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1

An algorithm for identifying clusters of functionally related genes in genomes  

E-print Network

An increasing body of literature shows that genomes of eukaryotes can contain clusters of functionally related genes. Most approaches to identify gene clusters utilize microarray data or metabolic pathway databases to find groups of genes on chromo...

Yi, Gang Man

2009-05-15

2

Comparative and functional analysis of cardiovascular-related genes  

SciTech Connect

The ability to detect putative cis-regulatory elements in cardiovascular-related genes has been accelerated by the availability of genomic sequence data from numerous vertebrate species and the recent development of comparative genomic tools. This improvement is anticipated to lead to a better understanding of the complex regulatory architecture of cardiovascular (CV) genes and how genetic variants in these non-coding regions can potentially play a role in cardiovascular disease. This manuscript reviews a recently established database dedicated to the comparative sequence analysis of 250 human CV genes of known importance, 37 of which currently contain sequence comparison data for organisms beyond those of human, mouse and rat. These data have provided a glimpse into the variety of possible insights from deep vertebrate sequence comparisons and the identification of putative gene regulatory elements.

Cheng, Jan-Fang; Pennacchio, Len A.

2003-09-01

3

A MACHINE LEARNING APPROACH TO QUERY TIME-SERIES MICROARRAY DATA SETS FOR FUNCTIONALLY RELATED GENES USING HIDDEN MARKOV MODELS  

E-print Network

to cooperate; these groups of genes are called functional modules. Modular organization of genetic functions has been evident since 1999. Detecting functionally related genes in a genome and detecting all genes belonging to particular functional modules...

Senf, Alexander J.

2011-02-04

4

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

MedlinePLUS

... age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene variants that affect the function of immune cells in young, healthy people. Interestingly, ...

5

Identification of Three Related Human GRO Genes Encoding Cytokine Functions  

Microsoft Academic Search

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

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

6

Structure-function relation in retinoid regulated gene expression  

Microsoft Academic Search

Retinoids are known to inhibit proliferation of and induce terminal differentiation of many normal and transformed cells. It has been postulated that retinoids exert their effect by altering gene expression. HL-60 cells and macrophages both respond to retinoic acid action by the rapid induction of the enzyme tissue transglutaminase. The induction has been shown to be due to increased transcription

Susmita Poddar

1988-01-01

7

Is there a general relationship between estimated chromosome distances in interphase and location of genes with related functions?  

Microsoft Academic Search

The problem of a possible clustering of human chromosomes containing genes with related functions was examined in the interphase nucleus of lymphocytes by a statistical comparison of distances between chromosomes containing such functionally related genes with all sets of chromosome distances. The gene locus assignments were taken from a recent review (McKusick 1982); the chromosomal distances were those estimated by

F. Vogel; J. Krfiger

1983-01-01

8

UNDERSTANDING THE GLOBAL PROPERTIES OF FUNCTIONALLY-RELATED GENE NETWORKS USING THE  

E-print Network

functionally-related gene networks among humans, fruit flies, worms and yeast exhibit the small-world property nodes can effectively disrupt the network. On the other hand, attacks on highly connected nodes the characterizations of physical interactions between protein-protein, protein-nucleic-acid, protein

Dasgupta, Partha

9

Developmental and Functional Expression of miRNA-Stability Related Genes in the Nervous System  

PubMed Central

In the nervous system, control of gene expression by microRNAs (miRNAs) has been investigated in fundamental processes, such as development and adaptation to ambient demands. The action of these short nucleotide sequences on specific genes depends on intracellular concentration, which in turn reflects the balance of biosynthesis and degradation. Whereas mechanisms underlying miRNA biogenesis has been investigated in recent studies, little is known about miRNA-stability related proteins. We first detected two genes in the retina that have been associated to miRNA stability, XRN2 and PAPD4. These genes are highly expressed during retinal development, however with distinct subcellular localization. We investigated whether these proteins are regulated during specific phases of the cell cycle. Combined analyses of nuclei position in neuroblastic layer and labeling using anti-cyclin D1 revealed that both proteins do not accumulate in S or M phases of the cell cycle, being poorly expressed in progenitor cells. Indeed, XRN2 and PAPD4 were observed mainly after neuronal differentiation, since low expression was also observed in astrocytes, endothelial and microglial cells. XRN2 and PAPD4 are expressed in a wide variety of neurons, including horizontal, amacrine and ganglion cells. To evaluate the functional role of both genes, we carried out experiments addressed to the retinal adaptation in response to different ambient light conditions. PAPD4 is upregulated after 3 and 24 hours of dark- adaptation, revealing that accumulation of this protein is governed by ambient light levels. Indeed, the fast and functional regulation of PAPD4 was not related to changes in gene expression, disclosing that control of protein levels occurs by post-transcriptional mechanisms. Furthermore, we were able to quantify changes in PAPD4 in specific amacrine cells after dark -adaptation, suggesting for circuitry-related roles in visual perception. In summary, in this study we first described the ontogenesis and functional expression of these two miRNA-stability related proteins in the retina. PMID:23700402

Casado, Otavio Augusto Nocera; Kihara, Alexandre Hiroaki

2013-01-01

10

DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis.  

PubMed

Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3' untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation. PMID:23144874

Mayol, Gemma; Martín-Subero, José I; Ríos, José; Queiros, Ana; Kulis, Marta; Suńol, Mariona; Esteller, Manel; Gómez, Soledad; Garcia, Idoia; de Torres, Carmen; Rodríguez, Eva; Galván, Patricia; Mora, Jaume; Lavarino, Cinzia

2012-01-01

11

DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis  

PubMed Central

Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3? untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation. PMID:23144874

Mayol, Gemma; Martin-Subero, Jose I.; Rios, Jose; Queiros, Ana; Kulis, Marta; Sunol, Mariona; Esteller, Manel; Gomez, Soledad; Garcia, Idoia; de Torres, Carmen; Rodriguez, Eva; Galvan, Patricia; Mora, Jaume; Lavarino, Cinzia

2012-01-01

12

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

ERIC Educational Resources Information Center

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…

Gericke, Niklas Markus; Hagberg, Mariana

2007-01-01

13

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

PubMed Central

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

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

2014-01-01

14

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

PubMed

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

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

2013-01-01

15

Inhibition of Calcitonin Gene-Related Peptide Function: A Promising Strategy for Treating Migraine  

PubMed Central

The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine. Serum levels of CGRP, which are elevated during a migraine attack, have been reported to return to normal with alleviation of pain. In addition, CGRP administration has been shown to cause a migraine-like headache in susceptible individuals. Importantly, CGRP receptors are found on many cell types within the trigeminovascular system that are thought to play important roles in controlling inflammatory and nociceptive processes. Based on these findings, it was proposed that blockage of CGRP receptor function and, hence, the physiological effects of CGRP would be effective in aborting a migraine attack. This review will summarize key preclinical data that support the therapeutic potential of using CGRP receptor antagonists or molecules that bind CGRP within the context of current neurovascular theories on migraine pathology. PMID:18808507

Durham, Paul L.

2011-01-01

16

Redundant functions of the genes knirps and knirps-related for the establishment of anterior Drosophila head structures.  

PubMed Central

Developmental gene functions of Drosophila are typically characterized by a recognizable mutant phenotype. When molecular probes of such genes were used to isolate homologues, distinct spatially and temporally restricted expression patterns were observed in vertebrates as well. However, corresponding "gene knock-outs" often revealed subtle or no scorable phenotypes, a phenomenon attributed to redundant gene functions. We found that the evolutionarily related genes knirps (kni) and knirps-related (knrl) contribute to a similar phenomenon in Drosophila. The two closely situated genes show identical expression patterns in the developing embryo, including the posterior and anterior expression domains in the blastoderm. Here we show that the two biochemically equivalent gene products are both functional in the head anlage and that the lack of one gene activity can be overcome by the activity of the other. Whereas kni is also required for abdominal segmentation, knrl is nonfunctional in its posterior expression domain. Thus, the kni/knrl pair of genes provides a region-specific buffering system, rather than a case of global functional redundancy. Images PMID:8078924

Gonzalez-Gaitan, M; Rothe, M; Wimmer, E A; Taubert, H; Jackle, H

1994-01-01

17

Functional effects of congenital myopathy-related mutations in gamma-tropomyosin gene.  

PubMed

Missense mutations in human TPM3 gene encoding ?-tropomyosin expressed in slow muscle type 1 fibers, were associated with three types of congenital myopathies-nemaline myopathy, cap disease and congenital fiber type disproportion. Functional effects of the following substitutions: Leu100Met, Ala156Thr, Arg168His, Arg168Cys, Arg168Gly, Lys169Glu, and Arg245Gly, were examined in biochemical assays using recombinant tropomyosin mutants and native proteins isolated from skeletal muscle. Most, but not all, mutations decreased the affinity of tropomyosin for actin alone and in complex with troponin (±Ca(2+)). All studied tropomyosin mutants reduced Ca-induced activation but had no effect on the inhibition of actomyosin cross-bridges. Ca(2+)-sensitivity of the actomyosin interactions, as well as cooperativity of myosin-induced activation of the thin filament was affected by individual tropomyosin mutants with various degrees. Decreased motility of the reconstructed thin filaments was a result of combined functional defects caused by myopathy-related tropomyosin mutants. We conclude that muscle weakness and structural abnormalities observed in TPM3-related congenital myopathies result from reduced capability of the thin filament to fully activate actin-myosin cross-bridges. PMID:22749829

Robaszkiewicz, Katarzyna; Dudek, El?bieta; Kasprzak, Andrzej A; Moraczewska, Joanna

2012-10-01

18

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

Microsoft Academic Search

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

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

2006-01-01

19

Functional characterization of the zebrafish WHSC1-related gene, a homolog of human NSD2.  

PubMed

Methylation of specific lysine residues of histone H3 and H4 has been reported to be important in the structuring of chromatin and for the transcription of certain genes. Proteins with SET domains have been shown to methylate specific lysine residues of histone H3 and H4. We isolated a SET domain-containing gene from the zebrafish (Danio rerio). The gene has the highest sequence similarity to human NSD2, also known as Wolf-Hirschhorn syndrome candidate 1 or WHSC1, and therefore, was named DrWhsc1. DrWhsc1 mRNA is expressed in various tissues with the highest level in testis. Morpholino oligonucleotides for the DrWhsc1 gene affected early embryogenesis in zebrafish, such as endbrain enlargement, abnormal cartilage, marked reduction of bone, and incomplete motor neuron formation. Such developmental abnormalities are also observed in Wolf-Hirschhorn syndrome patients and Whsc1-deficient mice. In addition, suppression of the DrWhsc1 gene or defect in the SET domain of DrWhsc1 resulted in impairment of di-methylation of histone H3K36 at early embryogenesis. These results indicate that DrWhsc1 is a functional homolog of WHSC1 and that the SET domain of DrWhsc1 is essential for di-methylation of histone H3K36 in zebrafish. PMID:20946879

Yamada-Okabe, Toshiko; Imamura, Kentaro; Kawaguchi, Nanami; Sakai, Haruya; Yamashita, Michiaki; Matsumoto, Naomichi

2010-11-12

20

The rhp6+ gene of Schizosaccharomyces pombe: a structural and functional homolog of the RAD6 gene from the distantly related yeast Saccharomyces cerevisiae.  

PubMed Central

The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin conjugating enzyme and is required for DNA repair, DNA-damage-induced mutagenesis and sporulation. Here, we show that RAD6 and the rhp6+ gene from the distantly related yeast Schizosaccharomyces pombe share a high degree of structural and functional homology. The predominantly acidic carboxyl-terminal 21 amino acids present in the RAD6 protein are absent in the rhp6(+)-encoded protein; otherwise, the two proteins are very similar, with 77% identical residues. Like rad6, null mutations of the rhp6+ gene confer a defect in DNA repair, UV mutagenesis and sporulation, and the RAD6 and rhp6+ genes can functionally substitute for one another. These observations suggest that functional interactions between RAD6 (rhp6+) protein and other components of the DNA repair complex have been conserved among eukaryotes. Images Fig.3. PMID:2184030

Reynolds, P; Koken, M H; Hoeijmakers, J H; Prakash, S; Prakash, L

1990-01-01

21

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

PubMed Central

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

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

2013-01-01

22

Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human  

PubMed Central

Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins) in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available. PMID:21124763

Pu, Shuye; Turinsky, Andrei L.; Vlasblom, James; On, Tuan; Xiong, Xuejian; Emili, Andrew; Zhang, Zhaolei; Greenblatt, Jack; Parkinson, John; Wodak, Shoshana J.

2010-01-01

23

Functional Characterization of a Juvenile Hormone Esterase Related Gene in the Moth Sesamia nonagrioides through RNA Interference  

PubMed Central

Juvenile hormone esterase (JHE) is a carboxylesterase that has attracted great interest because of its critical role in regulating larval to adult transition in insects and other arthropods. Previously, we characterized an ecdysteroid sensitive and juvenile hormone non-susceptible juvenile hormone esterase related gene (SnJHER) in the corn stalk borer, Sesamia nonagrioides. SnJHER was rhythmically up-regulated close to each molt during the corn stalk borer’s larval development. In this paper we attempted to functionally characterize SnJHER using several reverse genetics techniques. To functionally characterize SnJHER, we experimented with different dsRNA administration methods, including hemolymph, bacterial or baculovirus-mediated RNA interference, (RNAi). Our findings indicate the potential implication of SnJHER in the developmental programming of Sesamia nonagrioides. It is still unclear whether SnJHER is closely related to the authentic JHE gene, with different or similar biological functions. PMID:24040087

Kontogiannatos, Dimitrios; Swevers, Luc; Maenaka, Katsumi; Park, Enoch Y.; Iatrou, Kostas; Kourti, Anna

2013-01-01

24

From Gene Networks to Gene Function  

PubMed Central

We propose a novel method to identify functionally related genes based on comparisons of neighborhoods in gene networks. This method does not rely on gene sequence or protein structure homologies, and it can be applied to any organism and a wide variety of experimental data sets. The character of the predicted gene relationships depends on the underlying networks;they concern biological processes rather than the molecular function. We used the method to analyze gene networks derived from genome-wide chromatin immunoprecipitation experiments, a large-scale gene deletion study, and from the genomic positions of consensus binding sites for transcription factors of the yeast Saccharomyces cerevisiae. We identified 816 functional relationships between 159 genes and show that these relationships correspond to protein–protein interactions, co-occurrence in the same protein complexes, and/or co-occurrence in abstracts of scientific articles. Our results suggest functions for seven previously uncharacterized yeast genes: KIN3 and YMR269W may be involved in biological processes related to cell growth and/or maintenance, whereas IES6, YEL008W, YEL033W, YHL029C, YMR010W, and YMR031W-A are likely to have metabolic functions. PMID:14656964

Schlitt, Thomas; Palin, Kimmo; Rung, Johan; Dietmann, Sabine; Lappe, Michael; Ukkonen, Esko; Brazma, Alvis

2003-01-01

25

Discovery of genes related to insecticide resistance in Bactrocera dorsalis by functional genomic analysis of a de novo assembled transcriptome.  

PubMed

Insecticide resistance has recently become a critical concern for control of many insect pest species. Genome sequencing and global quantization of gene expression through analysis of the transcriptome can provide useful information relevant to this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of the world's most destructive agricultural pests, and recently it has been used as a target for studies of genetic mechanisms related to insecticide resistance. However, prior to this study, the molecular data available for this species was largely limited to genes identified through homology. To provide a broader pool of gene sequences of potential interest with regard to insecticide resistance, this study uses whole transcriptome analysis developed through de novo assembly of short reads generated by next-generation sequencing (NGS). The transcriptome of B. dorsalis was initially constructed using Illumina's Solexa sequencing technology. Qualified reads were assembled into contigs and potential splicing variants (isotigs). A total of 29,067 isotigs have putative homologues in the non-redundant (nr) protein database from NCBI, and 11,073 of these correspond to distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546 isotigs contain coding sequences that are at least 80% complete and appear to represent B. dorsalis genes. We observed a strong correlation between the completeness of the assembled sequences and the expression intensity of the transcripts. The assembled sequences were also used to identify large numbers of genes potentially belonging to families related to insecticide resistance. A total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major enzyme families involved in insecticide metabolism and resistance, were identified. In addition, 36 isotigs were discovered to contain target site sequences related to four classes of resistance genes. Identified sequence motifs were also analyzed to characterize putative polypeptide translational products and associate them with specific genes and protein functions. PMID:22879883

Hsu, Ju-Chun; Chien, Ting-Ying; Hu, Chia-Cheng; Chen, Mei-Ju May; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S; Chen, Chien-Yu

2012-01-01

26

The kynurenine pathway in major depression: haplotype analysis of three related functional candidate genes.  

PubMed

A consistent finding in major depressive disorder (MDD) research is dysfunction of the immune system. One of the relevant metabolic pathways in this regard is the kynurenine pathway. In patients with major depression, an imbalance between neuroprotective and neurotoxic arms of the pathway with lower plasma kynurenic acid concentration was demonstrated. Therefore, we investigated Single Nucleotide Polymorphism (SNP) and haplotype association of three candidate genes of the three enzymes involved in this metabolism. The three genes, namely, tryptophan hydroxylase 2 (TPH2), kynurenine 3 monooxygenase (KMO) and kynurenine amino transferase 3 (KAT III) SNPs and haplotype association analysis was performed in 338 (266 major depression and 72 bipolar depression) unrelated Caucasian patients with major depressive episodes and 310 age, gender and ethnicity matched controls. In sliding window analyses using PLINK of the haplotypes of KAT III, all windows which include the first SNP (rs12729558), the overall haplotype distribution (OMNIBUS) was significantly different between patients with a major depressive episode and control for all windows, with p-values ranging between 1.75 × 10=5 and 0.006. This is due to the haplotype CGCTCT (referring to 6 SNP window analysis), which is found in about 5.7% of patients and 1.9% of healthy controls. It was due to CGCTCT haplotype and the frequencies of this haplotype in both bipolar patients and patients with major depression showed significantly higher than the control population (p<0.001). This haplotype of KAT III gene CGCTCT may have effect on the function of this enzyme in formation of kynurenic acid in some patients with major depressive episodes. PMID:21492941

Claes, Stephan; Myint, Aye-Mu; Domschke, Katharina; Del-Favero, Jurgen; Entrich, Kathrin; Engelborghs, Sebastiaan; De Deyn, Peter; Mueller, Norbert; Baune, Bernhard; Rothermundt, Matthias

2011-08-15

27

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

PubMed

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

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

2012-07-31

28

Combination Training in Aging Individuals Modifies Functional Connectivity and Cognition, and Is Potentially Affected by Dopamine-Related Genes  

PubMed Central

Background Aging is a major co-risk factor in many neurodegenerative diseases. Cognitive enrichment positively affects the structural plasticity of the aging brain. In this study, we evaluated effects of a set of structured multimodal activities (Combination Training; CT) on cognitive performances, functional connectivity, and cortical thickness of a group of healthy elderly individuals. CT lasted six months. Methodology Neuropsychological and occupational performances were evaluated before and at the end of the training period. fMRI was used to assess effects of training on resting state network (RSN) functional connectivity using Independent Component Analysis (ICA). Effects on cortical thickness were also studied. Finally, we evaluated whether specific dopamine-related genes can affect the response to training. Principal Findings Results of the study indicate that CT improves cognitive/occupational performances and reorganizes functional connectivity. Intriguingly, individuals responding to CT showed specific dopamine-related genotypes. Indeed, analysis of dopamine-related genes revealed that carriers of DRD3 ser9gly and COMT Val158Met polymorphisms had the greatest benefits from exposure to CT. Conclusions and Significance Overall, our findings support the idea that exposure to a set of structured multimodal activities can be an effective strategy to counteract aging-related cognitive decline and also indicate that significant capability of functional and structural changes are maintained in the elderly. PMID:22937122

Pieramico, Valentina; Esposito, Roberto; Sensi, Francesca; Cilli, Franco; Mantini, Dante; Mattei, Peter A.; Frazzini, Valerio; Ciavardelli, Domenico; Gatta, Valentina; Ferretti, Antonio; Romani, Gian Luca; Sensi, Stefano L.

2012-01-01

29

Brassica GLABRA2 genes: analysis of function related to seed oil content and development of functional markers.  

PubMed

Regulation of seed oil accumulation in oilseed rape (Brassica napus) has important economic significance. However, few genes have been characterized that affect final seed oil content. Through a mutant identification, the class IV homeodomain-ZIP transcription factor GLABRA2 (GL2) has been found to regulate seed oil accumulation in Arabidopsis, in addition to its role in trichome development. In this study, we isolated four distinct orthologues of GL2 from B. napus (AC-genome), B. rapa (A) and B. oleracea (C), using an overlapping-PCR strategy. The four GL2 orthologues were very similar, with 96.10-99.69% identity in exon regions, 75.45-93.84% in intron regions, 97.34-99.87% in amino acid sequences. Alignments of the four genes revealed that the A-genome sequences of BnaA.GL2.a from B. napus and BraA.GL2.a from B. rapa are more similar than the others, and likewise the C-genome sequences of BnaC.GL2.b from B. napus and BolC.GL2.a from B. oleracea are more similar. BnaA.GL2.a and BraA.GL2.a from the A-genome are highly expressed in roots, whilst BnaC.GL2.b and BolC.GL2.a from the C-genome are preferentially expressed in seeds. Transgenic ectopic overexpression and suppression of BnaC.GL2.b in Arabidopsis allowed further investigation of the effect on seed oil content. Overexpression generated two phenotypes: the wild-type-like and the gl2-mutant-like (an Arabidopsis glabrous mutant of gl2-2), with increases in seed oil content of 3.5-5.0% in the gl2-mutant-like transgenic plants. Suppression resulted in increases of 2.5-6.1% in seed oil content, and reduced trichome number at the leaf margins. These results suggest that BnaC.GL2.b can negatively regulate oil accumulation in Arabidopsis seeds. As a result of comparing the four GL2 genes, three A/C-genome-specific primer sets were developed and a C-genome-specific EcoRV cleavage site was identified, which can be used as functional markers to distinguish these orthologues within Brassica species. The genes identified and their molecular markers developed in this study will be valuable both for oilseed rape breeding focusing on improvement of seed oil content, and for detecting gene flow between populations. PMID:20162256

Chai, Guohua; Bai, Zetao; Wei, Fang; King, Graham J; Wang, Chenggang; Shi, Lei; Dong, Caihua; Chen, Hong; Liu, Shengyi

2010-05-01

30

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

Microsoft Academic Search

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

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

2005-01-01

31

SARP19 and vdg3 gene families are functionally related during abalone metamorphosis.  

PubMed

The transcriptional activity of the SARP19-I1 and vdg3-I1 genes increases over tenfold when Haliotis diversicolor larvae shift from the pelagic to benthic lifestyle, signifying the important role of these genes during abalone metamorphosis. In this study, eight paralogous SARP19 genes and six paralogous vdg3 genes were identified from H. diversicolor transcriptomes. Phylogenetic analyses were performed, and the spatio-temporal expression patterns of these genes were separately determined by quantitative polymerase chain reaction (qPCR) and whole mount in situ hybridization (WMISH). Five SARP19 paralogs and five vdg3 paralogs showed at least a tenfold increase in expression after settlement. Among these differentially expressed genes, three SARP19 paralogs and four vdg3 paralogs were verified as being spatially expressed in the digestive glands of newly settled postlarvae. We proposed that a hypothesis of coevolution between the two gene families might explain the similarities in their expression patterns and their phylogenetics. PMID:25115590

He, Teng-Fei; Chen, Jun; Zhang, Jie; Ke, Cai-Huan; You, Wei-Wei

2014-12-01

32

Functional characterization of the zebrafish WHSC1-related gene, a homolog of human NSD2  

Microsoft Academic Search

Methylation of specific lysine residues of histone H3 and H4 has been reported to be important in the structuring of chromatin and for the transcription of certain genes. Proteins with SET domains have been shown to methylate specific lysine residues of histone H3 and H4.We isolated a SET domain-containing gene from the zebrafish (Danio rerio). The gene has the highest

Toshiko Yamada-Okabe; Kentaro Imamura; Nanami Kawaguchi; Haruya Sakai; Michiaki Yamashita; Naomichi Matsumoto

2010-01-01

33

Calcitonin Gene-Related Peptide Regulates Type IV Hypersensitivity through Dendritic Cell Functions  

PubMed Central

Dendritic cells (DCs) play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP), is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1) results in higher cytokine production in response to LPS (lipopolysaccharide). On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH) model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2? DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs. PMID:24466057

Mikami, Norihisa; Sueda, Kaori; Ogitani, Yusuke; Otani, Ippei; Takatsuji, Miku; Wada, Yasuko; Watanabe, Keiko; Yoshikawa, Rintaro; Nishioka, Satoshi; Hashimoto, Nagisa; Miyagi, Yayoi; Fukada, So-ichiro; Yamamoto, Hiroshi; Tsujikawa, Kazutake

2014-01-01

34

Expression of endometrial immune-related genes possibly functioning during early pregnancy in the mare.  

PubMed

Despite enormous efforts, biochemical and molecular mechanisms associated with equine reproduction, particularly processes of pregnancy establishment, have not been well characterized. Previously, PCR-selected suppression subtraction hybridization analysis was executed to identify unique molecules functioning in the equine endometrium during periods of pregnancy establishment, and granzyme B (GZMB) cDNA was found in the pregnant endometrial cDNA library. Because GZMB is produced from natural killer (NK) cells, endometrial expression of GZMB and immune-related transcripts were characterized in this study. The level of GZMB mRNA is higher in the pregnant endometrium than in non-pregnant ones. This expression was also confirmed through Western blot and immunohistochemical analyses. IL-2 mRNA declined as pregnancy progressed, while IL-15, IFNG and TGFB1 transcripts increased on day 19 and/or 25. Analyses of IL-4 and IL-12 mRNAs demonstrated the increase in these transcripts as pregnancy progressed. Increase in CCR5 and CCR4 mRNAs indicated that both Th1 and Th2 cells coexisted in the day 25 pregnant endometrium. Taken together, the endometrial expression of immune-related transcripts suggests that immunological responses are present even before the trophectoderm actually attaches to the uterine epithelial cells. PMID:23138119

Tachibana, Yurika; Nakano, Yasuko; Nagaoka, Kentaro; Kikuchi, Masato; Nambo, Yasuo; Haneda, Shingo; Matsui, Motozumi; Miyake, Yo-Ichi; Imakawa, Kazuhiko

2013-01-01

35

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

E-print Network

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...

Catena, Amanda M.

