönch, Kim; Doornbos-van der Meer, Berber; Huitema, Minke G.; Stegeman, Coen A.; Heeringa, Peter; Kallenberg, Cees G. M.; Westra, Johanna

    2014-01-01

    Objective Differential gene expression in CD177+ and CD177? neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). Methods Neutrophils were isolated from healthy controls (HC) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177? subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177? subsets in microarray analysis were re-assessed using quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. Results The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177? neutrophils resulted in 14 genes with fold change (fc) >3 difference in expression. Interestingly, 10 of these genes have been reported to change significantly in expression during neutrophil maturation, and most of these genes were granule protein (GP) coding genes. mRNA expression levels measured by RT-PCR of a number of these GP, and of PR3 and MPO were higher in the CD177? neutrophil subset in HC, however, particular granule protein amounts were comparable between CD177+ and CD177? neutrophil subsets. AAV patients had higher amounts of CD177+ neutrophils, but contrary to neutrophils from HC expression of GP-genes was increased, possibly due to activation. Conclusion The neutrophil population can be distinguished by membrane expression of CD177 into subsets that are different in expression of GP mRNA but not in GP protein production. GP gene expression is also elevated in AAV patients, which is not explained by skewed distribution of CD177+ and CD177? subsets but may be associated with neutrophil activation during on-going inflammation. PMID:24926686

  19. Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution

    PubMed Central

    Sun, Liguang; Guo, Jianfei; Brown, Robert; Amagai, Takashi; Zhao, Yong; Su, Dong-Ming

    2010-01-01

    SUMMARY Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or non-hematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle due to shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreERT (uCreERT) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreERT-fx/fx mice showed an accelerated age-related thymic involution due to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3–6 months of age, resembling the naturally aged (18–22-month-old) murine thymus. By intrathymically supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and defective peripheral CD4+ T-cell function could be partially rescued. The results support the notion that decline of a single epithelial cell-autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age-related thymic involution in mice. PMID:20156205

  20. Characterization of the rainbow trout spleen transcriptome and identification of immune-related genes

    PubMed Central

    Ali, Ali; Rexroad, Caird E.; Thorgaard, Gary H.; Yao, Jianbo; Salem, Mohamed

    2014-01-01

    Resistance against diseases affects profitability of rainbow trout. Limited information is available about functions and mechanisms of teleost immune pathways. Immunogenomics provides powerful tools to determine disease resistance genes/gene pathways and develop genetic markers for genomic selection. RNA-Seq sequencing of the rainbow trout spleen yielded 93,532,200 reads (100 bp). High quality reads were assembled into 43,047 contigs. 26,333 (61.17%) of the contigs had hits to the NR protein database and 7024 (16.32%) had hits to the KEGG database. Gene ontology showed significant percentages of transcripts assigned to binding (51%), signaling (7%), response to stimuli (9%) and receptor activity (4%) suggesting existence of many immune-related genes. KEGG annotation revealed 2825 sequences belonging to “organismal systems” with the highest number of sequences, 842 (29.81%), assigned to immune system. A number of sequences were identified for the first time in rainbow trout belonging to Toll-like receptor signaling (35), B cell receptor signaling pathway (44), T cell receptor signaling pathway (56), chemokine signaling pathway (73), Fc gamma R-mediated phagocytosis (52), leukocyte transendothelial migration (60) and NK cell mediated cytotoxicity (42). In addition, 51 transcripts were identified as spleen-specific genes. The list includes 277 full-length cDNAs. The presence of a large number of immune-related genes and pathways similar to other vertebrates suggests that innate and adaptive immunity in fish are conserved. This study provides deep-sequence data of rainbow trout spleen transcriptome and identifies many new immune-related genes and full-length cDNAs. This data will help identify allelic variations suitable for genomic selection and genetic manipulation in aquaculture. PMID:25352861

  1. Functional hierarchy and phenotypic suppression among Drosophila homeotic genes: the labial and empty spiracles genes.

    PubMed Central

    Macías, A; Morata, G

    1996-01-01

    The Drosophila homeotic cluster (HOM-C) is made up of eight genes, which specify the identity of cephalic, thoracic and abdominal segments. These genes can be ordered in a hierarchy which correlates with their position along the 5'-3' transcriptional direction. When they are absent, thoracic and abdominal body segments develop the same'ground' pattern, which is thoracic-like but also includes cephalic structures (sclerotic plates). We find that these plates are specified by the homeobox gene empty spiracles (ems) which is not a member of the HOM-C and which is expressed in all body segments. ems mutations, however, only produce defects in anterior head structures and the posterior spiracles. The ems product has the potential to induce sclerotic plates but this potential is suppressed by any of the HOM-C genes, including the labial gene, which we show to be the lowest ranking of the HOM-C hierarchy. This suppression does not occur at the transcriptional or translational level because the ems function is suppressed in cells containing the ems product. Thus, this appears to be the first case of phenotypic suppression operating in normal development. We propose that ems was originally a member of the HOM-C which escaped from the complex and has also acquired new functions during evolution. Images PMID:8617208

  2. Ets Related Gene and Smad3 Proteins Collaborate to Activate Transforming Growth Factor-Beta Mediated Signaling Pathway in ETS Related Gene-Positive Prostate Cancer Cells

    PubMed Central

    Fang, Jinbo; Xu, Huali; Yang, Chunshu; Morsalin, Sharif; Kayarthodi, Shubhalaxmi; Rungsrisuriyachai, Kunchala; Gunnal, Ujwala; Mckenzie, Brittany; Rao, Veena N.; Reddy, E. Shyam P.

    2015-01-01

    TGF-?/Smads signaling plays a significant role in the regulation of growth of normal and prostate cancer cells. Smad proteins function as important mediators of intracellular signal transduction of transforming growth factor-? (TGF-?). TGF-? signaling pathway is known to regulate cell proliferation, differentiation, apoptosis and play a major role in some human diseases and cancers. Following their phosphorylation by TGF-? receptor-I, Receptor-regulated Smads (including Smad2 and Smad3 proteins) form a heteromeric complex with co-Smad (Smad4) and then translocate into the nucleus where they bind and regulate the expression of target genes. ERG (Ets Related Gene) belongs to the ETS family of transcriptional factors. Chromosomal rearrangement of TMPRSS2 gene and ERG gene has been found in majority of prostate cancers. Over-expression of full length or truncated ERG proteins have been shown to associate with a higher rate of recurrent and unfavorable prognosis of prostate cancer. In order to understand how ERG oncoprotein regulates TGF-?/Smads signaling pathway, we have studied the effect of ERG on TGF-?/Smad3 signaling pathway. In this study, we demonstrate that ERG oncoprotein physically interacts with Smad3 protein and stabilizes phospho-Smad3 protein and thereby enhance TGF-?/Smad3 signaling pathway in prostate cells. Thus, ERG oncoprotein plays an important role in prostate tumorigenesis by using a novel mechanism to activate TGF-?/Smad3 signaling pathway. PMID:25745638

  3. Glycan-related gene expression signatures in breast cancer subtypes; relation to survival.

    PubMed

    Potapenko, Ivan O; Lüders, Torben; Russnes, Hege G; Helland, Ĺslaug; Sřrlie, Therese; Kristensen, Vessela N; Nord, Silje; Lingjćrde, Ole C; Břrresen-Dale, Anne-Lise; Haakensen, Vilde D

    2015-04-01

    Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their association to clinical parameters. Five expression datasets of 454 invasive breast carcinomas, 31 ductal carcinomas in situ (DCIS), and 79 non-malignant breast tissue samples were analysed. Results were validated in 1960 breast carcinomas. 419 genes encoding glycosylation-related proteins were selected. The DCIS samples appeared expression-wise similar to carcinomas, showing altered gene expression related to glycosaminoglycans (GAGs) and N-glycans when compared to non-malignant samples. In-situ lesions with different aggressiveness potentials demonstrated changes in glycosaminoglycan sulfation and adhesion proteins. Subtype-specific expression patterns revealed down-regulation of genes encoding glycan-binding proteins in the luminal A and B subtypes. Clustering basal-like samples using a consensus list of genes differentially expressed across discovery datasets produced two clusters with significantly differing prognosis in the validation dataset. Finally, our analyses suggest that glycolipids may play an important role in carcinogenesis of breast tumors - as demonstrated by association of B3GNT5 and UGCG genes to patient survival. In conclusion, most glycan-specific changes occur early in the carcinogenic process. We have identified glycan-related alterations specific to breast cancer subtypes including a prognostic signature for two basal-like subgroups. Future research in this area may potentially lead to markers for better prognostication and treatment stratification of breast cancer patients. PMID:25655580

  4. Dating and functional characterization of duplicated genes in the apple (Malus domestica Borkh.) by analyzing EST data

    PubMed Central

    2010-01-01

    Background Gene duplication is central to genome evolution. In plants, genes can be duplicated through small-scale events and large-scale duplications often involving polyploidy. The apple belongs to the subtribe Pyrinae (Rosaceae), a diverse lineage that originated via allopolyploidization. Both small-scale duplications and polyploidy may have been important mechanisms shaping the genome of this species. Results This study evaluates the gene duplication and polyploidy history of the apple by characterizing duplicated genes in this species using EST data. Overall, 68% of the apple genes were clustered into families with a mean copy-number of 4.6. Analysis of the age distribution of gene duplications supported a continuous mode of small-scale duplications, plus two episodes of large-scale duplicates of vastly different ages. The youngest was consistent with the polyploid origin of the Pyrinae 37-48 MYBP, whereas the older may be related to ?-triplication; an ancient hexapolyploidization previously characterized in the four sequenced eurosid genomes and basal to the eurosid-asterid divergence. Duplicated genes were studied for functional diversification with an emphasis on young paralogs; those originated during or after the formation of the Pyrinae lineage. Unequal assignment of single-copy genes and gene families to Gene Ontology categories suggested functional bias in the pattern of gene retention of paralogs. Young paralogs related to signal transduction, metabolism, and energy pathways have been preferentially retained. Non-random retention of duplicated genes seems to have mediated the expansion of gene families, some of which may have substantially increased their members after the origin of the Pyrinae. The joint analysis of over-duplicated functional categories and phylogenies, allowed evaluation of the role of both polyploidy and small-scale duplications during this process. Finally, gene expression analysis indicated that 82% of duplicated genes, including 80% of young paralogs, showed uncorrelated expression profiles, suggesting extensive subfunctionalization and a role of gene duplication in the acquisition of novel patterns of gene expression. Conclusions This study reports a genome-wide analysis of the mode of gene duplication in the apple, and provides evidence for its role in genome functional diversification by characterising three major processes: selective retention of paralogs, amplification of gene families, and changes in gene expression. PMID:20470375

  5. Genome-Wide Distribution, Organisation and Functional Characterization of Disease Resistance and Defence Response Genes across Rice Species

    PubMed Central

    Singh, Sangeeta; Chand, Suresh; Singh, N. K.; Sharma, Tilak Raj

    2015-01-01

    The resistance (R) genes and defense response (DR) genes have become very important resources for the development of disease resistant cultivars. In the present investigation, genome-wide identification, expression, phylogenetic and synteny analysis was done for R and DR-genes across three species of rice viz: Oryza sativa ssp indica cv 93-11, Oryza sativa ssp japonica and wild rice species, Oryza brachyantha. We used the in silico approach to identify and map 786 R -genes and 167 DR-genes, 672 R-genes and 142 DR-genes, 251 R-genes and 86 DR-genes in the japonica, indica and O. brachyanth a genomes, respectively. Our analysis showed that 60.5% and 55.6% of the R-genes are tandemly repeated within clusters and distributed over all the rice chromosomes in indica and japonica genomes, respectively. The phylogenetic analysis along with motif distribution shows high degree of conservation of R- and DR-genes in clusters. In silico expression analysis of R-genes and DR-genes showed more than 85% were expressed genes showing corresponding EST matches in the databases. This study gave special emphasis on mechanisms of gene evolution and duplication for R and DR genes across species. Analysis of paralogs across rice species indicated 17% and 4.38% R-genes, 29% and 11.63% DR-genes duplication in indica and Oryza brachyantha, as compared to 20% and 26% duplication of R-genes and DR-genes in japonica respectively. We found that during the course of duplication only 9.5% of R- and DR-genes changed their function and rest of the genes have maintained their identity. Syntenic relationship across three genomes inferred that more orthology is shared between indica and japonica genomes as compared to brachyantha genome. Genome wide identification of R-genes and DR-genes in the rice genome will help in allele mining and functional validation of these genes, and to understand molecular mechanism of disease resistance and their evolution in rice and related species. PMID:25902056

  6. Genome Holography: Deciphering Function-Form Motifs from Gene Expression Data

    E-print Network

    Jacob, Eshel Ben

    Genome Holography: Deciphering Function-Form Motifs from Gene Expression Data Asaf Madi1 information from the vast amount of raw gene-expression data obtained from the microarray measurements here is based on investigating the gene-gene correlations. We analyze a database of gene expression

  7. Immunity-related genes in Ixodes scapularis—perspectives from genome information

    PubMed Central

    Smith, Alexis A.; Pal, Utpal

    2014-01-01

    Ixodes scapularis, commonly known as the deer tick, transmits a wide array of human and animal pathogens including Borrelia burgdorferi. Despite substantial advances in our understanding of immunity in model arthropods, including other disease vectors, precisely how I. scapularis immunity functions and influences persistence of invading pathogens remains largely unknown. This review provides a comprehensive analysis of the recently sequenced I. scapularis genome for the occurrence of immune-related genes and related pathways. We will also discuss the potential influence of immunity-related genes on the persistence of tick-borne pathogens with an emphasis on the Lyme disease pathogen B. burgdorferi. Further enhancement of our knowledge of tick immune responses is critical to understanding the molecular basis of the persistence of tick-borne pathogens and development of novel interventions against the relevant infections. PMID:25202684

  8. A Multifunctional Mutagenesis System for Analysis of Gene Function in Zebrafish

    PubMed Central

    Quach, Helen Ngoc Bao; Tao, Shijie; Vrljicak, Pavle; Joshi, Adita; Ruan, Hua; Sukumaran, Rashmi; Varshney, Gaurav K.; LaFave, Matthew C.; Burgess, Shawn M.; Winkler, Christoph; Emelyanov, Alexander; Parinov, Sergey; Sampath, Karuna

    2015-01-01

    Since the sequencing of the human reference genome, many human disease-related genes have been discovered. However, understanding the functions of all the genes in the genome remains a challenge. The biological activities of these genes are usually investigated in model organisms such as mice and zebrafish. Large-scale mutagenesis screens to generate disruptive mutations are useful for identifying and understanding the activities of genes. Here, we report a multifunctional mutagenesis system in zebrafish using the maize Ds transposon. Integration of the Ds transposable element containing an mCherry reporter for protein trap events and an EGFP reporter for enhancer trap events produced a collection of transgenic lines marking distinct cell and tissue types, and mutagenized genes in the zebrafish genome by trapping and prematurely terminating endogenous protein coding sequences. We obtained 642 zebrafish lines with dynamic reporter gene expression. The characterized fish lines with specific expression patterns will be made available through the European Zebrafish Resource Center (EZRC), and a database of reporter expression is available online (http://fishtrap.warwick.ac.uk/). Our approach complements other efforts using zebrafish to facilitate functional genomic studies in this model of human development and disease. PMID:25840430

  9. A Multifunctional Mutagenesis System for Analysis of Gene Function in Zebrafish.

    PubMed

    Quach, Helen Ngoc Bao; Tao, Shijie; Vrljicak, Pavle; Joshi, Adita; Ruan, Hua; Sukumaran, Rashmi; Varshney, Gaurav K; LaFave, Matthew C; Burgess, Shawn M; Winkler, Christoph; Emelyanov, Alexander; Parinov, Sergey; Sampath, Karuna

    2015-01-01

    Since the sequencing of the human reference genome, many human disease-related genes have been discovered. However, understanding the functions of all the genes in the genome remains a challenge. The biological activities of these genes are usually investigated in model organisms such as mice and zebrafish. Large-scale mutagenesis screens to generate disruptive mutations are useful for identifying and understanding the activities of genes. Here, we report a multifunctional mutagenesis system in zebrafish using the maize Ds transposon. Integration of the Ds transposable element containing an mCherry reporter for protein trap events and an EGFP reporter for enhancer trap events produced a collection of transgenic lines marking distinct cell and tissue types, and mutagenized genes in the zebrafish genome by trapping and prematurely terminating endogenous protein coding sequences. We obtained 642 zebrafish lines with dynamic reporter gene expression. The characterized fish lines with specific expression patterns will be made available through the European Zebrafish Resource Center (EZRC), and a database of reporter expression is available online (http://fishtrap.warwick.ac.uk/). Our approach complements other efforts using zebrafish to facilitate functional genomic studies in this model of human development and disease. PMID:25840430

  10. Brain galanin system genes interact with life stresses in depression-related phenotypes

    PubMed Central

    Juhasz, Gabriella; Hullam, Gabor; Eszlari, Nora; Gonda, Xenia; Antal, Peter; Anderson, Ian Muir; Hökfelt, Tomas G. M.; Deakin, J. F. William; Bagdy, Gyorgy

    2014-01-01

    Galanin is a stress-inducible neuropeptide and cotransmitter in serotonin and norepinephrine neurons with a possible role in stress-related disorders. Here we report that variants in genes for galanin (GAL) and its receptors (GALR1, GALR2, GALR3), despite their disparate genomic loci, conferred increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events in a European white population cohort totaling 2,361 from Manchester, United Kingdom and Budapest, Hungary. Bayesian multivariate analysis revealed a greater relevance of galanin system genes in highly stressed subjects compared with subjects with moderate or low life stress. Using the same method, the effect of the galanin system genes was stronger than the effect of the well-studied 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4). Conventional multivariate analysis using general linear models demonstrated that interaction of galanin system genes with life stressors explained more variance (1.7%, P = 0.005) than the life stress-only model. This effect replicated in independent analysis of the Manchester and Budapest subpopulations, and in males and females. The results suggest that the galanin pathway plays an important role in the pathogenesis of depression in humans by increasing the vulnerability to early and recent psychosocial stress. Correcting abnormal galanin function in depression could prove to be a novel target for drug development. The findings further emphasize the importance of modeling environmental interaction in finding new genes for depression. PMID:24706871

  11. Remote control of gene function by local translation.

    PubMed

    Jung, Hosung; Gkogkas, Christos G; Sonenberg, Nahum; Holt, Christine E

    2014-03-27

    The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function. PMID:24679524

  12. Functional gene variants of CYP3A4.

    PubMed

    Werk, A N; Cascorbi, I

    2014-09-01

    Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more drugs in clinical use than any other foreign compound-metabolizing enzyme in humans. Recently, increasing evidence has been found showing that variants in the CYP3A4 gene have functional significance and--in rare cases--lead to loss of activity, implying tremendous consequences for patients. This review article highlights the functional consequences of all CYP3A4 variants recognized by the Human Cytochrome P450 (CYP) Allele Nomenclature Database. PMID:24926778

  13. Molecular Evolution of Candidate Genes for Crop-Related Traits in Sunflower (Helianthus annuus L.)

    E-print Network

    Burke, John M.