2010-07-14

36

The function of a regulatory gene, scrX related to differentiation in Streptomyces coelicolor  

Microsoft Academic Search

A new gene,scrX fromStreptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons\\u000a inscrX which are AAA, AAA and ATA.scrX gene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino\\u000a acids also revealed that ScrX belonged to Ic1R

Haihua Yang; Yuqing Tian; Junyong Jia; Huarong Tan; K. F. Chater

2000-01-01

37

Implications of human genome structural heterogeneity: functionally related genes tend to reside in organizationally similar genomic regions  

PubMed Central

Background In an earlier study, we hypothesized that genomic segments with different sequence organization patterns (OPs) might display functional specificity despite their similar GC content. Here we tested this hypothesis by dividing the human genome into 100 kb segments, classifying these segments into five compositional groups according to GC content, and then characterizing each segment within the five groups by oligonucleotide counting (k-mer analysis; also referred to as compositional spectrum analysis, or CSA), to examine the distribution of sequence OPs in the segments. We performed the CSA on the entire DNA, i.e., its coding and non-coding parts the latter being much more abundant in the genome than the former. Results We identified 38 OP-type clusters of segments that differ in their compositional spectrum (CS) organization. Many of the segments that shared the same OP type were enriched with genes related to the same biological processes (developmental, signaling, etc.), components of biochemical complexes, or organelles. Thirteen OP-type clusters showed significant enrichment in genes connected to specific gene-ontology terms. Some of these clusters seemed to reflect certain events during periods of horizontal gene transfer and genome expansion, and subsequent evolution of genomic regions requiring coordinated regulation. Conclusions There may be a tendency for genes that are involved in the same biological process, complex or organelle to use the same OP, even at a distance of ~ 100 kb from the genes. Although the intergenic DNA is non-coding, the general pattern of sequence organization (e.g., reflected in over-represented oligonucleotide “words”) may be important and were protected, to some extent, in the course of evolution. PMID:24684786

2014-01-01

38

The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase.  

PubMed Central

The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein with homology to both the mammalian protein disulfide isomerase (PDI) and the yeast PDI homolog encoded by the essential PDI1 gene. Deletion or overexpression of EUG1 causes no growth defects under a variety of conditions. EUG1 mRNA and protein levels are dramatically increased in response to the accumulation of native or unglycosylated proteins in the endoplasmic reticulum. Overexpression of the EUG1 gene allows yeast cells to grow in the absence of the PDI1 gene product. Depletion of the PDI1 protein in Saccharomyces cerevisiae causes a soluble vacuolar glycoprotein to accumulate in its endoplasmic reticulum form, and this phenotype is only partially relieved by the overexpression of EUG1. Taken together, our results indicate that PDI1 and EUG1 encode functionally related proteins that are likely to be involved in interacting with nascent polypeptides in the yeast endoplasmic reticulum. Images PMID:1406650

Tachibana, C; Stevens, T H

1992-01-01

39

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

PubMed

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

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

2013-09-01

40

Functional Variant in the Autophagy-Related 5 Gene Promotor is Associated with Childhood Asthma  

Microsoft Academic Search

Rationale and ObjectiveAutophagy is a cellular process directed at eliminating or recycling cellular proteins. Recently, the autophagy pathway has been implicated in immune dysfunction, the pathogenesis of inflammatory disorders, and response to viral infection. Associations between two genes in the autophagy pathway, ATG5 and ATG7, with childhood asthma were investigated.MethodsUsing genetic and experimental approaches, we examined the association of 13

Lisa J. Martin; Jayanta Gupta; Soma S. S. K. Jyothula; Melinda Butsch Kovacic; Jocelyn M. Biagini Myers; Tia L. Patterson; Mark B. Ericksen; Hua He; Aaron M. Gibson; Tesfaye M. Baye; Sushil Amirisetty; Anna M. Tsoras; Youbao Sha; N. Tony Eissa; Gurjit K. Khurana Hershey

2012-01-01

41

Brassica GLABRA2 genes: analysis of function related to seed oil content and development of functional markers  

Microsoft Academic Search

Regulation of seed oil accumulation in oilseed rape (Brassica napus) has important economic significance. However, few genes have been characterized that affect final seed oil content. Through\\u000a a mutant identification, the class IV homeodomain-ZIP transcription factor GLABRA2 (GL2) has been found to regulate seed oil\\u000a accumulation in Arabidopsis, in addition to its role in trichome development. In this study, we

Guohua Chai; Zetao Bai; Fang Wei; Graham J. King; Chenggang Wang; Lei Shi; Caihua Dong; Hong Chen; Shengyi Liu

2010-01-01

42

The Impact of Mitochondrial DNA and Nuclear Genes Related to Mitochondrial Functioning on the Risk of Parkinson's Disease  

PubMed Central

Mitochondrial dysfunction and oxidative stress are the major factors implicated in Parkinson’s disease (PD) pathogenesis. The maintenance of healthy mitochondria is a very complex process coordinated bi-genomically. Here, we review association studies on mitochondrial haplogroups and subhaplogroups, discussing the underlying molecular mechanisms. We also focus on variation in the nuclear genes (NDUFV2, PGC-1alpha, HSPA9, LRPPRC, MTIF3, POLG1, and TFAM encoding NADH dehydrogenase (ubiquinone) flavoprotein 2, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, mortalin, leucine-rich pentatricopeptide repeat containing protein, translation initiation factor 3, mitochondrial DNA polymerase gamma, and mitochondrial transcription factor A, respectively) primarily linked to regulation of mitochondrial functioning that recently have been associated with PD risk. Possible interactions between mitochondrial and nuclear genetic variants and related proteins are discussed. PMID:24532986

Gaweda-Walerych, Katarzyna; Zekanowski, Cezary

2013-01-01

43

Parallel re-modeling of EF-1? function: divergent EF-1? genes co-occur with EFL genes in diverse distantly related eukaryotes  

PubMed Central

Background Elongation factor-1? (EF-1?) and elongation factor-like (EFL) proteins are functionally homologous to one another, and are core components of the eukaryotic translation machinery. The patchy distribution of the two elongation factor types across global eukaryotic phylogeny is suggestive of a ‘differential loss’ hypothesis that assumes that EF-1? and EFL were present in the most recent common ancestor of eukaryotes followed by independent differential losses of one of the two factors in the descendant lineages. To date, however, just one diatom and one fungus have been found to have both EF-1? and EFL (dual-EF-containing species). Results In this study, we characterized 35 new EF-1?/EFL sequences from phylogenetically diverse eukaryotes. In so doing we identified 11 previously unreported dual-EF-containing species from diverse eukaryote groups including the Stramenopiles, Apusomonadida, Goniomonadida, and Fungi. Phylogenetic analyses suggested vertical inheritance of both genes in each of the dual-EF lineages. In the dual-EF-containing species we identified, the EF-1? genes appeared to be highly divergent in sequence and suppressed at the transcriptional level compared to the co-occurring EFL genes. Conclusions According to the known EF-1?/EFL distribution, the differential loss process should have occurred independently in diverse eukaryotic lineages, and more dual-EF-containing species remain unidentified. We predict that dual-EF-containing species retain the divergent EF-1? homologues only for a sub-set of the original functions. As the dual-EF-containing species are distantly related to each other, we propose that independent re-modelling of EF-1? function took place in multiple branches in the tree of eukaryotes. PMID:23800323

2013-01-01

44

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

PubMed Central

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

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

2014-01-01

45

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

PubMed

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

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

2014-01-01

46

Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs  

Microsoft Academic Search

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire

Y Osher; D Hamer; J Benjamin

2000-01-01

47

Expression profiling reveals functionally redundant multiple-copy genes related to zinc, iron and cadmium responses in Brassica rapa.  

PubMed

Genes underlying environmental adaptability tend to be over-retained in polyploid plant species. Zinc deficiency (ZnD) and iron deficiency (FeD), excess Zn (ZnE) and cadmium exposure (CdE) are major environmental problems for crop cultivation, but little is known about the differential expression of duplicated genes upon these stress conditions. Applying Tag-Seq technology to leaves of Brassica rapa grown under FeD, ZnD, ZnE or CdE conditions, with normal conditions as a control, we examined global gene expression changes and compared the expression patterns of multiple paralogs. We identified 812, 543, 331 and 447 differentially expressed genes under FeD, ZnD, ZnE and CdE conditions, respectively, in B. rapa leaves. Genes involved in regulatory networks centered on the transcription factors bHLH038 or bHLH100 were differentially expressed under (ZnE-induced) FeD. Further analysis revealed that genes associated with Zn, Fe and Cd responses tended to be over-retained in the B. rapa genome. Most of these multiple-copy genes showed the same direction of expression change under stress conditions. We conclude that the duplicated genes involved in trace element responses in B. rapa are functionally redundant, making the regulatory network more complex in B. rapa than in Arabidopsis thaliana. PMID:24738937

Li, Jimeng; Liu, Bo; Cheng, Feng; Wang, Xiaowu; Aarts, Mark G M; Wu, Jian

2014-07-01

48

The Arabidopsis Wall Associated Kinase-Like 10 Gene Encodes a Functional Guanylyl Cyclase and Is Co-Expressed with Pathogen Defense Related Genes  

PubMed Central

Background Second messengers have a key role in linking environmental stimuli to physiological responses. One such messenger, guanosine 3?,5?-cyclic monophosphate (cGMP), has long been known to be an essential signaling molecule in many different physiological processes in higher plants, including biotic stress responses. To date, however, the guanylyl cyclase (GC) enzymes that catalyze the formation of cGMP from GTP have largely remained elusive in higher plants. Principal Findings We have identified an Arabidopsis receptor type wall associated kinase–like molecule (AtWAKL10) as a candidate GC and provide experimental evidence to show that the intracellular domain of AtWAKL10431–700 can generate cGMP in vitro. Further, we also demonstrate that the molecule has kinase activity indicating that AtWAKL10 is a twin-domain catalytic protein. A co-expression and stimulus-specific expression analysis revealed that AtWAKL10 is consistently co-expressed with well characterized pathogen defense related genes and along with these genes is induced early and sharply in response to a range of pathogens and their elicitors. Conclusions We demonstrate that AtWAKL10 is a twin-domain, kinase-GC signaling molecule that may function in biotic stress responses that are critically dependent on the second messenger cGMP. PMID:20126659

Morse, Monique; Donaldson, Lara; Kwezi, Lusisizwe; Gehring, Chris

2010-01-01

49

An endogenous artificial microRNA system for unraveling the function of root endosymbioses related genes in Medicago truncatula  

PubMed Central

Background Legumes have the unique capacity to undergo two important root endosymbioses: the root nodule symbiosis and the arbuscular mycorrhizal symbiosis. Medicago truncatula is widely used to unravel the functions of genes during these root symbioses. Here we describe the development of an artificial microRNA (amiR)-mediated gene silencing system for M. truncatula roots. Results The endogenous microRNA (miR) mtr-miR159b was selected as a backbone molecule for driving amiR expression. Heterologous expression of mtr-miR159b-amiR constructs in tobacco showed that the backbone is functional and mediates an efficient gene silencing. amiR-mediated silencing of a visible marker was also effective after root transformation of M. truncatula constitutively expressing the visible marker. Most importantly, we applied the novel amiR system to shed light on the function of a putative transcription factor, MtErf1, which was strongly induced in arbuscule-containing cells during mycorrhizal symbiosis. MtPt4 promoter driven amiR-silencing led to strongly decreased transcript levels and deformed, non-fully truncated arbuscules indicating that MtErf1 is required for arbuscule development. Conclusions The endogenous amiR system demonstrated here presents a novel and highly efficient tool to unravel gene functions during root endosymbioses. PMID:23679580

2013-01-01

50

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

PubMed Central

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

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

51

Gene Expression Changes Related to Endocrine Function and Decline in Reproduction in Fathead Minnow (Pimephales promelas) after Dietary Methylmercury Exposure  

PubMed Central

Background Methylmercury (MeHg) is a known neurotoxic agent, but the mechanisms by which MeHg may act on reproductive pathways are relatively unknown. Several studies have indicated potential changes in hormone levels as well as declines in vertebrates with increasing dietary MeHg exposure. Objectives The purpose of this study was to identify alterations in gene expression associated with MeHg exposure, specifically those associated with previously observed changes in reproduction and reproductive biomarkers. Fathead minnows, Pimephales promelas, were fed one of three diets that were similar to documented concentrations of MeHg in the diets of wild invertivorous and piscivorous fish. We used a commercial macroarray in conjunction with quantitative polymerase chain reaction to examine gene expression in fish in relation to exposure to these environmentally relevant doses of MeHg. Results Expression of genes commonly associated with endocrine disruption was altered with Hg exposure. Specifically, we observed a marked up-regulation in vitellogenin mRNA in individual Hg-exposed males and a significant decline in vitellogenin gene expression in female fish with increasing Hg concentrations. Other genes identified by the macroarray experiment included those associated with egg fertilization and development, sugar metabolism, apoptosis, and electron transport. We also observed differences in expression patterns between male and female fish not related to genes specifically associated with reproduction, indicating a potential physiological difference in the reaction of males and females to MeHg. Conclusion Gene expression data may provide insight into the mechanisms by which MeHg affects reproduction in fish and indicate how MeHg differs in its effect from other heavy metals and endocrine-disrupting compounds. PMID:16966085

Klaper, Rebecca; Rees, Christopher B.; Drevnick, Paul; Weber, Daniel; Sandheinrich, Mark; Carvan, Michael J.

2006-01-01

52

Reciprocal sympatho-sensory control: functional role of nucleotides and calcitonin gene-related peptide in a peripheral neuroeffector junction.  

PubMed

The rat vas deferens has scattered sensory afferens plus a dense network of sympathetic motor efferens; these fibers are not known to interact functionally. We ascertained whether sensory fibers modulate the release of sympathetic transmitters through the release of calcitonin gene-related peptide (CGRP) and reciprocally assessed whether sympathetic transmitters modulate the overflow of ir-CGRP from sensory fibers. The tissue overflow of electrically evoked sympathetic co-transmitters (ATP/metabolites, noradrenaline (NA), and immunoreactive neuropeptide tyrosine (ir-NPY)) and the motor responses elicited were quantified following either exogenous CGRP or capsaicin application to elicit peptide release. Conversely, the outflow of ir-CGRP was examined in the presence of sympathetic transmitters. Exogenous CGRP reduced in a concentration-dependent manner the electrically evoked outflow of ATP/metabolites, NA, and ir-NPY with EC(50) values of 1.3, 0.18, and 1.9 nM, respectively. CGRP also reduced the basal NA overflow. The CGRP-evoked modulation was blocked by CGRP8-37 or H-89. Release of endogenous CGRP by capsaicin significantly reduced the basal overflow of NA, ir-NPY, and the electrically evoked sympathetic transmitter release. ADP, 2-methylthioadenosine-5'-O-diphosphate (2-MeSADP), or UTP decreased the electrically evoked ir-CGRP overflow, whereas clonidine, ?,?-methyleneadenosine 5'-triphosphate (?,?-mATP), or adenosine (ADO) were inactive. CGRP acting postjunctionally also reduced the motor responses elicited by exogenous NA, ATP, or electrically evoked contractions. We conclude that CGRP exerts a presynaptic modulator role on sympathetic nerve endings and reciprocally ATP or related nucleotides influence the release of ir-CGRP from sensory fibers, highlighting a dynamic sympatho-sensory control between sensory fibers and sympathetic nerve ending. Postjunctional CGRP receptors further contribute to reduce the tissue sympathetic motor tone implying a pre and postjunctional role of CGRP as a sympathetic tone modulator. PMID:22178987

Donoso, M V; Hermosilla, D; Navarrete, C; Álvarez, P; Lillo, J G; Huidobro-Toro, J P

2012-02-17

53

Mouse Genetics: Determining gene function  

E-print Network

Mouse Genetics: Determining gene function An International Centre for Mouse Genetics Mammalian Genetics Unit #12;Determining gene function · Mutagenesis approaches · Gene-driven, phenotype for Mouse Genetics Mammalian Genetics Unit #12;An International Centre for Mouse Genetics Mammalian Genetics

Goldschmidt, Christina

54

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

PubMed Central

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

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

2013-01-01

55

Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression  

SciTech Connect

One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin {alpha}, karyopherin {beta}, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.

Kim, Sung Young; Ryu, Sung Jin; Ahn, Hong Ju; Choi, Hae Ri; Kang, Hyun Tae [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)] [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Sang Chul, E-mail: scpark@snu.ac.kr [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

2010-01-01

56

TinII intron, an enhancer to affect the function of the cytoplasmic male sterility related gene T in Brassica juncea.  

PubMed

The T gene, which was cloned from the mitochondria of tumorous stem mustard (Brassica juncea var. tumida), is a cytoplasmic male sterility (CMS)-related gene that can produce two transcripts, T1170 and T1243. The latter is transcribed with the uncleaved intron TinII. In our previous study, transgenic Arabidopsis thaliana plants over-expressing the T1243 transcript (OE-T1243) showed a severe male-sterile phenotype, whereas OE-T1170 plants did not. However, the functional mechanism of the T gene in B. Juncea remained unknown. In this study, microscopic analyses of paraffin sections of anthers confirmed that OE-T1243 plants did not produce normal pollen, whereas OE-T1170 plants did. We analyzed the transcription of 15 anther development-related genes and found that transcript levels of nozzle/sporocyteless and barely any meristem 1 and 2 were markedly lower in OE-T1243 plants than those in wild type, while the transcript levels of these genes in OE-T1170 plants were unchanged. To investigate the potential roles of TinII, we inserted the TinII sequence upstream of a minimal region (-60) of the cauliflower mosaic virus 35S promoter fused to the 5' end of the ?-glucuronidase (GUS) reporter gene. Analysis of the transgenic plants suggested that TinII acted as an enhancer to significantly increase GUS expression. The potential action mechanism is that the TinII intron acts as an enhancer to affect the function of the CMS-related gene T. PMID:24302291

Jin, ZhuPing; Wu, LingLing; Cao, JiaShu; Chen, ZhuJun; Pei, YanXi

2013-12-01

57

Predicting gene function from images of cells  

E-print Network

This dissertation shows that biologically meaningful predictions can be made by analyzing images of cells. In particular, groups of related genes and their biological functions can be predicted using images from large ...

Jones, Thouis Raymond, 1971-

2007-01-01

58

Molecular and functional analysis of the large 5' promoter region of CFTR gene revealed pathogenic mutations in CF and CFTR-related disorders.  

PubMed

Patients with cystic fibrosis (CF) manifest a multisystemic disease due to mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR); despite extensive testing of coding regions, a proportion of CF alleles remains unidentified. We studied 118 patients with CF and CFTR-related disorders, most with one or both unknown mutations after the scanning of CFTR coding regions, and a non-CF control group (n = 75) by sequencing the 6000-bp region at the 5' of the CFTR gene. We identified 23 mutations, of which 9 were novel. We expressed such mutations in vitro using four cell systems to explore their functional effect, relating the data to the clinical expression of each patient. Some mutations reduced expression of the gene reporter firefly luciferase in various cell lines and may act as disease-causing mutations. Other mutations caused an increase in luciferase expression in some cell lines. One mutation had a different effect in different cells. For other mutations, the expression assay excluded a functional role. Gene variants in the large 5' region may cause altered regulation of CFTR gene expression, acting as disease-causing mutations or modifiers of its clinical phenotype. Studies of in vitro expression in different cell systems may help reveal the effect of such mutations. PMID:23470247

Giordano, Sonia; Amato, Felice; Elce, Ausilia; Monti, Maria; Iannone, Carla; Pucci, Pietro; Seia, Manuela; Angioni, Adriano; Zarrilli, Federica; Castaldo, Giuseppe; Tomaiuolo, Rossella

2013-05-01

59

FunGene: the functional gene pipeline and repository  

PubMed Central

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes. PMID:24101916

Fish, Jordan A.; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C. Titus; Tiedje, James M.; Cole, James R.

2013-01-01

60

Interaction of dopamine system genes and cognitive functions in patients with schizophrenia and their relatives and in healthy subjects from the general population  

Microsoft Academic Search

Linkage between the DRD4 and COMT genes and cognitive measures characterizing verbal memory, executive functions, and associative\\u000a processes was studied in 150 patients with schizophrenia, 83 of their relatives, and 118 mentally healthy subjects without\\u000a any family history of psychoses, with the aim of detecting the main effects of the polymorphic markers ?809G\\/A and ?521C\\/T\\u000a (DRD4) and Val158Met (COMT) when

M. V. Alfimova; V. E. Golimbet; I. K. Gritsenko; T. V. Lezheiko; L. I. Abramova; M. A. Strel’tsova; I. V. Khlopina; R. Ebstein

2007-01-01

61

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

PubMed Central

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

Castillo-Morales, Atahualpa; Monzon-Sandoval, Jimena; Urrutia, Araxi O.; Gutierrez, Humberto

2014-01-01

62

Relative Value Function Approximation  

Microsoft Academic Search

A form of temporal difference learning is presented that learns the relative utility of states,instead of the absolute utility. This formulation backs up decisions instead of values, makingit possible to learn a simpler function for defining a decision-making policy. A nonlinearrelative value function can be learned without increasing the dimensionality of the inputs.Contents1 Introduction 12 Approximating Absolute Utility 13 Approximating

Doina Precup; Paul E. Utgoff

1997-01-01

63

Can intermediate-frequency magnetic fields affect memory function-related gene expressions in hippocampus of C57BL/6J mice?  

PubMed

Recently, a cooking appliance based on the principle of electromagnetic induction has come to be used domestically on a widespread basis; this induction heating cooking hob mainly generates intermediate-frequency magnetic fields (IF-MF). However, whether electromagnetic fields originating from household appliances represent a health risk remains uncertain. We investigated the effect of IF-MF on the expressions of memory function-related genes and related transduction molecules in the mouse hippocampus. Male and female C57BL/6J mice were allotted to a control (sham-exposed), an exposure, or a recovery (one week after exposure) group and were exposed to IF-MF (21 kHz, 3.8 mT) one hour per day for 2 weeks. Twenty-four hour after final exposure, the expression levels of memory function-related genes and the mRNA levels for signal transduction pathway molecules in the hippocampi were examined using real-time RT-PCR. The relative mRNA expression levels of the N-methyl-D aspartate (NMDA) receptor subunits NR1, NR2A, and NR2B as well as transcription factors (calcium/calmodulin-dependent protein kinase (CaMK) -IV, cyclic AMP responsive element binding protein (CREB) -1) and neurotrophins (nerve growth factor (NGF), and brain-derived neurotrophic factors (BDNF)) were not significantly altered in the IF-MF-exposed mice. We also examined the morphology of the hippocampus using a histological analysis, but no changes in the IF-MF-exposed mice were seen. This is the first in vivo study to show that IF-MF exposure did not affect the expression levels of memory function-related genes in the hippocampus of C57BL/6J mice. The present findings suggest that IF-MF exposure may not affect cognitive function in the present animal model. PMID:23535396

Win-Shwe, Tin-Tin; Ohtani, Shin; Ushiyama, Akira; Fujimaki, Hidekazu; Kunugita, Naoki

2013-01-01

64

Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke  

PubMed Central

Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, the rare allele of this SNP has been repeatedly shown to exert a recessive effect. Therefore, in the current study, we tested for the same recessive model. First, the genotype distributions between all the controls and all the stroke cases were compared. Then to reduce heterogeneity, we explored several population subsets by selecting young stroke subjects (using 45 years of age as the cutoff point), age- and sex-comparable controls, plaque-free controls, and stroke subtypes. Results We did not find any significant association for the entire data set (OR = 0.94, p = 0.74) or for the subset analyses using age- and sex-comparable controls (p = 0.70) and plaque-free controls (p = 0.91). Analyses of the four stroke subtypes also failed to show any significant associations (p = 0.42 – 0.98). For both young and old subjects, the GG genotype of rs11066001 was similar in the stroke cases and unmatched controls (8.1% vs. 9.4% in young subjects and 8.0% vs. 7.8% in old subjects). Comparing stroke cases with plaque-free controls also failed to find any significant association. Conclusions The BRAP polymorphism may not play an important role in ischemic stroke in the studied population. PMID:23356535

2013-01-01

65

Connectionist Approaches for Predicting Mouse Gene Function from Gene Expression  

E-print Network

Therapy. Identifying gene function based on gene expression data is much easier in prokaryotes than ways, especially in Gene Therapy [5]. Identifying gene function in prokaryotes is much easier thanConnectionist Approaches for Predicting Mouse Gene Function from Gene Expression Emad Andrews

Bonner, Anthony

66

Genome-wide inventory of metal homeostasis-related gene products including a functional phytochelatin synthase in the hypogeous mycorrhizal fungus Tuber melanosporum.  

PubMed

Ectomycorrhizal fungi are thought to enhance mineral nutrition of their host plants and to confer increased tolerance toward toxic metals. However, a global view of metal homeostasis-related genes and pathways in these organisms is still lacking. Building upon the genome sequence of Tuber melanosporum and on transcriptome analyses, we set out to systematically identify metal homeostasis-related genes in this plant-symbiotic ascomycete. Candidate gene products (101) were subdivided into three major functional classes: (i) metal transport (58); (ii) oxidative stress defence (32); (iii) metal detoxification (11). The latter class includes a small-size metallothionein (TmelMT) that was functionally validated in yeast, and phytochelatin synthase (TmelPCS), the first enzyme of this kind to be described in filamentous ascomycetes. Recombinant TmelPCS was shown to support GSH-dependent, metal-activated phytochelatin synthesis in vitro and to afford increased Cd/Cu tolerance to metal hypersensitive yeast strains. Metal transporters, especially those related to Cu and Zn trafficking, displayed the highest expression levels in mycorrhizae, suggesting extensive translocation of both metals to root cells as well as to fungal metalloenzymes (e.g., laccase) that are strongly upregulated in symbiotic hyphae. PMID:21094264

Bolchi, Angelo; Ruotolo, Roberta; Marchini, Gessica; Vurro, Emanuela; di Toppi, Luigi Sanitŕ; Kohler, Annegret; Tisserant, Emilie; Martin, Francis; Ottonello, Simone

2011-06-01

67

The functional landscape of mouse gene expression  

Microsoft Academic Search

ABSTRACT: BACKGROUND: Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related

Wen Zhang; Quaid D Morris; Richard Chang; Ofer Shai; Malina A Bakowski; Nicholas Mitsakakis; Naveed Mohammad; Mark D Robinson; Ralph Zirngibl; Eszter Somogyi; Nancy Laurin; Eftekhar Eftekharpour; Eric Sat; Jörg Grigull; Qun Pan; Wen-Tao Peng; Nevan Krogan; Jack Greenblatt; Michael Fehlings; Derek van der Kooy; Jane Aubin; Benoit G Bruneau; Janet Rossant; Benjamin J Blencowe; Brendan J Frey; Timothy R Hughes

2004-01-01

68

Using co-expression to redefine functional gene sets for gene set enrichment analysis  

E-print Network

Manually curated gene sets related to a biological function often contain genes that are not tightly co-regulated transcriptionally. which obscures the evidence of coordinated differential expression of these gene sets in ...