    Molecular Evolution of Candidate Genes for Crop-Related Traits in Sunflower (Helianthus annuus L Evolution of Candidate Genes for Crop-Related Traits in Sunflower (Helianthus annuus L.). PLoS ONE 9(6): e

  14. Genome-wide identification and divergent transcriptional expression of StAR-related lipid transfer (START) genes in teleosts.

    PubMed

    Teng, Huajing; Cai, Wanshi; Zeng, Kun; Mao, Fengbiao; You, Mingcong; Wang, Tao; Zhao, Fangqing; Sun, Zhongsheng

    2013-04-25

    The lipid transfer reactions and the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) genes have a major role in lipid metabolism. However, START genes and their physiological functions in teleost fishes are relatively unknown. Through genome-wide screening, we identified and annotated 91 START genes in 5 teleost species. Although START domain-containing proteins are augmented in teleost genomes relative to tetrapod genomes, a similar number of genes are shared between them. Asymmetry of paralogous gene loss within the teleost START family and an extra copy of some START genes in teleosts resulting from fish-specific genome duplication have been demonstrated. A distinct transcriptional expression pattern within members of some START groups under different developmental stages suggests divergent functions within the same group in the developmental process. In addition, an asymmetric molecular evolution rate deviating from the neutral expectation has been observed in 7 of 14 teleost fish extra-duplicated pairs. The present study provides valuable information for increasing our understanding of the evolution and gene expression divergence under developmental stages of the START gene family in teleost fishes. PMID:23415839

  15. Gamma and Related Functions Generalized for Sequences

    ERIC Educational Resources Information Center

    Ollerton, R. L.

    2008-01-01

    Given a sequence g[subscript k] greater than 0, the "g-factorial" product [big product][superscript k] [subscript i=1] g[subscript i] is extended from integer k to real x by generalizing properties of the gamma function [Gamma](x). The Euler-Mascheroni constant [gamma] and the beta and zeta functions are also generalized. Specific examples include…

  16. Comparative genomic analysis of dha regulon and related genes for anaerobic glycerol metabolism in bacteria.

    PubMed

    Sun, Jibin; van den Heuvel, Joop; Soucaille, Philippe; Qu, Yinbo; Zeng, An-Ping

    2003-01-01

    The dihydroxyacetone (dha) regulon of bacteria encodes genes for the anaerobic metabolism of glycerol. In this work, genomic data are used to analyze and compare the dha regulon and related genes in different organisms in silico with respect to gene organization, sequence similarity, and possible functions. Database searches showed that among the organisms, the genomes of which have been sequenced so far, only two, i.e., Klebsiella pneumoniae MGH 78578 and Clostridium perfringens contain a complete dha regulon bearing all known enzymes. The components and their organization in the dha regulon of these two organisms differ considerably from each other and also from the previously partially sequenced dha regulons in Citrobacter freundii, Clostridium pasteurianum, and Clostridium butyricum. Unlike all of the other organisms, genes for the oxidative and reductive pathways of anaerobic glycerol metabolism in C. perfringens are located in two separate organization units on the chromosome. Comparisons of deduced protein sequences of genes with similar functions showed that the dha regulon components in K. pneumoniae and C. freundii have high similarities (80-95%) but lower similarities to those of the Clostridium species (30-80%). Interestingly, the protein sequence similarities among the dha genes of the Clostridium species are in many cases even lower than those between the Clostridium species and K. pneumoniae or C. freundii, suggesting two different types of dha regulon in the Clostridium species studied. The in silico reconstruction and comparison of dha regulons revealed several new genes in the microorganisms studied. In particular, a novel dha kinase that is phosphoenolpyruvate-dependent is identified and experimentally confirmed for K. pneumoniae in addition to the known ATP-dependent dha kinase. This finding gives new insights into the regulation of glycerol metabolism in K. pneumoniae and explains some hitherto not well understood experimental observations. PMID:12675558

  17. An introduction to functional independency in relational database normalization

    Microsoft Academic Search

    Tennyson X. Chen; Sean Shuangquan Liu; Martin D. Meyer; Donald Gotterbarn

    2007-01-01

    In this paper, we discuss the deficiencies of normal form definitions based on Functional Dependency and introduce a new normal form concept based on Functional Independency. Functional Independency has not been systematically investigated while there is a very strong theoretical foundation for the study of Functional Dependency in relational database normalization. This paper will demonstrate that considering Functional Dependency alone

  18. Functional evolution of cis-regulatory modules at a homeotic gene in Drosophila.

    PubMed

    Ho, Margaret C W; Johnsen, Holly; Goetz, Sara E; Schiller, Benjamin J; Bae, Esther; Tran, Diana A; Shur, Andrey S; Allen, John M; Rau, Christoph; Bender, Welcome; Fisher, William W; Celniker, Susan E; Drewell, Robert A

    2009-11-01

    It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox) genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs). How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab) mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions, functionally critical transcription factor binding sites within embryonic enhancer CRMs are highly conserved. These results have implications for understanding mechanisms of gene expression during embryonic development, enhancer function, and the molecular evolution of eukaryotic regulatory modules. PMID:19893611

  19. Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

    PubMed Central

    Takahara, Yoshiyuki; Takahashi, Mitsuo; Zhang, Qing-Wei; Wagatsuma, Hirotaka; Mori, Maiko; Tamori, Akihiro; Shiomi, Susumu; Nishiguchi, Shuhei

    2008-01-01

    AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis. PMID:18395900

  20. Sugarcane functional genomics: gene discovery for agronomic trait development.

    PubMed

    Menossi, M; Silva-Filho, M C; Vincentz, M; Van-Sluys, M-A; Souza, G M

    2008-01-01

    Sugarcane is a highly productive crop used for centuries as the main source of sugar and recently to produce ethanol, a renewable bio-fuel energy source. There is increased interest in this crop due to the impending need to decrease fossil fuel usage. Sugarcane has a highly polyploid genome. Expressed sequence tag (EST) sequencing has significantly contributed to gene discovery and expression studies used to associate function with sugarcane genes. A significant amount of data exists on regulatory events controlling responses to herbivory, drought, and phosphate deficiency, which cause important constraints on yield and on endophytic bacteria, which are highly beneficial. The means to reduce drought, phosphate deficiency, and herbivory by the sugarcane borer have a negative impact on the environment. Improved tolerance for these constraints is being sought. Sugarcane's ability to accumulate sucrose up to 16% of its culm dry weight is a challenge for genetic manipulation. Genome-based technology such as cDNA microarray data indicates genes associated with sugar content that may be used to develop new varieties improved for sucrose content or for traits that restrict the expansion of the cultivated land. The genes can also be used as molecular markers of agronomic traits in traditional breeding programs. PMID:18273390

  1. Integrative approaches for predicting protein function and prioritizing genes for complex phenotypes using protein interaction networks.

    PubMed

    Ma, Xiaotu; Chen, Ting; Sun, Fengzhu

    2014-09-01

    With the rapid development of biotechnologies, many types of biological data including molecular networks are now available. However, to obtain a more complete understanding of a biological system, the integration of molecular networks with other data, such as molecular sequences, protein domains and gene expression profiles, is needed. A key to the use of networks in biological studies is the definition of similarity among proteins over the networks. Here, we review applications of similarity measures over networks with a special focus on the following four problems: (i) predicting protein functions, (ii) prioritizing genes related to a phenotype given a set of seed genes that have been shown to be related to the phenotype, (iii) prioritizing genes related to a phenotype by integrating gene expression profiles and networks and (iv) identification of false positives and false negatives from RNAi experiments. Diffusion kernels are demonstrated to give superior performance in all these tasks, leading to the suggestion that diffusion kernels should be the primary choice for a network similarity metric over other similarity measures such as direct neighbors and shortest path distance. PMID:23788799

  2. Impaired barrier function by dietary fructo-oligosaccharides (FOS) in rats is accompanied by increased colonic mitochondrial gene expression

    PubMed Central

    Rodenburg, Wendy; Keijer, Jaap; Kramer, Evelien; Vink, Carolien; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg MJ

    2008-01-01

    Background Dietary non-digestible carbohydrates stimulate the gut microflora and are therefore presumed to improve host resistance to intestinal infections. However, several strictly controlled rat infection studies showed that non-digestible fructo-oligosaccharides (FOS) increase, rather than decrease, translocation of Salmonella towards extra-intestinal sites. In addition, it was shown that FOS increases intestinal permeability already before infection. The mechanism responsible for this adverse effect of FOS is unclear. Possible explanations are altered mucosal integrity due to changes in tight junctions or changes in expression of defense molecules such as antimicrobials and mucins. To examine the mechanisms underlying weakening of the intestinal barrier by FOS, a controlled dietary intervention study was performed. Two groups of 12 rats were adapted to a diet with or without FOS. mRNA was collected from colonic mucosa and changes in gene expression were assessed for each individual rat using Agilent rat whole genome microarrays. Results Among the 997 FOS induced genes we observed less mucosal integrity related genes than expected with the clear permeability changes. FOS did not induce changes in tight junction genes and only 8 genes related to mucosal defense were induced by FOS. These small effects are unlikely the cause for the clear increase in intestinal permeability that is observed. FOS significantly increased expression of 177 mitochondria-related genes. More specifically, induced expression of genes involved in all five OXPHOS complexes and the TCA cycle was observed. These results indicate that dietary FOS influences intestinal mucosal energy metabolism. Furthermore, increased expression of 113 genes related to protein turnover, including proteasome genes, ribosomal genes and protein maturation related genes, was seen. FOS upregulated expression of the peptide hormone proglucagon gene, in agreement with previous studies, as well as three other peptide hormone genes; peptide YY, pancreatic polypeptide and cholecystokinin. Conclusion We conclude that altered energy metabolism may underly colonic barrier function disruption due to FOS feeding in rats. PMID:18371188

  3. Intestinal structure and function related to toxicology.

    PubMed Central

    Crane, R K

    1979-01-01

    The study of toxic effects on small intestinal function is complicated by the integration of the activity of the small intestine with the activities of other regions of the GI tract. Also, the barrier and portal functions of the intestine are not as clearly defined as sometimes assumed. The intestinal surface functions as a barrier to the ingress of large quantities of large water soluble molecules. Lipidic substances enter the body quite readily as do small water-soluble molecules. The small intestinal surface is more a portal than a barrier, with its portal functions divided between nonspecific diffusional entry, which depends on physical properties and electric charge, and entry by specific membrane transport, which depends upon chemical structure. The implications of these properties of the small intestine for toxicological studies are stressed. PMID:540622

  4. GENOME-WIDE ANALYSIS OF AGING AND LEARNING-RELATED GENES IN THE HIPPOCAMPAL DENTATE GYRUS

    PubMed Central

    Burger, Corinna; Lopez, M. Cecilia; Baker, Henry V.; Mandel, Ronald J.; Muzyczka, Nick

    2008-01-01

    We have previously described the transcriptional changes that occur in the hippocampal CA1 field of aged rats following a Morris Water Maze (MWM) training paradigm. In this report we proceed with the analysis of the dentate region from the same animals. Animals were first identified as age learning-impaired or age-superior learners when compared to young rats based on their performance in the MWM. Messenger RNA was isolated from the dentate gyrus of each animal to interrogate Affymetrix RAE 230A rat genome microarrays. Microarray profiling identified 1129 genes that were differentially expressed between aged and young rats as a result of aging, and independent of their behavioral training (p<0.005). We applied Ingenuity Pathway Analysis (IPA) algorithms to identify the significant biological processes underlying age-related changes in the dentate gyrus. The most significant functions, as calculated by IPA, included cell movement, cell growth and proliferation, nervous system development and function, cellular assembly and organization, cell morphology and cell death. These significant processes are consistent with age-related changes in neurogenesis, and the neurogenic markers were generally found to be downregulated in senescent animals. In addition, statistical analysis of the different experimental groups of aged animals recognized 85 genes (p<0.005) that were different in the dentate gyrus of aged rats that had learned the MWM when compared to learning impaired and a number of controls for stress, exercise and non-spatial learning. The list of learning-related genes expressed in the dentate adds to the set of genes we previously described in the CA1 region. This long list of genes constitutes a starting tool to elucidating the molecular pathways involved in learning and memory formation. PMID:18234529

  5. Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo

    PubMed Central

    Cui, Miao; Siriwon, Natnaree; Li, Enhu; Davidson, Eric H.; Peter, Isabelle S.

    2014-01-01

    Wnt signaling affects cell-fate specification processes throughout embryonic development. Here we take advantage of the well-studied gene regulatory networks (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene regulatory functions of the entire Wnt-signaling system. Five wnt genes, three frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf genes are expressed in dynamic spatial patterns in the pregastrular embryo of Strongylocentrotus purpuratus. We present a comprehensive analysis of these genes in each embryonic domain. Total functions of the Wnt-signaling system in regulatory gene expression throughout the embryo were studied by use of the Porcupine inhibitor C59, which interferes with zygotic Wnt ligand secretion. Morpholino-mediated knockdown of each expressed Wnt ligand demonstrated that individual Wnt ligands are functionally distinct, despite their partially overlapping spatial expression. They target specific embryonic domains and affect particular regulatory genes. The sum of the effects of blocking expression of individual wnt genes is shown to equal C59 effects. Remarkably, zygotic Wnt-signaling inputs are required for only three general aspects of embryonic specification: the broad activation of endodermal GRNs, the regional specification of the immediately adjacent stripe of ectoderm, and the restriction of the apical neurogenic domain. All Wnt signaling in this pregastrular embryo is short range (and/or autocrine). Furthermore, we show that the transcriptional drivers of wnt genes execute important specification functions in the embryonic domains targeted by the ligands, thus connecting the expression and function of wnt genes by encoded cross-regulatory interactions within the specific regional GRNs. PMID:25385617

  6. New type IV pili-related genes involved in early stages of Ralstonia solanacearum potato infection.

    PubMed

    Siri, María Inés; Sanabria, Analía; Boucher, Christian; Pianzzola, María Julia

    2014-07-01

    This study provides insights into the pathogenesis of Ralstonia solanacearum, in particular with regards to strains belonging to phylotype IIB, sequevar 1 (IIB-1) and their interaction with potato, its natural host. We performed a comparative genomic analysis among IIB-1 R. solanacearum strains with different levels of virulence in order to identify candidate virulence genes. With this approach, we identified a 33.7-kb deletion in a strain showing reduced virulence on potato. This region contains a cluster of six genes putatively involved in type IV pili (Tfp) biogenesis. Functional analysis suggests that these proteins contribute to several Tfp-related functions such as twitching motility and biofilm formation. In addition, this genetic cluster was found to contribute to early bacterial wilt pathogenesis and colonization fitness of potato roots. PMID:24625029

  7. Function of cancer associated genes revealed by modern univariate and multivariate association tests.

    PubMed

    Gorfine, Malka; Goldstein, Boaz; Fishman, Alla; Heller, Ruth; Heller, Yair; Lamm, Ayelet T

    2015-01-01

    Copy number variation (CNV) plays a role in pathogenesis of many human diseases, especially cancer. Several whole genome CNV association studies have been performed for the purpose of identifying cancer associated CNVs. Here we undertook a novel approach to whole genome CNV analysis, with the goal being identification of associations between CNV of different genes (CNV-CNV) across 60 human cancer cell lines. We hypothesize that these associations point to the roles of the associated genes in cancer, and can be indicators of their position in gene networks of cancer-driving processes. Recent studies show that gene associations are often non-linear and non-monotone. In order to obtain a more complete picture of all CNV associations, we performed omnibus univariate analysis by utilizing dCov, MIC, and HHG association tests, which are capable of detecting any type of association, including non-monotone relationships. For comparison we used Spearman and Pearson association tests, which detect only linear or monotone relationships. Application of dCov, MIC and HHG tests resulted in identification of twice as many associations compared to those found by Spearman and Pearson alone. Interestingly, most of the new associations were detected by the HHG test. Next, we utilized dCov's and HHG's ability to perform multivariate analysis. We tested for association between genes of unknown function and known cancer-related pathways. Our results indicate that multivariate analysis is much more effective than univariate analysis for the purpose of ascribing biological roles to genes of unknown function. We conclude that a combination of multivariate and univariate omnibus association tests can reveal significant information about gene networks of disease-driving processes. These methods can be applied to any large gene or pathway dataset, allowing more comprehensive analysis of biological processes. PMID:25965968

  8. Function of Cancer Associated Genes Revealed by Modern Univariate and Multivariate Association Tests

    PubMed Central

    Fishman, Alla; Heller, Ruth; Heller, Yair; Lamm, Ayelet T.

    2015-01-01

    Copy number variation (CNV) plays a role in pathogenesis of many human diseases, especially cancer. Several whole genome CNV association studies have been performed for the purpose of identifying cancer associated CNVs. Here we undertook a novel approach to whole genome CNV analysis, with the goal being identification of associations between CNV of different genes (CNV-CNV) across 60 human cancer cell lines. We hypothesize that these associations point to the roles of the associated genes in cancer, and can be indicators of their position in gene networks of cancer-driving processes. Recent studies show that gene associations are often non-linear and non-monotone. In order to obtain a more complete picture of all CNV associations, we performed omnibus univariate analysis by utilizing dCov, MIC, and HHG association tests, which are capable of detecting any type of association, including non-monotone relationships. For comparison we used Spearman and Pearson association tests, which detect only linear or monotone relationships. Application of dCov, MIC and HHG tests resulted in identification of twice as many associations compared to those found by Spearman and Pearson alone. Interestingly, most of the new associations were detected by the HHG test. Next, we utilized dCov's and HHG's ability to perform multivariate analysis. We tested for association between genes of unknown function and known cancer-related pathways. Our results indicate that multivariate analysis is much more effective than univariate analysis for the purpose of ascribing biological roles to genes of unknown function. We conclude that a combination of multivariate and univariate omnibus association tests can reveal significant information about gene networks of disease-driving processes. These methods can be applied to any large gene or pathway dataset, allowing more comprehensive analysis of biological processes. PMID:25965968

  9. Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga Nannochloropsis oceanica CCMP1779

    PubMed Central

    Tsai, Chia-Hong; Bullard, Blair; Cornish, Adam J.; Harvey, Christopher; Reca, Ida-Barbara; Thornburg, Chelsea; Achawanantakun, Rujira; Buehl, Christopher J.; Campbell, Michael S.; Cavalier, David; Childs, Kevin L.; Clark, Teresa J.; Deshpande, Rahul; Erickson, Erika; Armenia Ferguson, Ann; Handee, Witawas; Kong, Que; Li, Xiaobo; Liu, Bensheng; Lundback, Steven; Peng, Cheng; Roston, Rebecca L.; Sanjaya; Simpson, Jeffrey P.; TerBush, Allan; Warakanont, Jaruswan; Zäuner, Simone; Farre, Eva M.; Hegg, Eric L.; Jiang, Ning; Kuo, Min-Hao; Lu, Yan; Niyogi, Krishna K.; Ohlrogge, John; Osteryoung, Katherine W.; Shachar-Hill, Yair; Sears, Barbara B.; Sun, Yanni; Takahashi, Hideki; Yandell, Mark; Shiu, Shin-Han; Benning, Christoph

    2012-01-01

    Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogen-depleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica–specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing academic community focused on this genus. PMID:23166516

  10. Genome-Wide Analysis of the Expansin Gene Superfamily Reveals Grapevine-Specific Structural and Functional Characteristics

    PubMed Central

    Tornielli, Giovanni Battista; Fasoli, Marianna; Venturini, Luca; Pezzotti, Mario; Zenoni, Sara

    2013-01-01

    Background Expansins are proteins that loosen plant cell walls in a pH-dependent manner, probably by increasing the relative movement among polymers thus causing irreversible expansion. The expansin superfamily (EXP) comprises four distinct families: expansin A (EXPA), expansin B (EXPB), expansin-like A (EXLA) and expansin-like B (EXLB). There is experimental evidence that EXPA and EXPB proteins are required for cell expansion and developmental processes involving cell wall modification, whereas the exact functions of EXLA and EXLB remain unclear. The complete grapevine (Vitis vinifera) genome sequence has allowed the characterization of many gene families, but an exhaustive genome-wide analysis of expansin gene expression has not been attempted thus far. Methodology/Principal Findings We identified 29 EXP superfamily genes in the grapevine genome, representing all four EXP families. Members of the same EXP family shared the same exon–intron structure, and phylogenetic analysis confirmed a closer relationship between EXP genes from woody species, i.e. grapevine and poplar (Populus trichocarpa), compared to those from Arabidopsis thaliana and rice (Oryza sativa). We also identified grapevine-specific duplication events involving the EXLB family. Global gene expression analysis confirmed a strong correlation among EXP genes expressed in mature and green/vegetative samples, respectively, as reported for other gene families in the recently-published grapevine gene expression atlas. We also observed the specific co-expression of EXLB genes in woody organs, and the involvement of certain grapevine EXP genes in berry development and post-harvest withering. Conclusion Our comprehensive analysis of the grapevine EXP superfamily confirmed and extended current knowledge about the structural and functional characteristics of this gene family, and also identified properties that are currently unique to grapevine expansin genes. Our data provide a model for the functional characterization of grapevine gene families by combining phylogenetic analysis with global gene expression profiling. PMID:23614035

  11. Early and sustained altered expression of aging-related genes in young 3xTg-AD mice.

    PubMed

    Gatta, V; D'Aurora, M; Granzotto, A; Stuppia, L; Sensi, S L

    2014-01-01

    Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD (3xTg-AD) and wild-type (WT) mice. The aim of the study was to assess similarities between aging- and AD-related modifications of gene expression and investigate possible interactions between the two processes. Global gene expression profiles of hippocampal tissue obtained from 3xTg-AD and WT mice at 3 and 12 months of age (m.o.a.) were analyzed by hierarchical clustering. Interaction among transcripts was then studied with the Ingenuity Pathway Analysis (IPA) software, a tool that discloses functional networks and/or pathways associated with sets of specific genes of interest. Cluster analysis revealed the selective presence of hundreds of upregulated and downregulated transcripts. Functional analysis showed transcript involvement mainly in neuronal death and autophagy, mitochondrial functioning, intracellular calcium homeostasis, inflammatory response, dendritic spine formation, modulation of synaptic functioning, and cognitive decline. Thus, overexpression of AD-related genes (such as mutant APP, PS1, and hyperphosphorylated tau, the three genes that characterize our model) appears to favor modifications of additional genes that are involved in AD development and progression. The study also showed overlapping changes in 3xTg-AD at 3 m.o.a. and WT mice at 12 m.o.a., thereby suggesting altered expression of aging-related genes that occurs earlier in 3xTg-AD mice. PMID:24525730

  12. RASSF tumor suppressor gene family: biological functions and regulation.

    PubMed

    Volodko, Natalia; Gordon, Marilyn; Salla, Mohamed; Ghazaleh, Haya Abu; Baksh, Shairaz

    2014-08-19

    Genetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NF?B activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation. PMID:24607545

  13. Systemic VHL gene functions and the VHL disease

    PubMed Central

    Bader, Hannah L.; Hsu, Tien

    2012-01-01

    The von Hippel-Lindau tumor suppressor gene (VHL) is best known as an E3 ubiquitin ligase that negatively regulates the hypoxia inducible factor (HIF). VHL mutations are the genetic defects underlying several human diseases including polycythemia, familial VHL tumor syndrome and sporadic renal cell carcinoma. VHL mutations can lead to cell-autonomous phenotypes in the tumor cells. However, non-tumor cell-autonomous functions of VHL have also been noted. VHL tumor-derived cytokines can promote inflammation and induce mobilization of endothelial progenitor cells. Up-regulation of HIF caused by VHL loss-of-function mutants, including heterozygotes, has been shown to increase the activities of hematopoietic stem cells, endothelial cells and myeloid cells. As such, systemic functions of VHL likely play important roles in the development of VHL disease. PMID:22673568

  14. Digestive organ in the female reproductive tract borrows genes from multiple organ systems to adopt critical functions.

    PubMed

    Meslin, Camille; Plakke, Melissa S; Deutsch, Aaron B; Small, Brandon S; Morehouse, Nathan I; Clark, Nathan L

    2015-06-01

    Persistent adaptive challenges are often met with the evolution of novel physiological traits. Although there are specific examples of single genes providing new physiological functions, studies on the origin of complex organ functions are lacking. One such derived set of complex functions is found in the Lepidopteran bursa copulatrix, an organ within the female reproductive tract that digests nutrients from the male ejaculate or spermatophore. Here, we characterized bursa physiology and the evolutionary mechanisms by which it was equipped with digestive and absorptive functionality. By studying the transcriptome of the bursa and eight other tissues, we revealed a suite of highly expressed and secreted gene products providing the bursa with a combination of stomach-like traits for mechanical and enzymatic digestion of the male spermatophore. By subsequently placing these bursa genes in an evolutionary framework, we found that the vast majority of their novel digestive functions were co-opted by borrowing genes that continue to be expressed in nonreproductive tissues. However, a number of bursa-specific genes have also arisen, some of which represent unique gene families restricted to Lepidoptera and may provide novel bursa-specific functions. This pattern of promiscuous gene borrowing and relatively infrequent evolution of tissue-specific duplicates stands in contrast to studies of the evolution of novelty via single gene co-option. Our results suggest that the evolution of complex organ-level phenotypes may often be enabled (and subsequently constrained) by changes in tissue specificity that allow expression of existing genes in novel contexts, such as reproduction. The extent to which the selective pressures encountered in these novel roles require resolution via duplication and sub/neofunctionalization is likely to be determined by the need for specialized reproductive functionality. Thus, complex physiological phenotypes such as that found in the bursa offer important opportunities for understanding the relative role of pleiotropy and specialization in adaptive evolution. PMID:25725432

  15. Transcriptional regulation and multiple functions of MAO genes

    PubMed Central

    Wu, Jason Boyang; Chen, Kevin

    2011-01-01

    Monoamine oxidase (MAO) A and MAO B are a crucial pair of isoenzymes, which oxidatively deaminate monoamine neurotransmitters and dietary amines with a production of hydrogen peroxide. These two isoenzymes have different but overlapping substrate and inhibitor specificities. MAO A and MAO B share 70% amino acid sequence identity and show different temporal and spatial expressions in both humans and mice. Abnormal MAO A or MAO B activity has been implicated in numerous neurological and psychiatric disorders. A better understanding of the transcriptional regulation of MAO A and MAO B genes may help explain the differential tissue-specific expression of these two isoenzymes and provide insights into the molecular basis of the disorders associated with MAO dysfunction. This review discusses the recent progress in the transcriptional regulation and multiple functions of MAO A and MAO B genes. PMID:21359973

  16. Multiple Gene Duplication and Rapid Evolution in the groEL Gene: Functional Implications

    Microsoft Academic Search

    Kshama Goyal; Rohini Qamra; Shekhar C. Mande

    2006-01-01

    The chaperonins, GroEL and GroES, are present ubiquitously and provide a paradigm in the understanding of assisted protein\\u000a folding. Due to its essentiality of function, GroEL exhibits high sequence conservation across species. Complete genome sequencing\\u000a has shown the occurrence of duplicate or multiple copies of groEL genes in bacteria such as Mycobacterium tuberculosis and Corynebacterium glutamicum. Monophyly of each bacterial

  17. Functional Relationships between Genes Associated with Differentiation Potential of Aged Myogenic Progenitors

    PubMed Central

    Nagarajan, Radhakrishnan; Datta, Sujay; Scutari, Marco; Beggs, Marjorie L.; Nolen, Greg T.; Peterson, Charlotte A.

    2010-01-01

    Aging is accompanied by considerable heterogeneity with possible co-expression of differentiation pathways. The present study investigates the interplay between crucial myogenic, adipogenic, and Wnt-related genes orchestrating aged myogenic progenitor differentiation (AMPD) using clonal gene expression profiling in conjunction with Bayesian structure learning (BSL) techniques. The expression of three myogenic regulatory factor genes (Myogenin, Myf-5, MyoD1), four genes involved in regulating adipogenic potential (C/EBP?, DDIT3, FoxC2, PPAR?), and two genes in the Wnt signaling pathway (Lrp5, Wnt5a) known to influence both differentiation programs were determined across 34 clones by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Three control genes were used for normalization of the clonal expression data (18S, GAPDH, and B2M). Constraint-based BSL techniques, namely (a) PC Algorithm, (b) Grow-shrink (GS) algorithm, and (c) Incremental Association Markov Blanket (IAMB) were used to model the functional relationships (FRs) in the form of acyclic networks from the clonal expression profiles. A novel resampling approach that obviates the need for a user-defined confidence threshold is proposed to identify statistically significant FRs at small sample sizes. Interestingly, the resulting acyclic network consisted of FRs corresponding to myogenic, adipogenic, Wnt-related genes and their interaction. A significant number of these FRs were robust to normalization across the three house-keeping genes and the choice of the BSL technique. The results presented elucidate the delicate balance between differentiation pathways (i.e., myogenic as well as adipogenic) and possible cross-talk between pathways in AMPD. PMID:21423363

  18. Gene expression profile during functional maturation of a central mammalian synapse.

    PubMed

    Körber, Christoph; Dondzillo, Anna; Eisenhardt, Gisela; Herrmannsdörfer, Frank; Wafzig, Oliver; Kuner, Thomas

    2014-09-01

    Calyx of Held giant presynaptic terminals in the auditory brainstem form glutamatergic axosomatic synapses that have advanced to one of the best-studied synaptic connections of the mammalian brain. As the auditory system matures and adjusts to high-fidelity synaptic transmission, the calyx undergoes extensive structural and functional changes - in mice, it is formed at about postnatal day 3 (P3), achieves immature function until hearing onset at about P10 and can be considered mature from P21 onwards. This setting provides a unique opportunity to examine the repertoire of genes driving synaptic structure and function during postnatal maturation. Here, we determined the gene expression profile of globular bushy cells (GBCs), neurons giving rise to the calyx of Held, at different maturational stages (P3, P8, P21). GBCs were retrogradely labelled by stereotaxic injection of fluorescent cholera toxin-B, and their mRNA content was collected by laser microdissection. Microarray profiling, successfully validated with real time quantitative polymerase chain reaction and nCounter approaches, revealed genes regulated during maturation. We found that mostly genes implicated in the general cell biology of the neuron were regulated, while most genes related to synaptic function were regulated around the onset of hearing. Among these, voltage-gated ion channels and calcium-binding proteins were strongly regulated, whereas most genes involved in the synaptic vesicle cycle were only moderately regulated. These results suggest that changes in the expression patterns of ion channels and calcium-binding proteins are a dominant factor in defining key synaptic properties during maturation of the calyx of Held. PMID:24995587

  19. Functional analysis of genes for benzoate metabolism in the albicidin biosynthetic region of Xanthomonas albilineans

    Microsoft Academic Search

    Saeed M. Hashimi; Robert G. Birch

    2010-01-01

    Albicidins are potent DNA-gyrase-inhibiting antibiotics and phytotoxins synthesised by Xanthomonas albilineans. Functions have been deduced for some clustered biosynthetic genes, including a PKS-NRPS megasynthase, methyltransferases\\u000a and regulatory genes, and resistance genes including a transporter and a gyrase-binding protein. More puzzling is the presence\\u000a in this cluster of apparent aromatic metabolism genes. Here, we describe functional analysis of several such genes

  20. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation

    Microsoft Academic Search

    Christopher S. Raymond; Mark W. Murphy; M. Gerard O'Sullivan; Vivian J. Bardwell; David Zarkower

    2000-01-01

    The only molecular similarity in sex determination found so far among phyla is between the Drosophila doublesex (dsx) and Caenorhabditis elegans mab-3 genes. dsx and mab-3 contain a zinc finger-like DNA-binding motif called the DM domain, perform several related regulatory functions, and are at least partially interchangeable in vivo. A DM domain gene called Dmrt1 has been implicated in male

  1. [Interspecific polymorphism of the glucosyltransferase domain of the sucrose synthase gene in the genus Malus and related species of Rosaceae].

    PubMed

    Boris, K V; Kochieva, E Z; Kudryavtsev, A M

    2014-12-01

    The sequences that encode the main functional glucosyltransferase domain of sucrose synthase genes have been identified for the first time in 14 species of the genus Malus and related species of the family Rosaceae, and their polymorphism was investigated. Single nucleotide substitutions leading to amino acid substitutions in the protein sequence, including the conservative transmembrane motif sequence common to all sucrose synthase genes of higher plants, were detected in the studied sequences. PMID:25975155

  2. Tumor suppressor function of Betaig-H3 gene in radiation carcinogenesis

    NASA Astrophysics Data System (ADS)

    Zhao, Y. L.; Piao, C. Q.; Hei, T. K.

    Interaction between cell and extracellular matrix (ECM) plays a crucial role in tumor invasiveness and metastasis. Using an immortalized human bronchial epithelial (BEP2D) cell model, we showed previously that expression of a list of genes including Betaig-h3 (induced by transforming growth factor-?) DCC (deleted in colorectal cancer), p21 cip1, c-fos , Heat shock protein (HSP27) and cytokeratin 14 were differentially expressed in several independently generated, radiation-induced tumor cell lines (TL1-TL5) relative to parental BEP2D cells. Our previous data further demonstrated that loss of tumor suppressor gene(s) as a likely mechanism of radiation carcinogenesis. In the present study, we chose Betaig-h3 and DCC that were downregulated in tumorigenic cells for further study. Restored expression of Betaig-h3 gene, not DCC gene, by transfecting cDNA into tumor cells resulted in a significant reduction in tumor growth. While integrin receptor ?5?1 was overexpressed in tumor cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumor progression by regulating integrin ?5?1 receptor. Furthermore, exogenous TGF-?1 induced expression of Betaig-h3 gene and inhibited the growth of both control and tumorigenic BEP2D cells. Therefore, downregulation of Betaig-h3 gene may results from the decreased expression of upstream mediators such as TGF-?. The findings provide strong evidence that the Betaig-h3 gene has tumor suppressor function in radiation-induced tumorigenic human bronchial epithelial cells and suggest a potential target for interventional therapy.