Kodysh, Yuliya

2007-01-01

69

Candidate genes, pathways and mechanisms for bipolar (manic–depressive) and related disorders: an expanded convergent functional genomics approach  

Microsoft Academic Search

Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant—methamphetamine, and a mood stabilizer—valproate), with human data (linkage loci from human genetic studies, changes in postmortem brains from patients), as a bayesian strategy

C A Ogden; M E Rich; N J Schork; M P Paulus; M A Geyer; J B Lohr; R Kuczenski; A B Niculescu

2004-01-01

70

A siderophore biosynthesis gene cluster from the fish pathogen Photobacterium damselae subsp. piscicida is structurally and functionally related to the Yersinia high-pathogenicity island.  

PubMed

Photobacterium damselae subsp. piscicida, the causative agent of fish pasteurellosis, produces a siderophore which is distinct from that produced by P. damselae subsp. damselae. Using suppression subtractive hybridization, a subsp. piscicida-specific DNA region of 35 kb was identified in strain DI21, and 11 genes were defined: dahP, araC1, araC2, frpA, irp8, irp2, irp1, irp3, irp4, irp9 and irp5. The sequence of the predicted proteins encoded by these genes showed significant similarity with the proteins responsible for the synthesis and transport of the siderophore yersiniabactin, encoded within the Yersinia high-pathogenicity island (HPI). Southern hybridization demonstrated that this gene cluster is exclusive to some European subsp. piscicida isolates. Database searches revealed that a similar gene cluster is present in Photobacterium profundum SS9 and Vibrio cholerae RC385. An irp1 gene (encoding a putative non-ribosomal peptide synthetase) insertional mutant (CS31) was impaired for growth under iron-limiting conditions and unable to produce siderophores, and showed an approximately 100-fold decrease in degree of virulence for fish. The subsp. piscicida DI21 strain, but not CS31, promoted the growth of a Yersinia enterocolitica irp1 mutant. Furthermore, a yersiniabactin-producing Y. enterocolitica strain as well as purified yersiniabactin were able to cross-feed strains DI21 and CS31, suggesting that the subsp. piscicida siderophore might be functionally and structurally related to yersiniabactin. The differential occurrence among P. damselae strains, and the low sequence similarity to siderophore synthesis genes described in other members of the Vibrionaceae, suggest that this genetic system might have been acquired by horizontal transfer in P. damselae subsp. piscicida, and might have a common evolutionary origin with the Yersinia HPI. PMID:17074903

Osorio, Carlos R; Juiz-Río, Sandra; Lemos, Manuel L

2006-11-01

71

SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors  

PubMed Central

SFMBT1 (Scm [Sex comb on midleg] with four MBT [malignant brain tumor] domains 1) is a poorly characterized mammalian MBT domain-containing protein homologous to Drosophila SFMBT, a Polycomb group protein involved in epigenetic regulation of gene expression. Here, we show that SFMBT1 regulates transcription in somatic cells and during spermatogenesis through the formation of a stable complex with LSD1 and CoREST. When bound to its gene targets, SFMBT1 recruits its associated proteins and causes chromatin compaction and transcriptional repression. SFMBT1, LSD1, and CoREST share a large fraction of target genes, including those encoding replication-dependent histones. Simultaneous occupancy of histone genes by SFMBT1, LSD1, and CoREST is regulated during the cell cycle and correlates with the loss of RNA polymerase II at these promoters during G2, M, and G1. The interplay between the repressive SFMBT1–LSD1–CoREST complex and RNA polymerase II contributes to the timely transcriptional regulation of histone genes in human cells. SFMBT1, LSD1, and CoREST also form a stable complex in germ cells, and their chromatin binding activity is regulated during spermatogenesis. PMID:23592795

Zhang, Jin; Bonasio, Roberto; Strino, Francesco; Kluger, Yuval; Holloway, J. Kim; Modzelewski, Andrew J.; Cohen, Paula E.; Reinberg, Danny

2013-01-01

72

High frequency of rare copy number variants affecting functionally related genes in patients with structural brain malformations.  

PubMed

During the past years, significant advances have been made in our understanding of the development of the human brain, and much of this knowledge comes from genetic studies of disorders associated with abnormal brain development. We employed array-comparative genomic hybridization (CGH) to investigate copy number variants (CNVs) in a cohort of 169 patients with various structural brain malformations including lissencephaly, polymicrogyria, focal cortical dysplasia, and corpus callosum agenesis. The majority of the patients had intellectual disabilities (ID) and suffered from symptomatic epilepsy. We detected at least one rare CNV in 38 patients (22.5%). All genes located within the rare CNVs were subjected to enrichment analysis for specific Gene Ontology Terms or Kyoto Encyclopedia of Genes and Genomes pathways and to protein-protein network analysis. Based on these analyses, we propose that genes involved in "axonal transport," "cation transmembrane transporter activity," and the "c-Jun N-terminal kinase (JNK) cascade" play a significant role in the etiology of brain malformations. This is to the best of our knowledge the first systematic study of CNVs in patients with structural brain malformations and our data show that CNVs play an important role in the etiology of these malformations, either as direct causes or as genetic risk factors. PMID:21882292

Kariminejad, Roxana; Lind-Thomsen, Allan; Tümer, Zeynep; Erdogan, Fikret; Ropers, Hans H; Tommerup, Niels; Ullmann, Reinhard; Mřller, Rikke S

2011-12-01

73

Closely Related Archaeal Haloarcula hispanica Icosahedral Viruses HHIV-2 and SH1 Have Nonhomologous Genes Encoding Host Recognition Functions  

PubMed Central

Studies on viral capsid architectures and coat protein folds have revealed the evolutionary lineages of viruses branching to all three domains of life. A widespread group of icosahedral tailless viruses, the PRD1-adenovirus lineage, was the first to be established. A double ?-barrel fold for a single major capsid protein is characteristic of these viruses. Similar viruses carrying genes coding for two major capsid proteins with a more complex structure, such as Thermus phage P23-77 and haloarchaeal virus SH1, have been isolated. Here, we studied the host range, life cycle, biochemical composition, and genomic sequence of a new isolate, Haloarcula hispanica icosahedral virus 2 (HHIV-2), which resembles SH1 despite being isolated from a different location. Comparative analysis of these viruses revealed that their overall architectures are very similar except that the genes for the receptor recognition vertex complexes are unrelated even though these viruses infect the same hosts. PMID:22357274

Jaakkola, Salla T.; Penttinen, Reetta K.; Vilen, Silja T.; Jalasvuori, Matti; Ronnholm, Gunilla; Bamford, Jaana K. H.; Bamford, Dennis H.

2012-01-01

74

Delineating the structural, functional and evolutionary relationships of sucrose phosphate synthase gene family II in wheat and related grasses  

Microsoft Academic Search

Background  Sucrose phosphate synthase (SPS) is an important component of the plant sucrose biosynthesis pathway. In the monocotyledonous\\u000a Poaceae, five SPS genes have been identified. Here we present a detailed analysis of the wheat SPSII family in wheat. A set of homoeologue-specific primers was developed in order to permit both the detection of sequence variation,\\u000a and the dissection of the individual

Shailendra Sharma; Nese Sreenivasulu; Vokkaliga Thammegowda Harshavardhan; Christiane Seiler; Shiveta Sharma; Zaynali Nezhad Khalil; Eduard Akhunov; Sunish Kumar Sehgal; Marion S Röder

2010-01-01

75

Cloning, Characterization and Primary Function Study of a Novel Gene, Cymg1, Related to Family 2 Cystatins  

Microsoft Academic Search

Cystatins are cysteine proteinase inhibitors. We found two expression sequence tags (ESTs), CA463109 and AV042522, from a mouse testis library using Digital differential display (DDD). By electrical hybridization, a novel gene, Cymg1 (GenBank accession No. AY600990), which has a full length of 0.78 kb, and contains four exons and three introns, was cloned from a mouse testis cDNA library. The

Yang XIANG; Dong-Song NIE; Jian WANG; Xiao-Jun TAN; Yun DENG; Shu-Wei LUO; Guang-Xiu LU

2005-01-01

76

A method for finding communities of related genes  

Microsoft Academic Search

genes and 1 million related articles in the Medline databaseb alone. Moreover, genes act in a complex interrelated way, so information from many experiments is necessary to explain the function of a typical gene. A comprehensive study of even a simple cellular process involving several genes might require a researcher to be familiar with hundreds of articles. Merely locating all

Dennis M. Wilkinson; Bernardo A. Hubermana

2004-01-01

77

Functional implications related to the gene structure of the elongation factor EF-Tu from Halobacterium marismortui.  

PubMed

The primary structure of the gene for the elongation factor EF-Tu from the halophilic archaebacterium Halobacterium marismortui (hEF-Tu) is described. It is the first gene of a halophilic elongation factor EF-Tu to be sequenced. When the sequence of hEF-Tu is compared to that of homologous proteins from other organisms, the highest identity (61%) is found with EF-Tu from Methanococcus vannielii, a non-halophilic archaebacterium. In the search for halophilic characteristics therefore the most appropriate comparison is with the M. vannielii sequence. The excess of acidic amino acid residues in the hEF-Tu sequence (already observed in the composition of other halophilic proteins) results to a large extent from changes of Lys, Asn or Gln to Asp or Glu. A structural analysis algorithm applied to the halophilic sequence places these acidic residues on the surface of the protein. The corresponding residues in the crystal structure of the first domain of EF-Tu from E. coli (the only EF-Tu structure available) are grouped in patches on the protein surface, in each of which several residues that may be far apart in the sequence come quite close to each other in the tertiary structure. PMID:2155402

Baldacci, G; Guinet, F; Tillit, J; Zaccai, G; de Recondo, A M

1990-02-11

78

A recombination repair gene of Schizosaccharomyces pombe, rhp57, is a functional homolog of the Saccharomyces cerevisiae RAD57 gene and is phylogenetically related to the human XRCC3 gene.  

PubMed Central

To identify Schizosaccharomyces pombe genes involved in recombination repair, we identified seven mutants that were hypersensitive to both methyl methanesulfonate (MMS) and gamma-rays and that contained mutations that caused synthetic lethality when combined with a rad2 mutation. One of the mutants was used to clone the corresponding gene from a genomic library by complementation of the MMS-sensitive phenotype. The gene obtained encodes a protein of 354 amino acids whose sequence is 32% identical to that of the Rad57 protein of Saccharomyces cerevisiae. An rhp57 (RAD57 homolog of S. pombe) deletion strain was more sensitive to MMS, UV, and gamma-rays than the wild-type strain and showed a reduction in the frequency of mitotic homologous recombination. The MMS sensitivity was more severe at lower temperature and was suppressed by the presence of a multicopy plasmid bearing the rhp51 gene. An rhp51 rhp57 double mutant was as sensitive to UV and gamma-rays as an rhp51 single mutant, indicating that rhp51 function is epistatic to that of rhp57. These characteristics of the rhp57 mutants are very similar to those of S. cerevisiae rad57 mutants. Phylogenetic analysis suggests that Rhp57 and Rad57 are evolutionarily closest to human Xrcc3 of the RecA/Rad51 family of proteins. PMID:10747044

Tsutsui, Y; Morishita, T; Iwasaki, H; Toh, H; Shinagawa, H

2000-01-01

79

Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography  

NASA Astrophysics Data System (ADS)

Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

2014-01-01

80

A novel functional low-density lipoprotein receptor-related protein 6 gene alternative splice variant is associated with Alzheimer's disease.  

PubMed

We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6?3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6?3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/?-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6?3 isoform is a novel splice variant, which shows diminished Wnt/?-catenin signaling activity and might have a functional role in individuals with AD. PMID:23218566

Alarcón, Marcelo A; Medina, Matías A; Hu, Qubai; Avila, Miguel E; Bustos, Bernabé I; Pérez-Palma, Eduardo; Peralta, Alexis; Salazar, Paulina; Ugarte, Giorgia D; Reyes, Ariel E; Martin, George M; Opazo, Carlos; Moon, Randall T; De Ferrari, Giancarlo V

2013-06-01

81

Relations and functions Countability  

E-print Network

A set is a collection or group of objects or elements or members (Cantor 1895). the collection) if and only if (iff) they have the same elements. The elements of a set need not be related in any way. {3 elements or members. b is an element of the set L; b is in L; L contains b: b L z is not an element of L

Way, Andy

82

Molecular characterization, expression pattern, and functional analysis of the OsIRL gene family encoding intracellular Ras-group-related LRR proteins in rice  

Microsoft Academic Search

Leucine-rich repeat proteins constitute a large gene family and play important roles in plant growth and development. Among\\u000a them, Arabidopsis PIRL is a plant-specific class of intracellular Ras-group-related leucine-rich repeat proteins. In this study, we identified\\u000a eight homologues of PIRLs in rice and designated them as OsIRL proteins. We described the gene structures, chromosome localizations,\\u000a protein motifs, and phylogenetic relationships

Changjun You; Xiaoxia Dai; Xingwang Li; Lei Wang; Guoxing Chen; Jinghua Xiao; Changyin Wu

2010-01-01

83

The effect of the cleidocranial dysplasia-related novel 1116_1119insC mutation in the RUNX2 gene on the biological function of mesenchymal cells.  

PubMed

Bone extracellular matrix deposition or bone formation by differentiated osteoblasts begins at late stage during bone formation and lasts throughout life. Human mesenchymal stem cells (MSCs) from bone marrow or dental pulp can respectively differentiate into osteoblasts and odontoblasts in vitro. However, the relationship between MSCs and bone/tooth development in cleidocranial dysplasia (CCD) patient is still unclear. In this study, we investigated a patient with CCD, which is an autosomal-dominant, heritable skeletal disease caused by runt-related transcription factor 2 gene (RUNX2) mutation and is characterized by bone and dental anomalies. We found that the mutation is localized at c. 1116_1119insC, p. Q374fsX384 and the proliferative ability and osteogenic potential of the MSCs isolated from the bone marrow and dental pulp of the patient (RUNX2(+/m)) were decreased compared to normal individuals (RUNX2(+/+)). Furthermore, we were unable to recover the differentiation potential of RUNX2(+/m) MSCs isolated from the bone marrow (BMMSCs) upon manipulation of the Wnt/?-catenin pathway, which plays a critical role in stem/progenitor cell self-renewal and adult human MSCs differentiation. In conclusion, we identified a novel insertion/frameshift mutation in the RUNX2 gene that caused a typical CCD phenotype and altered the biological function of RUNX2(+/m) MSCs. The reduced ability of MSCs to differentiate into osteoblasts might provide an explanation for the defects of bone and teeth in the CCD patient. Finally, we demonstrated that manipulation of the Wnt/?-catenin signaling pathway could not overcome this absence. PMID:23376464

Ding, Bofu; Li, Chanjuan; Xuan, Kun; Liu, Na; Tang, Liang; Liu, Yali; Guo, Weihua; Liu, Weihong; Jin, Yan

2013-04-01

84

Function of the DISC1 Gene  

NSDL National Science Digital Library

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.

2009-04-14

85

Towards integrative gene functional similarity measurement  

PubMed Central

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

2014-01-01

86

?7 Nicotinic receptor gene delivery into mouse hippocampal neurons leads to functional receptor expression, improved spatial memory-related performance, and tau hyperphosphorylation  

Microsoft Academic Search

Brain ?7 nicotinic receptors have become therapeutic targets for Alzheimer’s disease (AD) based on their memory-enhancing and neuroprotective actions. This study investigated the feasibility of increasing neuronal ?7 receptor functions using a gene delivery approach based on neuron-selective recombinant adeno-associated virus (rAAV)–derived vectors. In order to determine whether ?7 receptor-mediated cytotoxicity was dependent on receptor density, rat ?7 nicotinic receptors

K. Ren; J. Thinschmidt; J. Liu; L. Ai; R. L. Papke; M. A. King; J. A. Hughes; E. M. Meyer

2007-01-01

87

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

PubMed

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

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

88

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

PubMed Central

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, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. Results The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. Conclusion PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out to dissect the PHB gene function. The conserved gene evolution indicated that the study in the model species can be translated to human and mammalian studies. PMID:20946606

2010-01-01

89

Distribution of typical denitrifying functional genes and diversity of the nirS-encoding bacterial community related to environmental characteristics of river sediments  

NASA Astrophysics Data System (ADS)

Denitrification in river sediments leads to nitrate removal from the aquatic system; therefore, it is necessary to understand functional diversity of denitrifier communities in the system. Sediment samples (0-25 cm depth) were collected from three typical locations along the Pearl River. The real-time PCR approach was used to measure the abundance of nitrate (narG), nitrite (nirS, nirK and nrfA), and nitrous oxide (nosZ) reductase genes from the sediment samples. Assemblages of nirS, nirK and nosZ indicated that complete denitrification occurred in sediment cores, with the greatest number of gene copies from 5-15 cm depth. Dissimilatory nitrate reduction appeared to be important below 15 cm depth, based on increasing gene copies of narG and nrfA with sediment depth. There was a close match (78-94 %) between the nirS sequences recovered from Pearl River sediment and those detected in estuarine and marine sediments as well as active sludge, suggesting that domestic sewage inputs and irregular tides. Canonical correspondence analysis indicated that the spatial distribution of denitrifying bacteria was highly correlated with dissolved inorganic N (DIN: NH4+, NO2genes and the nirS-encoding denitrifier community in the river sediment. Our results also reveal a variety of novel denitrifying bacteria in the river sediment.

Huang, S.; Chen, C.; Wu, Q.; Zhang, R.; Yang, X.

2011-05-01

90

Discovery of Tumor Suppressor Gene Function.  

ERIC Educational Resources Information Center

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)

Oppenheimer, Steven B.

1995-01-01

91

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

PubMed Central

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

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

2013-01-01

92

Functional Genes and Proteins of Clonorchis sinensis  

PubMed Central

During the past several decades, researches on parasite genetics have progressed from biochemical and serodiagnostic studies to protein chemistry, molecular biology, and functional gene studies. Nowadays, bioinformatics, genomics, and proteomics approaches are being applied by Korean parasitology researchers. As for Clonorchis sinensis, investigations have been carried out to identify its functional genes using forward and reverse genetic approaches and to characterize the biochemical and biological properties of its gene products. The authors review the proteins of cloned genes, which include antigenic proteins, physiologic and metabolic enzymes, and the gene expression profile of Clonorchis sinensis. PMID:19885336

Kim, Tae Im; Na, Byoung-Kuk

2009-01-01

93

Identification and Functional Analysis of Light-Responsive Unique Genes and Gene Family Members in Rice  

Microsoft Academic Search

Functional redundancy limits detailed analysis of genes in many organisms. Here, we report a method to efficiently overcome this obstacle by combining gene expression data with analysis of gene-indexed mutants. Using a rice NSF45K oligo-microarray to compare 2-week-old light- and dark-grown rice leaf tissue, we identified 365 genes that showed significant 8-fold or greater induction in the light relative to

Ki-Hong Jung; Jinwon Lee; Chris Dardick; Young-Su Seo; Peijian Cao; Patrick Canlas; Jirapa Phetsom; Xia Xu; Shu Ouyang; Kyungsook An; Yun-Ja Cho; Geun-Cheol Lee; Yoosook Lee; Gynheung An; Pamela C. Ronald

2008-01-01

94

Distribution of typical denitrifying functional genes and diversity of the nirS-encoding bacterial community related to environmental characteristics of river sediments  

NASA Astrophysics Data System (ADS)

Denitrification in river sediments leads to nitrate removal from the aquatic system; therefore, it is necessary to understand functional diversity of denitrifier communities in the system. Sediment samples (0-25 cm depth) were collected from three typical locations along the Pearl River. The real-time PCR approach was used to measure the abundance of nitrate (narG), nitrite (nirS, nirK and nrfA), and nitrous oxide (nosZ) reductase genes from the sediment samples. Assemblages of nirS, nirK and nosZ indicated that complete denitrification occurred in sediment cores, with the greatest number of gene copies from 5-15 cm depth. Dissimilatory nitrate reduction appeared to be important below 15 cm depth, based on increasing gene copies of narG and nrfA with sediment depth. There was a close match (78-94 %) between the nirS sequences recovered from the Pearl River sediment and those detected in estuarine and marine sediments as well as active sludge, suggesting that the nitrogen source in the Pearl River sediment was affected by domestic sewage inputs and irregular tides. Canonical correspondence analysis indicated that the spatial distribution of denitrifying bacteria was highly correlated with dissolved inorganic nitrogen (including NH4+, NO2- and NO3-) concentrations in sediment. It was concluded that the difference in dissolved inorganic nitrogen concentrations along the sediment profile influenced the distribution of denitrifying genes and the nirS-encoding denitrifier community in the river sediment. In addition, a variety of novel denitrifying bacteria were revealed in the river sediment.

Huang, S.; Chen, C.; Yang, X.; Wu, Q.; Zhang, R.

2011-10-01

95

Neofunctionalization of Duplicated Tic40 Genes Caused a Gain-of-Function Variation Related to Male Fertility in Brassica oleracea Lineages.  

PubMed

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

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

2014-11-01

96

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

PubMed Central

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

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

97

Functional divergence in the Arabidopsis LOB-domain gene family  

PubMed Central

The Arabidopsis LOB-domain (LBD) gene family is composed by 43 members divided in two classes based on amino acid conservation within the LOB-domain. The LOB domain is known to be responsible for DNA binding and protein-protein interactions. There is very little functional information available for most genes in the LBD family and many lbd single mutants do not exhibit conspicuous phenotypes. One plausible explanation for the limited loss-of-function phenotypes observed in this family is that LBD genes exhibit significant functional redundancy. Here we discuss an example of one phylogenetic subgroup of the LBD family, in which genes that are closely related based on phylogeny exhibit distinctly different expression patterns and do not have overlapping functions. We discuss the challenges of using phylogenetic analyses to predict redundancy in gene families. PMID:23073009

Mangeon, Amanda; Lin, Wan-ching; Springer, Patricia S.

2012-01-01

98

Antagonistic functional duality of cancer genes.  

PubMed

Cancer evolution is a stochastic process both at the genome and gene levels. Most of tumors contain multiple genetic subclones, evolving in either succession or in parallel, either in a linear or branching manner, with heterogeneous genome and gene alterations, extensively rewired signaling networks, and addicted to multiple oncogenes easily switching with each other during cancer progression and medical intervention. Hundreds of discovered cancer genes are classified according to whether they function in a dominant (oncogenes) or recessive (tumor suppressor genes) manner in a cancer cell. However, there are many cancer "gene-chameleons", which behave distinctly in opposite way in the different experimental settings showing antagonistic duality. In contrast to the widely accepted view that mutant NADP(+)-dependent isocitrate dehydrogenases 1/2 (IDH1/2) and associated metabolite 2-hydroxyglutarate (R)-enantiomer are intrinsically "the drivers" of tumourigenesis, mutant IDH1/2 inhibited, promoted or had no effect on cell proliferation, growth and tumorigenicity in diverse experiments. Similar behavior was evidenced for dozens of cancer genes. Gene function is dependent on genetic network, which is defined by the genome context. The overall changes in karyotype can result in alterations of the role and function of the same genes and pathways. The diverse cell lines and tumor samples have been used in experiments for proving gene tumor promoting/suppressive activity. They all display heterogeneous individual karyotypes and disturbed signaling networks. Consequently, the effect and function of gene under investigation can be opposite and versatile in cells with different genomes that may explain antagonistic duality of cancer genes and the cell type- or the cellular genetic/context-dependent response to the same protein. Antagonistic duality of cancer genes might contribute to failure of chemotherapy. Instructive examples of unexpected activity of cancer genes and "paradoxical" effects of different anticancer drugs depending on the cellular genetic context/signaling network are discussed. PMID:23933273

Stepanenko, A A; Vassetzky, Y S; Kavsan, V M

2013-10-25

99

Functional Genetic Polymorphisms in CYP2C19 Gene in Relation to Cardiac Side Effects and Treatment Dose in a Methadone Maintenance Cohort  

PubMed Central

Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations. PMID:24016178

Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C.H.; Chang, Yao-Sheng

2013-01-01

100

Expression Sensitivity Analysis of Human Disease Related Genes  

PubMed Central

Background. Genome-wide association studies (GWAS) have shown its revolutionary power in seeking the influenced loci on complex diseases genetically. Thousands of replicated loci for common traits are helpful in diseases risk assessment. However it is still difficult to elucidate the variations in these loci that directly cause susceptibility to diseases by disrupting the expression or function of a protein currently. Results. We evaluate the expression features of disease related genes and find that different diseases related genes show different expression perturbation sensitivities in various conditions. It is worth noting that the expression of some robust disease-genes doesn't show significant change in their corresponding diseases, these genes might be easily ignored in the expression profile analysis. Conclusion. Gene ontology enrichment analysis indicates that robust disease-genes execute essential function in comparison with sensitive disease-genes. The diseases associated with robust genes seem to be relatively lethal like cancer and aging. On the other hand, the diseases associated with sensitive genes are apparently nonlethal like psych and chemical dependency diseases. PMID:24350280

Ma, Liang-Xiao; Wang, Ya-Jun; Li, Xuan; Hao, Pei

2013-01-01

101

Genes and gene networks implicated in aggression related behaviour.  

PubMed

Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour. PMID:25142712

Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

2014-10-01

102

HLA Immune Function Genes in Autism  

PubMed Central

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

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

2012-01-01

103

The ubiquilin gene family: evolutionary patterns and functional insights  

PubMed Central

Background Ubiquilins are proteins that function as ubiquitin receptors in eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the genesis of neurodegenerative diseases. However, ubiquilin functions are still poorly understood. Results In this study, evolutionary and functional data are combined to determine the origin and diversification of the ubiquilin gene family and to characterize novel potential roles of ubiquilins in mammalian species, including humans. The analysis of more than six hundred sequences allowed characterizing ubiquilin diversity in all the main eukaryotic groups. Many organisms (e. g. fungi, many animals) have single ubiquilin genes, but duplications in animal, plant, alveolate and excavate species are described. Seven different ubiquilins have been detected in vertebrates. Two of them, here called UBQLN5 and UBQLN6, had not been hitherto described. Significantly, marsupial and eutherian mammals have the most complex ubiquilin gene families, composed of up to 6 genes. This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis. A gene with related features has independently arisen in species of the Drosophila genus. Positive selection acting on some mammalian ubiquilins has been detected. Conclusions The ubiquilin gene family is highly conserved in eukaryotes. The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues. PMID:24674348

2014-01-01

104

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

PubMed Central

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

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

105

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

PubMed

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

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

2013-01-01

106

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

PubMed Central

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

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

2013-01-01

107

Predicting gene function using similarity learning  

PubMed Central

Background Computational methods that make use of heterogeneous biological datasets to predict gene function provide a cost-effective and rapid way for annotating genomes. A common framework shared by many such methods is to construct a combined functional association network from multiple networks representing different sources of data, and use this combined network as input to network-based or kernel-based learning algorithms. In these methods, a key factor contributing to the prediction accuracy is the network quality, which is the ability of the network to reflect the functional relatedness of gene pairs. To improve the network quality, a large effort has been spent on developing methods for network integration. These methods, however, produce networks, which then remain unchanged, and nearly no effort has been made to optimize the networks after their construction. Results Here, we propose an alternative method to improve the network quality. The proposed method takes as input a combined network produced by an existing network integration algorithm, and reconstructs this network to better represent the co-functionality relationships between gene pairs. At the core of the method is a learning algorithm that can learn a measure of functional similarity between genes, which we then use to reconstruct the input network. In experiments with yeast and human, the proposed method produced improved networks and achieved more accurate results than two other leading gene function prediction approaches. Conclusions The results show that it is possible to improve the accuracy of network-based gene function prediction methods by optimizing combined networks with appropriate similarity measures learned from data. The proposed learning procedure can handle noisy training data and scales well to large genomes. PMID:24266903

2013-01-01

108

RNA interference for wheat functional gene analysis  

Microsoft Academic Search

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

Daolin Fu; Cristobal Uauy; Ann Blechl; Jorge Dubcovsky

2007-01-01

109

A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking.  