  3. Functional Associations by Response Overlap (FARO), a Functional Genomics Approach Matching Gene Expression Phenotypes

    Microsoft Academic Search

    Henrik Bjřrn Nielsen; John Mundy; Hanni Willenbrock; Ivan Baxter

    2007-01-01

    The systematic comparison of transcriptional responses of organisms is a powerful tool in functional genomics. For example, mutants may be characterized by comparing their transcript profiles to those obtained in other experiments querying the effects on gene expression of many experimental factors including treatments, mutations and pathogen infections. Similarly, drugs may be discovered by the relationship between the transcript profiles

  4. In vitro gene regulatory networks predict in vivo function of liver

    PubMed Central

    2010-01-01

    Background Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity. PMID:21073692

  5. Polyamidoamine dendrimer and oleic acid-functionalized graphene as biocompatible and efficient gene delivery vectors.

    PubMed

    Liu, Xiahui; Ma, Dongmei; Tang, Hao; Tan, Liang; Xie, Qingji; Zhang, Youyu; Ma, Ming; Yao, Shouzhuo

    2014-06-11

    Functionalized graphene has good potential in biomedical applications. To address a better and multiplex design of graphene-based gene vectors, the graphene-oleate-polyamidoamine (PAMAM) dendrimer hybrids were synthesized by the oleic acid adsorption and covalent linkage of PAMAM dendrimers. The micromorphology, electrical charge property, and amount of free amine groups of the graphene-oleate-PAMAM hybrids were characterized, and the peripheral functional groups were identified. The PAMAM dendrimers could be tethered onto graphene surface in high density. The graphene-oleate-PAMAM hybrids exhibit relatively good dispersity and stability in aqueous solutions. To evaluate the potential application of the hybrids in gene delivery vectors, cytotoxicity to HeLa and MG-63 cells and gene (plasmid DNA of enhanced green fluorescent protein) transfection capacity of the hybrids were investigated in detail. The graphene-oleate-PAMAM hybrids show mammalian cell type- and dose-dependent in vitro cytotoxicity. Under the optimal condition, the hybrids possess good biocompatibility and gene transfection capacity. The surface modification of graphene with oleic acid and PAMAM improves the gene transfection efficiency 13 times in contrast to the ultrasonicated graphene. Moreover, the hybrids show better transfection efficiency than the graphene oxide-PAMAM without the oleic acid modification. PMID:24836601

  6. Colorado potato beetle (Coleoptera) gut transcriptome analysis: expression of RNA interference-related genes.

    PubMed

    Swevers, L; Huvenne, H; Menschaert, G; Kontogiannatos, D; Kourti, A; Pauchet, Y; ffrench-Constant, R; Smagghe, G

    2013-12-01

    In the search for new methods of pest control, the potential of RNA interference (RNAi) is being explored. Because the gut is the first barrier for the uptake of double-stranded (ds)RNA, pyrosequencing of the gut transcriptome is a powerful tool for obtaining the necessary sequences for specific dsRNA-mediated pest control. In the present study, a dataset representing the gut transcriptome of the Colorado potato beetle (CPB; Leptinotarsa decemlineata) was generated and analysed for the presence of RNAi-related genes. Almost all selected genes that were implicated in silencing efficiency at different levels in the RNAi pathway (core machinery, associated intracellular factors, dsRNA uptake, antiviral RNAi, nucleases), which uses different types of small RNA (small interfering RNA, microRNA and piwi-RNA), were expressed in the CPB gut. Although the database is of lower quality, the majority of the RNAi genes are also found to be present in the gut transcriptome of the tobacco hornworm [TH; Manduca sexta (19 out of 35 genes analysed)]. The high quality of the CPB transcriptome database will lay the foundation for future gene expression and functional studies regarding the gut and RNAi. PMID:24580832

  7. Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy

    PubMed Central

    Baird, Andrew; Lee, Jisook; Podvin, Sonia; Kurabi, Arwa; Dang, Xitong; Coimbra, Raul; Costantini, Todd; Bansal, Vishal; Eliceiri, Brian P

    2014-01-01

    In humans, esophageal cancer-related gene 4 (ECRG4) is encoded by four exons in the c2orf40 locus of chromosome 2. Translation of ECRG4 messenger ribonucleic acid produces a 148 amino acid-secreted 17 KDa protein that is then processed to 14, ten, eight, six, four, and two KDa peptides, depending on the cell in which the gene is expressed. As hypermethylation at the c2orf40 locus inhibits ECRG4 gene expression in many epithelial cancers, several investigators have speculated that ECRG4 is a candidate tumor suppressor. Indeed, overexpression of ECRG4 inhibits cell proliferation in vitro, but it also has a wide range of effects in vivo beyond its antitumor activity. ECRG4 overexpression affects apoptosis, senescence, cell migration, inflammation, injury, and infection responsiveness. ECRG4 activities also depend on its cellular localization, secretion, and post-translational processing. These cytokine/chemokine-like characteristics argue that ECRG4 is not a traditional candidate tumor suppressor gene, as originally predicted by its downregulation in cancer. We review how insights into the regulation of ECRG4 gene expression, knowledge of its primary structure, and the study of its emerging physiological functions come together to support a much more complex role for ECRG4 at the interface of inflammation, infection, and malignancy. PMID:25580077

  8. Evolution of xyloglucan-related genes in green plants

    PubMed Central

    2010-01-01

    Background The cell shape and morphology of plant tissues are intimately related to structural modifications in the primary cell wall that are associated with key processes in the regulation of cell growth and differentiation. The primary cell wall is composed mainly of cellulose immersed in a matrix of hemicellulose, pectin, lignin and some structural proteins. Xyloglucan is a hemicellulose polysaccharide present in the cell walls of all land plants (Embryophyta) and is the main hemicellulose in non-graminaceous angiosperms. Results In this work, we used a comparative genomic approach to obtain new insights into the evolution of the xyloglucan-related enzymatic machinery in green plants. Detailed phylogenetic analyses were done for enzymes involved in xyloglucan synthesis (xyloglucan transglycosylase/hydrolase, ?-xylosidase, ?-galactosidase, ?-glucosidase and ?-fucosidase) and mobilization/degradation (?-(1?4)-glucan synthase, ?-fucosyltransferases, ?-galactosyltransferases and ?-xylosyl transferase) based on 12 fully sequenced genomes and expressed sequence tags from 29 species of green plants. Evidence from Chlorophyta and Streptophyta green algae indicated that part of the Embryophyta xyloglucan-related machinery evolved in an aquatic environment, before land colonization. Streptophyte algae have at least three enzymes of the xyloglucan machinery: xyloglucan transglycosylase/hydrolase, ?-(1?4)-glucan synthase from the celullose synthase-like C family and ?-xylosidase that is also present in chlorophytes. Interestingly, gymnosperm sequences orthologs to xyloglucan transglycosylase/hydrolases with exclusively hydrolytic activity were also detected, suggesting that such activity must have emerged within the last common ancestor of spermatophytes. There was a positive correlation between the numbers of founder genes within each gene family and the complexity of the plant cell wall. Conclusions Our data support the idea that a primordial xyloglucan-like polymer emerged in streptophyte algae as a pre-adaptation that allowed plants to subsequently colonize terrestrial habitats. Our results also provide additional evidence that charophycean algae and land plants are sister groups. PMID:21054875

  9. New relations among associated Legendre functions and spherical harmonics

    Microsoft Academic Search

    S. J. Claessens

    2005-01-01

    Several new relations among associated Legendre functions (ALFs) are derived, most of which relate a product of an ALF with trigonometric functions to a weighted summation over ALFs, where the weights only depend on the degree and order of the ALF. These relations are, for example, useful in applications such as the computation of geopotential coefficients and computation of ellipsoidal

  10. Loss of gene function through rapid mitotic cycles in the Drosophila embryo.

    PubMed

    Rothe, M; Pehl, M; Taubert, H; Jäckle, H

    1992-09-10

    The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development. PMID:1522901

  11. Estrogen-related receptor ? (ERR?) and ERR? are essential coordinators of cardiac metabolism and function.

    PubMed

    Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M; Patel, Vickas V; Pei, Liming

    2015-04-01

    Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor ? (ERR?) and ERR? are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERR? and ERR? together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERR? and ERR? influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERR? and cardiac ERR? develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

  12. Functional lipids and lipoplexes for improved gene delivery

    PubMed Central

    Zhang, Xiao-Xiang; McIntosh, Thomas J.; Grinstaff, Mark W.

    2013-01-01

    Cationic lipids are the most common non-viral vectors used in gene delivery with a few currently being investigated in clinical trials. However, like most other synthetic vectors, these vectors suffer from low transfection efficiencies. Among the various approaches to address this challenge, functional lipids (i.e., lipids responding to a stimuli) offer a myriad of opportunities for basic studies of nucleic acid–lipid interactions and for in vitro and in vivo delivery of nucleic acid for a specific biological/medical application. This manuscript reviews recent advances in pH, redox, and charge-reversal sensitive lipids. PMID:21621581

  13. Analysis of the [lambda] S? gene function by mutational suppressors 

    E-print Network

    Sohaskey, Charles David

    1992-01-01

    ? 10 per input phage particle (Data not shown). To avoid isolating true revertants, smaller plaques were chosen for further analysis. While some second-site pseudorevertants might be missed this way, it was reasoned that most plaques that were... of bacteriophage I is required for lysis of the host. The S protein forms a hole in the inner membrane allowing escape of the phage-encoded murein hydrolysis activity. In order to establish a functional map of the S gene, pseudo-revertants were obtained...

  14. Systematic Learning of Gene Functional Classes From DNA Array Expression Data by Using Multilayer Perceptrons

    PubMed Central

    Mateos, Alvaro; Dopazo, Joaquín; Jansen, Ronald; Tu, Yuhai; Gerstein, Mark; Stolovitzky, Gustavo

    2002-01-01

    Recent advances in microarray technology have opened new ways for functional annotation of previously uncharacterised genes on a genomic scale. This has been demonstrated by unsupervised clustering of co-expressed genes and, more importantly, by supervised learning algorithms. Using prior knowledge, these algorithms can assign functional annotations based on more complex expression signatures found in existing functional classes. Previously, support vector machines (SVMs) and other machine-learning methods have been applied to a limited number of functional classes for this purpose. Here we present, for the first time, the comprehensive application of supervised neural networks (SNNs) for functional annotation. Our study is novel in that we report systematic results for ?100 classes in the Munich Information Center for Protein Sequences (MIPS) functional catalog. We found that only ?10% of these are learnable (based on the rate of false negatives). A closer analysis reveals that false positives (and negatives) in a machine-learning context are not necessarily “false” in a biological sense. We show that the high degree of interconnections among functional classes confounds the signatures that ought to be learned for a unique class. We term this the “Borges effect” and introduce two new numerical indices for its quantification. Our analysis indicates that classification systems with a lower Borges effect are better suitable for machine learning. Furthermore, we introduce a learning procedure for combining false positives with the original class. We show that in a few iterations this process converges to a gene set that is learnable with considerably low rates of false positives and negatives and contains genes that are biologically related to the original class, allowing for a coarse reconstruction of the interactions between associated biological pathways. We exemplify this methodology using the well-studied tricarboxylic acid cycle. PMID:12421757

  15. Sex-related gene expression profiles in the adrenal cortex in the mature rat: microarray analysis with emphasis on genes involved in steroidogenesis.

    PubMed

    Trejter, Marcin; Hochol, Anna; Tyczewska, Marianna; Ziolkowska, Agnieszka; Jopek, Karol; Szyszka, Marta; Malendowicz, Ludwik K; Rucinski, Marcin

    2015-03-01

    Notable sex-related differences exist in mammalian adrenal cortex structure and function. In adult rats, the adrenal weight and the average volume of zona fasciculata cells of females are larger and secrete greater amounts of corticosterone than those of males. The molecular bases of these sex-related differences are poorly understood. In this study, to explore the molecular background of these differences, we defined zone- and sex-specific transcripts in adult male and female (estrous cycle phase) rats. Twelve-week-old rats of both genders were used and samples were taken from the zona glomerulosa (ZG) and zona fasciculata/reticularis (ZF/R) zones. Transcriptome identification was carried out using the Affymetrix(®) Rat Gene 1.1 ST Array. The microarray data were compared by fold change with significance according to moderated t-statistics. Subsequently, we performed functional annotation clustering using the Gene Ontology (GO) and Database for Annotation, Visualization and Integrated Discovery (DAVID). In the first step, we explored differentially expressed transcripts in the adrenal ZG and ZF/R. The number of differentially expressed transcripts was notably higher in the female than in the male rats (702 vs. 571). The differentially expressed genes which were significantly enriched included genes involved in steroid hormone metabolism, and their expression levels in the ZF/R of adult female rats were significantly higher compared with those in the male rats. In the female ZF/R, when compared with that of the males, prevailing numbers of genes linked to cell fraction, oxidation/reduction processes, response to nutrients and to extracellular stimuli or steroid hormone stimuli were downregulated. The microarray data for key genes involved directly in steroidogenesis were confirmed by qPCR. Thus, when compared with that of the males, in the female ZF/R, higher expression levels of genes involved directly in steroid hormone synthesis were accompanied by lower expression levels of genes regulating basal cell functions. PMID:25572386

  16. Tracing evolutionary relicts of positive selection on eight malaria-related immune genes in mammals.

    PubMed

    Huang, Bing-Hong; Liao, Pei-Chun

    2015-07-01

    Plasmodium-induced malaria widely infects primates and other mammals. Multiple past studies have revealed that positive selection could be the main evolutionary force triggering the genetic diversity of anti-malaria resistance-associated genes in human or primates. However, researchers focused most of their attention on the infra-generic and intra-specific genome evolution rather than analyzing the complete evolutionary history of mammals. Here we extend previous research by testing the evolutionary link of natural selection on eight candidate genes associated with malaria resistance in mammals. Three of the eight genes were detected to be affected by recombination, including TNF-?, iNOS and DARC. Positive selection was detected in the rest five immunogenes multiple times in different ancestral lineages of extant species throughout the mammalian evolution. Signals of positive selection were exposed in four malaria-related immunogenes in primates: CCL2, IL-10, HO1 and CD36. However, selection signals of G6PD have only been detected in non-primate eutherians. Significantly higher evolutionary rates and more radical amino acid replacement were also detected in primate CD36, suggesting its functional divergence from other eutherians. Prevalent positive selection throughout the evolutionary trajectory of mammalian malaria-related genes supports the arms race evolutionary hypothesis of host genetic response of mammalian immunogenes to infectious pathogens. PMID:25201904

  17. Approximations of relations by continuous functions

    Microsoft Academic Search

    L'. Holá; R. A. McCoy; J. Pelant

    2007-01-01

    Let X be a Tychonoff space, C(X) be the space of all continuous real-valued functions defined on X and CL(X×R) be the hyperspace of all nonempty closed subsets of X×R. We prove the following result. Let X be a countably paracompact normal space. The following are equivalent: (a) dimX=0; (b) the closure of C(X) in CL(X×R) with the Vietoris topology

  18. Extending relational algebra and relational calculus with set-valued attributes and aggregate functions

    Microsoft Academic Search

    G. Özsoyo?lu; Z. Meral Özsoyoglu; Victor Matos

    1987-01-01

    In commercial network database management systems, set-valued fields and aggregate functions are commonly supported. However, the relational database model, as defined by Codd, does not include set-valued attributes or aggregate functions. Recently, Klug extended the relational model by incorporating aggregate functions and by defining relational algebra and calculus languages.In this paper, relational algebra and relational calculus database query languages (as

  19. Association Analysis of 94 Candidate Genes and Schizophrenia-Related Endophenotypes

    PubMed Central

    Swerdlow, Neal R.; Radant, Allen D.; Braff, David L.

    2012-01-01

    While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI), P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility. The observation of extensive pleiotropy for some genes and singular associations for others in our data may suggest both converging and independent genetic (and neural) pathways mediating schizophrenia risk and pathogenesis. PMID:22253750

  20. Association of Polymorphisms in Natural Killer Cell–Related Genes With Preterm Birth

    PubMed Central

    Harmon, Quaker E.; Engel, Stephanie M.; Olshan, Andrew F.; Moran, Thomas; Stuebe, Alison M.; Luo, Jingchun; Wu, Michael C.; Avery, Christy L.

    2013-01-01

    Inflammation is implicated in preterm birth, but genetic studies of inflammatory genes have yielded inconsistent results. Maternal DNA from 1,646 participants in the Pregnancy, Infection, and Nutrition Cohort, enrolled in Orange and Wake counties, North Carolina (1995–2005), were genotyped for 432 tag single-nucleotide polymorphisms (SNPs) in 30 candidate genes. Gene-level and SNP associations were modeled within strata of genetic ancestry. Six genes were associated with preterm birth among European Americans: interleukin 12A (IL12A); colony-stimulating factor 2 (CSF2); interferon ? receptor 2 (IFNGR2); killer cell immunoglobulin–like receptor, three domain, long cytoplasmic tail, 2 (KIR3DL2); interleukin 4 (IL4); and interleukin 13 (IL13). Of these, relatively strong single-SNP associations were seen in IFNGR2 and KIR3DL2. Among the 4 genes related to natural killer cell function, 2 (IL12A and CSF2) were consistently associated with reduced risk of prematurity for both European and African Americans. SNPs tagging a locus control region for IL4 and IL13 were associated with an increased risk of spontaneous preterm birth for European Americans (rs3091307; risk ratio = 1.9; 95% confidence interval: 1.4, 2.5). Although gene-level associations were detected only in European Americans, single-SNP associations among European and African Americans were often similar in direction, though estimated with less precision among African Americans. In conclusion, we identified novel associations between variants in the natural killer cell immune pathway and prematurity in this biracial US population. PMID:23982189

  1. Initial characterization of shade avoidance response suggests functional diversity between Populus phytochrome B genes.

    SciTech Connect

    Karve, Abhijit A [ORNL; Weston, David [ORNL; Jawdy, Sara [ORNL; Gunter, Lee E [ORNL; Allen, Sara M [ORNL; Yang, Xiaohan [ORNL; Wullschleger, Stan D [ORNL; Tuskan, Gerald A [ORNL

    2012-01-01

    Shade avoidance signaling in higher plants involves perception of the incident red/far-red (R/FR) light by phytochromes and the modulation of downstream transcriptional networks to regulate developmental plasticity in relation to heterogeneous light environments. In this study, we characterized the expression and functional features of Populus phytochrome (PHY) gene family as well as the transcriptional responses of Populus to the changes in R/FR light. Expression data indicated that PHYA is the predominant PHY in the dark grown Populus seedling whereas PHYBs are most abundant in mature tissue types. Out of three Populus PHYs, PHYA is light labile and localized to cytosol in dark whereas both PHYB1 and PHYB2 are light stable and are localized to nucleus in mesophyll protoplasts. When expressed in Arabidopsis, PHYB1 rescued Arabidopsis phyB mutant phenotype whereas PHYB2 did not, suggesting functional diversification between these two gene family members. However, phenotypes of transgenic Populus lines with altered expression of PHYB1, PHYB2 or both and the expression of candidate shade response genes in these transgenic lines suggest that PHYB1 and PHYB2 may have distinct yet overlapping functions. The RNAseq results and analysis of Populus exposed to enriched-FR light indicate that genes associated in cell wall modification and brassinosteroid signaling were induced under far red light. Overall our data indicate that Populus transcriptional responses are at least partially conserved with Arabidopsis.

  2. PainNetworks: A web-based resource for the visualisation of pain-related genes in the context of their network associations

    PubMed Central

    Perkins, James R.; Lees, Jonathan; Antunes-Martins, Ana; Diboun, Ilhem; McMahon, Stephen B.; Bennett, David L.H.; Orengo, Christine

    2013-01-01

    Hundreds of genes are proposed to contribute to nociception and pain perception. Historically, most studies of pain-related genes have examined them in isolation or alongside a handful of other genes. More recently the use of systems biology techniques has enabled us to study genes in the context of the biological pathways and networks in which they operate. Here we describe a Web-based resource, available at http://www.PainNetworks.org. It integrates interaction data from various public databases with information on known pain genes taken from several sources (eg, The Pain Genes Database) and allows the user to examine a gene (or set of genes) of interest alongside known interaction partners. This information is displayed by the resource in the form of a network. The user can enrich these networks by using data from pain-focused gene expression studies to highlight genes that change expression in a given experiment or pairs of genes showing correlated expression patterns across different experiments. Genes in the networks are annotated in several ways including biological function and drug binding. The Web site can be used to find out more about a gene of interest by looking at the function of its interaction partners. It can also be used to interpret the results of a functional genomics experiment by revealing putative novel pain-related genes that have similar expression patterns to known pain-related genes and by ranking genes according to their network connections with known pain genes. We expect this resource to grow over time and become a valuable asset to the pain community. PMID:24036287

  3. Ergot alkaloids: structure diversity, biosynthetic gene clusters and functional proof of biosynthetic genes.

    PubMed

    Wallwey, Christiane; Li, Shu-Ming

    2011-03-01

    Ergot alkaloids are toxins and important pharmaceuticals which are produced biotechnologically on an industrial scale. They have been identi?ed in two orders of fungi and three families of higher plants. The most important producers are fungi of the genera Claviceps, Penicillium and Aspergillus (all belonging to the Ascomycota). Chemically, ergot alkaloids are characterised by the presence of a tetracyclic ergoline ring, and can be divided into three classes according to their structural features, i.e. amide- or peptide-like amide derivatives of D-lysergic acid and the clavine alkaloids. Signi?cant progress has been achieved on the molecular biological and biochemical investigations of ergot alkaloid biosynthesis in the last decade. By gene cloning and genome mining, gene clusters for ergot alkaloid biosynthesis have been identi?ed in at least 8 different ascomycete species. Functions of most structure genes have been assigned to reaction steps in the biosynthesis of ergot alkaloids by gene inactivation experiments or biochemical characterisation of the overproduced proteins. PMID:21186384

  4. Identification of gene products encoded by the latency-related gene of bovine herpesvirus 1.

    PubMed Central

    Hossain, A; Schang, L M; Jones, C

    1995-01-01

    Bovine herpesvirus 1 (BHV-1) establishes a latent infection in sensory ganglionic neurons of infected animals. Expression of latency-related (LR) gene products is controlled by a 980-bp fragment (LR promoter). DNA sequence analysis revealed that two major open reading frames (ORFs) are in the LR gene. Antibodies directed against both ORFs were generated in rabbits by using synthetic peptides. Antibody P2, which is directed to sequences near the amino terminus of ORF 2, recognized a 41-kDa protein in lytically infected cells, suggesting that ORF 2 encodes a protein. When the LR gene was inserted into a mammalian expression vector and subsequently transfected into COS-7 cells, a 41-kDa protein was detected by use of silver-stained sodium dodecyl sulfate-polyacrylamide gels and by the P2 antibody. In contrast, this protein was not detected in mock-transfected cells. Deletion of DNA sequences containing ORF 2 blocked synthesis of the 41-kDa protein in COS-7 cells. Reverse transcriptase-mediated PCRs indicated that splicing occurs near the C terminus of ORF 2. Further studies indicated that LR RNA was alternatively spliced in latently infected cattle and that a fraction of LR RNA was poly(A)+. Taken together, these studies suggested that a spliced LR transcript has the potential to encode a 41-kDa protein. PMID:7636978

  5. Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

    PubMed Central

    Tadros, Sherif F.; D’Souza, Mary; Zhu, Xiaoxia

    2010-01-01

    To understand possible causative roles of apoptosis gene regulation in age-related hearing loss (presbycusis), apoptotic gene expression patterns in the CBA mouse cochlea of four different age and hearing loss groups were compared, using GeneChip and real-time (qPCR) microarrays. GeneChip transcriptional expression patterns of 318 apoptosis-related genes were analyzed. Thirty eight probes (35 genes) showed significant differences in expression. The significant gene families include Caspases, B-cell leukemia/lymphoma2 family, P53, Cal-pains, Mitogen activated protein kinase family, Jun oncogene, Nuclear factor of kappa light chain gene enhancer in B-cells inhibitor-related and tumor necrosis factor-related genes. The GeneChip results of 31 genes were validated using the new TaqMan® Low Density Array (TLDA). Eight genes showed highly correlated results with the GeneChip data. These genes are: activating transcription factor3, B-cell leukemia/lymphoma2, Bcl2-like1, caspase4 apoptosis-related cysteine protease 4, Calpain2, dual specificity phosphatase9, tumor necrosis factor receptor superfamily member12a, and Tumor necrosis factor superfamily member13b, suggesting they may play critical roles in inner ear aging. PMID:18839313

  6. Functional analysis of rice HOMEOBOX4 ( Oshox4 ) gene reveals a negative function in gibberellin responses

    Microsoft Academic Search

    Mingqiu Dai; Yongfeng Hu; Qian Ma; Yu Zhao; Dao-Xiu Zhou

    2008-01-01

    The homeodomain-leucine zipper (HD-Zip) putative transcription factor genes are divided into 4 families. In this work, we\\u000a studied the function of a rice HD-Zip I gene, H\\u000a OME\\u000a O\\u000a BO\\u000a X4 (Oshox4). Oshox4 transcripts were detected in leaf and floral organ primordia but excluded from the shoot apical meristem and the protein\\u000a was nuclear localized. Over-expression of Oshox4 in rice

  7. Functional and evolutionary analyses on expressed intronless genes in the mouse genome

    Microsoft Academic Search

    Kishore Ramaji Sakharkar; Meena Kishore Sakharkar; Cymbeline T. Culiat; Vincent T. K. Chow; Shazib Pervaiz

    2006-01-01

    Using computational approaches we have identified 2017 expressed intronless genes in the mouse genome. Evolutionary analysis reveals that 56 intronless genes are conserved among the three domains of life – bacteria, archea and eukaryotes. These highly conserved intronless genes were found to be involved in essential housekeeping functions. About 80% of expressed mouse intronless genes have orthologs in eukaryotic genomes

  8. What's that gene (or protein)? Online resources for exploring functions of genes, transcripts, and proteins

    PubMed Central

    Hutchins, James R. A.

    2014-01-01

    The genomic era has enabled research projects that use approaches including genome-scale screens, microarray analysis, next-generation sequencing, and mass spectrometry–based proteomics to discover genes and proteins involved in biological processes. Such methods generate data sets of gene, transcript, or protein hits that researchers wish to explore to understand their properties and functions and thus their possible roles in biological systems of interest. Recent years have seen a profusion of Internet-based resources to aid this process. This review takes the viewpoint of the curious biologist wishing to explore the properties of protein-coding genes and their products, identified using genome-based technologies. Ten key questions are asked about each hit, addressing functions, phenotypes, expression, evolutionary conservation, disease association, protein structure, interactors, posttranslational modifications, and inhibitors. Answers are provided by presenting the latest publicly available resources, together with methods for hit-specific and data set–wide information retrieval, suited to any genome-based analytical technique and experimental species. The utility of these resources is demonstrated for 20 factors regulating cell proliferation. Results obtained using some of these are discussed in more depth using the p53 tumor suppressor as an example. This flexible and universally applicable approach for characterizing experimental hits helps researchers to maximize the potential of their projects for biological discovery. PMID:24723265

  9. Independent evolution of functional MHC class II DRB genes in New World bat species.

    PubMed

    Schad, Julia; Voigt, Christian C; Greiner, Sabine; Dechmann, Dina K N; Sommer, Simone

    2012-07-01

    Genes of the major histocompatibility complex (MHC) play a pivotal role in the vertebrate immune system and are attractive markers for functional, fitness-related, genetic variation. Although bats (Chiroptera) represent the second largest mammalian order and are prone to various emerging infectious diseases, little is known about MHC evolution in bats. In the present study, we examined expressed MHC class II DRB sequences (exons 1 to 4) of New World bat species, Saccopteryx bilineata, Carollia perspicillata, Noctilio albiventris and Noctilio leporinus (only exon 2). We found a wide range of copy number variation of DRB loci with one locus detected in the genus Noctilio and up to ten functional loci observed in S. bilineata. Sequence variation between alleles of the same taxa was high with evidence for positive selection. We found statistical support for recombination or gene conversion events among sequences within the same but not between bat species. Phylogenetic relationships among DRB alleles provided strong evidence for independent evolution of the functional MHC class II DRB genes in the three investigated species, either by recent gene duplication, or homogenization of duplicated loci by frequent gene conversion events. Phylogenetic analysis of all available chiropteran DRB exon 2 sequences confirmed their monophyletic origin within families, but revealed a possible trans-species mode of evolution pattern in congeneric bat species, e.g. within the genera Noctilio and Myotis. This is the first study investigating phylogenetic relationships of MHC genes within bats and therefore contributes to a better understanding of MHC evolution in one of the most dominant mammalian order. PMID:22426641

  10. Estrogen-related receptor {alpha} modulates the expression of adipogenesis-related genes during adipocyte differentiation

    SciTech Connect

    Ijichi, Nobuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Yagi, Ken [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Okazaki, Yasushi [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan) and Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)]. E-mail: INOUE-GER@h.u-tokyo.ac.jp

    2007-07-06

    Estrogen-related receptor {alpha} (ERR{alpha}) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERR{alpha} in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR{alpha} and ERR{alpha}-related transcriptional coactivators, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator-1{alpha} (PGC-1{alpha}) and PGC-1{beta}, can be up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. Gene knockdown by ERR{alpha}-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPAR{gamma}, and PGC-1{alpha} in 3T3-L1 cells in the adipogenesis medium. ERR{alpha} and PGC-1{beta} mRNA expression can be also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore, stable expression of ERR{alpha} in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERR{alpha} may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.

  11. Genetic polymorphisms and endometriosis: contribution of genes that regulate vascular function and tissue remodeling.

    PubMed

    Trovó de Marqui, Alessandra Bernadete

    2012-01-01

    Endometriosis is a benign gynecological disease characterized by the presence and growth of endometrial cells outside the uterus. Genetic, endocrine, immunological, and environmental factors have been suggested in its pathogenesis. A great number of studies have related genetic polymorphisms as a factor that contributes to the development of endometriosis. This review presents a detailed description of the contribution of genetic polymorphisms in genes that regulate vascular function and tissue remodeling in endometriosis (alpha 2-HS glycoprotein [AHSG], epidermal growth factor receptor [EGFR], vascular endothelial growth factor [VEGF], endostatin, plasminogen activator inhibitor 1 [PAI-1], angiotensin I-converting enzyme [ACE], and matrix metalloproteinases [MMPs]). Some polymorphisms of the VEGF (-460 C/T, +405 G/C, +936 C/T), PAI, MMP-1, 2, and 3 genes were widely studied, while polymorphisms of the AHSG, EGF, endostatin, and VEGF (-1154 G/A, -2578 A/C) genes were not. In this latter case, additional studies are required to confirm the findings of the few studies that have analyzed these single nucleotide polymorphisms (SNPs). Additionally, studies that found a positive or negative association of SNP with endometriosis emphasize the relevance of studies with a large number of control cases to confirm their findings. The haplotype analysis was performed only for the VEGF (-460, +405, -1154 and -2578), ACE (-240/2350) and MMP-1, 2, 3, and 9 genes, and in most of them, there was no association with endometriosis. Of the eight works that analyzed haplotypes of the VEGF gene, five did not associate them with endometriosis. Haplotypes of ACE and MMP-2 genes were not associated with endometriosis, while those of MMP-1, 3, and 9 genes were related to a high risk for the disease. PMID:23090236

  12. The dystrophin gene and cognitive function in the general population.

    PubMed

    Vojinovic, Dina; Adams, Hieab Hh; van der Lee, Sven J; Ibrahim-Verbaas, Carla A; Brouwer, Rutger; van den Hout, Mirjam Cgn; Oole, Edwin; van Rooij, Jeroen; Uitterlinden, Andre; Hofman, Albert; van IJcken, Wilfred Fj; Aartsma-Rus, Annemieke; van Ommen, GertJan B; Ikram, M Arfan; van Duijn, Cornelia M; Amin, Najaf

    2015-06-01

    The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10(-4)), rs147546024:A>G showed strong association (?=1.786, P-value=2.56 × 10(-4)) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (?=-0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations. PMID:25227141

  13. 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.

    PubMed

    Li, Lin; Li, Hui; Li, JiYing; Xu, ShuTu; Yang, XiaoHong; Li, JianSheng; Yan, JianBing

    2010-06-01

    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. PMID:20602272

  14. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene

    Microsoft Academic Search

    Jamie W. Foster; Marina A. Dominguez-Steglich; Silvana Guioli; Cheni Kwok; Polly A. Weller; Milena Stevanovic; Jean Weissenbach; Sahar Mansour; Ian D. Young; Peter N. Goodfellow; J. David Brook; Alan J. Schafer

    1994-01-01

    Induction of testis development in mammals requires the presence of the Y-chromosome gene SPY. This gene must exert its effect by interacting with other genes in the sex-determination pathway. Cloning of a translocation chromosome breakpoint from a sex-reversed patient with campomelic dysplasia, followed by mutation analysis of an adjacent gene, indicates that SOX9, an SRY-related gene, is involved in both

  15. Association of MHC Class I chain-related A (MICA) gene polymorphism with Type I diabetes

    Microsoft Academic Search

    G. Gambelunghe; M. Ghaderi; A. Cosentino; Ad. Falorni; P. Brunetti; Al. Falorni; C. B. Sanjeevi

    2000-01-01

    Aims\\/hypothesis. A distinct family of MHC genes has been identified in the class III region and denominated MHC Class I chain-related genes\\u000a (MIC). The MIC-A gene is located between the TNFA and the HLA-B genes. The aim of our study was to test the association of the polymorphism of the MIC-A gene with Type I (insulin-dependent) diabetes mellitus and evaluate

  16. Induction of STAT3-related genes in fast degenerating cone photoreceptors of cpfl1 mice.

    PubMed

    Schaeferhoff, K; Michalakis, S; Tanimoto, N; Fischer, M D; Becirovic, E; Beck, S C; Huber, G; Rieger, N; Riess, O; Wissinger, B; Biel, M; Seeliger, M W; Bonin, M

    2010-09-01

    Cone dystrophies are genetic diseases characterized by loss of cone photoreceptor function and severe impairment of daylight vision. Loss of function is accompanied by a progressive degeneration of cones limiting potential therapeutic interventions. In this study we combined microarray-based gene-expression analysis with electroretinography and immunohistochemistry to characterize the pathological processes in the cone photoreceptor function loss 1 (cpfl1) mouse model. The cpfl1-mouse is a naturally arising mouse mutant with a loss-of-function mutation in the cone-specific Pde6c gene. Cpfl1-mice displayed normal rod-specific light responses while cone-specific responses were strongly diminished. Despite the lack of a general retinal degeneration, the cone-specific functional defect resulted in a marked activation of GFAP, a hallmark of Müller-cell gliosis. Microarray-based network-analysis confirmed activation of Müller-glia-specific transcripts. Unexpectedly, we found up-regulation of the cytokine LIF and the anti-apoptotic transcription factor STAT3 in cpfl1 cone photoreceptors. We postulate that STAT3-related pathways are induced in cpfl1 cone photoreceptors to counteract degeneration. PMID:20467778

  17. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

    PubMed Central

    Korostynski, Michal; Kaminska-Chowaniec, Dorota; Piechota, Marcin; Przewlocki, Ryszard

    2006-01-01

    Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q < 0.01) revealed inter-strain variation in the expression of ~3% of the analyzed transcripts. A combination of three methods of array pre-processing was used to compile a list of ranked transcripts covered by 1528 probe-sets significantly different between the mouse strains under comparison. Using Gene Ontology analysis, over-represented patterns of genes associated with cytoskeleton and involved in synaptic transmission were identified. Differential expression of several genes with relevant neurobiological function (e.g. GABA-A receptor alpha subunits) was validated by quantitative RT-PCR. Analysis of correlations between gene expression and behavioural data revealed connection between the level of mRNA for K homology domain containing, RNA binding, signal transduction associated 1 (Khdrbs1) and ATPase Na+/K+ alpha2 subunit (Atp1a2) with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt) gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids. PMID:16772024

  18. Expression of helminth genes in Leishmania: an experimental transfection system to test immunological function

    Microsoft Academic Search

    R. M. MAIZELS; N. GOMEZ-ESCOBAR; L. PRIETO-LAFUENTE; T. AEBISCHER

    2008-01-01

    SUMMARY Functional analysis of genes from parasitic helminths requires, at the present time, heterologous expression. We have adapted the well-characterized system of transfection in Leishmania protozoal parasites, as a means of analysing the effect of single filarial genes on the mammalian immune system. For example, testing the function of the Brugia malayi abundant larval transcript (ALT) gene-transfected Leishmania mexicana were

  19. Experimental analyses of gene-brain-behavior relations: some notes on their application.

    PubMed Central

    Kennedy, C H; Caruso, M; Thompson, T

    2001-01-01

    The fields of genetics and neuroscience are yielding findings useful in understanding complex behavior-environment relations. We believe that these developments in interdisciplinary basic research are of interest to applied behavior analysts because of the long history of basic findings being used by the readership of the Journal of Applied Behavior Analysis to improve everyday human activities. An awareness of contemporary developments in a range of basic research disciplines may facilitate the systematic replication of those functional relations in applied settings. In this context, we selectively review papers published in the Journal of the Experimental Analysis of Behavior and other basic research journals that relate to gene-brain-behavior relations. PMID:11800198

  20. From patenting genes to proteins: the search for utility via function.

    PubMed

    Ilag, Lawrence L; Ilag, Leodegario M; Ilag, Leodevico L

    2002-05-01

    The debate regarding the patenting of genes has extended into the post-genome era. With only approximately 35000 genes deduced from the draft sequence of the human genome, there are fears that a few companies have already gained monopoly on the potential benefits from this knowledge. Nevertheless, it is accepted that proteins determine gene function and function is not readily predicted from gene sequence. Furthermore, genes can encode multiple proteins and a single protein can have multiple functions. Here, we argue that unraveling the intrinsic complexity of proteins and their functions is the key towards determining the utility requirement for patenting protein inventions and consider the possible socioeconomic impact. PMID:11943374

  1. Selection of reference genes for gene expression studies related to intramuscular fat deposition in Capra hircus skeletal muscle.