PubMed

Sulfotransferase 1A1, an important member of sulfotransferase superfamily, is involved in the biotransformation of many compounds including tobacco carcinogens. A single nucleotide polymorphism (G638A) in the sulfotransferase 1A1 (SULT1A1) gene causes Arg213His amino acid change and consequently results in significantly reduced enzyme activity and thermostability. We thus hypothesized that the variant SULT1A1 allele may protect against the risk of lung cancer related to tobacco smoking. To examine this hypothesis, we analyzed 805 patients with lung cancer and 809 controls for this polymorphism in a hospital-based, case-control study. We observed that, compared with the GG genotype, the variant SULT1A1 genotype (638GA or AA) was associated with a significantly increased risk for overall lung cancer [odds ratio (OR) 1.85; 95% confidence interval (CI) 1.44-2.37]. Stratification analysis showed that the increased risk of lung cancer related to the variant SULT1A1 genotypes was more pronounced in younger subjects and limited to smokers but not non-smokers [OR 2.28 (95% CI 1.66-3.13) versus OR 1.35 (95% CI 0.91-1.99); P for homogeneity = 0.000]. Furthermore, the risk of lung cancer for the variant genotypes was increased consistently with cumulative smoking dose, with the ORs being 1.66 (95% CI, 0.75-3.68), 2.28 (95% CI, 1.47-3.54) and 3.35 (95% CI, 1.71-6.57) for those who smoked <15 pack-years, 15-36 pack-years and >36 pack-years, respectively (P for trend = 0.000). When analysis was stratified by histological subtypes of lung cancer, consistent results were observed for all three major types of the cancer, i.e. squamous cell carcinoma, adenocarcinoma and other types. Our results, which are against the original hypothesis, demonstrate that the variant SULT1A1 638A allele is associated with susceptibility to lung cancer in relation to tobacco smoking. PMID:14688021

Liang, Gang; Miao, Xiaoping; Zhou, Yifeng; Tan, Wen; Lin, Dongxin

2004-05-01

110

A novel method to quantify gene set functional association based on gene ontology  

PubMed Central

Numerous gene sets have been used as molecular signatures for exploring the genetic basis of complex disorders. These gene sets are distinct but related to each other in many cases; therefore, efforts have been made to compare gene sets for studies such as those evaluating the reproducibility of different experiments. Comparison in terms of biological function has been demonstrated to be helpful to biologists. We improved the measurement of semantic similarity to quantify the functional association between gene sets in the context of gene ontology and developed a web toolkit named Gene Set Functional Similarity (GSFS; http://bioinfo.hrbmu.edu.cn/GSFS). Validation based on protein complexes for which the functional associations are known demonstrated that the GSFS scores tend to be correlated with sequence similarity scores and that complexes with high GSFS scores tend to be involved in the same functional catalogue. Compared with the pairwise method and the annotation method, the GSFS shows better discrimination and more accurately reflects the known functional catalogues shared between complexes. Case studies comparing differentially expressed genes of prostate tumour samples from different microarray platforms and identifying coronary heart disease susceptibility pathways revealed that the method could contribute to future studies exploring the molecular basis of complex disorders. PMID:21998111

Lv, Sali; Li, Yan; Wang, Qianghu; Ning, Shangwei; Huang, Teng; Wang, Peng; Sun, Jie; Zheng, Yan; Liu, Weisha; Ai, Jing; Li, Xia

2012-01-01

111

WN: Gene functional classification from heterogeneous data  

E-print Network

In our attempts to understand cellular function at the molecular level, we must be able to synthesize information from disparate types of genomic data. We consider the problem of inferring gene functional classifications from a heterogeneous data set consisting of DNA microarray expression measurements and phylogenetic profiles from whole-genome sequence comparisons. We demonstrate the application of the support vector machine (SVM) learning algorithm to this functional inference task. Our results suggest the importance of exploiting prior information about the heterogeneity of the data. In particular, we propose an SVM kernel function that is explicitly heterogeneous. We also show how to use knowledge about heterogeneity to aid in feature selection. 1

Paul Pavlidis; Jinsong Cai; Jason Weston; William Noble Grundy

112

Cost benefit theory and optimal design of gene regulation functions  

NASA Astrophysics Data System (ADS)

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 constraints of biological systems. Here we address this by presenting a cost-benefit theory for gene regulation functions that takes into account temporally varying inputs in the environment and stochastic noise in the biological components. We apply this theory to the well-studied lac operon of E. coli. The present theory explains the shape of this regulation function in terms of temporal variation of the input signals, and of minimizing the deleterious effect of cell-cell variability in regulatory protein levels. We also apply the theory to understand the evolutionary tradeoffs in setting the number of regulatory proteins and for selection of feed-forward loops in genetic circuits. The present cost-benefit theory can be used to understand the shape of other gene regulatory functions in terms of environment and noise constraints.

Kalisky, Tomer; Dekel, Erez; Alon, Uri

2007-12-01

113

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

PubMed Central

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

Hao, Weilong; Palmer, Jeffrey D.

2009-01-01

114

Gene Transfers Between Distantly Related Organisms  

NASA Technical Reports Server (NTRS)

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.

Doolittle, Russell F.

2003-01-01

115

Bayesian modelling of shared gene function  

Microsoft Academic Search

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

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

2007-01-01

116

Rapid analysis of Jatropha curcas gene functions by virus-induced gene silencing.  

PubMed

Jatropha curcas L. is a small, woody tree of the Euphorbiaceae family. This plant can grow on marginal land in the tropical and subtropical regions and produces seeds containing up to 30% oil. Several Asian countries have selected Jatropha for large scale planting as a biodiesel feedstock. Nevertheless, Jatropha also possesses several undesirable traits that may limit its wide adoption. An improved understanding of plant development and the regulation of fatty acid (FA) and triacylglyceride biosynthesis in Jatropha is particularly facilitative for the development of elite crops. Here, we show that a tobacco rattle virus (TRV) vector can trigger virus-induced gene silencing (VIGS) in Jatropha. Our optimized method produced robust and reliable gene silencing in plants agroinoculated with recombinant TRV harbouring Jatropha gene sequences. We used VIGS to investigate possible functions of 13 Jatropha genes of several functional categories, including FA biosynthesis, developmental regulation and toxin biosynthesis, etc. Based on the effects of VIGS on the FA composition of newly emerged leaves, we determined the function of several genes implicated in FA biosynthesis. Moreover, VIGS was able to discriminate independent functions of related gene family members. Our results show that VIGS can be used for high-throughput screening of Jatropha genes whose functions can be assayed in leaves. PMID:19906247

Ye, Jian; Qu, Jing; Bui, Ha Thi Ngoc; Chua, Nam-Hai

2009-12-01

117

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

PubMed Central

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

2014-01-01

118

Molecular Genetic Analysis of the PLP1 Gene in 38 Families with PLP1 -related disorders: Identification and Functional Characterization of 11 Novel PLP1 Mutations  

Microsoft Academic Search

Background  The breadth of the clinical spectrum underlying Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is due to the extensive\\u000a allelic heterogeneity in the X-linked PLP1 gene encoding myelin proteolipid protein (PLP). PLP1 mutations range from gene duplications of variable size found in 60-70% of patients to intragenic lesions present in 15-20%\\u000a of patients.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Forty-eight male patients from 38 unrelated families

Serena Grossi; Stefano Regis; Roberta Biancheri; Matthew Mort; Susanna Lualdi; Enrico Bertini; Graziella Uziel; Odile Boespflug-Tanguy; Alessandro Simonati; Fabio Corsolini; Ercan Demir; Valentina Marchiani; Antonio Percesepe; Franco Stanzial; Andrea Rossi; Catherine Vaurs-Barričre; David N Cooper; Mirella Filocamo

2011-01-01

119

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

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

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

2003-01-01

120

ARABIDILLO gene homologues in basal land plants: species-specific gene duplication and likely functional redundancy.  

PubMed

ARABIDILLO proteins regulate multicellular root development in Arabidopsis thaliana. Conserved ARABIDILLO homologues are present throughout land plants, even in early-evolving plants that do not possess complex root architecture, suggesting that ARABIDILLO genes have additional functions. Here, we have cloned and characterised ARABIDILLO gene homologues from two early-evolving land plants, the bryophyte Physcomitrella patens and the lycophyte Selaginella moellendorffii. We show that two of the PHYSCODILLO genes (PHYSCODILLO1A and -1B) exist as a tail-to-tail tandem array of two almost identical 12 kb sequences, while a third related gene (PHYSCODILLO2) is located elsewhere in the Physcomitrella genome. Physcomitrella possesses a very low percentage of tandemly arrayed genes compared with the later-evolving plants whose genomes have been sequenced to date. Thus, PHYSCODILLO1A and -1B genes represent a relatively unusual gene arrangement. PHYSCODILLO promoters are active largely in the haploid gametophyte, with additional activity at the foot of the sporophyte. The pattern of promoter activity is uniform in filamentous and leafy tissues, suggesting pleiotropic gene functions and likely functional redundancy: the latter possibility is confirmed by the lack of discernible phenotype in a physcodillo2 deletion mutant. Interestingly, the pattern of PHYSCODILLO promoter activity in female reproductive organs is strikingly similar to that of an Arabidopsis homologue, suggesting co-option of some PHYSCODILLO functions or regulation into both the sporophyte and gametophyte. In conclusion, our work identifies and characterises some of the earliest-evolving land plant ARABIDILLO homologues. We confirm that all land plant ARABIDILLO genes arose from a single common ancestor and suggest that PHYSCODILLO proteins have novel and pleiotropic functions, some of which may be conserved in later-evolving plants. PMID:22945313

Moody, Laura A; Saidi, Younousse; Smiles, Emma J; Bradshaw, Susan J; Meddings, Matthew; Winn, Peter J; Coates, Juliet C

2012-12-01

121

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

E-print Network

in many ways, especially in Gene Therapy [18]. Identifying gene function in prokaryotes is much easierNeural Networks Approaches for Discovering the Learnable Correlation between Gene Function and Gene University of Toronto Toronto, ON. emad@cs.toronto.edu Abstract. Identifying gene function has many useful

Bonner, Anthony

122

Mutualistic polydnaviruses share essential replication gene functions with pathogenic ancestors.  

PubMed

Viruses are usually thought to form parasitic associations with hosts, but all members of the family Polydnaviridae are obligate mutualists of insects called parasitoid wasps. Phylogenetic data founded on sequence comparisons of viral genes indicate that polydnaviruses in the genus Bracovirus (BV) are closely related to pathogenic nudiviruses and baculoviruses. However, pronounced differences in the biology of BVs and baculoviruses together with high divergence of many shared genes make it unclear whether BV homologs still retain baculovirus-like functions. Here we report that virions from Microplitis demolitor bracovirus (MdBV) contain multiple baculovirus-like and nudivirus-like conserved gene products. We further show that RNA interference effectively and specifically knocks down MdBV gene expression. Coupling RNAi knockdown methods with functional assays, we examined the activity of six genes in the MdBV conserved gene set that are known to have essential roles in transcription (lef-4, lef-9), capsid assembly (vp39, vlf-1), and envelope formation (p74, pif-1) during baculovirus replication. Our results indicated that MdBV produces a baculovirus-like RNA polymerase that transcribes virus structural genes. Our results also supported a conserved role for vp39, vlf-1, p74, and pif-1 as structural components of MdBV virions. Additional experiments suggested that vlf-1 together with the nudivirus-like gene int-1 also have novel functions in regulating excision of MdBV proviral DNAs for packaging into virions. Overall, these data provide the first experimental insights into the function of BV genes in virion formation. PMID:23671417

Burke, Gaelen R; Thomas, Sarah A; Eum, Jai H; Strand, Michael R

2013-01-01

123

Inflammation and Neurological Disease-Related Genes are Differentially Expressed in Depressed Patients with Mood Disorders and Correlate with Morphometric and Functional Imaging Abnormalities  

PubMed Central

Depressed patients show evidence of both proinflammatory changes and neurophysiological abnormalities such as increased amygdala reactivity and volumetric decreases of the hippocampus and ventromedial prefrontal cortex (vmPFC). However, very little is known about the relationship between inflammation and neuroimaging abnormalities in mood disorders. A whole genome expression analysis of peripheral blood mononuclear cells yielded 12 protein-coding genes (ADM, APBB3, CD160, CFD, CITED2, CTSZ, IER5, NFKBIZ, NR4A2, NUCKS1, SERTAD1, TNF) that were differentially expressed between 29 unmedicated depressed patients with a mood disorder (8 bipolar disorder, 21 major depressive disorder) and 24 healthy controls (HCs). Several of these genes have been implicated in neurological disorders and/or apoptosis. Ingenuity Pathway Analysis yielded two genes networks, one centered around TNF with NFK?, TGF?, and ERK as connecting hubs, and the second network indicating cell cycle and/or kinase signaling anomalies. fMRI scanning was conducted using a backward-masking task in which subjects were presented with emotionally-valenced faces. Compared with HCs, the depressed subjects displayed a greater hemodynamic response in the right amygdala, left hippocampus, and the ventromedial prefrontal cortex to masked sad versus happy faces. The mRNA levels of several genes were significantly correlated with the hemodynamic response of the amygdala, vmPFC and hippocampus to masked sad versus happy faces. Differentially-expressed transcripts were significantly correlated with thickness of the left subgenual ACC, and volume of the hippocampus and caudate. Our results raise the possibility that molecular-level immune dysfunction can be mapped onto macro-level neuroimaging abnormalities, potentially elucidating a mechanism by which inflammation leads to depression. PMID:23064081

Savitz, Jonathan; Frank, Mark Barton; Victor, Teresa; Bebak, Melissa; Marino, Julie H.; Bellgowan, Patrick S.F.; McKinney, Brett A.; Bodurka, Jerzy; Teague, T. Kent; Drevets, Wayne C.

2012-01-01

124

Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities.  

PubMed

Depressed patients show evidence of both proinflammatory changes and neurophysiological abnormalities such as increased amygdala reactivity and volumetric decreases of the hippocampus and ventromedial prefrontal cortex (vmPFC). However, very little is known about the relationship between inflammation and neuroimaging abnormalities in mood disorders. A whole genome expression analysis of peripheral blood mononuclear cells yielded 12 protein-coding genes (ADM, APBB3, CD160, CFD, CITED2, CTSZ, IER5, NFKBIZ, NR4A2, NUCKS1, SERTAD1, TNF) that were differentially expressed between 29 unmedicated depressed patients with a mood disorder (8 bipolar disorder, 21 major depressive disorder) and 24 healthy controls (HCs). Several of these genes have been implicated in neurological disorders and/or apoptosis. Ingenuity Pathway Analysis yielded two genes networks, one centered around TNF with NFK?, TGF?, and ERK as connecting hubs, and the second network indicating cell cycle and/or kinase signaling anomalies. fMRI scanning was conducted using a backward-masking task in which subjects were presented with emotionally-valenced faces. Compared with HCs, the depressed subjects displayed a greater hemodynamic response in the right amygdala, left hippocampus, and the ventromedial prefrontal cortex to masked sad versus happy faces. The mRNA levels of several genes were significantly correlated with the hemodynamic response of the amygdala, vmPFC and hippocampus to masked sad versus happy faces. Differentially-expressed transcripts were significantly correlated with thickness of the left subgenual ACC, and volume of the hippocampus and caudate. Our results raise the possibility that molecular-level immune dysfunction can be mapped onto macro-level neuroimaging abnormalities, potentially elucidating a mechanism by which inflammation leads to depression. PMID:23064081

Savitz, Jonathan; Frank, Mark Barton; Victor, Teresa; Bebak, Melissa; Marino, Julie H; Bellgowan, Patrick S F; McKinney, Brett A; Bodurka, Jerzy; Kent Teague, T; Drevets, Wayne C

2013-07-01

125

Gene functional dynamics: environment as a trigger?  

PubMed

Recent decades have seen the deciphering of the human genome and, also, progress in studies related to the effects of space-weather on humans. The progress in genetics allows us to connect many human pathologies with specific gene abnormalities. Concomitantly it has been shown that many congenital and adherent diseases, and the timing of death are connected with space factors such as solar activity (SA), geomagnetic activity (GMA), cosmic ray activity (CRA), and space neutron and proton flux. Here arises the question to what extent gene expression is affected by the aforementioned space physical activity parameters. This is the motto of this hypothetical paper. In conclusion, the space-weather-related timing of many medical events invites presumption that gene activity is a changing phenomenon and space weather components may be playing a regulatory role in these changes. PMID:24259246

Stoupel, Eliyahu G

2014-05-01

126

Pancreatic function and gene deletion F508 in cystic fibrosis.  

PubMed Central

In view of the possible relation between pancreatic function and cystic fibrosis (CF) gene mutations, a detailed study on Italian patients was performed. Seventy pancreatic insufficient and 48 pancreatic sufficient patients were included after very accurate characterisation of their pancreatic and digestive function, all performed in the same CF centre. The CF gene deletion F508 was tested to define the patients' genotypes. The results confirm that the mutation correlates with pancreatic insufficiency, and is recessive to other, as yet unreported, mutant alleles that determine pancreatic sufficiency. An indication that duodenal bicarbonate output is more severely reduced in the presence of deletion F508 is also presented. The data are discussed in relation to a hypothesis on the primary effects of CF gene deletion F508. PMID:2277379

Borgo, G; Mastella, G; Gasparini, P; Zorzanello, A; Doro, R; Pignatti, P F

1990-01-01

127

Pancreatic function and gene deletion F508 in cystic fibrosis.  

PubMed

In view of the possible relation between pancreatic function and cystic fibrosis (CF) gene mutations, a detailed study on Italian patients was performed. Seventy pancreatic insufficient and 48 pancreatic sufficient patients were included after very accurate characterisation of their pancreatic and digestive function, all performed in the same CF centre. The CF gene deletion F508 was tested to define the patients' genotypes. The results confirm that the mutation correlates with pancreatic insufficiency, and is recessive to other, as yet unreported, mutant alleles that determine pancreatic sufficiency. An indication that duodenal bicarbonate output is more severely reduced in the presence of deletion F508 is also presented. The data are discussed in relation to a hypothesis on the primary effects of CF gene deletion F508. PMID:2277379

Borgo, G; Mastella, G; Gasparini, P; Zorzanello, A; Doro, R; Pignatti, P F

1990-11-01

128

Calcitonin gene-related peptide and menopause  

PubMed Central

The review summarizes recent findings with respect to pathophysiological role of calcitonin gene-related peptide (CGRP), in postmenopausal symptoms and diseases, which has opened horizons in understanding pathophysiology of menopause in a better way. Current evidences strongly propose a need to develop CGRP receptor antagonists, which may prove beneficial in many prevalent menopausal symptom/diseases such as vasomotor symptoms, cardiovascular risk, obesity, and major depressive disorder, in which CGRP levels are elevated. PMID:21799630

Sharma, Sudhaa; Mahajan, Annil; Tandon, Vishal R.

2010-01-01

129

Microbial Functional Gene Diversity with a Shift of Subsurface Redox Conditions during In Situ Uranium Reduction  

PubMed Central

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 (Eh) 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

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.

2012-01-01

130

GO-based Functional Dissimilarity of Gene Sets  

PubMed Central

Background The Gene Ontology (GO) provides a controlled vocabulary for describing the functions of genes and can be used to evaluate the functional coherence of gene sets. Many functional coherence measures consider each pair of gene functions in a set and produce an output based on all pairwise distances. A single gene can encode multiple proteins that may differ in function. For each functionality, other proteins that exhibit the same activity may also participate. Therefore, an identification of the most common function for all of the genes involved in a biological process is important in evaluating the functional similarity of groups of genes and a quantification of functional coherence can helps to clarify the role of a group of genes working together. Results To implement this approach to functional assessment, we present GFD (GO-based Functional Dissimilarity), a novel dissimilarity measure for evaluating groups of genes based on the most relevant functions of the whole set. The measure assigns a numerical value to the gene set for each of the three GO sub-ontologies. Conclusions Results show that GFD performs robustly when applied to gene set of known functionality (extracted from KEGG). It performs particularly well on randomly generated gene sets. An ROC analysis reveals that the performance of GFD in evaluating the functional dissimilarity of gene sets is very satisfactory. A comparative analysis against other functional measures, such as GS2 and those presented by Resnik and Wang, also demonstrates the robustness of GFD. PMID:21884611

2011-01-01

131

Highlights of glycosylation and adhesion related genes involved in myogenesis  

PubMed Central

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

2014-01-01

132

A widespread class of reverse transcriptase-related cellular genes  

PubMed Central

Reverse transcriptases (RTs) polymerize DNA on RNA templates. They fall into several structurally related but distinct classes and form an assemblage of RT-like enzymes that, in addition to RTs, also includes certain viral RNA-dependent RNA polymerases (RdRP) synthesizing RNA on RNA templates. It is generally believed that most RT-like enzymes originate from retrotransposons or viruses and have no specific function in the host cell, with telomerases being the only notable exception. Here we report on the discovery and properties of a unique class of RT-related cellular genes collectively named rvt. We present evidence that rvts are not components of retrotransposons or viruses, but single-copy genes with a characteristic domain structure that may contain introns in evolutionarily conserved positions, occur in syntenic regions, and evolve under purifying selection. These genes can be found in all major taxonomic groups including protists, fungi, animals, plants, and even bacteria, although they exhibit patchy phylogenetic distribution in each kingdom. We also show that the RVT protein purified from one of its natural hosts, Neurospora crassa, exists in a multimeric form and has the ability to polymerize NTPs as well as dNTPs in vitro, with a strong preference for NTPs, using Mn2+ as a cofactor. The existence of a previously unknown class of single-copy RT-related genes calls for reevaluation of the current views on evolution and functional roles of RNA-dependent polymerases in living cells. PMID:21876125

Gladyshev, Eugene A.; Arkhipova, Irina R.

2011-01-01

133

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function  

E-print Network

, we will explore the functions and roles of plastid encoded genes in metabolism and their evolutionary take place in plastids, including synthesis of starch, fatty acids, pigments and amino acids (reviewed

dePamphilis, Claude

134

dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors.  

PubMed

dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-kappaB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment "niche." Our findings also demonstrate a role for Dlk1 in mediating the immune response. PMID:17182623

Abdallah, Basem M; Boissy, Patrice; Tan, Qihua; Dahlgaard, Jesper; Traustadottir, Gunnhildur A; Kupisiewicz, Katarzyna; Laborda, Jorge; Delaisse, Jean-Marie; Kassem, Moustapha

2007-03-01

135

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

SciTech Connect

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.

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

136

Gene autoregulation via intronic microRNAs and its functions  

PubMed Central

Background MicroRNAs, post-transcriptional repressors of gene expression, play a pivotal role in gene regulatory networks. They are involved in core cellular processes and their dysregulation is associated to a broad range of human diseases. This paper focus on a minimal microRNA-mediated regulatory circuit, in which a protein-coding gene (host gene) is targeted by a microRNA located inside one of its introns. Results Autoregulation via intronic microRNAs is widespread in the human regulatory network, as confirmed by our bioinformatic analysis, and can perform several regulatory tasks despite its simple topology. Our analysis, based on analytical calculations and simulations, indicates that this circuitry alters the dynamics of the host gene expression, can induce complex responses implementing adaptation and Weber’s law, and efficiently filters fluctuations propagating from the upstream network to the host gene. A fine-tuning of the circuit parameters can optimize each of these functions. Interestingly, they are all related to gene expression homeostasis, in agreement with the increasing evidence suggesting a role of microRNA regulation in conferring robustness to biological processes. In addition to model analysis, we present a list of bioinformatically predicted candidate circuits in human for future experimental tests. Conclusions The results presented here suggest a potentially relevant functional role for negative self-regulation via intronic microRNAs, in particular as a homeostatic control mechanism of gene expression. Moreover, the map of circuit functions in terms of experimentally measurable parameters, resulting from our analysis, can be a useful guideline for possible applications in synthetic biology. PMID:23050836

2012-01-01

137

Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions  

PubMed Central

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

Eswaran, Jeyanthy; Kumar, Rakesh

2011-01-01

138

Legendre polynomials and related functions  

E-print Network

=O. ((5-7) Differentiating this equation yn times with respect to X & using the well known formula i~~) (mj (~ (), ~(~-i) &m-2) w (uv) =U ytmv v'+, u y we obtain (~t z) 1 m i~) (ml (&-z ) y -&(~+I) )(p +(n-m)(nfl+~) y = 0 or~ a (&-&')(y ) -2(I... iI)X(y )'+ (n-e)(n+ tnii) y' I = 0, (I&. 8) whose form 1s identical with(IS-6). The functions P& tX), qa(X)are independent solutions of (IS-7) and henos also of (I5-8), Hence in- dependent solutions of (IS-6) are P?(II) d Q?(II) dx Ifl Hence...

Adams, Richard McGary

2012-06-07

139

A Relational Derivation of a Functional Program  

Microsoft Academic Search

This article is an introduction to the use of relational calculi in deriving programs. We present a derivation in a relational language of a functional program that adds one bit to a binary number. The resulting program is unsurprising, being the standard 'column of half{adders', but the derivation illustrates a number of points about working with relations rather than functions.

Graham Hutton

1992-01-01

140

Bacterial community assembly based on functional genes rather than species  

PubMed Central

The principles underlying the assembly and structure of complex microbial communities are an issue of long-standing concern to the field of microbial ecology. We previously analyzed the community membership of bacterial communities associated with the green macroalga Ulva australis, and proposed a competitive lottery model for colonization of the algal surface in an attempt to explain the surprising lack of similarity in species composition across different algal samples. Here we extend the previous study by investigating the link between community structure and function in these communities, using metagenomic sequence analysis. Despite the high phylogenetic variability in microbial species composition on different U. australis (only 15% similarity between samples), similarity in functional composition was high (70%), and a core of functional genes present across all algal-associated communities was identified that were consistent with the ecology of surface- and host-associated bacteria. These functions were distributed widely across a variety of taxa or phylogenetic groups. This observation of similarity in habitat (niche) use with respect to functional genes, but not species, together with the relative ease with which bacteria share genetic material, suggests that the key level at which to address the assembly and structure of bacterial communities may not be “species” (by means of rRNA taxonomy), but rather the more functional level of genes. PMID:21825123

Burke, Catherine; Steinberg, Peter; Rusch, Doug; Kjelleberg, Staffan; Thomas, Torsten

2011-01-01

141

Horizontal gene transfer of microbial cellulases into nematode genomes is associated with functional assimilation and gene turnover  

PubMed Central

Background Natural acquisition of novel genes from other organisms by horizontal or lateral gene transfer is well established for microorganisms. There is now growing evidence that horizontal gene transfer also plays important roles in the evolution of eukaryotes. Genome-sequencing and EST projects of plant and animal associated nematodes such as Brugia, Meloidogyne, Bursaphelenchus and Pristionchus indicate horizontal gene transfer as a key adaptation towards parasitism and pathogenicity. However, little is known about the functional activity and evolutionary longevity of genes acquired by horizontal gene transfer and the mechanisms favoring such processes. Results We examine the transfer of cellulase genes to the free-living and beetle-associated nematode Pristionchus pacificus, for which detailed phylogenetic knowledge is available, to address predictions by evolutionary theory for successful gene transfer. We used transcriptomics in seven Pristionchus species and three other related diplogastrid nematodes with a well-defined phylogenetic framework to study the evolution of ancestral cellulase genes acquired by horizontal gene transfer. We performed intra-species, inter-species and inter-genic analysis by comparing the transcriptomes of these ten species and tested for cellulase activity in each species. Species with cellulase genes in their transcriptome always exhibited cellulase activity indicating functional integration into the host's genome and biology. The phylogenetic profile of cellulase genes was congruent with the species phylogeny demonstrating gene longevity. Cellulase genes show notable turnover with elevated birth and death rates. Comparison by sequencing of three selected cellulase genes in 24 natural isolates of Pristionchus pacificus suggests these high evolutionary dynamics to be associated with copy number variations and positive selection. Conclusion We could demonstrate functional integration of acquired cellulase genes into the nematode's biology as predicted by theory. Thus, functional assimilation, remarkable gene turnover and selection might represent key features of horizontal gene transfer events in nematodes. PMID:21232122

2011-01-01

142

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

Microsoft Academic Search

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,

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

2010-01-01

143

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

PubMed Central

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

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

144

On the relation between promoter divergence and gene expression evolution  

E-print Network

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

Barkai, Naama

145

How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems  

Microsoft Academic Search

Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct

Dennis L. Murphy; Meredith A. Fox; Kiara R. Timpano; Pablo R. Moya; Renee Ren-Patterson; Anne M. Andrews; Andrew Holmes; Klaus-Peter Lesch; Jens R. Wendland

2008-01-01

146

Relating equivalence relations to equivalence relations: A relational framing model of complex human functioning  

PubMed Central

The current study aimed to develop a behavior-analytic model of analogical reasoning. In Experiments 1 and 2 subjects (adults and children) were trained and tested for the formation of four, three-member equivalence relations using a delayed matching-to-sample procedure. All subjects (Experiments 1 and 2) were exposed to tests that examined relations between equivalence and non-equivalence relations. For example, on an equivalence-equivalence relation test, the complex sample B1/C1 and the two complex comparisons B3/C3 and B3/C4 were used, and on a nonequivalence-nonequivalence relation test the complex sample B1/C2 was presented with the same two comparisons. All subjects consistently related equivalence relations to equivalence relations and nonequivalence relations to nonequivalence relations (e.g., picked B3/C3 in the presence of B1/C1 and picked B3/C4 in the presence of B1/C2). In Experiment 3, the equivalence responding, the equivalence-equivalence responding, and the nonequivalence-nonequivalence responding was successfully brought under contextual control. Finally, it was shown that the contextual cues could function successfully as comparisons, and the complex samples and comparisons could function successfully as contextual cues and samples, respectively. These data extend the equivalence paradigm and contribute to a behaviour-analytic interpretation of analogical reasoning and complex human functioning, in general. PMID:22477120

Barnes, Dermot; Hegarty, Neil; Smeets, Paul M.

1997-01-01

147

Genes related to immunity, as expressed in the alfalfa leafcutting bee, Megachile rotundata, during pathogen challenge.  

PubMed

Virtually nothing is known about disease resistance in solitary bees, so expressed sequence tag (EST) databases were developed to search for immune response genes in the alfalfa leafcutting bee. We identified 104 putative immunity-related genes from both healthy and pathogen-challenged bee larvae, and 12 more genes using PCR amplification. The genes identified coded for proteins with a wide variety of innate immune response functions, including pathogen recognition, phagocytosis, the prophenoloxidase cascade, melanization, coagulation and several signalling pathways. Some immune response genes were highly conserved with honey bee genes, and more distantly related to other insects. The data presented provides the first analysis of immune function in a solitary bee and provides a foundation for the further analysis of gene expression patterns in bees. PMID:19863668

Xu, J; James, R

2009-11-01

148

Functional-Network-Based Gene Set Analysis Using Gene-Ontology  

PubMed Central

To account for the functional non-equivalence among a set of genes within a biological pathway when performing gene set analysis, we introduce GOGANPA, a network-based gene set analysis method, which up-weights genes with functions relevant to the gene set of interest. The genes are weighted according to its degree within a genome-scale functional network constructed using the functional annotations available from the gene ontology database. By benchmarking GOGANPA using a well-studied P53 data set and three breast cancer data sets, we will demonstrate the power and reproducibility of our proposed method over traditional unweighted approaches and a competing network-based approach that involves a complex integrated network. GOGANPA’s sole reliance on gene ontology further allows GOGANPA to be widely applicable to the analysis of any gene-ontology-annotated genome. PMID:23418449

Chang, Billy; Kustra, Rafal; Tian, Weidong

2013-01-01

149

Predicting Gene Function From Patterns of Annotation  

E-print Network

Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA The Gene Ontology Ontology Consortium (Gene Ontology Consortium 2000) provides a standardized vocabulary for the annotation experimentally. A variety of approaches for predicting Gene Ontology (GO) attributes have been attempted. Natural

Roth, Frederick

150

Mining the Gene Wiki for functional genomic knowledge  

PubMed Central

Background Ontology-based gene annotations are important tools for organizing and analyzing genome-scale biological data. Collecting these annotations is a valuable but costly endeavor. The Gene Wiki makes use of Wikipedia as a low-cost, mass-collaborative platform for assembling text-based gene annotations. The Gene Wiki is comprised of more than 10,000 review articles, each describing one human gene. The goal of this study is to define and assess a computational strategy for translating the text of Gene Wiki articles into ontology-based gene annotations. We specifically explore the generation of structured annotations using the Gene Ontology and the Human Disease Ontology. Results Our system produced 2,983 candidate gene annotations using the Disease Ontology and 11,022 candidate annotations using the Gene Ontology from the text of the Gene Wiki. Based on manual evaluations and comparisons to reference annotation sets, we estimate a precision of 90-93% for the Disease Ontology annotations and 48-64% for the Gene Ontology annotations. We further demonstrate that this data set can systematically improve the results from gene set enrichment analyses. Conclusions The Gene Wiki is a rapidly growing corpus of text focused on human gene function. Here, we demonstrate that the Gene Wiki can be a powerful resource for generating ontology-based gene annotations. These annotations can be used immediately to improve workflows for building curated gene annotation databases and knowledge-based statistical analyses. PMID:22165947

2011-01-01

151

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

PubMed Central

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

Bettembourg, Charles; Diot, Christian; Dameron, Olivier

2014-01-01

152

Genome-wide Approaches Reveal Functional Vascular Endothelial Growth Factor (VEGF)-inducible Nuclear Factor of Activated T Cells (NFAT) c1 Binding to Angiogenesis-related Genes in the Endothelium.  

PubMed

VEGF is a key regulator of endothelial cell migration, proliferation, and inflammation, which leads to activation of several signaling cascades, including the calcineurin-nuclear factor of activated T cells (NFAT) pathway. NFAT is not only important for immune responses but also for cardiovascular development and the pathogenesis of Down syndrome. By using Down syndrome model mice and clinical patient samples, we showed recently that the VEGF-calcineurin-NFAT signaling axis regulates tumor angiogenesis and tumor metastasis. However, the connection between genome-wide views of NFAT-mediated gene regulation and downstream gene function in the endothelium has not been studied extensively. Here we performed comprehensive mapping of genome-wide NFATc1 binding in VEGF-stimulated primary cultured endothelial cells and elucidated the functional consequences of VEGF-NFATc1-mediated phenotypic changes. A comparison of the NFATc1 ChIP sequence profile and epigenetic histone marks revealed that predominant NFATc1-occupied peaks overlapped with promoter-associated histone marks. Moreover, we identified two novel NFATc1 regulated genes, CXCR7 and RND1. CXCR7 knockdown abrogated SDF-1- and VEGF-mediated cell migration and tube formation. siRNA treatment of RND1 impaired vascular barrier function, caused RhoA hyperactivation, and further stimulated VEGF-mediated vascular outgrowth from aortic rings. Taken together, these findings suggest that dynamic NFATc1 binding to target genes is critical for VEGF-mediated endothelial cell activation. CXCR7 and RND1 are NFATc1 target genes with multiple functions, including regulation of cell migration, tube formation, and barrier formation in endothelial cells. PMID:25157100

Suehiro, Jun-Ichi; Kanki, Yasuharu; Makihara, Chihiro; Schadler, Keri; Miura, Mai; Manabe, Yuuka; Aburatani, Hiroyuki; Kodama, Tatsuhiko; Minami, Takashi

2014-10-17

153

Universal R-matrix and functional relations  

NASA Astrophysics Data System (ADS)

We collect and systematize general definitions and facts on the application of quantum groups to the construction of functional relations in the theory of integrable systems. As an example, we reconsider the case of the quantum group Uq(L({sl}_2)) related to the six-vertex model. We prove the full set of the functional relations in the form independent of the representation of the quantum group in the quantum space and specialize them to the case of the six-vertex model.

Boos, Herman; Göhmann, Frank; Klümper, Andreas; Nirov, Khazret S.; Razumov, Alexander V.

2014-06-01

154

Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes  

PubMed Central

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process. PMID:22912585

Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhaes, Joao Pedro

2012-01-01

155

Age-related regulation of genes: slow homeostatic changes and age-dimension technology  

NASA Astrophysics Data System (ADS)

Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

2002-11-01

156

Odd-skipped related 2 regulates genes related to proliferation and development  

SciTech Connect

Cell proliferation is a biological process in which chromosomes replicate in one cell and equally divide into two daughter cells. Our previous findings suggested that Odd-skipped related 2 (Osr2) plays an important role in cellular quiescence and proliferation under epigenetic regulation. However, the mechanism used by Osr2 to establish and maintain proliferation is unknown. To examine the functional role of Osr2 in cell proliferation, we analyzed its downstream target genes using microarray analysis following adenovirus-induced overexpression of Osr2 as well as knockdown with Osr2 siRNA, which showed that Osr2 regulates a multitude of genes involved in proliferation and the cell cycle, as well as development. Additional proliferation assays also indicated that Osr2 likely functions to elicit cell proliferation. Together, these results suggest that Osr2 plays important roles in proliferation and development.

Kawai, Shinji, E-mail: skawai@dent.osaka-u.ac.jp [Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871 (Japan)] [Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871 (Japan); Abiko, Yoshimitsu [Department of Biochemistry, Nihon University School of Dentistry at Matsudo, Matsudo-Chiba 271-8587 (Japan)] [Department of Biochemistry, Nihon University School of Dentistry at Matsudo, Matsudo-Chiba 271-8587 (Japan); Amano, Atsuo [Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871 (Japan)] [Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871 (Japan)

2010-07-23

157

Functions Encoded by Pyrrolnitrin Biosynthetic Genes from Pseudomonas fluorescens  

Microsoft Academic Search

Pyrrolnitrin is a secondary metabolite derived from tryptophan and has strong antifungal activity. Recently we described four genes, prnABCD, from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin. In the work presented here, we describe the function of each prn gene product. The four genes encode proteins identical in size and serology to proteins present in wild-type Pseudomonas fluorescens, but

SABINE KIRNER; PHILIP E. HAMMER; D. STEVEN HILL; ANNETT ALTMANN; ILONA FISCHER; LAURA J. WEISLO; MIKE LANAHAN; KARL-HEINZ VAN PEE; JAMES M. LIGON

1998-01-01

158

Transport of Magnesium by a Bacterial Nramp-Related Gene  

PubMed Central

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

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

2014-01-01

159

A Genome-Wide Screen Indicates Correlation between Differentiation and Expression of Metabolism Related Genes  

PubMed Central

Differentiated tissues may be considered as materials with distinct properties. The differentiation program of a given tissue ensures that it acquires material properties commensurate with its function. It may be hypothesized that some of these properties are acquired through production of tissue-specific metabolites synthesized by metabolic enzymes. To establish correlation between metabolism and organogenesis we have carried out a genome-wide expression study of metabolism related genes by RNA in-situ hybridization. 23% of the metabolism related genes studied are expressed in a tissue-restricted but not tissue-exclusive manner. We have conducted the screen on whole mount chicken (Gallus gallus) embryos from four distinct developmental stages to correlate dynamic changes in expression patterns of metabolic enzymes with spatio-temporally unique developmental events. Our data strongly suggests that unique combinations of metabolism related genes, and not specific metabolic pathways, are upregulated during differentiation. Further, expression of metabolism related genes in well established signaling centers that regulate different aspects of morphogenesis indicates developmental roles of some of the metabolism related genes. The database of tissue-restricted expression patterns of metabolism related genes, generated in this study, should serve as a resource for systematic identification of these genes with tissue-specific functions during development. Finally, comprehensive understanding of differentiation is not possible unless the downstream genes of a differentiation cascade are identified. We propose, metabolic enzymes constitute a significant portion of these downstream target genes. Thus our study should help elucidate different aspects of tissue differentiation. PMID:23717462

Shende, Akhilesh; Singh, Anupama; Meena, Anil; Ghosal, Ritika; Ranganathan, Madhav; Bandyopadhyay, Amitabha

2013-01-01

160

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

PubMed

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

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

161

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

PubMed Central

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

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

2006-01-01

162

Recent Achievement in Gene Cloning and Functional Genomics in Soybean  

PubMed Central

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

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

2013-01-01

163

Executive Functioning and Alcohol-Related Aggression  

Microsoft Academic Search

The primary goal of this investigation was to determine whether executive functioning (EF) would moderate the alcohol-aggression relation. Participants were 310 (152 men and 158 women) healthy social drinkers between 21 and 35 years of age. EF as well as non-EF skills were measured with 13 validated neuropsychological tests. Following the consumption of either an alcoholic or a placebo beverage,

Peter R. Giancola

2004-01-01

164

Methods for transient assay of gene function in floral tissues  

PubMed Central

Background There is considerable interest in rapid assays or screening systems for assigning gene function. However, analysis of gene function in the flowers of some species is restricted due to the difficulty of producing stably transformed transgenic plants. As a result, experimental approaches based on transient gene expression assays are frequently used. Biolistics has long been used for transient over-expression of genes of interest, but has not been exploited for gene silencing studies. Agrobacterium-infiltration has also been used, but the focus primarily has been on the transient transformation of leaf tissue. Results Two constructs, one expressing an inverted repeat of the Antirrhinum majus (Antirrhinum) chalcone synthase gene (CHS) and the other an inverted repeat of the Antirrhinum transcription factor gene Rosea1, were shown to effectively induce CHS and Rosea1 gene silencing, respectively, when introduced biolistically into petal tissue of Antirrhinum flowers developing in vitro. A high-throughput vector expressing the Antirrhinum CHS gene attached to an inverted repeat of the nos terminator was also shown to be effective. Silencing spread systemically to create large zones of petal tissue lacking pigmentation, with transmission of the silenced state spreading both laterally within the affected epidermal cell layer and into lower cell layers, including the epidermis of the other petal surface. Transient Agrobacterium-mediated transformation of petal tissue of tobacco and petunia flowers in situ or detached was also achieved, using expression of the reporter genes GUS and GFP to visualise transgene expression. Conclusion We demonstrate the feasibility of using biolistics-based transient RNAi, and transient transformation of petal tissue via Agrobacterium infiltration to study gene function in petals. We have also produced a vector for high throughput gene silencing studies, incorporating the option of using T-A cloning to insert the gene sequence of interest. These techniques should allow analysis of gene function in a much broader range of flower species. PMID:17207290

Shang, Yongjin; Schwinn, Kathy E; Bennett, Michael J; Hunter, Donald A; Waugh, Toni L; Pathirana, Nilangani N; Brummell, David A; Jameson, Paula E; Davies, Kevin M

2007-01-01

165

Functional hypervariability and gene diversity of cardioactive neuropeptides.  

PubMed

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions. PMID:20923766

Möller, Carolina; Melaun, Christian; Castillo, Cecilia; Díaz, Mary E; Renzelman, Chad M; Estrada, Omar; Kuch, Ulrich; Lokey, Scott; Marí, Frank

2010-12-24

166

GeneFarm, structural and functional annotation of Arabidopsis gene and protein families by a network  

E-print Network

GeneFarm, structural and functional annotation of Arabidopsis gene and protein families11 , Christophe Geourjon8 , Jean-Michel Grienenberger10 , Guy Houlne´10 , Elisabeth Jamet10 , Fre on every member of each gene family. Performing a family-wide annotation makes the task easier and *To whom

Gent, Universiteit

167

Implications of functional similarity for gene regulatory interactions  

PubMed Central

If one gene regulates another, those two genes are likely to be involved in many of the same biological functions. Conversely, shared biological function may be suggestive of the existence and nature of a regulatory interaction. With this in mind, we develop a measure of functional similarity between genes based on annotations made to the Gene Ontology in which the magnitude of their functional relationship is also indicative of a regulatory relationship. In contrast to other measures that have previously been used to quantify the functional similarity between genes, our measure scales the strength of any shared functional annotation by the frequency of that function's appearance across the entire set of annotations. We apply our method to both Escherichia coli and Saccharomyces cerevisiae gene annotations and find that the strength of our scaled similarity measure is more predictive of known regulatory interactions than previously published measures of functional similarity. In addition, we observe that the strength of the scaled similarity measure is correlated with the structural importance of links in the known regulatory network. By contrast, other measures of functional similarity are not indicative of any structural importance in the regulatory network. We therefore conclude that adequately adjusting for the frequency of shared biological functions is important in the construction of a functional similarity measure aimed at elucidating the existence and nature of regulatory interactions. We also compare the performance of the scaled similarity with a high-throughput method for determining regulatory interactions from gene expression data and observe that the ontology-based approach identifies a different subset of regulatory interactions compared with the gene expression approach. We show that combining predictions from the scaled similarity with those from the reconstruction algorithm leads to a significant improvement in the accuracy of the reconstructed network. PMID:22298814

Glass, Kimberly; Ott, Edward; Losert, Wolfgang; Girvan, Michelle

2012-01-01

168

A yeast functional screen predicts new candidate ALS disease genes  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having a more severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery. PMID:22065782

Couthouis, Julien; Hart, Michael P.; Shorter, James; DeJesus-Hernandez, Mariely; Erion, Renske; Oristano, Rachel; Liu, Annie X.; Ramos, Daniel; Jethava, Niti; Hosangadi, Divya; Epstein, James; Chiang, Ashley; Diaz, Zamia; Nakaya, Tadashi; Ibrahim, Fadia; Kim, Hyung-Jun; Solski, Jennifer A.; Williams, Kelly L.; Mojsilovic-Petrovic, Jelena; Ingre, Caroline; Boylan, Kevin; Graff-Radford, Neill R.; Dickson, Dennis W.; Clay-Falcone, Dana; Elman, Lauren; McCluskey, Leo; Greene, Robert; Kalb, Robert G.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Ludolph, Albert; Robberecht, Wim; Andersen, Peter M.; Nicholson, Garth A.; Blair, Ian P.; King, Oliver D.; Bonini, Nancy M.; Van Deerlin, Vivianna; Rademakers, Rosa; Mourelatos, Zissimos; Gitler, Aaron D.

2011-01-01

169

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

PubMed

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

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

2013-01-01

170

Evolutionary, structural and functional relationships revealed by comparative analysis of syntenic genes in Rhizobiales  

PubMed Central

Background Comparative genomics has provided valuable insights into the nature of gene sequence variation and chromosomal organization of closely related bacterial species. However, questions about the biological significance of gene order conservation, or synteny, remain open. Moreover, few comprehensive studies have been reported for rhizobial genomes. Results We analyzed the genomic sequences of four fast growing Rhizobiales (Sinorhizobium meliloti, Agrobacterium tumefaciens, Mesorhizobium loti and Brucella melitensis). We made a comprehensive gene classification to define chromosomal orthologs, genes with homologs in other replicons such as plasmids, and those which were species-specific. About two thousand genes were predicted to be orthologs in each chromosome and about 80% of these were syntenic. A striking gene colinearity was found in pairs of organisms and a large fraction of the microsyntenic regions and operons were similar. Syntenic products showed higher identity levels than non-syntenic ones, suggesting a resistance to sequence variation due to functional constraints; also, an unusually high fraction of syntenic products contained membranal segments. Syntenic genes encode a high proportion of essential cell functions, presented a high level of functional relationships and a very low horizontal gene transfer rate. The sequence variability of the proteins can be considered the species signature in response to specific niche adaptation. Comparatively, an analysis with genomes of Enterobacteriales showed a different gene organization but gave similar results in the synteny conservation, essential role of syntenic genes and higher functional linkage among the genes of the microsyntenic regions. Conclusion Syntenic bacterial genes represent a commonly evolved group. They not only reveal the core chromosomal segments present in the last common ancestor and determine the metabolic characteristics shared by these microorganisms, but also show resistance to sequence variation and rearrangement, possibly due to their essential character. In Rhizobiales and Enterobacteriales, syntenic genes encode a high proportion of essential cell functions and presented a high level of functional relationships. PMID:16229745

Guerrero, Gabriela; Peralta, Humberto; Aguilar, Alejandro; Diaz, Rafael; Villalobos, Miguel Angel; Medrano-Soto, Arturo; Mora, Jaime

2005-01-01

171

RNA interference can be used to disrupt gene function in tardigrades.  

PubMed

How morphological diversity arises is a key question in evolutionary developmental biology. As a long-term approach to address this question, we are developing the water bear Hypsibius dujardini (Phylum Tardigrada) as a model system. We expect that using a close relative of two well-studied models, Drosophila (Phylum Arthropoda) and Caenorhabditis elegans (Phylum Nematoda), will facilitate identifying genetic pathways relevant to understanding the evolution of development. Tardigrades are also valuable research subjects for investigating how organisms and biological materials can survive extreme conditions. Methods to disrupt gene activity are essential to each of these efforts, but no such method yet exists for the Phylum Tardigrada. We developed a protocol to disrupt tardigrade gene functions by double-stranded RNA-mediated RNA interference (RNAi). We showed that targeting tardigrade homologs of essential developmental genes by RNAi produced embryonic lethality, whereas targeting green fluorescent protein did not. Disruption of gene functions appears to be relatively specific by two criteria: targeting distinct genes resulted in distinct phenotypes that were consistent with predicted gene functions and by RT-PCR, RNAi reduced the level of a target mRNA and not a control mRNA. These studies represent the first evidence that gene functions can be disrupted by RNAi in the phylum Tardigrada. Our results form a platform for dissecting tardigrade gene functions for understanding the evolution of developmental mechanisms and survival in extreme environments. PMID:23187800

Tenlen, Jennifer R; McCaskill, Shaina; Goldstein, Bob

2013-05-01

172

RNA interference can be used to disrupt gene function in tardigrades  

PubMed Central

How morphological diversity arises is a key question in evolutionary developmental biology. As a long-term approach to address this question, we are developing the water bear Hypsibius dujardini (Phylum Tardigrada) as a model system. We expect that using a close relative of two well-studied models, Drosophila (Phylum Arthropoda) and Caenorhabditis elegans (Phylum Nematoda), will facilitate identifying genetic pathways relevant to understanding the evolution of development. Tardigrades are also valuable research subjects for investigating how organisms and biological materials can survive extreme conditions. Methods to disrupt gene activity are essential to each of these efforts, but no such method yet exists for the Phylum Tardigrada. We developed a protocol to disrupt tardigrade gene functions by double-stranded RNA-mediated RNA interference (RNAi). We show that targeting tardigrade homologs of essential developmental genes by RNAi produced embryonic lethality, whereas targeting green fluorescent protein did not. Disruption of gene functions appears to be relatively specific by two criteria: targeting distinct genes resulted in distinct phenotypes that were consistent with predicted gene functions, and by RT-PCR, RNAi reduced the level of a target mRNA and not a control mRNA. These studies represent the first evidence that gene functions can be disrupted by RNAi in the phylum Tardigrada. Our results form a platform for dissecting tardigrade gene functions for understanding the evolution of developmental mechanisms and survival in extreme environments. PMID:23187800

Tenlen, Jennifer R.; McCaskill, Shaina; Goldstein, Bob

2012-01-01

173

Functional Identification of the Proteus mirabilis Core Lipopolysaccharide Biosynthesis Genes?  