    PubMed

    Zhu, Wuzheng; Lin, Yaqiu; Liao, Honghai; Wang, Yong

    2015-01-01

    The identification of suitable reference genes is critical for obtaining reliable results from gene expression studies using quantitative real-time PCR (qPCR) because the expression of reference genes may vary considerably under different experimental conditions. In most cases, however, commonly used reference genes are employed in data normalization without proper validation, which may lead to incorrect data interpretation. Here, we aim to select a set of optimal reference genes for the accurate normalization of gene expression associated with intramuscular fat (IMF) deposition during development. In the present study, eight reference genes (PPIB, HMBS, RPLP0, B2M, YWHAZ, 18S, GAPDH and ACTB) were evaluated by three different algorithms (geNorm, NormFinder and BestKeeper) in two types of muscle tissues (longissimus dorsi muscle and biceps femoris muscle) across different developmental stages. All three algorithms gave similar results. PPIB and HMBS were identified as the most stable reference genes, while the commonly used reference genes 18S and GAPDH were the most variably expressed, with expression varying dramatically across different developmental stages. Furthermore, to reveal the crucial role of appropriate reference genes in obtaining a reliable result, analysis of PPARG expression was performed by normalization to the most and the least stable reference genes. The relative expression levels of PPARG normalized to the most stable reference genes greatly differed from those normalized to the least stable one. Therefore, evaluation of reference genes must be performed for a given experimental condition before the reference genes are used. PPIB and HMBS are the optimal reference genes for analysis of gene expression associated with IMF deposition in skeletal muscle during development. PMID:25794179

  2. Selection of Reference Genes for Gene Expression Studies Related to Intramuscular Fat Deposition in Capra hircus Skeletal Muscle

    PubMed Central

    Zhu, Wuzheng; Lin, Yaqiu; Liao, Honghai; Wang, Yong

    2015-01-01

    The identification of suitable reference genes is critical for obtaining reliable results from gene expression studies using quantitative real-time PCR (qPCR) because the expression of reference genes may vary considerably under different experimental conditions. In most cases, however, commonly used reference genes are employed in data normalization without proper validation, which may lead to incorrect data interpretation. Here, we aim to select a set of optimal reference genes for the accurate normalization of gene expression associated with intramuscular fat (IMF) deposition during development. In the present study, eight reference genes (PPIB, HMBS, RPLP0, B2M, YWHAZ, 18S, GAPDH and ACTB) were evaluated by three different algorithms (geNorm, NormFinder and BestKeeper) in two types of muscle tissues (longissimus dorsi muscle and biceps femoris muscle) across different developmental stages. All three algorithms gave similar results. PPIB and HMBS were identified as the most stable reference genes, while the commonly used reference genes 18S and GAPDH were the most variably expressed, with expression varying dramatically across different developmental stages. Furthermore, to reveal the crucial role of appropriate reference genes in obtaining a reliable result, analysis of PPARG expression was performed by normalization to the most and the least stable reference genes. The relative expression levels of PPARG normalized to the most stable reference genes greatly differed from those normalized to the least stable one. Therefore, evaluation of reference genes must be performed for a given experimental condition before the reference genes are used. PPIB and HMBS are the optimal reference genes for analysis of gene expression associated with IMF deposition in skeletal muscle during development. PMID:25794179

  3. Functional characterization of BRCA1 gene variants by mini-gene splicing assay

    PubMed Central

    Steffensen, Ane Y; Dandanell, Mette; Jřnson, Lars; Ejlertsen, Bent; Gerdes, Anne-Marie; Nielsen, Finn C; Hansen, Thomas vO

    2014-01-01

    Mutational screening of the breast cancer susceptibility gene BRCA1 leads to the identification of numerous pathogenic variants such as frameshift and nonsense variants, as well as large genomic rearrangements. The screening moreover identifies a large number of variants, for example, missense, silent, and intron variants, which are classified as variants of unknown clinical significance owing to the lack of causal evidence. Variants of unknown clinical significance can potentially have an impact on splicing and therefore functional examinations are warranted to classify whether these variants are pathogenic or benign. Here we validate a mini-gene splicing assay by comparing the results of 24 variants with previously published data from RT-PCR analysis on RNA from blood samples/lymphoblastoid cell lines. The analysis showed an overall concordance of 100%. In addition, we investigated 13 BRCA1 variants of unknown clinical significance or putative variants affecting splicing by in silico analysis and mini-gene splicing assay. Both the in silico analysis and mini-gene splicing assay classified six BRCA1 variants as pathogenic (c.80+1G>A, c.132C>T (p.=), c.213?1G>A, c.670+1delG, c.4185+1G>A, and c.5075?1G>C), whereas six BRCA1 variants were classified as neutral (c.-19-22_-19-21dupAT, c.302?15C>G, c.547+14delG, c.4676?20A>G, c.4987?21G>T, and c.5278?14C>G) and one BRCA1 variant remained unclassified (c.670+16G>A). In conclusion, our study emphasizes that in silico analysis and mini-gene splicing assays are important for the classification of variants, especially if no RNA is available from the patient. This knowledge is crucial for proper genetic counseling of patients and their family members. PMID:24667779

  4. Identification of functionally methylated regions based on discriminant analysis through integrating methylation and gene expression data.

    PubMed

    Zhang, Yuanyuan; Zhang, Junying

    2015-06-16

    DNA methylation is essential not only in cellular differentiation but also in diseases. Identification of differentially methylated patterns between case and control groups is important in understanding the mechanism and possible functionality of complex diseases. We propose a method to find possible functionally methylated regions which not only are differentially methylated but also have an effect on gene expression. It integrates methylation and gene expression data and is based on distance discriminant analysis (DDA). In the procedure of identifying differentially methylated regions (DMRs), we do not need to cluster methylation sites or partition the genome in advance. Therefore, the identified DMRs have a larger coverage than those of bump hunting and Ong's methods. Furthermore, through incorporating gene expression data as a complementary source, whether these DMRs are functional is determined through estimating the difference of the corresponding genes. Through a comparison of our approach with bump hunting and Ong's methods for simulation data, it is shown that our method is more powerful in identifying DMRs which have a larger distance in the genome, or only consist of a few sites and have higher sensitivity and specificity. Also, our method is more robust to heterogeneity of data. Applied to different real datasets, we find that most of the functional DMRs are hyper-methylated and located at CpG rich regions (e.g. islands, TSS200 and TSS1500), consistent with the fact that the methylation levels of CpG islands are higher in tumors than normal. Through comparing and analyzing the results of different datasets, we find that the change of methylation in some regions may be related to diseases through changing expression of the corresponding genes, and show the effectiveness of our method. PMID:25865601

  5. Functional analysis of yeast gene families involved in metabolism of vitamins B1 and B6.

    PubMed

    Rodríguez-Navarro, Susana; Llorente, Bertrand; Rodríguez-Manzaneque, María Teresa; Ramne, Anna; Uber, Genoveva; Marchesan, Denis; Dujon, Bernard; Herrero, Enrique; Sunnerhagen, Per; Pérez-Ortín, José E

    2002-10-01

    In order to clarify their physiological functions, we have undertaken a characterization of the three-membered gene families SNZ1-3 and SNO1-3. In media lacking vitamin B(6), SNZ1 and SNO1 were both required for growth in certain conditions, but neither SNZ2, SNZ3, SNO2 nor SNO3 were required. Copies 2 and 3 of the gene products have, in spite of their extremely close sequence similarity, slightly different functions in the cell. We have also found that copies 2 and 3 are activated by the lack of thiamine and that the Snz proteins physically interact with the thiamine biosynthesis Thi5 protein family. Whereas copy 1 is required for conditions in which B(6) is essential for growth, copies 2 and 3 seem more related with B(1) biosynthesis during the exponential phase. PMID:12271461

  6. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P. (Knoxville, TN)

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  7. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P. (Knoxville, TN)

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  8. Perilipin, a critical regulator of fat storage and breakdown, is a target gene of estrogen receptor-related receptor {alpha}

    SciTech Connect

    Akter, Mst. Hasina; Yamaguchi, Tomohiro; Hirose, Fumiko [Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297 (Japan); Osumi, Takashi [Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297 (Japan)], E-mail: osumi@sci.u-hyogo.ac.jp

    2008-04-11

    Perilipin is a protein localized on lipid droplet surfaces in adipocytes and steroidogenic cells, playing a central role in regulated lipolysis. Expression of the perilipin gene is markedly induced during adipogenesis. We found that transcription from the perilipin gene promoter is activated by an orphan nuclear receptor, estrogen receptor-related receptor (ERR){alpha}. A response element to this receptor was identified in the promoter region by a gene reporter assay, the electrophoretic-gel mobility-shift assay and the chromatin immunoprecipitation assay. Peroxisome proliferator-activated receptor {gamma} coactivator (PGC)-1{alpha} enhanced, whereas small heterodimer partner (SHP) repressed, the transactivating function of ERR{alpha} on the promoter. Thus, the perilipin gene expression is regulated by a transcriptional network controlling energy metabolism, substantiating the functional importance of perilipin in the maintenance of body energy balance.

  9. GeoChip-based insights into the microbial functional gene repertoire of marine sponges (high microbial abundance, low microbial abundance) and seawater.

    PubMed

    Bayer, Kristina; Moitinho-Silva, Lucas; Brümmer, Franz; Cannistraci, Carlo V; Ravasi, Timothy; Hentschel, Ute

    2014-12-01

    The GeoChip 4.2 gene array was employed to interrogate the microbial functional gene repertoire of sponges and seawater collected from the Red Sea and the Mediterranean. Complementary amplicon sequencing confirmed the microbial community composition characteristic of high microbial abundance (HMA) and low microbial abundance (LMA) sponges. By use of GeoChip, altogether 20,273 probes encoding for 627 functional genes and representing 16 gene categories were identified. Minimum curvilinear embedding analyses revealed a clear separation between the samples. The HMA/LMA dichotomy was stronger than any possible geographic pattern, which is shown here for the first time on the level of functional genes. However, upon inspection of individual genes, very few specific differences were discernible. Differences were related to microbial ammonia oxidation, ammonification, and archaeal autotrophic carbon fixation (higher gene abundance in sponges over seawater) as well as denitrification and radiation-stress-related genes (lower gene abundance in sponges over seawater). Except for few documented specific differences the functional gene repertoire between the different sources appeared largely similar. This study expands previous reports in that functional gene convergence is not only reported between HMA and LMA sponges but also between sponges and seawater. PMID:25318900

  10. Paradata for 'ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression'

    NSDL National Science Digital Library

    This record contains paradata for the resource 'ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression'

  11. NLRC5 exclusively transactivates MHC class I and related genes through a distinctive SXY module.

    PubMed

    Ludigs, Kristina; Seguín-Estévez, Queralt; Lemeille, Sylvain; Ferrero, Isabel; Rota, Giorgia; Chelbi, Sonia; Mattmann, Chantal; MacDonald, H Robson; Reith, Walter; Guarda, Greta

    2015-03-01

    MHC class II (MHCII) genes are transactivated by the NOD-like receptor (NLR) family member CIITA, which is recruited to SXY enhancers of MHCII promoters via a DNA-binding "enhanceosome" complex. NLRC5, another NLR protein, was recently found to control transcription of MHC class I (MHCI) genes. However, detailed understanding of NLRC5's target gene specificity and mechanism of action remained lacking. We performed ChIP-sequencing experiments to gain comprehensive information on NLRC5-regulated genes. In addition to classical MHCI genes, we exclusively identified novel targets encoding non-classical MHCI molecules having important functions in immunity and tolerance. ChIP-sequencing performed with Rfx5(-/-) cells, which lack the pivotal enhanceosome factor RFX5, demonstrated its strict requirement for NLRC5 recruitment. Accordingly, Rfx5-knockout mice phenocopy Nlrc5 deficiency with respect to defective MHCI expression. Analysis of B cell lines lacking RFX5, RFXAP, or RFXANK further corroborated the importance of the enhanceosome for MHCI expression. Although recruited by common DNA-binding factors, CIITA and NLRC5 exhibit non-redundant functions, shown here using double-deficient Nlrc5(-/-)CIIta(-/-) mice. These paradoxical findings were resolved by using a "de novo" motif-discovery approach showing that the SXY consensus sequence occupied by NLRC5 in vivo diverges significantly from that occupied by CIITA. These sequence differences were sufficient to determine preferential occupation and transactivation by NLRC5 or CIITA, respectively, and the S box was found to be the essential feature conferring NLRC5 specificity. These results broaden our knowledge on the transcriptional activities of NLRC5 and CIITA, revealing their dependence on shared enhanceosome factors but their recruitment to distinct enhancer motifs in vivo. Furthermore, we demonstrated selectivity of NLRC5 for genes encoding MHCI or related proteins, rendering it an attractive target for therapeutic intervention. NLRC5 and CIITA thus emerge as paradigms for a novel class of transcriptional regulators dedicated for transactivating extremely few, phylogenetically related genes. PMID:25811463

  12. Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

    PubMed

    Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

    2015-06-01

    The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate < 0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. PMID:25805767

  13. Characterization of CMIX, a chicken homeobox gene related to the Xenopus gene mix.1.

    PubMed

    Peale, F V; Sugden, L; Bothwell, M

    1998-07-01

    Members of the TGFbeta, Wnt and FGF families act in concert to induce and pattern the mesoderm of gastrulating embryos. Downstream effectors for these growth factors include homeobox proteins, which also feed back to activate and repress upstream signaling pathways (e.g. Fainsod, A., Steinbeisser, H., De Robertis, E.M. 1994. On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo. EMBO J. 13, 5015-5025; Carnac, G., Kodjabachian, L., Gurdon, J.B., Lemaire, P. 1996. The homeobox gene Siamois is a target of the Wnt dorsalization pathway and triggers organizer activity in the absence of mesoderm. Development 122, 3055-3065). As well as having interwoven upstream and downstream regulatory pathways Mix.1, siamois and goosecoid, all paired-type homeobox genes, may physically interact with each other as heterodimers to regulate dorsal-ventral polarity (Mead, P.E., Brivanlou, I.H., Kelley, C.M., Zon, L.I. 1996. BMP-4 responsive regulation of dorsal-ventral patterning by the homeobox protein Mix.1. Nature 382, 357-360). We report here a chicken paired-type homeobox gene, CMIX, with a homeodomain having 72% aa identity to its nearest homolog, Xenopus Mix.1. CMIX is expressed in the epiblast of the posterior marginal zone of early chick embryos, and later along the entire anterior-posterior axis of the primitive streak in cells of the medial ectoderm, in nascent mesoderm, but not in endoderm. Coincident with formation of prechordal mesoderm, CMIX mRNA levels rapidly decline throughout the embryo. PMID:9739137

  14. Characterization and functional analysis of ABSCISIC ACID INSENSITIVE3-like genes from Physcomitrella patens

    E-print Network

    Quatrano, Ralph S.

    Characterization and functional analysis of ABSCISIC ACID INSENSITIVE3-like genes from Physcomitrella patens is known to respond to abscisic acid (ABA) by activating gene expression5, abscisic acid, Physcomitrella, transcriptional regulation, VP1. Introduction The phytohormone

  15. A Relational Approach to Functional Decomposition of Logic Circuits

    Microsoft Academic Search

    Tony T. Lee; Tong Ye

    2006-01-01

    Functional decomposition of logic circuits has profound influence on all quality as- pects of the cost-effective implementation of modern digital systems. In this paper, a relational approach to the decomposition of logic circuits is proposed. This ap- proach is parallel to the normalization of relational databases, they are governed by the same concepts of functional dependency (FD) and multi-valued dependency

  16. Investigation of the hub genes and related mechanism in ovarian cancer via bioinformatics analysis

    PubMed Central

    2013-01-01

    Background Ovarian cancer is a cancerous growth arising from the ovary. Objective This study was aimed to explore the molecular mechanism of the development and progression of the ovarian cancer. Methods We first identified the differentially expressed genes (DEGs) between the ovarian cancer samples and the healthy controls by analyzing the GSE14407 affymetrix microarray data, and then the functional enrichments of the DEGs were investigated. Furthermore, we constructed the protein-protein interaction network of the DEGs using the STRING online tools to find the genes which might play important roles in the progression of ovarian cancer. In addition, we performed the enrichment analysis to the PPI network. Results Our study screened 659 DEGs, including 77 up- and 582 down-regulated genes. These DEGs were enriched in pathways such as Cell cycle, p53 signaling pathway, Pathways in cancer and Drug metabolism. CCNE1, CCNB2 and CYP3A5 were the significant genes identified from these pathways. Protein-protein interaction (PPI) network was constructed and network Module A was found closely associated with ovarian cancer. Hub nodes such as VEGFA, CALM1, BIRC5 and POLD1 were found in the PPI network. Module A was related to biological processes such as mitotic cell cycle, cell cycle, nuclear division, and pathways namely Cell cycle, Oocyte meiosis and p53 signaling pathway. Conclusions It indicated that ovarian cancer was closely associated to the dysregulation of p53 signaling pathway, drug metabolism, tyrosine metabolism and cell cycle. Besides, we also predicted genes such as CCNE1, CCNB2, CYP3A5 and VEGFA might be target genes for diagnosing the ovarian cancer. PMID:24341673

  17. Functional Polymorphisms in COX-2 Gene Are Correlated with the Risk of Oral Cancer

    PubMed Central

    Li, Dong; Hao, Shu-Hong; Sun, Yan; Hu, Chun-Mei; Ma, Zhi-Hua; Wang, Zhi Ming; Liu, Jie; Liu, Hong Bo; Ye, Ming; Zhang, Yu Fei; Yang, Dong Sheng; Shi, Guang