PubMed Central

In this study, we report the identification of genes required for the biosynthesis of the core lipopolysaccharides (LPSs) of two strains of Proteus mirabilis. Since P. mirabilis and Klebsiella pneumoniae share a core LPS carbohydrate backbone extending up to the second outer-core residue, the functions of the common P. mirabilis genes was elucidated by genetic complementation studies using well-defined mutants of K. pneumoniae. The functions of strain-specific outer-core genes were identified by using as surrogate acceptors LPSs from two well-defined K. pneumoniae core LPS mutants. This approach allowed the identification of two new heptosyltransferases (WamA and WamC), a galactosyltransferase (WamB), and an N-acetylglucosaminyltransferase (WamD). In both strains, most of these genes were found in the so-called waa gene cluster, although one common core biosynthetic gene (wabO) was found outside this cluster. PMID:20622068

Aquilini, Eleonora; Azevedo, Joana; Jimenez, Natalia; Bouamama, Lamiaa; Tomas, Juan M.; Regue, Miguel

2010-01-01

174

Gene rearrangement and Chernobyl related thyroid cancers  

PubMed Central

The increase in thyroid carcinoma post-Chernobyl has been largely confined to a specific subtype of papillary carcinoma (solid/follicular). This subtype is observed predominantly in children under 10 in unirradiated populations, but maintains a high frequency in those aged 10–15 from those areas exposed to fallout from the Chernobyl accident. The aim of this study was to link morphology with molecular biology. We examined 106 papillary carcinomas from children under the age of 15 at operation. All were examined for rearrangements of the RET oncogene by reverse transcription polymerase chain reaction (RT-PCR); a subset of these cases were also examined for mutations of the three ras oncogenes, exon 10 of the thyroid stimulating hormone receptor, associated more usually with a follicular rather than papillary morphology, and exons 5, 6, 7 and 8 of the p53 gene, commonly involved in undifferentiated thyroid carcinoma. Rearrangements of the RET oncogene were found in 44% of papillary carcinomas in which we studied fresh material; none of the tumours examined showed mutation in any of the other genes. The two rearrangements resulting from inversion of part of chromosome 10 (PTC1 and PTC3) accounted for the majority of RET rearrangements identified, with PTC1 being associated with papillary carcinomas of the classic and diffuse sclerosing variants and PTC3 with the solid/follicular variant. © 2000 Cancer Research Campaign PMID:10646883

Santoro, M; Thomas, G A; Vecchio, G; Williams, G H; Fusco, A; Chiappetta, G; Pozcharskaya, V; Bogdanova, T I; Demidchik, E P; Cherstvoy, E D; Voscoboinik, L; Tronko, N D; Carss, A; Bunnell, H; Tonnachera, M; Parma, J; Dumont, J E; Keller, G; Hofler, H; Williams, E D

2000-01-01

175

Vitamin D related genes in lung development and asthma pathogenesis  

PubMed Central

Background Poor maternal vitamin D intake is a risk factor for subsequent childhood asthma, suggesting that in utero changes related to vitamin D responsive genes might play a crucial role in later disease susceptibility. We hypothesized that vitamin D pathway genes are developmentally active in the fetal lung and that these developmental genes would be associated with asthma susceptibility and regulation in asthma. Methods Vitamin D pathway genes were derived from PubMed and Gene Ontology surveys. Principal component analysis was used to identify characteristic lung development genes. Results Vitamin D regulated genes were markedly over-represented in normal human (odds ratio OR 2.15, 95% confidence interval CI: 1.69-2.74) and mouse (OR 2.68, 95% CI: 2.12-3.39) developing lung transcriptomes. 38 vitamin D pathway genes were in both developing lung transcriptomes with >63% of genes more highly expressed in the later than earlier stages of development. In immortalized B-cells derived from 95 asthmatics and their unaffected siblings, 12 of the 38 (31.6%) vitamin D pathway lung development genes were significantly differentially expressed (OR 3.00, 95% CI: 1.43-6.21), whereas 11 (29%) genes were significantly differentially expressed in 43 control versus vitamin D treated immortalized B-cells from Childhood Asthma Management Program subjects (OR 2.62, 95% CI: 1.22-5.50). 4 genes, LAMP3, PIP5K1B, SCARB2 and TXNIP were identified in both groups; each displays significant biologic plausibility for a role in asthma. Conclusions Our findings demonstrate a significant association between early lung development and asthma–related phenotypes for vitamin D pathway genes, supporting a genomic mechanistic basis for the epidemiologic observations relating maternal vitamin D intake and childhood asthma susceptibility. PMID:24188128

2013-01-01

176

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

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

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

2013-03-01

177

Combining classifiers to predict gene function in Arabidopsis thaliana using large-scale gene expression measurements  

PubMed Central

Background Arabidopsis thaliana is the model species of current plant genomic research with a genome size of 125 Mb and approximately 28,000 genes. The function of half of these genes is currently unknown. The purpose of this study is to infer gene function in Arabidopsis using machine-learning algorithms applied to large-scale gene expression data sets, with the goal of identifying genes that are potentially involved in plant response to abiotic stress. Results Using in house and publicly available data, we assembled a large set of gene expression measurements for A. thaliana. Using those genes of known function, we first evaluated and compared the ability of basic machine-learning algorithms to predict which genes respond to stress. Predictive accuracy was measured using ROC50 and precision curves derived through cross validation. To improve accuracy, we developed a method for combining these classifiers using a weighted-voting scheme. The combined classifier was then trained on genes of known function and applied to genes of unknown function, identifying genes that potentially respond to stress. Visual evidence corroborating the predictions was obtained using electronic Northern analysis. Three of the predicted genes were chosen for biological validation. Gene knockout experiments confirmed that all three are involved in a variety of stress responses. The biological analysis of one of these genes (At1g16850) is presented here, where it is shown to be necessary for the normal response to temperature and NaCl. Conclusion Supervised learning methods applied to large-scale gene expression measurements can be used to predict gene function. However, the ability of basic learning methods to predict stress response varies widely and depends heavily on how much dimensionality reduction is used. Our method of combining classifiers can improve the accuracy of such predictions – in this case, predictions of genes involved in stress response in plants – and it effectively chooses the appropriate amount of dimensionality reduction automatically. The method provides a useful means of identifying genes in A. thaliana that potentially respond to stress, and we expect it would be useful in other organisms and for other gene functions. PMID:17888165

Lan, Hui; Carson, Rachel; Provart, Nicholas J; Bonner, Anthony J

2007-01-01

178

Buffering of crucial functions by paleologous duplicated genes may contribute cyclicality to angiosperm genome duplication  

PubMed Central

Genome duplication followed by massive gene loss has permanently shaped the genomes of many higher eukaryotes, particularly angiosperms. It has long been believed that a primary advantage of genome duplication is the opportunity for the evolution of genes with new functions by modification of duplicated genes. If so, then patterns of genetic diversity among strains within taxa might reveal footprints of selection that are consistent with this advantage. Contrary to classical predictions that duplicated genes may be relatively free to acquire unique functionality, we find among both Arabidopsis ecotypes and Oryza subspecies that SNPs encode less radical amino acid changes in genes for which there exists a duplicated copy at a “paleologous” locus than in “singleton” genes. Preferential retention of duplicated genes encoding long complex proteins and their unexpectedly slow divergence (perhaps because of homogenization) suggest that a primary advantage of retaining duplicated paleologs may be the buffering of crucial functions. Functional buffering and functional divergence may represent extremes in the spectrum of duplicated gene fates. Functional buffering may be especially important during “genomic turmoil” immediately after genome duplication but continues to act ?60 million years later, and its gradual deterioration may contribute cyclicality to genome duplication in some lineages. PMID:16467140

Chapman, Brad A.; Bowers, John E.; Feltus, Frank A.; Paterson, Andrew H.

2006-01-01

179

Iroquois genes: genomic organization and function in vertebrate neural development  

Microsoft Academic Search

We review recent work that shows that the iroquois (Iro\\/Irx) homeobox genes have conserved genomic organization in Drosophila and vertebrates. In addition, these genes play pivotal functions in the initial specification of the vertebrate neuroectoderm, and, in collaboration with other transcription factors, later subdivision of the anterior–posterior and dorso-ventral axis of the neuroectoderm.

José Luis Gómez-Skarmeta; Juan Modolell

2002-01-01

180

A Framework for Exploring Functional Variability in Olfactory Receptor Genes  

E-print Network

Haven, Connecticut, United States of America, 4 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America Background. Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional

Crasto, Chiquito

181

Functional screening in Drosophila identifies Alzheimer's disease susceptibility genes  

E-print Network

; Accepted September 20, 2013 Using a Drosophila model of Alzheimer's disease (AD), we systematically, cell-based strategies, as well as model organism studies. These efforts To whom correspondence shouldFunctional screening in Drosophila identifies Alzheimer's disease susceptibility genes

Perrimon, Norbert

182

Functional independence of circadian clocks that regulate plant gene expression  

E-print Network

Functional independence of circadian clocks that regulate plant gene expression Simon C. Thain and behaviour of most eukaryotes, controlling an orderly succession of physiological processes in plants. Peripheral plant and animal tissues also maintain circadian rhythms when isolated in culture

Millar, Andrew J.

183

Manipulation of gene function in Xenopus laevis  

PubMed Central

Xenopus laevis embryos are particularly well suited to address questions requiring either knockdown or overexpression of genes in a tissue-specific fashion during vertebrate embryonic development. These manipulations are achieved by targeted injection of either antisense morpholino oligonucleotides, or synthetic mRNAs, respectively, into the early embryo. Herein we offer detailed protocols describing how to design and perform these experiments successfully, as well as a brief discussion of considerations for performing a microarray analysis in this organism. PMID:21805261

Mimoto, Mizuho S.; Christian, Jan L.

2012-01-01

184

Antiviral function of tilapia hepcidin 1-5 and its modulation of immune-related gene expressions against infectious pancreatic necrosis virus (IPNV) in Chinook salmon embryo (CHSE)-214 cells.  

PubMed

Antimicrobial peptides, small cysteine-rich molecules, play vital roles in host defense mechanisms against pathogen infection. Recently, tilapia hepcidin (TH)1-5, was characterized, and its antimicrobial functions against several pathogens were reported. Herein, we investigated the antiviral functions of TH1-5 against infectious pancreatic necrosis virus (IPNV) in Chinook salmon embryo (CHSE)-214 cells. The presence of TH1-5 enhanced the survival of CHSE-214 cells infected with IPNV. Additionally, the number of plaques formed by the cytopathic effect of IPNV in CHSE-214 cells decreased when IPNV was preincubated with TH1-5. This observation demonstrates the antiviral function of TH1-5. Real-time PCR studies showed the modulation of interleukin, annexin, and other viral-responsive gene expressions by TH1-5. When TH1-5 and IPNV were used to co-treat CHSE-214 cells, then cells were re-challenged with IPNV at 24h, the cells did not survive the IPNV infection. This shows that in the absence of TH1-5, viral re-challenge killed CHSE-214 cells. In conclusion TH1-5 protected CHSE-214 cells against IPNV by direct antimicrobial and immunomodulatory functions. PMID:20863896

Rajanbabu, Venugopal; Chen, Jyh-Yih

2011-01-01

185

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

PubMed Central

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

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

2013-01-01

186

Relating significance and relations of differentially expressed genes in response to Aspergillus flavus infection in maize.  

PubMed

Aspergillus flavus is a pathogenic fungus infecting maize and producing aflatoxins that are health hazards to humans and animals. Characterizing host defense mechanism and prioritizing candidate resistance genes are important to the development of resistant maize germplasm. We investigated methods amenable for the analysis of the significance and relations among maize candidate genes based on the empirical gene expression data obtained by RT-qPCR technique from maize inbred lines. We optimized a pipeline of analysis tools chosen from various programs to provide rigorous statistical analysis and state of the art data visualization. A network-based method was also explored to construct the empirical gene expression relational structures. Maize genes at the centers in the network were considered as important candidate genes for maize DNA marker studies. The methods in this research can be used to analyze large RT-qPCR datasets and establish complex empirical gene relational structures across multiple experimental conditions. PMID:24770700

Asters, Matthew C; Williams, W Paul; Perkins, Andy D; Mylroie, J Erik; Windham, Gary L; Shan, Xueyan

2014-01-01

187

Sex chromosome complement regulates expression of mood-related genes  

PubMed Central

Background Studies on major depressive and anxiety disorders suggest dysfunctions in brain corticolimbic circuits, including altered gamma-aminobutyric acid (GABA) and modulatory (serotonin and dopamine) neurotransmission. Interestingly, sexual dimorphisms in GABA, serotonin, and dopamine systems are also reported. Understanding the mechanisms behind these sexual dimorphisms may help unravel the biological bases of the heightened female vulnerability to mood disorders. Here, we investigate the contribution of sex-related factors (sex chromosome complement, developmental gonadal sex, or adult circulating hormones) to frontal cortex expression of selected GABA-, serotonin-, and dopamine-related genes. Methods As gonadal sex is determined by sex chromosome complement, the role of sex chromosomes cannot be investigated individually in humans. Therefore, we used the Four Core Genotypes (FCG) mouse model, in which sex chromosome complement and gonadal sex are artificially decoupled, to examine the expression of 13 GABA-related genes, 6 serotonin- and dopamine-related genes, and 8 associated signal transduction genes under chronic stress conditions. Results were analyzed by three-way ANOVA (sex chromosome complement?×?gonadal sex?×?circulating testosterone). A global perspective of gene expression changes was provided by heatmap representation and gene co-expression networks to identify patterns of transcriptional activities related to each main factor. Results We show that under chronic stress conditions, sex chromosome complement influenced GABA/serotonin/dopamine-related gene expression in the frontal cortex, with XY mice consistently having lower gene expression compared to XX mice. Gonadal sex and circulating testosterone exhibited less pronounced, more complex, and variable control over gene expression. Across factors, male conditions were associated with a tightly co-expressed set of signal transduction genes. Conclusions Under chronic stress conditions, sex-related factors differentially influence expression of genes linked to mood regulation in the frontal cortex. The main factor influencing expression of GABA-, serotonin-, and dopamine-related genes was sex chromosome complement, with an unexpected pro-disease effect in XY mice relative to XX mice. This effect was partially opposed by gonadal sex and circulating testosterone, although all three factors influenced signal transduction pathways in males. Since GABA, serotonin, and dopamine changes are also observed in other psychiatric and neurodegenerative disorders, these findings have broader implications for the understanding of sexual dimorphism in adult psychopathology. PMID:24199867

2013-01-01

188

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

PubMed

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

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

2002-11-01

189

Different Genes Interact with Particulate Matter and Tobacco Smoke Exposure in Affecting Lung Function Decline in the General Population  

Microsoft Academic Search

BackgroundOxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes.ObjectivesWe studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions

Ivan Curjuric; Medea Imboden; Rachel Nadif; Ashish Kumar; Christian Schindler; Margot Haun; Florian Kronenberg; Nino Künzli; Harish Phuleria; Dirkje S. Postma; Erich W. Russi; Thierry Rochat; Florence Demenais; Nicole M. Probst-Hensch

2012-01-01

190

Diverse types of genetic variation converge on functional gene networks involved in schizophrenia  

PubMed Central

Despite the successful identification of several relevant genomic loci, the underlying molecular mechanisms of schizophrenia remain largely unclear. We developed a computational approach (NETBAG+) that allows an integrated analysis of diverse disease-related genetic data using a unified statistical framework. The application of this approach to schizophrenia-associated genetic variations, obtained using unbiased whole-genome methods, allowed us to identify several cohesive gene networks related to axon guidance, neuronal cell mobility, synaptic function and chromosomal remodeling. The genes forming the networks are highly expressed in the brain, with higher brain expression during prenatal development. The identified networks are functionally related to genes previously implicated in schizophrenia, autism and intellectual disability. A comparative analysis of copy number variants associated with autism and schizophrenia suggests that although the molecular networks implicated in these distinct disorders may be related, the mutations associated with each disease are likely to lead, at least on average, to different functional consequences. PMID:23143521

Gilman, Sarah R; Chang, Jonathan; Xu, Bin; Bawa, Tejdeep S; Gogos, Joseph A; Karayiorgou, Maria; Vitkup, Dennis

2013-01-01

191

Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation  

PubMed Central

Microglia, the resident immune cell of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the mouse retinas of ages ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, C3 and CFB, previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS. PMID:23608111

Ma, Wenxin; Cojocaru, Radu; Gotoh, Norimoto; Gieser, Linn; Villasmil, Rafael; Cogliati, Tiziana; Swaroop, Anand; Wong, Wai T.

2013-01-01

192

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

PubMed Central

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

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

2013-01-01

193

FUNCTIONAL ANNOTATION OF OIL PALM GENES USING AN AUTOMATED BIOINFORMATICS APPROACH FUNCTIONAL ANNOTATION OF OIL PALM  

E-print Network

FUNCTIONAL ANNOTATION OF OIL PALM GENES USING AN AUTOMATED BIOINFORMATICS APPROACH 35 FUNCTIONAL ANNOTATION OF OIL PALM GENES USING AN AUTOMATED BIOINFORMATICS APPROACH LAURA B WILLIS*; PHILIP A LESSARDBank, and duplicate entries were eliminated by pairwise BLAST searches, resulting in a collection of unique oil palm

Sinskey, Anthony J.

194

Role of G-protein-coupled Receptor-related Genes in Insecticide Resistance of the Mosquito, Culex quinquefasciatus.  

PubMed

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

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

2014-01-01

195

Role of G-protein-coupled Receptor-related Genes in Insecticide Resistance of the Mosquito, Culex quinquefasciatus  

PubMed Central

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, HAmCqG8 and MAmCqG6, respectively. To characterize the function of these up-regulated GPCR-related genes in resistance, the up-regulated GPCR-related genes were knockdown in HAmCqG8 and MAmCqG6 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

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

2014-01-01

196

Predicting Gene-Regulation Functions: Lessons from Temperate Bacteriophages  

PubMed Central

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

Teif, Vladimir B.

2010-01-01

197

Functional Gene-Set Analysis Does Not Support a Major Role for Synaptic Function in Attention Deficit/Hyperactivity Disorder (ADHD)  

PubMed Central

Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood-onset neuropsychiatric disorders. Despite high heritability estimates, genome-wide association studies (GWAS) have failed to find significant genetic associations, likely due to the polygenic character of ADHD. Nevertheless, genetic studies suggested the involvement of several processes important for synaptic function. Therefore, we applied a functional gene-set analysis to formally test whether synaptic functions are associated with ADHD. Gene-set analysis tests the joint effect of multiple genetic variants in groups of functionally related genes. This method provides increased statistical power compared to conventional GWAS. We used data from the Psychiatric Genomics Consortium including 896 ADHD cases and 2455 controls, and 2064 parent-affected offspring trios, providing sufficient statistical power to detect gene sets representing a genotype relative risk of at least 1.17. Although all synaptic genes together showed a significant association with ADHD, this association was not stronger than that of randomly generated gene sets matched for same number of genes. Further analyses showed no association of specific synaptic function categories with ADHD after correction for multiple testing. Given current sample size and gene sets based on current knowledge of genes related to synaptic function, our results do not support a major role for common genetic variants in synaptic genes in the etiology of ADHD. PMID:25055203

Hammerschlag, Anke R.; Polderman, Tinca J. C.; de Leeuw, Christiaan; Tiemeier, Henning; White, Tonya; Smit, August B.; Verhage, Matthijs; Posthuma, Danielle

2014-01-01

198

Relating Perturbation Magnitude to Temporal Gene Expression in Biological Systems  

SciTech Connect

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.

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

2009-03-19

199

Genome Function and Nuclear Architecture: From Gene Expression to Nanoscience  

E-print Network

understanding of the functions of genomic sequences is still quite limited. Progress dependsGenome Function and Nuclear Architecture: From Gene Expression to Nanoscience Timothy P. O'Brien,1 Heidelberg, Germany; 3 German Cancer Research Center, 69120 Heidelberg, Germany; 4 National Cancer Institute

Langowski, Jörg

200

Calreticulin: one protein, one gene, many functions.  

PubMed Central

The endoplasmic reticulum (ER) plays a critical role in the synthesis and chaperoning of membrane-associated and secreted proteins. The membrane is also an important site of Ca(2+) storage and release. Calreticulin is a unique ER luminal resident protein. The protein affects many cellular functions, both in the ER lumen and outside of the ER environment. In the ER lumen, calreticulin performs two major functions: chaperoning and regulation of Ca(2+) homoeostasis. Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters. The protein also affects intracellular Ca(2+) homoeostasis by modulation of ER Ca(2+) storage and transport. Studies on the cell biology of calreticulin revealed that the ER membrane is a very dynamic intracellular compartment affecting many aspects of cell physiology. PMID:10567207

Michalak, M; Corbett, E F; Mesaeli, N; Nakamura, K; Opas, M

1999-01-01

201

Expression profiling of starch metabolism-related plastidic translocator genes in rice  

Microsoft Academic Search

The genes encoding the major putative rice plastidic translocators involved in the carbon flow related to starch metabolism\\u000a were identified by exhaustive database searches. The genes identified were two for the triose phosphate\\/phosphate translocator\\u000a (TPT), five for the glucose 6-phosphate\\/phosphate translocator (GPT) including putatively non-functional ones, four for the phosphoenolpyruvate\\/phosphate translocator (PPT), three for the putative ADP-glucose translocator (or Brittle-1

Kentaro Toyota; Masahiro Tamura; Takashi Ohdan; Yasunori Nakamura

2006-01-01

202

Reovirus-Induced Alterations in Gene Expression Related to Cell Cycle Regulation  

Microsoft Academic Search

Mammalian reovirus infection results in perturbation of host cell cycle progression. Since reovirus infection is known to activate cellular transcription factors, we investigated alterations in cell cycle-related gene expression following HEK293 cell infection by using the Affymetrix U95A microarray. Serotype 3 reovirus infection results in differential expression of 10 genes classified as encoding proteins that function at the G1-to-S transition,

George J. Poggioli; Roberta L. DeBiasi; Ryan Bickel; Robert Jotte; Aaron Spalding; Gary L. Johnson; Kenneth L. Tyler

2002-01-01

203

DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions  

PubMed Central

Background Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA), and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes) has not been comprehensively analyzed. Results We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs). These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain. Conclusions A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions. PMID:20723256

2010-01-01

204

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

SciTech Connect

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.

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

205

Gene expression pattern for putative chloroplast localized COPII related proteins with emphasis on Rab related proteins.  

PubMed

Vesicle transport occurs in the cytosol through COPI, COPII and a clathrin coated vesicle system for transport of lipids and proteins to different subcellular compartments. All three systems consist of several different protein components to maintain a functional transport. In chloroplasts photosynthesis takes place in thylakoids. Thylakoids contain a large amount of lipids and proteins but none of these components are produced there. Transport of lipids occurs from the envelope membrane where they are produced and through the aqueous stroma before being directed to the thylakoids. Nuclear encoded proteins use distinct pathways for entering thylakoids after import into chloroplasts. Transport of lipids through stroma requires either lipid transfer proteins, association between the envelope and the thylakoid membrane, or a vesicle transport system similar to the cytosolic one. No evidence exists for lipid transfer proteins in chloroplasts, nor for a consistent association between the envelope and the thylakoid membrane. However, vesicle transport has support from e.g., biochemical and genetics data as well as transelectron microscopy data. Moreover, a recent bioinformatics study revealed putatively COPII related proteins to be chloroplast localized in Arabidopsis and thus function in vesicle transport in chloroplasts. Here we present gene expression profiles of these putatively COPII related chloroplast localized proteins using Genevestigator (https://www.genevestigator.com/gv/) with special emphasis on Rab related proteins since they represent several stage of vesicle transport e.g., uncoating, tethering and fusion. PMID:24577429

Alezzawi, Mohamed; Karim, Sazzad; Khan, Nadir Zaman; Aronsson, Henrik

2014-01-01

206

Identification of Colorectal Cancer Related Genes with mRMR and Shortest Path in Protein-Protein Interaction Network  

PubMed Central

One of the most important and challenging problems in biomedicine and genomics is how to identify the disease genes. In this study, we developed a computational method to identify colorectal cancer-related genes based on (i) the gene expression profiles, and (ii) the shortest path analysis of functional protein association networks. The former has been used to select differentially expressed genes as disease genes for quite a long time, while the latter has been widely used to study the mechanism of diseases. With the existing protein-protein interaction data from STRING (Search Tool for the Retrieval of Interacting Genes), a weighted functional protein association network was constructed. By means of the mRMR (Maximum Relevance Minimum Redundancy) approach, six genes were identified that can distinguish the colorectal tumors and normal adjacent colonic tissues from their gene expression profiles. Meanwhile, according to the shortest path approach, we further found an additional 35 genes, of which some have been reported to be relevant to colorectal cancer and some are very likely to be relevant to it. Interestingly, the genes we identified from both the gene expression profiles and the functional protein association network have more cancer genes than the genes identified from the gene expression profiles alone. Besides, these genes also had greater functional similarity with the reported colorectal cancer genes than the genes identified from the gene expression profiles alone. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying colorectal cancer genes. It has not escaped our notice that the method can be applied to identify the genes of other diseases as well. PMID:22496748

Liu, Lei; Cai, Yu-Dong; Chou, Kuo-Chen

2012-01-01

207

An integrative evolution theory of histo-blood group ABO and related genes.  

PubMed

The ABO system is one of the most important blood group systems in transfusion/transplantation medicine. However, the evolutionary significance of the ABO gene and its polymorphism remained unknown. We took an integrative approach to gain insights into the significance of the evolutionary process of ABO genes, including those related not only phylogenetically but also functionally. We experimentally created a code table correlating amino acid sequence motifs of the ABO gene-encoded glycosyltransferases with GalNAc (A)/galactose (B) specificity, and assigned A/B specificity to individual ABO genes from various species thus going beyond the simple sequence comparison. Together with genome information and phylogenetic analyses, this assignment revealed early appearance of A and B gene sequences in evolution and potentially non-allelic presence of both gene sequences in some animal species. We argue: Evolution may have suppressed the establishment of two independent, functional A and B genes in most vertebrates and promoted A/B conversion through amino acid substitutions and/or recombination; A/B allelism should have existed in common ancestors of primates; and bacterial ABO genes evolved through horizontal and vertical gene transmission into 2 separate groups encoding glycosyltransferases with distinct sugar specificities. PMID:25307962

Yamamoto, Fumiichiro; Cid, Emili; Yamamoto, Miyako; Saitou, Naruya; Bertranpetit, Jaume; Blancher, Antoine

2014-01-01

208

Thermospermine modulates expression of auxin-related genes in Arabidopsis  

PubMed Central

Thermospermine, a structural isomer of spermine, is widely distributed in the plant kingdom and has been shown to play a role in repressing xylem differentiation by studies of its deficient mutant, acaulis5 (acl5), in Arabidopsis. Our results of microarray and real-time PCR analyses revealed that, in addition to a number of genes involved in xylem differentiation, genes related to auxin signaling were up-regulated in acl5 seedlings. These genes include MONOPTEROS, an auxin response factor gene, which acts as a master switch for auxin-dependent procambium formation, and its target genes. Their expression was reduced by exogenous treatment with thermospermine or by transgenic induction of the ACL5 gene. We examined the effect of synthetic polyamines on the expression of these auxin-related genes and on the vascular phenotype of acl5, and found that tetramines containing the NC3NC3N chain could mimic the effect of thermospermine but longer polyamines containing the same chain had little or no such effect. We also found that thermospermine had an inhibitory effect on lateral root formation in wild-type seedlings and it was mimicked by synthetic tetramines with the NC3NC3N chain. These results suggest the importance of the NC3NC3N chain of thermospermine in its action in modulating auxin signaling. PMID:24672532

Tong, Wurina; Yoshimoto, Kaori; Kakehi, Jun-Ichi; Motose, Hiroyasu; Niitsu, Masaru; Takahashi, Taku

2014-01-01

209

Algal genes in the closest relatives of animals.  

PubMed

The spread of photosynthesis is one of the most important but controversial topics in eukaryotic evolution. Because of massive gene transfer from plastids to the nucleus and because of the possibility that plastids have been lost in evolution, algal genes in aplastidic organisms often are interpreted as footprints of photosynthetic ancestors. These putative plastid losses, in turn, have been cited as support for scenarios involving the spread of plastids in broadscale eukaryotic evolution. Phylogenomic analyses identified more than 100 genes of possible algal origin in Monosiga, a unicellular species from choanoflagellates, a group considered to be the closest protozoan relatives of animals and to be primitively heterotrophic. The vast majority of these algal genes appear to be derived from haptophytes, diatoms, or green plants. Furthermore, more than 25% of these algal genes are ultimately of prokaryotic origin and were spread secondarily to Monosiga. Our results show that the presence of algal genes may be expected in many phagotrophs or taxa of phagotrophic ancestry and therefore does not necessarily represent evidence of plastid losses. The ultimate prokaryotic origin of some algal genes and their simultaneous presence in both primary and secondary photosynthetic eukaryotes either suggest recurrent gene transfer events under specific environments or support a more ancient origin of primary plastids. PMID:20627874

Sun, Guiling; Yang, Zefeng; Ishwar, Arjun; Huang, Jinling

2010-12-01

210

Consequences of recurrent gene flow from crops to wild relatives.  

PubMed Central

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

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

2003-01-01

211

Relating the Implementation Techniques of Functional and Functional Logic Languages  

Microsoft Academic Search

Functional logic languages are declarative programming languages that integratethe programming paradigms of functional and logic languages within a single framework.They are extensions of functional languages with principles derived from logicprogramming. Narrowing, the evaluation mechanism of functional logic languages,can be defined as a generalization of reduction, the evaluation mechanism of purelyfunctional languages. The unidirectional pattern matching, which is used for parameter...

Rita Loogen; RWTH Aachen

1993-01-01

212

Modulation of nocioceptive transmission with calcitonin gene-related peptide receptor antagonists in the thalamus.  

PubMed

Calcitonin gene-related peptide receptor antagonists are effective acute migraine treatments without the vascular contraindications associated with triptans. While it has been demonstrated that calcitonin gene-related peptide receptor antagonists act in the central nervous system, their effects in preclinical migraine models have been investigated in only the trigeminocervical complex. Migraine is a complex neurological disorder; sites in the brainstem and forebrain are clearly involved in its expression. We have performed electrophysiological recordings in thalamic neurons of rats responding to nocioceptive trigeminovascular inputs and tested the effect of olcegepant, a calcitonin gene-related peptide receptor antagonist (1 mg/kg, intravenously), on cell firing. We further tested the effect of microiontophoresed calcitonin gene-related peptide and the receptor antagonists calcitonin gene-related peptide 8-37 and olcegepant on thalamic cell firing, elicited by stimulation of the superior sagittal sinus or by microiontophoretic application of l-glutamate. Additionally, we used immunofluorescent staining to demonstrate the presence of functional calcitonin gene-related peptide receptors in the ventroposteromedial thalamic nucleus by specifically co-staining for the calcitonin gene-related peptide receptor subunits calcitonin receptor-like receptor and receptor activity modifying protein 1. Intravenously administered olcegepant significantly inhibited cell firing evoked by stimulation of the superior sagittal sinus as well as the background activity. Microiontophoresis of calcitonin gene-related peptide 8-37 also showed a significant inhibition of l-glutamate-evoked cell firing and firing evoked by stimulation of the superior sagittal sinus. Immunofluorescent staining confirmed the presence of the components of a functional calcitonin gene-related peptide receptor, the calcitonin receptor-like receptor and the receptor activity modifying protein 1, within the area of the ventroposteromedial thalamic nucleus. This is the first report on the efficacy of calcitonin gene-related peptide receptor antagonists at the level of third-order neurons in the migraine pathway, showing that the central effects of calcitonin gene-related peptide receptor antagonists extend beyond the trigeminocervical complex at least to the sensory thalamus. PMID:20802202

Summ, Oliver; Charbit, Annabelle R; Andreou, Anna P; Goadsby, Peter J

2010-09-01

213

Functional Homology of Chemotaxis Genes Escherichia coli and Salmonella typhimurium  

Microsoft Academic Search

Generally nonchemotactic mutants of Escherichia coli and Salmonella typhi- murium were analyzed by interspecies complementation tests to determine the functional correspondence between the che genes of these two organisms. The E. coli che region was introduced into Salnonella recipients by means of a series of F-prime elements. Wild-type che genes of E. coli F'420 complemented all che mutants of Sabnonella

Anthony L. Defranco; JOHN S. PARKINSON; D. E. KOSHLAND

1979-01-01

214

Knots in the family tree: evolutionary relationships and functions of knox homeobox genes  

Microsoft Academic Search

Knotted-like homeobox (knox) genes constitute a gene family in plants. Class I knox genes are expressed in shoot apical meristems, and (with notable exceptions) not in lateral organ primordia. Class II genes have more diverse expression patterns. Loss and gain of function mutations indicate that knox genes are important regulators of meristem function. Gene duplication has contributed to the evolution

Leonore Reiser; Patricia Sánchez-Baracaldo; Sarah Hake

2000-01-01

215

Chromosome substitution strains: gene discovery functional analysis and systems studies  

PubMed Central

Laboratory mice are valuable in biomedical research in part because of the extraordinary diversity of genetic resources that are available for studies of complex genetic traits and as models for human biology and disease. Chromosome substitution strains (CSSs) are important in this resource portfolio because of their demonstrated use for gene discovery, genetic and epigenetic studies, functional characterizations, and systems analysis. CSSs are made by replacing a single chromosome in a host strain with the corresponding chromosome from a donor strain. A complete CSS panel involves a total of 22 engineered inbred strains, one for each of the 19 autosomes, one each for the X and Y chromosomes, and one for mitochondria. A genome survey simply involves comparing each phenotype for each of the CSSs with the phenotypes of the host strain. The CSS panels that are available for laboratory mice have been used to dissect a remarkable variety of phenotypes and to characterize an impressive array of disease models. These surveys have revealed considerable phenotypic diversity even among closely related progenitor strains, evidence for strong epistasis and for heritable epigenetic changes. Perhaps most importantly, and presumably because of their unique genetic constitution, CSSs, and congenic strains derived from them, the genetic variants underlying quantitative trait loci (QTLs) are readily identified and functionally characterized. Together these studies show that CSSs are important resource for laboratory mice. PMID:22961226

Nadeau, Joseph H.; Forejt, Jiri; Takada, Toyoyuki; Shiroishi, Toshihiko

2014-01-01

216

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

PubMed Central

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.

2014-01-01

217

Learning Gene Functional Classi ? cations from Multiple Data Types  

E-print Network

In our attempts to understand cellular function at the molecular level, we must be able to synthesize information from disparate types of genomic data. We consider the problem of inferring gene functional classi ? cations from a heterogeneous data set consisting of DNA microarray expression measurements and phylogenetic pro ? les from whole-genome sequence comparisons. We demonstrate the application of the support vector machine (SVM) learning algorithm to this functional inference task. Our results suggest the importance of exploiting prior information about the heterogeneity of the data. In particular, we propose an SVM kernel function that is explicitly heterogeneous. In addition, we describe feature scaling methods for further exploiting prior knowledge of heterogeneity by giving each data type different weights. Key words: gene functional classi ? cation, phylogenetic pro ? les, microarray expression analysis. 1.

Paul Pavlidis; Jason Weston; Jinsong Cai; William Stafford Noble

218

Searching for functional gene modules with interaction component models  

PubMed Central

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

2010-01-01

219

Characterization of a Vibrio alginolyticus Strain, Isolated from Alaskan Oysters, Carrying a Hemolysin Gene Similar to the Thermostable Direct Hemolysin-Related Hemolysin Gene (trh) of Vibrio parahaemolyticus?  

PubMed Central

A Vibrio strain isolated from Alaskan oysters and classified by its biochemical characteristics as Vibrio alginolyticus possessed a thermostable direct hemolysin-related hemolysin (trh) gene previously reported only in Vibrio parahaemolyticus. This trh-like gene was cloned and sequenced and was 98% identical to the trh2 gene of V. parahaemolyticus. This gene seems to be functional since it was transcriptionally active in early-stationary-phase growing cells. To our knowledge, this is the first report of V. alginolyticus possessing a trh gene. PMID:17056701

Gonzalez-Escalona, Narjol; Blackstone, George M.; DePaola, Angelo

2006-01-01

220

Calcitonin gene-related peptide: an update on the biology  

PubMed Central

Purpose of review This review includes the most relevant and recent studies on the biology of calcitonin gene-related peptide (CGRP) as it pertains to primary headaches and particularly to migraine. Especial attention was given to those published within the last year. Recent findings The development of CGRP receptor antagonists is discussed in detail, as well as recent advances in our understanding of CGRP actions in migraine. Finally, other important functions of CGRP outside of the nervous system are briefly discussed. Summary The advent of CGRP receptor antagonists as a novel therapy for migraine attacks may represent a new era in the acute management of migraine. More than a simple addition to the currently available treatments, this group of drugs may become an outstanding option for patients with cardiovascular disease, given the lack of associated vasoconstriction. Furthermore, nonpeptide CGRP receptor antagonists, CGRP antibodies and CGRP-binding RNA-Spiegelmer are valuable research tools that will further advance our understanding of migraine pathophysiology. PMID:19434786

Recober, Ana; Russo, Andrew F.

2010-01-01

221

Reovirus-induced alterations in gene expression related to cell cycle regulation.  

PubMed

Mammalian reovirus infection results in perturbation of host cell cycle progression. Since reovirus infection is known to activate cellular transcription factors, we investigated alterations in cell cycle-related gene expression following HEK293 cell infection by using the Affymetrix U95A microarray. Serotype 3 reovirus infection results in differential expression of 10 genes classified as encoding proteins that function at the G(1)-to-S transition, 11 genes classified as encoding proteins that function at G(2)-to-M transition, and 4 genes classified as encoding proteins that function at the mitotic spindle checkpoint. Serotype 1 reovirus infection results in differential expression of four genes classified as encoding proteins that function at the G(1)-to-S transition and three genes classified as encoding proteins that function at G(2)-to-M transition but does not alter any genes classified as encoding proteins that function at the mitotic spindle checkpoint. We have previously shown that serotype 3, but not serotype 1, reovirus infection induces a G(2)-to-M transition arrest resulting from an inhibition of cdc2 kinase activity. Of the differentially expressed genes encoding proteins regulating the G(2)-to-M transition, chk1, wee1, and GADD45 are known to inhibit cdc2 kinase activity. A hypothetical model describing serotype 3 reovirus-induced inhibition of cdc2 kinase is presented, and reovirus-induced perturbations of the G(1)-to-S, G(2)-to-M, and mitotic spindle checkpoints are discussed. PMID:11861824

Poggioli, George J; DeBiasi, Roberta L; Bickel, Ryan; Jotte, Robert; Spalding, Aaron; Johnson, Gary L; Tyler, Kenneth L

2002-03-01

222

Reovirus-Induced Alterations in Gene Expression Related to Cell Cycle Regulation  

PubMed Central

Mammalian reovirus infection results in perturbation of host cell cycle progression. Since reovirus infection is known to activate cellular transcription factors, we investigated alterations in cell cycle-related gene expression following HEK293 cell infection by using the Affymetrix U95A microarray. Serotype 3 reovirus infection results in differential expression of 10 genes classified as encoding proteins that function at the G1-to-S transition, 11 genes classified as encoding proteins that function at G2-to-M transition, and 4 genes classified as encoding proteins that function at the mitotic spindle checkpoint. Serotype 1 reovirus infection results in differential expression of four genes classified as encoding proteins that function at the G1-to-S transition and three genes classified as encoding proteins that function at G2-to-M transition but does not alter any genes classified as encoding proteins that function at the mitotic spindle checkpoint. We have previously shown that serotype 3, but not serotype 1, reovirus infection induces a G2-to-M transition arrest resulting from an inhibition of cdc2 kinase activity. Of the differentially expressed genes encoding proteins regulating the G2-to-M transition, chk1, wee1, and GADD45 are known to inhibit cdc2 kinase activity. A hypothetical model describing serotype 3 reovirus-induced inhibition of cdc2 kinase is presented, and reovirus-induced perturbations of the G1-to-S, G2-to-M, and mitotic spindle checkpoints are discussed. PMID:11861824

Poggioli, George J.; DeBiasi, Roberta L.; Bickel, Ryan; Jotte, Robert; Spalding, Aaron; Johnson, Gary L.; Tyler, Kenneth L.

2002-01-01

223

Gene expression signatures but not cell cycle checkpoint functions distinguish AT carriers from normal individuals  

PubMed Central

Ataxia telangiectasia (AT) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia-mutated gene (ATM). AT carriers with one mutant ATM allele are usually not severely affected although they carry an increased risk of developing cancer. There has not been an easy and reliable diagnostic method to identify AT carriers. Cell cycle checkpoint functions upon ionizing radiation (IR)-induced DNA damage and gene expression signatures were analyzed in the current study to test for differential responses in human lymphoblastoid cell lines with different ATM genotypes. While both dose- and time-dependent G1 and G2 checkpoint functions were highly attenuated in ATM?/? cell lines, these functions were preserved in ATM+/? cell lines equivalent to ATM+/+ cell lines. However, gene expression signatures at both baseline (consisting of 203 probes) and post-IR treatment (consisting of 126 probes) were able to distinguish ATM+/? cell lines from ATM+/+ and ATM?/? cell lines. Gene ontology (GO) and pathway analysis of the genes in the baseline signature indicate that ATM function-related categories, DNA metabolism, cell cycle, cell death control, and the p53 signaling pathway, were overrepresented. The same analyses of the genes in the IR-responsive signature revealed that biological categories including response to DNA damage stimulus, p53 signaling, and cell cycle pathways were overrepresented, which again confirmed involvement of ATM functions. The results indicate that AT carriers who have unaffected G1 and G2 checkpoint functions can be distinguished from normal individuals and AT patients by expression signatures of genes related to ATM functions. PMID:23943852

Zhang, Liwen; Simpson, Dennis A.; Innes, Cynthia L.; Chou, Jeff; Bushel, Pierre R.; Paules, Richard S.; Kaufmann, William K.

2013-01-01

224

Involvement of Trichoderma Trichothecenes in the Biocontrol Activity and Induction of Plant Defense-Related Genes  

PubMed Central

Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studied. PMID:22562989

Malmierca, M. G.; Cardoza, R. E.; Alexander, N. J.; McCormick, S. P.; Hermosa, R.; Monte, E.

2012-01-01

225

Involvement of Trichoderma trichothecenes in the biocontrol activity and induction of plant defense-related genes.  

PubMed

Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studied. PMID:22562989

Malmierca, M G; Cardoza, R E; Alexander, N J; McCormick, S P; Hermosa, R; Monte, E; Gutiérrez, S

2012-07-01

226

Identification of programmed cell death related genes in bamboo.  

PubMed

The event of bamboo flowering and subsequent death of bamboo cells, a rare phenomenon is an interesting model to study gene expression/function in the context of the programmed cell death (PCD) in plant. To identify genes involved in autolytic cell death in bamboo (Bambusa arundinacea/Bambusa bambos Voss), a suppressive subtractive cDNA hybridization (SSH) was performed between cDNA isolated from control (healthy), as driver and test internodal tissue (45days after setting of seeds), as tester. In-silico data revealed that 82% of total ESTs (231) were non-significant (unidentified proteins) while remaining ESTs were classified as protein with known/predicted function/s. Among these, net distribution and differential expression patterns of 11 important B. arundinacea PCD specific ESTs were studied using RNA slot-blot, qRT-PCR and semi-quantitative RT. In-situ localization of mRNA-transcripts for selected bamboo PCD-specific ESTs namely V2Ba48 (Aldehyde dehydrogenase 2) and V2Ba19 (Glycogen phosphorylase) were detected using digoxigenin-labeled corresponding anti-sense RNA probes employing Confocal Laser Scanning Microscope (CLSM). Differential expression-kinetics of the aforementioned genes were confirmed during the progress of PCD after setting of seeds. Global appearance of V2Ba48, V2Ba19, V2Ba95 (Ubiquitin thioesterase) and V2Ba89 (Nebulin isoform 2) genes were identified in monocot (Oryza sativa) and dicots (Arabidopsis thaliana and Nicotiana tabacum). This is the first report on systematic analysis of genes involved in death of bamboo cells that may provide critical information regarding key metabolic/regulatory genes involved in plant PCD. PMID:22326529

Rai, Vineeta; Dey, Nrisingha

2012-04-15

227

Evolution of the Vertebrate Paralemmin Gene Family: Ancient Origin of Gene Duplicates Suggests Distinct Functions  

PubMed Central

Paralemmin-1 is a protein implicated in plasma membrane dynamics, the development of filopodia, neurites and dendritic spines, as well as the invasiveness and metastatic potential of cancer cells. However, little is known about its mode of action, or about the biological functions of the other paralemmin isoforms: paralemmin-2, paralemmin-3 and palmdelphin. We describe here evolutionary analyses of the paralemmin gene family in a broad range of vertebrate species. Our results suggest that the four paralemmin isoform genes (PALM1, PALM2, PALM3 and PALMD) arose by quadruplication of an ancestral gene in the two early vertebrate genome duplications. Paralemmin-1 and palmdelphin were further duplicated in the teleost fish specific genome duplication. We identified a unique sequence motif common to all paralemmins, consisting of 11 highly conserved residues of which four are invariant. A single full-length paralemmin homolog with this motif was identified in the genome of the sea lamprey Petromyzon marinus and an isolated putative paralemmin motif could be detected in the genome of the lancelet Branchiostoma floridae. This allows us to conclude that the paralemmin gene family arose early and has been maintained throughout vertebrate evolution, suggesting functional diversification and specific biological roles of the paralemmin isoforms. The paralemmin genes have also maintained specific features of gene organisation and sequence. This includes the occurrence of closely linked downstream genes, initially identified as a readthrough fusion protein with mammalian paralemmin-2 (Palm2-AKAP2). We have found evidence for such an arrangement for paralemmin-1 and -2 in several vertebrate genomes, as well as for palmdelphin and paralemmin-3 in teleost fish genomes, and suggest the name paralemmin downstream genes (PDG) for this new gene family. Thus, our findings point to ancient roles for paralemmins and distinct biological functions of the gene duplicates. PMID:22855693

Hultqvist, Greta; Ocampo Daza, Daniel; Larhammar, Dan; Kilimann, Manfred W.

2012-01-01

228

New gene functions in megakaryopoiesis and platelet formation  

PubMed Central

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

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.; Magi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gogele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O'Reilly, Paul F.; Shin, So-Youn; Esko, Tonu; 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, Francois; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amelie; Cambien, Francois; Chambers, John C.; Cucca, Francesco; D'Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Doring, 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; Kuhnel, 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; Nothlings, 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; Tonjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Volker, 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

229

Genome Holography: Deciphering Function-Form Motifs from Gene Expression Data  

PubMed Central

Background DNA chips allow simultaneous measurements of genome-wide response of thousands of genes, i.e. system level monitoring of the gene-network activity. Advanced analysis methods have been developed to extract meaningful information from the vast amount of raw gene-expression data obtained from the microarray measurements. These methods usually aimed to distinguish between groups of subjects (e.g., cancer patients vs. healthy subjects) or identifying marker genes that help to distinguish between those groups. We assumed that motifs related to the internal structure of operons and gene-networks regulation are also embedded in microarray and can be deciphered by using proper analysis. Methodology/Principal Findings The analysis presented here is based on investigating the gene-gene correlations. We analyze a database of gene expression of Bacillus subtilis exposed to sub-lethal levels of 37 different antibiotics. Using unsupervised analysis (dendrogram) of the matrix of normalized gene-gene correlations, we identified the operons as they form distinct clusters of genes in the sorted correlation matrix. Applying dimension-reduction algorithm (Principal Component Analysis, PCA) to the matrices of normalized correlations reveals functional motifs. The genes are placed in a reduced 3-dimensional space of the three leading PCA eigen-vectors according to their corresponding eigen-values. We found that the organization of the genes in the reduced PCA space recovers motifs of the operon internal structure, such as the order of the genes along the genome, gene separation by non-coding segments, and translational start and end regions. In addition to the intra-operon structure, it is also possible to predict inter-operon relationships, operons sharing functional regulation factors, and more. In particular, we demonstrate the above in the context of the competence and sporulation pathways. Conclusions/Significance We demonstrated that by analyzing gene-gene correlation from gene-expression data it is possible to identify operons and to predict unknown internal structure of operons and gene-networks regulation. PMID:18628959

Roth, Dalit; Regev, Tamar; Bransburg-Zabary, Sharron; Jacob, Eshel Ben

2008-01-01

230

Multiple gene duplication and rapid evolution in the groEL gene: functional implications.  

PubMed

The chaperonins, GroEL and GroES, are present ubiquitously and provide a paradigm in the understanding of assisted protein folding. Due to its essentiality of function, GroEL exhibits high sequence conservation across species. Complete genome sequencing 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 clade in the phylogenetic tree generated for the GroEL protein suggests a lineage-specific duplication. The duplicated groEL gene in Actinobacteria is not accompanied by the operonic groES despite the presence of upstream regulatory elements. Our analysis suggests that in these bacteria the duplicated groEL genes have undergone rapid evolution and divergence to function in a GroES-independent manner. Evaluation of multiple sequence alignment demonstrates that the duplicated genes have acquired mutations at functionally significant positions including those involved in substrate binding, ATP binding, and GroES binding and those involved in inter-ring and intra-ring interactions. We propose that the duplicate groEL genes in different bacterial clades have evolved independently to meet specific requirements of each clade. We also propose that the groEL gene, although essential and conserved, accumulates nonconservative substitutions to exhibit structural and functional variations. PMID:17103057

Goyal, Kshama; Qamra, Rohini; Mande, Shekhar C

2006-12-01

231

PDbase: a database of Parkinson's Disease-related genes and genetic variation using substantia nigra ESTs  

PubMed Central

Background Parkinson's disease (PD) is one of the most common neurodegenerative disorders, clinically characterized by impaired motor function. Since the etiology of PD is diverse and complex, many researchers have created PD-related research resources. However, resources for brain and PD studies are still lacking. Therefore, we have constructed a database of PD-related gene and genetic variations using the substantia nigra (SN) in PD and normal tissues. In addition, we integrated PD-related information from several resources. Results We collected the 6,130 SN expressed sequenced tags (ESTs) from brain SN normal tissues and PD patients SN tissues using full-cDNA library and normalized cDNA library construction methods from our previous study. The SN ESTs were clustered in 2,951 unigene clusters and assigned in 2,678 genes. We then found up-regulated 57 genes and down-regulated 48 genes by comparing normal and PD SN ESTs frequencies with over 0.9 cut-off probability of differential expression based on the Audic and Claverie method. In addition, we integrated disease-related information from public resources. To examine the characteristics of these PD-related genes, we analyzed alternative splicing events, single nucleotide polymorphism (SNP) markers located in the gene regions, repeat elements, gene regulation elements, and pathways and protein-protein interaction networks. Conclusion We constructed the PDbase database to capture the PD-related gene, genetic variation, and functional elements. This database contains 2,698 PD-related genes through ESTs discovered from human normal and PD patients SN tissues, and through integrating several public resources. PDbase provides the mitochondrion proteins, microRNA gene regulation elements, single nucleotide polymorphisms (SNPs) markers within PD-related gene structures, repeat elements, and pathways and networks with protein-protein interaction information. The PDbase information can aid in understanding the causation of PD. It is available at http://bioportal.kobic.re.kr/PDbase/. Supplementary data is available at http://bioportal.kobic.re.kr/PDbase/suppl.jsp PMID:19958497

2009-01-01

232

Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals  

PubMed Central

Background The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation. Results In a screen that covered ~40 per cent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis-regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i) previously described cases of gene battery-like regulation, (ii) previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii) predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in ~10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in ~30% of all kidney specific genes respectively. The results are publicly available at . Conclusion 21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design. PMID:15882449

Nelander, Sven; Larsson, Erik; Kristiansson, Erik; Mansson, Robert; Nerman, Olle; Sigvardsson, Mikael; Mostad, Petter; Lindahl, Per

2005-01-01

233

The mammalian gene function resource: the International Knockout Mouse Consortium.  

PubMed

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research. PMID:22968824

Bradley, Allan; Anastassiadis, Konstantinos; Ayadi, Abdelkader; Battey, James F; Bell, Cindy; Birling, Marie-Christine; Bottomley, Joanna; Brown, Steve D; Bürger, Antje; Bult, Carol J; Bushell, Wendy; Collins, Francis S; Desaintes, Christian; Doe, Brendan; Economides, Aris; Eppig, Janan T; Finnell, Richard H; Fletcher, Colin; Fray, Martin; Frendewey, David; Friedel, Roland H; Grosveld, Frank G; Hansen, Jens; Hérault, Yann; Hicks, Geoffrey; Hörlein, Andreas; Houghton, Richard; Hrabé de Angelis, Martin; Huylebroeck, Danny; Iyer, Vivek; de Jong, Pieter J; Kadin, James A; Kaloff, Cornelia; Kennedy, Karen; Koutsourakis, Manousos; Lloyd, K C Kent; Marschall, Susan; Mason, Jeremy; McKerlie, Colin; McLeod, Michael P; von Melchner, Harald; Moore, Mark; Mujica, Alejandro O; Nagy, Andras; Nefedov, Mikhail; Nutter, Lauryl M; Pavlovic, Guillaume; Peterson, Jane L; Pollock, Jonathan; Ramirez-Solis, Ramiro; Rancourt, Derrick E; Raspa, Marcello; Remacle, Jacques E; Ringwald, Martin; Rosen, Barry; Rosenthal, Nadia; Rossant, Janet; Ruiz Noppinger, Patricia; Ryder, Ed; Schick, Joel Zupicich; Schnütgen, Frank; Schofield, Paul; Seisenberger, Claudia; Selloum, Mohammed; Simpson, Elizabeth M; Skarnes, William C; Smedley, Damian; Stanford, William L; Stewart, A Francis; Stone, Kevin; Swan, Kate; Tadepally, Hamsa; Teboul, Lydia; Tocchini-Valentini, Glauco P; Valenzuela, David; West, Anthony P; Yamamura, Ken-ichi; Yoshinaga, Yuko; Wurst, Wolfgang

2012-10-01

234

The Innate Immune-Related Genes in Catfish  

PubMed Central

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

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

2012-01-01

235

Evolution of vertebrate genes related to prion and Shadoo proteins--clues from comparative genomic analysis.  