    2015-01-01

    Background. This meta-analysis investigated the association between functional COX-2 gene polymorphisms and the risk of oral cancer. Methods. Several electronic databases were searched for published studies using combinations of keywords related to COX-2 gene polymorphisms and oral cancer. After selection of relevant studies, following strict inclusion and exclusion criteria, data was performed using STATA 12.0 software. Results. We retrieved 83 studies from database search using specific search terms. After multiple rounds of selection and elimination, 7 studies were finally identified as suitable to be included in our present meta-analysis, based on their relevance and data integrity. These 7 studies contained a combined total of 2,296 oral cancer patients and 3,647 healthy controls. Our findings demonstrated that +837 T > C (rs5275) polymorphism in COX-2 showed statistically significant differences in gene frequencies in case and control groups in allele model and dominant model. Similar results were obtained with COX-2 gene polymorphism 765 G > C (rs20417). On the other hand, 1195 A > G (rs689466) polymorphism in COX-2 did not confer susceptibility to oral cancers. Conclusion. Based on our results, COX-2 gene polymorphisms, +837 T > C (rs5275) and ?765G > C (rs20417), showed clear links with oral cancer susceptibility, and the 1195A > G (rs689466) polymorphism did not show such a correlation. PMID:25977924

  18. Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora

    PubMed Central

    Traeger, Stefanie; Nowrousian, Minou

    2015-01-01

    During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. PMID:25873638

  19. Combining genetic diversity, informatics and metabolomics to facilitate annotation of plant gene function

    Microsoft Academic Search

    Takayuki Tohge; Alisdair R Fernie

    2010-01-01

    Given the ever-increasing number of species for which full-genome sequencing has been realized, there is a rising burden for gene functional annotation. In this study, we provide a detailed protocol that combines co-response gene analysis (using target genes of known function to allow the identification of nonannotated genes likely to be involved in a certain metabolic process) with the identification

  20. Cross-Species Comparison of Genes Related to Nutrient Sensing Mechanisms Expressed along the Intestine

    PubMed Central

    van der Wielen, Nikkie; van Avesaat, Mark; de Wit, Nicole J. W.; Vogels, Jack T. W. E.; Troost, Freddy; Masclee, Ad; Koopmans, Sietse-Jan; van der Meulen, Jan; Boekschoten, Mark V.; Müller, Michael; Hendriks, Henk F. J.; Witkamp, Renger F.; Meijerink, Jocelijn

    2014-01-01

    Introduction Intestinal chemosensory receptors and transporters are able to detect food-derived molecules and are involved in the modulation of gut hormone release. Gut hormones play an important role in the regulation of food intake and the control of gastrointestinal functioning. This mechanism is often referred to as “nutrient sensing”. Knowledge of the distribution of chemosensors along the intestinal tract is important to gain insight in nutrient detection and sensing, both pivotal processes for the regulation of food intake. However, most knowledge is derived from rodents, whereas studies in man and pig are limited, and cross-species comparisons are lacking. Aim To characterize and compare intestinal expression patterns of genes related to nutrient sensing in mice, pigs and humans. Methods Mucosal biopsy samples taken at six locations in human intestine (n?=?40) were analyzed by qPCR. Intestinal scrapings from 14 locations in pigs (n?=?6) and from 10 locations in mice (n?=?4) were analyzed by qPCR and microarray, respectively. The gene expression of glucagon, cholecystokinin, peptide YY, glucagon-like peptide-1 receptor, taste receptor T1R3, sodium/glucose cotransporter, peptide transporter-1, GPR120, taste receptor T1R1, GPR119 and GPR93 was investigated. Partial least squares (PLS) modeling was used to compare the intestinal expression pattern between the three species. Results and conclusion The studied genes were found to display specific expression patterns along the intestinal tract. PLS analysis showed a high similarity between human, pig and mouse in the expression of genes related to nutrient sensing in the distal ileum, and between human and pig in the colon. The gene expression pattern was most deviating between the species in the proximal intestine. Our results give new insights in interspecies similarities and provide new leads for translational research and models aiming to modulate food intake processes in man. PMID:25216051

  1. Heterologous virus-induced gene silencing as a promising approach in plant functional genomics.

    PubMed

    Hosseini Tafreshi, Seied Ali; Shariati, Mansour; Mofid, Mohammad Reza; Khayam Nekui, Mojtaba; Esmaeili, Abolghasem

    2012-03-01

    VIGS (virus induced gene silencing) is considered as a powerful genomics tool for characterizing the function of genes in a few closely related plant species. The investigations have been carried out mainly in order to test if a pre-existing VIGS vector can serve as an efficient tool for gene silencing in a diverse array of plant species. Another route of investigation has been the constructing of new viral vectors to act in their hosts. Our approach was the creation of a heterologous system in which silencing of endogenous genes was achieved by sequences isolated from evolutionary remote species. In this study, we showed that a TRV-based vector cloned with sequences from a gymnosperm, Taxus baccata L. silenced the endogenous phytoene desaturase in an angiosperm, N. benthamiana. Our results showed that inserts of between 390 and 724 bp isolated from a conserved fragment of the Taxus PDS led to silencing of its homolog in tobacco. The real time analysis indicated that the expression of PDS was reduced 2.1- to 4.0-fold in pTRV-TbPDS infected plants compared with buffer treated plants. Once the best insert is identified and the conditions are optimized for heterologous silencing by pTRV-TbPDS in tobacco, then we can test if TRV can serve as an efficient silencing vector in Taxus. This strategy could also be used to silence a diverse array of genes from a wide range of species which have no VIGS protocol. The results also showed that plants silenced heterologously by the VIGS system a minimally affected with respect to plant growth which may be ideal for studying the genes that their complete loss of function may lead to decrease of plant growth or plant death. PMID:21655951

  2. De novo assembly of Euphorbia fischeriana root transcriptome identifies prostratin pathway related genes

    PubMed Central

    2011-01-01

    Background Euphorbia fischeriana is an important medicinal plant found in Northeast China. The plant roots contain many medicinal compounds including 12-deoxyphorbol-13-acetate, commonly known as prostratin that is a phorbol ester from the tigliane diterpene series. Prostratin is a protein kinase C activator and is effective in the treatment of Human Immunodeficiency Virus (HIV) by acting as a latent HIV activator. Latent HIV is currently the biggest limitation for viral eradication. The aim of this study was to sequence, assemble and annotate the E. fischeriana transcriptome to better understand the potential biochemical pathways leading to the synthesis of prostratin and other related diterpene compounds. Results In this study we conducted a high throughput RNA-seq approach to sequence the root transcriptome of E. fischeriana. We assembled 18,180 transcripts, of these the majority encoded protein-coding genes and only 17 transcripts corresponded to known RNA genes. Interestingly, we identified 5,956 protein-coding transcripts with high similarity (> = 75%) to Ricinus communis, a close relative to E. fischeriana. We also evaluated the conservation of E. fischeriana genes against EST datasets from the Euphorbeacea family, which included R. communis, Hevea brasiliensis and Euphorbia esula. We identified a core set of 1,145 gene clusters conserved in all four species and 1,487 E. fischeriana paralogous genes. Furthermore, we screened E. fischeriana transcripts against an in-house reference database for genes implicated in the biosynthesis of upstream precursors to prostratin. This identified 24 and 9 candidate transcripts involved in the terpenoid and diterpenoid biosyntehsis pathways, respectively. The majority of the candidate genes in these pathways presented relatively low expression levels except for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (HDS) and isopentenyl diphosphate/dimethylallyl diphosphate synthase (IDS), which are required for multiple downstream pathways including synthesis of casbene, a proposed precursor to prostratin. Conclusion The resources generated in this study provide new insights into the upstream pathways to the synthesis of prostratin and will likely facilitate functional studies aiming to produce larger quantities of this compound for HIV research and/or treatment of patients. PMID:22151917

  3. Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy

    PubMed Central

    2011-01-01

    Background The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities. Methods Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated. Results Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients. Conclusions Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM. PMID:21689390

  4. Pneumocystis Encodes a Functional S-Adenosylmethionine Synthetase Gene?

    PubMed Central

    Kutty, Geetha; Hernandez-Novoa, Beatriz; Czapiga, Meggan; Kovacs, Joseph A.

    2008-01-01

    S-Adenosylmethionine (AdoMet) synthetase (EC 2.5.1.6) is the enzyme that catalyzes the synthesis of AdoMet, a molecule important for all cellular organisms. We have cloned and characterized an AdoMet synthetase gene (sam1) from Pneumocystis spp. This gene was transcribed primarily as an ?1.3-kb mRNA which encodes a protein containing 381 amino acids in P. carinii or P. murina and 382 amino acids in P. jirovecii. sam1 was also transcribed as part of an apparent polycistronic transcript of ?5.6 kb, together with a putative chromatin remodeling protein homologous to Saccharomyces cerevisiae, CHD1. Recombinant Sam1, when expressed in Escherichia coli, showed functional enzyme activity. Immunoprecipitation and confocal immunofluorescence analysis using an antipeptide antibody showed that this enzyme is expressed in P. murina. Thus, Pneumocystis, like other organisms, can synthesize its own AdoMet and may not depend on its host for the supply of this important molecule. PMID:18065654

  5. Evolution of the Glutamine Synthetase Gene, One of the Oldest Existing and Functioning Genes

    Microsoft Academic Search

    Y. Kumada; D. R. Benson; D. Hillemann; T. J. Hosted; D. A. Rochefort; C. J. Thompson; W. Wohlleben; Y. Tateno

    1993-01-01

    We performed molecular phylogenetic analyses of glutamine synthetase (GS) genes in order to investigate their evolutionary history. The analyses were done on 30 DNA sequences of the GS gene which included both prokaryotes and eukaryotes. Two types of GS genes are known at present: the GSI gene found so far only in prokaryotes and the GSII gene found in both

  6. An Allelic Series at the Paired Box Gene 6 (Pax6) Locus Reveals the Functional Specificity of Pax Genes*

    PubMed Central

    Carbe, Christian; Garg, Ankur; Cai, Zhigang; Li, Hongge; Powers, Andrea; Zhang, Xin

    2013-01-01

    The advent of the ocular and nervous system in metazoan evolution coincides with the diversification of a single ancestral paired box (Pax) gene into Pax6, Pax6(5a), and Pax2. To investigate the role of these Pax genes in neural development, we have generated an allelic series of knock-in models at the Pax6 locus. We showed that although Pax6(5a) and Pax2 could not replace Pax6 for its autoregulation in lens induction or for neural differentiation in retina, Pax6(5a) was sufficient for corneal-lenticular detachment. In brain development, cell proliferation in the cerebral cortex and dorsoventral patterning of the telencephalon and neural tube were partially rescued in either knock-in mutant. Contrary to the previous belief, our genetic studies showed that the Pax6 isoform Pax6(5a) could potentially play a role in neuronal differentiation in brain development. Importantly, Pax2 showed greater rescue efficiency than Pax6(5a) in the telencephalon even though the latter was identical to Pax6 outside the paired domain. In studying Ngn2, a Pax6 direct target gene in telencephalon, we showed that the level of Ngn2 expression correlated with the in vitro binding of Pax2, Pax6, and Pax6(5a) paired domain on its enhancer. Our results show that Pax6 is uniquely required for eye development, but in brain development, Pax6 can be functionally substituted by related Pax family genes that share a similar paired domain binding specificity. PMID:23515312

  7. Calcitonin Gene-Related Peptide Protects Against Hypertension-Induced Heart and Kidney Damage

    Microsoft Academic Search

    Scott C. Supowit; Arundhati Rao; Mark C. Bowers; Huawei Zhao; Gregory Fink; Barbara Steficek; Parag Patel; Khurshed A. Katki; Donald J. DiPette

    2010-01-01

    Calcitonin gene-related peptide is a potent vasodilator neuropeptide that is localized in perivascular sensory nerves. To determine whether -calcitonin gene-related peptide possesses protective activity against hypertension- induced end organ damage, hypertension was induced in -calcitonin gene-related\\/calcitonin peptide knockout and wild-type mice by uninephrectomy, deoxycorticosteroid administration, and 0.9% saline drinking water. These mice were instrumented previously for long-term telemetric blood pressure

  8. Expression profiling and regulation of genes related to silkworm posterior silk gland development and fibroin synthesis.

    PubMed

    Li, Jian-ying; Yang, Hui-juan; Lan, Tian-yun; Wei, Hao; Zhang, Hua-rong; Chen, Ming; Fan, Wei; Ma, Ying-ying; Zhong, Bo-xiong

    2011-08-01

    The posterior silk gland (PSG) is the most important suborgan responsible for the synthesis and secretion of silk core fibroin proteins in silkworm. Here, we performed genome-scale expression profiling analysis of silkworm PSG at the fourth molting (M4) and at day 1 (V1), day 3 (V3), day 5 (V5), and wandering stage (W) of the fifth instar by microarray analysis with 22?987 probes. We found that the five genes of silk proteins secreted from PSG including fibroin heavy (H) and light (L) chains, P25, seroin 1, and seroin 2 basically showed obvious up-regulation at V3 which lasted to V5, while slight down-regulation at W. The expression of translation-related genes including ribosomal proteins and translation initiation factors generally remained stable from M4 to V5, whereas it showed clear down-regulation at W. Clustering analysis of the 643 significantly differentially expressed transcripts revealed that 43 of the important genes including seroin 1 and sugar transporter protein had co-expression patterns which were consistent with the rate changes of fibroin synthesis and PSG growth. Pathway analysis disclosed that the genes in different clusters might have co-regulations and direct interactions. These genes were supposed to be involved in the fibroin synthesis and secretion. The differential expression of several hormone-related genes also suggested their functions on the regulation of PSG development and fibroin synthesis. 2D gel-based proteomics and phosphoproteomics profiling revealed that the phosphorylated proteins accounted for no more than one-sixth of the total proteins at each stage, which was much lower than the level in normal eukaryotic cells. Changes in the phosphorylation status and levels of several proteins such as actin-depolymerizing factor 1 and enolase might be deeply involved in fibroin secretion and tissue development. Shotgun proteomic profiling combined with label-free quantification analysis on the PSG at V3, V5, and W revealed that many small heat shock proteins (sHSP) were specially expressed at W, which was substantially consistent with the results from 2-DE analysis, and implied the close correlations of sHSP with the physiological states of PSG at W. A majority of significantly up-regulated proteins at V5 were related to ribosome pathway, which was different from the microarray results, implying that the translation-level regulation of ribosomal proteins might be critical for fibroin synthesis. In contrast, the ubiquitin-proteasome pathway related proteins appeared obviously up-regulated at W, suggesting that the programmed cell death process of PSG cells might be started before cocooning. PMID:21657221

  9. INFLAMMATION AND STRESS-RELATED CANDIDATE GENES, PLASMA INTERLEUKIN-6 LEVELS, AND LONGEVITY IN OLDER ADULTS

    PubMed Central

    Walston, Jeremy D.; Matteini, Amy M.; Nievergelt, Caroline; Lange, Leslie A.; Fallin, Dani M.; Barzilai, Nir; Ziv, Elad; Pawlikowska, Ludmila; Kwok, Pui; Cummings, Steve R.; Kooperberg, Charles; LaCroix, Andrea; Tracy, Russell P.; Atzmon, Gil; Lange, Ethan M.; Reiner, Alex P.

    2009-01-01

    Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5,000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%-20% higher baseline IL-6 concentration per copy among CHS European-American (EA) participants (all p<10?4). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p=0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415 – longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all 3 studies, the “risk” of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95%CI 0.62 – 1.02; p=0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes. PMID:19249341

  10. Resurrection of an ancestral gene: functional and evolutionary analyses of the Ngrol genes transferred from Agrobacterium to Nicotiana.

    PubMed

    Aoki, Seishiro

    2004-08-01

    The Ng rol genes, which have high similarity in sequence to the rol genes of Agrobacterium rhizogenes, are present in the genome of untransformed plants of Nicotiana glauca. It is thought that bacterial infection resulted in the transfer of the Ng rol genes to plants early in the evolution of the genus Nicotiana, since several species in this genus contain rol-like sequences but others do not. Plants transformed with the bacterial rol genes exhibit various developmental and morphological changes. The presence of rol-like sequences in plant genomes is therefore thought to have contributed to the evolution of Nicotiana species. This paper focuses on studies of the Ng rol genes in present-day plants and during the evolution of the genus Nicotiana. The functional sequences of several Ng rol genes may have been conserved after their ancient introduction from a bacterium to the plant. Resurrection of an ancestral function of one of the Ng rol genes, as examined by physiological and evolutionary analyses, is also described. The origin of the Ng rol genes is then considered, based on results of molecular phylogenetic analyses. The effects of the horizontal transfer of the Ng rol genes and mutations in the genes are discussed on the plants of the genus Nicotiana during evolution. PMID:15338429

  11. Analysis of CATMA transcriptome data identifies hundreds of novel functional genes and improves gene models in the Arabidopsis genome

    Microsoft Academic Search

    Sébastien Aubourg; Marie-Laure Martin-Magniette; Véronique Brunaud; Ludivine Taconnat; Frédérique Bitton; Sandrine Balzergue; Pauline E Jullien; Mathieu Ingouff; Vincent Thareau; Thomas Schiex; Alain Lecharny; Jean-Pierre Renou

    2007-01-01

    BACKGROUND: Since the finishing of the sequencing of the Arabidopsis thaliana genome, the Arabidopsis community and the annotator centers have been working on the improvement of gene annotation at the structural and functional levels. In this context, we have used the large CATMA resource on the Arabidopsis transcriptome to search for genes missed by different annotation processes. Probes on the

  12. Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III

    Microsoft Academic Search

    Pierre Gönczy; Christophe Echeverri; Karen Oegema; Alan Coulson; Steven J. M. Jones; Richard R. Copley; John Duperon; Jeff Oegema; Michael Brehm; Etienne Cassin; Eva Hannak; Matthew Kirkham; Silke Pichler; Kathrin Flohrs; Anoesjka Goessen; Sebastian Leidel; Anne-Marie Alleaume; Cécilie Martin; Nurhan Özlü; Peer Bork; Anthony A. Hyman

    2000-01-01

    Genome sequencing projects generate a wealth of information; however, the ultimate goal of such projects is to accelerate the identification of the biological function of genes. This creates a need for comprehensive studies to fill the gap between sequence and function. Here we report the results of a functional genomic screen to identify genes required for cell division in Caenorhabditis

  13. Glucose Deprivation Inhibits Multiple Key Gene Expression Events and Effector Functions in CD8+ T Cells

    PubMed Central

    Cham, Candace M.; Driessens, Gregory; O'Keefe, James P.; Gajewski, Thomas F.

    2010-01-01

    Summary We recently reported that differentiation of CD8+ T cells from the naďve to the effector state involves the upregulation of glucose-dependent metabolism. Glucose deprivation or inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) selectively inhibited production of IFN-? but not of IL-2. To determine a more global role of glucose metabolism on effector T cell function, we performed gene array analysis on CD8+ effector T cells stimulated in the presence or absence of 2-DG. We observed that expression of only 10% of genes induced by TCR/CD28 signaling was inhibited by 2-DG. Among these were genes for key cytokines, cell cycle molecules, and cytotoxic granule proteins. Consistent with these results, production of IFN-? and GM-CSF, cell cycle progression, upregulation of cyclin D2 protein, cytolytic activity, and upregulation of granzyme B protein but also conjugate formation were exquisitely glucose-dependent. In contrast to glucose, oxygen was little utilized by CD8+ effector T cells, and relative oxygen deprivation did not inhibit these CTL functional properties. Our results indicate a particularly critical role for glucose in regulating specific effector functions of CD8+ T cells, and have implications for the maintenance of the effector phase of cellular immune responses in target tissue microenvironments such as a solid tumor. PMID:18792400

  14. Gene transcription abnormalities in canine atopic dermatitis and related human eosinophilic allergic diseases

    PubMed Central

    Plager, Douglas A.; Torres, Sheila M.F.; Koch, Sandra N.; Kita, Hirohito

    2015-01-01

    Canine atopic dermatitis (AD) is clinically similar to human AD, implicating it as a useful model of human eosinophilic allergic disease. To identify cutaneous gene transcription changes in relatively early inflammation of canine AD, microarrays were used to monitor transcription in normal skin (n = 13) and in acute lesional AD (ALAD) and nearby visibly nonlesional AD (NLAD) skin (n = 13) from dogs. Scanning the putative abnormally transcribed genes, several potentially relevant genes, some abnormally transcribed in both NLAD and ALAD (e.g. IL6, NFAM1, MSRA, and SYK), were observed. Comparison for abnormally transcribed genes common to two related human diseases, human AD and asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP), further identified genes or gene sets likely relevant to eosinophilic allergic inflammation. These included: (1) genes associated with alternatively activated monocyte-derived cells, including members of the monocyte chemotactic protein (MCP) gene cluster, (2) members of the IL1 family gene cluster, (3) eosinophil-associated seven transmembrane receptor EMR1 and EMR3 genes, (4) interferon-inducible genes, and (5) keratin genes associated with hair and nail formation. Overall, numerous abnormally transcribed genes were observed only in canine AD; however, many others are common to related human eosinophilic allergic diseases and represent therapeutic targets testable in dogs with AD. PMID:22749291

  15. Localization of Shaw-related K + channel genes on mouse and human chromosomes

    Microsoft Academic Search

    M. Haas; D. C. Ward; J. Lee; A. D. Roses; V. Clarke; P. D'Eustachio; D. Lau; E. Vega-Saenz de Miera; B. Rudy

    1993-01-01

    Four related genes, Shaker, Shab, Shaw, and Shal, encode voltage-gated K+ channels in Drosophila. Multigene subfamilies corresponding to each of these Drosophila genes have been identified in rodents and primates; this suggests that the four genes are older than the common ancestor of present-day insects and mammals and that the expansion of each into a family occurred before the divergence

  16. RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA

    E-print Network

    Grishok, Alla

    -siRNAs exist in the nematode. We have characterized a system of RNAi-induced transcriptional gene silencing a microarray analysis of gene expression in RNA interference (RNAi)-related mutants rde-4, zfp-1, and alg-1 finger protein ZFP-1, not implicated in endogenous RNAi, regulate overlapping sets of genes. Notably

  17. A Cluster of Ten Novel MHC Class I Related Genes on Human Chromosome 6q24.2–q25.3

    Microsoft Academic Search

    Mirjana Radosavljevic; Michael J. Wilson; Oliver Clément; Sophie Wicker; Susan Gilfillan; Stephan Beck; John Trowsdale; Seiamak Bahram

    2002-01-01

    We have identified a novel family of human major histocompatibility complex (MHC) class I genes. This MHC class I related gene family is defined by 10 members, among which 6 encode potentially functional glycoproteins. The 180-kb cluster containing them has been generated by serial duplication and minimal diversification of an ancestral prototype. They are not located within the MHC on

  18. Rapid Evolution in a Conserved Gene Family. Evolution of the Actin Gene Family in the Sea Urchin Genus Heliocidaris and Related Genera

    E-print Network

    Kissinger, Jessica

    Rapid Evolution in a Conserved Gene Family. Evolution of the Actin Gene Family in the Sea Urchin of the actin gene family in two congeneric sea urchins that develop in radically different modes, Heliociduris genes to those of the the actin gene families of other closely related sea urchins and discuss

  19. Complex Evolution of a Y-Chromosomal Double Homeobox 4 (DUX4)-Related Gene Family in Hominoids

    PubMed Central

    Rappold, Gudrun A.; Schempp, Werner

    2009-01-01

    The human Y chromosome carries four human Y-chromosomal euchromatin/heterochromatin transition regions, all of which are characterized by the presence of interchromosomal segmental duplications. The Yq11.1/Yq11.21 transition region harbours a peculiar segment composed of an imperfectly organized tandem-repeat structure encoding four members of the double homeobox (DUX) gene family. By comparative fluorescence in situ hybridization (FISH) analysis we have documented the primary appearance of Y-chromosomal DUX genes (DUXY) on the gibbon Y chromosome. The major amplification and dispersal of DUXY paralogs occurred after the gibbon and hominid lineages had diverged. Orthologous DUXY loci of human and chimpanzee show a highly similar structural organization. Sequence alignment survey, phylogenetic reconstruction and recombination detection analyses of human and chimpanzee DUXY genes revealed the existence of all copies in a common ancestor. Comparative analysis of the circumjacent beta-satellites indicated that DUXY genes and beta-satellites evolved in concert. However, evolutionary forces acting on DUXY genes may have induced amino acid sequence differences in the orthologous chimpanzee and human DUXY open reading frames (ORFs). The acquisition of complete ORFs in human copies might relate to evolutionary advantageous functions indicating neo-functionalization. We propose an evolutionary scenario in which an ancestral tandem array DUX gene cassette transposed to the hominoid Y chromosome followed by lineage-specific chromosomal rearrangements paved the way for a species-specific evolution of the Y-chromosomal members of a large highly diverged homeobox gene family. PMID:19404400

  20. Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession.

    PubMed

    Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

    2015-01-01

    The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth's biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P?functional diversity was also highest in the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession. PMID:25943705

  1. Connectivity of vertebrate genomes: Paired-related homeobox (Prrx) genes in spotted gar, basal teleosts, and tetrapods?

    PubMed Central

    Braasch, Ingo; Guiguen, Yann; Loker, Ryan; Letaw, John H.; Ferrara, Allyse; Bobe, Julien; Postlethwait, John H.

    2014-01-01

    Teleost fish are important models for human biology, health, and disease. Because genome duplication in a teleost ancestor (TGD) impacts the evolution of teleost genome structure and gene repertoires, we must discriminate gene functions that are shared and ancestral from those that are lineage-specific in teleosts or tetrapods to accurately apply inferences from teleost disease models to human health. Generalizations must account both for the TGD and for divergent evolution between teleosts and tetrapods after the likely two rounds of genome duplication shared by all vertebrates. Progress in sequencing techniques provides new opportunities to generate genomic and transcriptomic information from a broad range of phylogenetically informative taxa that facilitate detailed understanding of gene family and gene function evolution. We illustrate here the use of new sequence resources from spotted gar (Lepisosteus oculatus), a rayfin fish that diverged from teleosts before the TGD, as well as RNA-Seq data from gar and multiple teleost lineages to reconstruct the evolution of the Paired-related homeobox (Prrx) transcription factor gene family, which is involved in the development of mesoderm and neural crest-derived mesenchyme. We show that for Prrx genes, the spotted gar genome and gene expression patterns mimic mammals better than teleosts do. Analyses force the seemingly paradoxical conclusion that regulatory mechanisms for the limb expression domains of Prrx genes existed before the evolution of paired appendages. Detailed evolutionary analyses like those reported here are required to identify fish species most similar to the human genome to optimally connect fish models to human gene functions in health and disease. PMID:24486528

  2. Ginseng Extracts Restore High-Glucose Induced Vascular Dysfunctions by Altering Triglyceride Metabolism and Downregulation of Atherosclerosis-Related Genes

    PubMed Central

    Chan, Gabriel Hoi-huen; Law, Betty Yuen-kwan; Chu, John Man-tak; Yue, Kevin Kin-man; Jiang, Zhi-hong; Lau, Chi-wai; Huang, Yu; Chan, Shun-wan; Ying-kit Yue, Patrick; Wong, Ricky Ngok-shun

    2013-01-01

    The king of herbs, Panax ginseng, has been used widely as a therapeutic agent vis-ŕ-vis its active pharmacological and physiological effects. Based on Chinese pharmacopeia Ben Cao Gang Mu and various pieces of literature, Panax ginseng was believed to exert active vascular protective effects through its antiobesity and anti-inflammation properties. We investigated the vascular protective effects of ginseng by administrating ginseng extracts to rats after the induction of diabetes. We found that Panax ginseng can restore diabetes-induced impaired vasorelaxation and can reduce serum triglyceride but not cholesterol level in the diabetic rats. The ginseng extracts also suppressed the expression of atherosclerosis-related genes and altered the expression of lipid-related genes. The results provide evidence that Panax ginseng improves vascular dysfunction induced by diabetes and the protective effects may possibly be due to the downregulation of atherosclerosis-related genes and altered lipid metabolism, which help to restore normal endothelium functions. PMID:24194784

  3. Parallel sites implicate functional convergence of the hearing gene prestin among echolocating mammals.

    PubMed

    Liu, Zhen; Qi, Fei-Yan; Zhou, Xin; Ren, Hai-Qing; Shi, Peng

    2014-09-01

    Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/?, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/? and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation. PMID:24951728

  4. A Hybrid Computational Method for the Discovery of Novel Reproduction-Related Genes

    PubMed Central

    Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Guohua; Huang, Tao; Cai, Yu-Dong

    2015-01-01

    Uncovering the molecular mechanisms underlying reproduction is of great importance to infertility treatment and to the generation of healthy offspring. In this study, we discovered novel reproduction-related genes with a hybrid computational method, integrating three different types of method, which offered new clues for further reproduction research. This method was first executed on a weighted graph, constructed based on known protein-protein interactions, to search the shortest paths connecting any two known reproduction-related genes. Genes occurring in these paths were deemed to have a special relationship with reproduction. These newly discovered genes were filtered with a randomization test. Then, the remaining genes were further selected according to their associations with known reproduction-related genes measured by protein-protein interaction score and alignment score obtained by BLAST. The in-depth analysis of the high confidence novel reproduction genes revealed hidden mechanisms of reproduction and provided guidelines for further experimental validations. PMID:25768094

  5. An unusual fibrillarin gene and protein: structure and functional implications.

    PubMed Central

    David, E; McNeil, J B; Basile, V; Pearlman, R E

    1997-01-01

    The diploid germinal nucleus of the ciliated protozoan Tetrahymena thermophila is unusual among eukaryotes in that it encodes a single copy of the gene for rRNA allowing identification of cis-acting mutations in rDNA affecting rRNA structure, function, and processing. The generally conserved nucleolar protein fibrillarin has been characterized from a number of systems and is involved in pre-rRNA processing. We have demonstrated that Tetrahymena has fibrillarin and have analyzed the cDNA and the genomic DNA encoding this protein. The derived amino acid sequence of the N-terminal region of Tetrahymena fibrillarin shows little similarity with the generally highly conserved glycine/arginine-rich N-terminal domain of other eukaryotic fibrillarins. The remainder of the amino acid sequence of the molecule is more conserved. Polyclonal antibodies generated against the full-length Tetrahymena fibrillarin expressed in bacteria recognize a protein of M(r) approximately 32,000 in whole-cell or nucleolar preparations. Immunocytochemistry localizes fibrillarin to nucleoli in the somatic macronuclei of vegetative cells. Transformation experiments demonstrate that fibrillarin is an essential protein in Tetrahymena. The Tetrahymena fibrillarin is expressed but does not complement a NOP1 null mutation when transformed into the yeast Saccharomyces cerevisiae, indicating less functional conservation among fibrillarins than previously suggested. Images PMID:9201715

  6. Discovering Implicit Entity Relation with the Gene-Citation-Gene Network

    PubMed Central

    Song, Min; Han, Nam-Gi; Kim, Yong-Hwan; Ding, Ying; Chambers, Tamy

    2013-01-01

    In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG) network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG) network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner. PMID:24358368

  7. Discovering implicit entity relation with the gene-citation-gene network.

    PubMed

    Song, Min; Han, Nam-Gi; Kim, Yong-Hwan; Ding, Ying; Chambers, Tamy

    2013-01-01

    In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG) network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG) network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner. PMID:24358368

  8. Effect of strontium ions substitution on gene delivery related properties of calcium phosphate nanoparticles

    Microsoft Academic Search

    A. HanifiM; M. H. Fathi; H. Mir Mohammad Sadeghi

    2010-01-01

    Gene therapy has been considered a strategy for delivery of therapeutic nucleic acids to a specific site. Calcium phosphates\\u000a are one gene delivery vector group of interest. However, low transfection efficiency has limited the use of calcium phosphate\\u000a in gene delivery applications. Present work aims at studying the fabrication of strontium substituted calcium phosphate nanoparticles\\u000a with improved gene delivery related

  9. Discovery of Genes Related to Witches Broom Disease in Paulownia tomentosa × Paulownia fortunei by a De Novo Assembled Transcriptome

    PubMed Central

    Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

    2013-01-01

    In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches’ Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene’s roles in the developmental process and in PaWB disease resistance. PMID:24278262

  10. RNA-Seq analysis of yak ovary: improving yak gene structure information and mining reproduction-related genes.

    PubMed

    Lan, DaoLiang; Xiong, XianRong; Wei, YanLi; Xu, Tong; Zhong, JinCheng; Zhi, XiangDong; Wang, Yong; Li, Jian

    2014-09-01

    RNA-Seq, a high-throughput (HT) sequencing technique, has been used effectively in large-scale transcriptomic studies, and is particularly useful for improving gene structure information and mining of new genes. In this study, RNA-Seq HT technology was employed to analyze the transcriptome of yak ovary. After Illumina-Solexa deep sequencing, 26826516 clean reads with a total of 4828772880 bp were obtained from the ovary library. Alignment analysis showed that 16992 yak genes mapped to the yak genome and 3734 of these genes were involved in alternative splicing. Gene structure refinement analysis showed that 7340 genes that were annotated in the yak genome could be extended at the 5' or 3' ends based on the alignments been the transcripts and the genome sequence. Novel transcript prediction analysis identified 6321 new transcripts with lengths ranging from 180 to 14884 bp, and 2267 of them were predicted to code proteins. BLAST analysis of the new transcripts showed that 1200?4933 mapped to the non-redundant (nr), nucleotide (nt) and/or SwissProt sequence databases. Comparative statistical analysis of the new mapped transcripts showed that the majority of them were similar to genes in Bos taurus (41.4%), Bos grunniens mutus (33.0%), Ovis aries (6.3%), Homo sapiens (2.8%), Mus musculus (1.6%) and other species. Functional analysis showed that these expressed genes were involved in various Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes pathways. GO analysis of the new transcripts found that the largest proportion of them was associated with reproduction. The results of this study will provide a basis for describing the normal transcriptome map of yak ovary and for future studies on yak breeding performance. Moreover, the results confirmed that RNA-Seq HT technology is highly advantageous in improving gene structure information and mining of new genes, as well as in providing valuable data to expand the yak genome information. PMID:24907937

  11. Comparative RNAi Screens in C. elegans and C. briggsae Reveal the Impact of Developmental System Drift on Gene Function

    PubMed Central

    Verster, Adrian J.; Ramani, Arun K.; McKay, Sheldon J.; Fraser, Andrew G.

    2014-01-01

    Although two related species may have extremely similar phenotypes, the genetic networks underpinning this conserved biology may have diverged substantially since they last shared a common ancestor. This is termed Developmental System Drift (DSD) and reflects the plasticity of genetic networks. One consequence of DSD is that some orthologous genes will have evolved different in vivo functions in two such phenotypically similar, related species and will therefore have different loss of function phenotypes. Here we report an RNAi screen in C. elegans and C. briggsae to identify such cases. We screened 1333 genes in both species and identified 91 orthologues that have different RNAi phenotypes. Intriguingly, we find that recently evolved genes of unknown function have the fastest evolving in vivo functions and, in several cases, we identify the molecular events driving these changes. We thus find that DSD has a major impact on the evolution of gene function and we anticipate that the C. briggsae RNAi library reported here will drive future studies on comparative functional genomics screens in these nematodes. PMID:24516395

  12. Comparative RNAi screens in C. elegans and C. briggsae reveal the impact of developmental system drift on gene function.

    PubMed

    Verster, Adrian J; Ramani, Arun K; McKay, Sheldon J; Fraser, Andrew G

    2014-02-01

    Although two related species may have extremely similar phenotypes, the genetic networks underpinning this conserved biology may have diverged substantially since they last shared a common ancestor. This is termed Developmental System Drift (DSD) and reflects the plasticity of genetic networks. One consequence of DSD is that some orthologous genes will have evolved different in vivo functions in two such phenotypically similar, related species and will therefore have different loss of function phenotypes. Here we report an RNAi screen in C. elegans and C. briggsae to identify such cases. We screened 1333 genes in both species and identified 91 orthologues that have different RNAi phenotypes. Intriguingly, we find that recently evolved genes of unknown function have the fastest evolving in vivo functions and, in several cases, we identify the molecular events driving these changes. We thus find that DSD has a major impact on the evolution of gene function and we anticipate that the C. briggsae RNAi library reported here will drive future studies on comparative functional genomics screens in these nematodes. PMID:24516395

  13. Multiple Thyrotropin ?-Subunit and Thyrotropin Receptor-Related Genes Arose during Vertebrate Evolution

    PubMed Central

    Maugars, Gersende; Dufour, Sylvie; Cohen-Tannoudji, Joëlle; Quérat, Bruno

    2014-01-01

    Thyroid-stimulating hormone (TSH) is composed of a specific ? subunit and an ? subunit that is shared with the two pituitary gonadotropins. The three ? subunits derive from a common ancestral gene