PubMed

Recent findings of new genes in fish related to the prion protein (PrP) gene PRNP, including our recent report of SPRN coding for Shadoo (Sho) protein found also in mammals, raise issues of their function and evolution. Here we report additional novel fish genes found in public databases, including a duplicated SPRN gene, SPRNB, in Fugu, Tetraodon, carp, and zebrafish encoding the Sho2 protein, and we use comparative genomic analysis to analyze the evolutionary relationships and to infer evolutionary trajectories of the complete data set. Phylogenetic footprinting performed on aligned human, mouse, and Fugu SPRN genes to define candidate regulatory promoter regions, detected 16 conserved motifs, three of which are known transcription factor-binding sites for a receptor and transcription factors specific to or associated with expression in brain. This result and other homology-based (VISTA global genomic alignment; protein sequence alignment and phylogenetics) and context-dependent (genomic context; relative gene order and orientation) criteria indicate fish and mammalian SPRN genes are orthologous and suggest a strongly conserved basic function in brain. Whereas tetrapod PRNPs share context with the analogous stPrP-2-coding gene in fish, their sequences are diverged, suggesting that the tetrapod and fish genes are likely to have significantly different functions. Phylogenetic analysis predicts the SPRN/SPRNB duplication occurred before divergence of fish from tetrapods, whereas that of stPrP-1 and stPrP-2 occurred in fish. Whereas Sho appears to have a conserved function in vertebrate brain, PrP seems to have an adaptive role fine-tuned in a lineage-specific fashion. An evolutionary model consistent with our findings and literature knowledge is proposed that has an ancestral prevertebrate SPRN-like gene leading to all vertebrate PrP-related and Sho-related genes. This provides a new framework for exploring the evolution of this unusual family of proteins and for searching for members in other fish branches and intermediate vertebrate groups. PMID:15342797

Premzl, Marko; Gready, Jill E; Jermiin, Lars S; Simonic, Tatjana; Marshall Graves, Jennifer A

2004-12-01

236

Massive Expansion of Ubiquitination-Related Gene Families within the Chlamydiae  

PubMed Central

Gene loss, gain, and transfer play an important role in shaping the genomes of all organisms; however, the interplay of these processes in isolated populations, such as in obligate intracellular bacteria, is less understood. Despite a general trend towards genome reduction in these microbes, our phylogenomic analysis of the phylum Chlamydiae revealed that within the family Parachlamydiaceae, gene family expansions have had pronounced effects on gene content. We discovered that the largest gene families within the phylum are the result of rapid gene birth-and-death evolution. These large gene families are comprised of members harboring eukaryotic-like ubiquitination-related domains, such as F-box and BTB-box domains, marking the largest reservoir of these proteins found among bacteria. A heterologous type III secretion system assay suggests that these proteins function as effectors manipulating the host cell. The large disparity in copy number of members in these families between closely related organisms suggests that nonadaptive processes might contribute to the evolution of these gene families. Gene birth-and-death evolution in concert with genomic drift might represent a previously undescribed mechanism by which isolated bacterial populations diversify. PMID:25069652

Domman, Daryl; Collingro, Astrid; Lagkouvardos, Ilias; Gehre, Lena; Weinmaier, Thomas; Rattei, Thomas; Subtil, Agathe; Horn, Matthias

2014-01-01

237

Expression profiling reveals functionally important genes and coordinately regulated signaling pathway genes during in vitro angiogenesis.  

PubMed

Angiogenesis is a complex multicellular process requiring the orchestration of many events including migration, alignment, proliferation, lumen formation, remodeling, and maturation. Such complexity indicates that not only individual genes but also entire signaling pathways will be crucial in angiogenesis. To define an angiogenic blueprint of regulated genes, we utilized our well-characterized three-dimensional collagen gel model of in vitro angiogenesis, in which the majority of cells synchronously progress through defined morphological stages culminating in the formation of capillary tubes. We developed a comprehensive three-tiered approach using microarray analysis, which allowed us to identify genes known to be involved in angiogenesis and genes hitherto unlinked to angiogenesis as well as novel genes and has proven especially useful for genes where the magnitude of change is small. Of interest is the ability to recognize complete signaling pathways that are regulated and genes clustering into ontological groups implicating the functional importance of particular processes. We have shown that consecutive members of the mitogen-activated protein kinase and leukemia inhibitory factor signaling pathways are altered at the mRNA level during in vitro angiogenesis. Thus, at least for the mitogen-activated protein kinase pathway, mRNA changes as well as the phosphorylation changes of these gene products may be important in the control of blood vessel morphogenesis. Furthermore, in this study, we demonstrated the power of virtual Northern blot analysis, as an alternative to quantitative RT-PCR, for measuring the magnitudes of differential gene expression. PMID:15840639

Hahn, C N; Su, Z J; Drogemuller, C J; Tsykin, A; Waterman, S R; Brautigan, P J; Yu, S; Kremmidiotis, G; Gardner, A; Solomon, P J; Goodall, G J; Vadas, M A; Gamble, J R

2005-06-16

238

Conic theta functions and their relations to theta Amanda Folsom  

E-print Network

Conic theta functions and their relations to theta functions Amanda Folsom , Winfried Kohnen, and Sinai Robins Abstract We study a class of polyhedral functions called conic theta functions, which reflection group, then its conic theta function lies in a graded ring of classical theta functions

Robins, Sinai

239

SOIL MICROBIOLOGY Laccase Gene Composition and Relative Abundance  

E-print Network

SOIL MICROBIOLOGY Laccase Gene Composition and Relative Abundance in Oak Forest Soil + Business Media, LLC 2008 Abstract Anthropogenic nitrogen (N) deposition affects a wide range of soil processes including phenol oxidase (PO) activity and soil organic matter dynamics. Depression of phenol

Bruns, Tom

240

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

PubMed Central

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

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

2012-01-01

241

Concerning the Zeros of Some Functions Related to Bessel Functions.  

National Technical Information Service (NTIS)

The real zeros of the Riccati-Bessel functions, their derivatives, and their cross products are investigated. Expansions analogous to those provided by McMahon and Olver for the zeros of the Bessel functions are obtained for the zeros of the derivatives o...

T. H. Boyer

1967-01-01

242

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

PubMed Central

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

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

2014-01-01

243

Identification of new tumor suppressor genes based on in vivo functional inactivation of a candidate gene  

Microsoft Academic Search

As a step towards developing a new functional test for the identification of tumor suppressor genes, human wild type and mutant RB genes were expressed in the mouse A9 fibrosarcoma cell line under the transcriptional regulation of the tetracycline repressor using two new vectors: pLNCtTA and pETI. Following passage of the transfectants in immunodeficient SCID mice, the wild type RB

Jingfeng Li; Alexei I Protopopov; Rinat Z Gizatullin; Csaba Kiss; Vladimir I Kashuba; Gösta Winberg; George Klein; Eugene R Zabarovsky

1999-01-01

244

Functional genomic analysis of cotton genes with agrobacterium-mediated virus-induced gene silencing.  

PubMed

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

Gao, Xiquan; Shan, Libo

2013-01-01

245

Relating Functional Groups to the Periodic Table  

ERIC Educational Resources Information Center

An introduction to organic chemistry functional groups and their ionic variants is presented. Functional groups are ordered by the position of their specific (hetero) atom in the periodic table. Lewis structures are compared with their corresponding condensed formulas. (Contains 5 tables.)

Struyf, Jef

2009-01-01

246

Gamma and Related Functions Generalized for Sequences  

ERIC Educational Resources Information Center

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…

Ollerton, R. L.

2008-01-01

247

Functional requirements for bacteriophage growth: Gene essentiality and expression in Mycobacteriophage Giles  

PubMed Central

Summary Bacteriophages represent a majority of all life forms, and the vast, dynamic population with early origins is reflected in their enormous genetic diversity. A large number of bacteriophage genomes have been sequenced. They are replete with novel genes without known relatives. We know little about their functions, which genes are required for lytic growth, and how they are expressed. Furthermore, the diversity is such that even genes with required functions – such as virion proteins and repressors – cannot always be recognized. Here we describe a functional genomic dissection of mycobacteriophage Giles, in which the virion proteins are identified, genes required for lytic growth are determined, the repressor is identified, and the transcription patterns determined. We find that although all of the predicted phage genes are expressed either in lysogeny or in lytic growth, 45% of the predicted genes are non-essential for lytic growth. We also describe genes required for DNA replication, show that recombination is required for lytic growth, and that Giles encodes a novel repressor. RNAseq analysis reveals abundant expression of a small non-coding RNA in a lysogen and in late lytic growth, although it is non-essential for lytic growth and does not alter lysogeny. PMID:23560716

Dedrick, Rebekah M.; Marinelli, Laura J.; Newton, Gerald L.; Pogliano, Kit; Pogliano, Joseph; Hatfull, Graham F.

2013-01-01

248

Gene Transfer of Calcitonin Gene-Related Peptide Prevents Vasoconstriction After Subarachnoid Hemorrhage  

Microsoft Academic Search

We sought to determine whether adenovirus-mediated gene transfer in vivo of calcitonin gene-related peptide (CGRP), a potent vasodilator, ameliorates cerebral vasoconstriction after experimental subarachnoid hemorrhage (SAH). Arterial blood was injected into the cisterna magna of rabbits to mimic SAH 5 days after injection of AdRSVCGRP (83108 pfu), AdRSVbgal (control virus), or vehicle. After injection of AdRSVCGRP, there was a 400-fold

Kazunori Toyoda; Frank M. Faraci; Yoshimasa Watanabe; Toshihiro Ueda; Jon J. Andresen; Yi Chu; Shoichiro Otake; Donald D. Heistad

249

Systematic Learning of Gene Functional Classes From DNA Array Expression Data by Using  

E-print Network

10598, USA Recent advances in microarray technology have opened new ways for functional annotation negatives). A closer analysis reveals that false positives (and negatives) in a machine-learning context positives and negatives and contains genes that are biologically related to the original class, allowing

Gerstein, Mark

250

[Rapid cloning and functional characterization of hypericin synthase gene].  

PubMed

Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, commonly known as St. John's wort. Hypericin has attracted a growing attention of the pharmaceutical industry because of its potential application to various therapies, including the treatment of depression and remarkable antiviral and photodynamic activities, hyp-1 gene encodes for phenolic coupling protein which catalyzes in vitro direct and specific conversion of emodin to hypericin which, however, has not formed common opinion so far. Six pairs of primers specific to hyp-1 gene were synthesized. The rapid cloning of hyp-1 gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pET32ahyp containing hyp-1 gene was constructed and was transformed into E. coli to induce heterologous expression. SDS-PAGE and Western blot results showed the recombinant Hyp-1 protein was expressed successfully in E. coli. The soluble fraction was used to test the function of the recombinant Hyp-1. Hypericin was detected by LC-MS/MS with emodin as a substrate under in vitro conditions. The above results corroborated the Hyp-1 function, a confusing question, which lay a material foundation for the synthesis of hypericin by synthetic biotechnology. PMID:22812015

Shi, Yan-Wei; Zhi, Xiao-Hui; Zheng, Hai-Na; Yang, Yan; Wang, Wei; An, Jian-Mei; Kong, Jian-Qiang

2012-05-01

251

Temporal expression analysis of angiogenesis-related genes in brain development  

PubMed Central

Background The current knowledge on molecular pathogenesis of cerebral vascular malformations (CVM), which are believed to arise during development, is very limited. To unravel the molecular mechanisms involved in CVMs, a detailed understanding of the brain vascular development at molecular level is crucial. In this study, we aimed to explore the temporal and comparative expression profile of angiogenesis-related genes in the establishment of brain vasculature. Methods Expression of a total of 113 angiogenesis-related genes during murine brain development has been analyzed using low-density array systems designed for angiogenesis-related genes. Bai1 (brain specific angiogenesis inhibitor-1), a recently identified novel anti-angiogenic gene, has been selected for further characterization. Results We found that 62 out of 113 analyzed genes have expression in brain development at varying levels. Nineteen of these were differentially expressed between embryonic and postnatal stages (>1.5 fold). Bai1 is strongly expressed on growing blood vessels of cerebral cortex and hippocampus, partially expressed in the lateral regions of striatum, but mostly absent on the thalamus. Conclusion By showing the comparative expression analysis of angiogenesis-related genes throughout brain development, the data presented here will be a crucial addition to further functional studies on cerebrovascular research. PMID:23020941

2012-01-01

252

Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.  

PubMed

Accumulated sequence analyses of the antibody repertoire have revealed that most autoantibodies and developmentally regulated antibodies share a small set of germline Ig-variable region (V) genes. The findings have prompted speculation that certain autoantibodies are of developmental importance and may be instrumental in maintaining homeostasis of the adult antibody repertoire. In order to evaluate this hypothesis critically, it is first necessary to determine the V gene usage in human antibodies against foreign substances. Unfortunately, only a few such antibodies have had their heavy and light chains characterized. To rectify the situation, we adapted the anchored polymerase chain reaction to clone and analyze rapidly the expressed V genes for three anti-virus IgG antibodies. The results show that all three heavy chain V (Vh) genes are highly homologous to the known autoantibody-related Vh genes. In contrast, two light chain V (VL) genes of the V lambda 1 subgroup are similar to a non-autoantibody-related germline V lambda 1 gene. Taken together with the reported Vh and VL sequences of several antibodies against viruses and bacteria, the data show that many antipathogen antibodies may use the same small set of Vh genes that encode autoantibodies, but diverse VL genes that are distinct from autoantibody-related VL genes. Thus, only a small portion of the potentially functional germline Vh genes are used recurrently to generate most antibodies in a normal antibody repertoire, regardless of their reactivities with either self or non-self. PMID:1334971

Huang, D F; Olee, T; Masuho, Y; Matsumoto, Y; Carson, D A; Chen, P P

1992-12-01

253

Titanium nanotubes activate genes related to bone formation in vitro  

PubMed Central

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

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

2012-01-01

254

Evolving protein functional diversity in new genes of Drosophila.  

PubMed

The mechanism by which protein functional diversity expands is an important evolutionary issue. Studies of recently evolved chimeric genes permit direct investigation of the origin of new protein functions before they become obscured by subsequent evolution. Found in several African Drosophila species, jingwei (jgw), a recently evolved gene with a domain derived from the still extant short-chain alcohol dehydrogenase (ADH) through retroposition, provides an opportunity to examine this previously undescribed process directly. We expressed JGW proteins in a microbial expression system and, after purification, investigated their enzymatic properties. We found that, unexpectedly, positive Darwinian selection for amino acid replacements outside the active site of JGW produced a novel dehydrogenase with altered substrate specificity compared with the ancestral ADH. Instead of detoxifying and assimilating ethanol like its Adh parental gene, we observe that JGW efficiently utilizes long-chain primary alcohols found in hormone and pheromone metabolism. These data suggest that protein functional diversity can expand rapidly under the joint forces of exon shuffling, gene duplication, and natural selection. PMID:15534206

Zhang, Jianming; Dean, Antony M; Brunet, Frédéric; Long, Manyuan

2004-11-16

255

Hearing impairment risk and interaction of folate metabolism related gene polymorphisms in an aging study  

Microsoft Academic Search

Background  Recent investigations demonstrated many genetic contributions to the development of human age-related hearing impairment (ARHI),\\u000a however, reports of factors associated with a reduction in the ARHI risk are rare. Folate metabolism is essential for cellular\\u000a functioning. Despite the extensive investigations regarding the roles of folate metabolism related gene polymorphisms in the\\u000a pathophysiology of complex diseases, such as cancer, cardio-cerebrovascular disease,

Yasue Uchida; Saiko Sugiura; Fujiko Ando; Tsutomu Nakashima; Hiroshi Shimokata

2011-01-01

256

Comparative Functional Analysis of ZFP36 Genes during Xenopus Development  

PubMed Central

ZFP36 constitutes a small family of RNA binding proteins (formerly known as the TIS11 family) that target mRNA and promote their degradation. In mammals, ZFP36 proteins are encoded by four genes and, although they show similar activities in a cellular RNA destabilization assay, there is still a limited knowledge of their mRNA targets and it is not known whether or not they have redundant functions. In the present work, we have used the Xenopus embryo, a model system allowing gain- and loss-of-function studies, to investigate, whether individual ZFP36 proteins had distinct or redundant functions. We show that overexpression of individual amphibian zfp36 proteins leads to embryos having the same defects, with alteration in somites segmentation and pronephros formation. In these embryos, members of the Notch signalling pathway such as hairy2a or esr5 mRNA are down-regulated, suggesting common targets for the different proteins. We also show that mouse Zfp36 protein overexpression gives the same phenotype, indicating an evolutionary conserved property among ZFP36 vertebrate proteins. Morpholino oligonucleotide-induced loss-of-function leads to defects in pronephros formation, reduction in tubule size and duct coiling alterations for both zfp36 and zfp36l1, indicating no functional redundancy between these two genes. Given the conservation in gene structure and function between the amphibian and mammalian proteins and the conserved mechanisms for pronephros development, our study highlights a potential and hitherto unreported role of ZFP36 gene in kidney morphogenesis. PMID:23342169

Treguer, Karine; Faucheux, Corinne; Veschambre, Philippe; Fedou, Sandrine; Theze, Nadine; Thiebaud, Pierre

2013-01-01

257

Mapping functional transcription factor networks from gene expression data.  

PubMed

A critical step in understanding how a genome functions is determining which transcription factors (TFs) regulate each gene. Accordingly, extensive effort has been devoted to mapping TF networks. In Saccharomyces cerevisiae, protein-DNA interactions have been identified for most TFs by ChIP-chip, and expression profiling has been done on strains deleted for most TFs. These studies revealed that there is little overlap between the genes whose promoters are bound by a TF and those whose expression changes when the TF is deleted, leaving us without a definitive TF network for any eukaryote and without an efficient method for mapping functional TF networks. This paper describes NetProphet, a novel algorithm that improves the efficiency of network mapping from gene expression data. NetProphet exploits a fundamental observation about the nature of TF networks: The response to disrupting or overexpressing a TF is strongest on its direct targets and dissipates rapidly as it propagates through the network. Using S. cerevisiae data, we show that NetProphet can predict thousands of direct, functional regulatory interactions, using only gene expression data. The targets that NetProphet predicts for a TF are at least as likely to have sites matching the TF's binding specificity as the targets implicated by ChIP. Unlike most ChIP targets, the NetProphet targets also show evidence of functional regulation. This suggests a surprising conclusion: The best way to begin mapping direct, functional TF-promoter interactions may not be by measuring binding. We also show that NetProphet yields new insights into the functions of several yeast TFs, including a well-studied TF, Cbf1, and a completely unstudied TF, Eds1. PMID:23636944

Haynes, Brian C; Maier, Ezekiel J; Kramer, Michael H; Wang, Patricia I; Brown, Holly; Brent, Michael R

2013-08-01

258

Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans  

PubMed Central

Background Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics. Results We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes. Conclusions This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases. PMID:23496871

2013-01-01

259

Intestinal structure and function related to toxicology.  

PubMed

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

Crane, R K

1979-12-01

260

The PMP22 Gene and Its Related Diseases  

PubMed Central

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

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

2012-01-01

261

Intra-relation reconstruction from inter-relation: miRNA to gene expression  

PubMed Central

Background In computational biology, a novel knowledge has been obtained mostly by identifying 'intra-relation,' the relation between entities on a specific biological level such as from gene expression or from microRNA (miRNA) and many such researches have been successful. However, intra-relations are not fully explaining complex cancer mechanisms because the inter-relation information between different levels of genomic data is missing, e.g. miRNA and its target genes. The 'inter-relation' between different levels of genomic data can be constructed from biological experimental data as well as genomic knowledge. Methods Previously, we have proposed a graph-based framework that integrates with multi-layers of genomic data, copy number alteration, DNA methylation, gene expression, and miRNA expression, for the cancer clinical outcome prediction. However, the limitation of previous work was that we integrated with multi-layers of genomic data without considering of inter-relationship information between genomic features. In this paper, we propose a new integrative framework that combines genomic dataset from gene expression and genomic knowledge from inter-relation between miRNA and gene expression for the clinical outcome prediction as a pilot study. Results In order to demonstrate the validity of the proposed method, the prediction of short-term/long-term survival for 82 patients in glioblastoma multiforme (GBM) was adopted as a base task. Based on our results, the accuracy of our predictive model increases because of incorporation of information fused over genomic dataset from gene expression and genomic knowledge from inter-relation between miRNA and gene expression. Conclusions In the present study, the intra-relation of gene expression was reconstructed from inter-relation between miRNA and gene expression for prediction of short-term/long-term survival of GBM patients. Our finding suggests that the utilization of external knowledge representing miRNA-mediated regulation of gene expression is substantially useful for elucidating the cancer phenotype. PMID:24521265

2013-01-01

262

The lysis genes of bacteriophage 21: structure and function  

E-print Network

(Campbell and Rolfe, 1975, Garret et al. , 1981). The most distal gene in the lysis "overlappon", le, is of unknown function and is required for lysis only under conditions of high osmolarity such as 10mH HgC12 (Young et al. , 1979). The fl gene encodes.... As mentioned above, respiratory poisons such as cyanide or dinitrophenol have been shown to trigger pg pr'ematurely in the lytic cycle, presumably by subverting the delayed action timing of pS (Campbell and Rolfe, 1975, Garret et al. , 1981). This model...

Bonovich, Maria Teresa

2012-06-07

263

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

PubMed Central

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

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

2013-01-01

264

Cancer-related genes transcriptionally induced by the fungicide penconazole.  

PubMed

Penconazole is a systemic triazole fungicide mainly used on grapes. The UE Maximum Residue Level (MRL) for penconazole is set at 0.2ppm in wine and grapes. In the aim of identifying potential biomarkers of exposure to penconazole and possibly highlighting its endocrine disrupting mode of action, we used a transcriptomics-based approach to detect genes, that are transcriptionally modulated by penconazole, by using an appropriate in vitro model. T-47D cells were treated with commercial penconazole or penconazole contaminated grape extracts for 4h at doses close to the MRL. The whole-genome transcriptomic profile was assessed by using genome 44K oligo-microarray slides. The list of common genes generated by the two treatments could be representative of potential markers of exposure. In order to understand the role of these genes in key events related to adversity, a pathway analysis was performed on a list of genes with the same modulation trend (up or down). The analysis returned a set of genes involved in Thyroid Cancer Pathway, thus confirming a role of penconazole in endocrine disrupting mediated effects and strongly suggesting a possible mode of action in thyroid carcinogenesis. PMID:23811263

Perdichizzi, Stefania; Mascolo, Maria Grazia; Silingardi, Paola; Morandi, Elena; Rotondo, Francesca; Guerrini, Angela; Prete, Luciana; Vaccari, Monica; Colacci, Annamaria

2014-02-01

265

Temporal Conversion Functions for Multitemporal Relational Databases  

Microsoft Academic Search

Most research in the field of algebras for temporal relational databases concerns the study of operations within each of the formats transaction-time, valid-time, bitemporal and snapshot. Nevertheless, data of different temporal format (multitemporal relational data) should be allowed to interact. Two possible scenarios for this problem are: (1) federated databases, where the interaction is required of databases of different temporal

Cristina De Castro

1996-01-01

266

Gene activation and deactivation related changes in the three-dimensional structure of chromatin.  

PubMed

Chromatin in the interphase nucleus is dynamic, decondensing where genes are activated and condensing where they are silenced. Local chromatin remodelling to a more open structure during gene activation is followed by changes in nucleosome distribution through the action of the transcriptional machinery. This leads to chromatin expansion and looping out of whole genomic regions. Such chromatin loops can extend beyond the chromosome territory. As several studies point to the location of transcription sites inside chromosome territories as well as at their periphery, extraterritorial loops cannot simply be a mechanism for making transcribed genes accessible to the transcriptional machinery and must occur for other reasons. The level of decondensation within an activated region varies greatly and probably depends on the density of activated genes and the number of engaged RNA polymerases. Genes that are silenced during development form a more closed chromatin structure. Specific histone modifications are correlated with gene activation and silencing, and silenced genes may become associated with heterochromatin protein 1 homologues or with polycomb group complexes. Several levels of chromatin packaging are found in the nucleus relating to the different functions of and performed by active genes; euchromatic and heterochromatic regions and the models explaining higher-order chromatin structure are still disputed. PMID:16075283

Wegel, Eva; Shaw, Peter

2005-11-01

267

Systematic Analysis of Experimental Phenotype Data Reveals Gene Functions  

PubMed Central

High-throughput phenotyping projects in model organisms have the potential to improve our understanding of gene functions and their role in living organisms. We have developed a computational, knowledge-based approach to automatically infer gene functions from phenotypic manifestations and applied this approach to yeast (Saccharomyces cerevisiae), nematode worm (Caenorhabditis elegans), zebrafish (Danio rerio), fruitfly (Drosophila melanogaster) and mouse (Mus musculus) phenotypes. Our approach is based on the assumption that, if a mutation in a gene leads to a phenotypic abnormality in a process , then must have been involved in , either directly or indirectly. We systematically analyze recorded phenotypes in animal models using the formal definitions created for phenotype ontologies. We evaluate the validity of the inferred functions manually and by demonstrating a significant improvement in predicting genetic interactions and protein-protein interactions based on functional similarity. Our knowledge-based approach is generally applicable to phenotypes recorded in model organism databases, including phenotypes from large-scale, high throughput community projects whose primary mode of dissemination is direct publication on-line rather than in the literature. PMID:23626672

Hoehndorf, Robert; Hardy, Nigel W.; Osumi-Sutherland, David; Tweedie, Susan; Schofield, Paul N.; Gkoutos, Georgios V.

2013-01-01

268

Human chromosome 21/Down syndrome gene function and pathway database.  

PubMed

Down syndrome, trisomy of human chromosome 21, is the most common genetic cause of intellectual disability. Correlating the increased expression, due to gene dosage, of the >300 genes encoded by chromosome 21 with specific phenotypic features is a goal that becomes more feasible with the increasing availability of large scale functional, expression and evolutionary data. These data are dispersed among diverse databases, and the variety of formats and locations, plus their often rapid growth, makes access and assimilation a daunting task. To aid the Down syndrome and chromosome 21 community, and researchers interested in the study of any chromosome 21 gene or ortholog, we are developing a comprehensive chromosome 21-specific database with the goals of (i) data consolidation, (ii) accuracy and completeness through expert curation, and (iii) facilitation of novel hypothesis generation. Here we describe the current status of data collection and the immediate future plans for this first human chromosome-specific database. PMID:16310977

Nikolaienko, Oleksii; Nguyen, Cao; Crinc, Linda S; Cios, Krzysztof J; Gardiner, Katheleen

2005-12-30

269

Differential expression of inflammation-related genes after intense exercise.  

PubMed

The present study focused on the identification of the difference in expression of inflammation-related genes after intense exercise by oligonucleotide microarray methods. This may finally lead to an improved understanding of underlying cellular and molecular mechanism of the immunological alterations in response to exercises. The study group consisted of three healthy road cyclists. Peripheral blood mononuclear cells (PBMCs) were collected preexercise, immediately post-exercise and after 15 min of recovery. The analysis of the expression profile of genes related to the inflammation was performed in PBMCs using HG-U133A oligonucleotide microarrays. 4 genes were found to be regulated by more than 2.0-fold (IL1R2, IL2RB, IL8, IL8RB). Venn diagram indicated that only one of differentially expressed genes (TXLNA) remains the same in each comparison. The balance of both pro- and anti-inflammatory cytokines after exercise seems to be important for athletes. Optimal inflammatory and immune response may help optimize exercise regimes, link physical activity with health and diagnose or prevent athletes from overtraining. PMID:24874932

Kimsa, Magdalena C; Strzalka-Mrozik, Barbara; Kimsa, Malgorzata W; Gola, Joanna; Kochanska-Dziurowicz, Aleksandra; Zebrowska, Aleksandra; Mazurek, Urszula

2014-01-01

270

Fungal genes related to calcium homeostasis and signalling are upregulated in symbiotic arbuscular mycorrhiza interactions.  

PubMed

Fluctuations in intracellular calcium levels generate signalling events and regulate different cellular processes. Whilst the implication of Ca(2+) in plant responses during arbuscular mycorrhiza (AM) interactions is well documented, nothing is known about the regulation or role of this secondary messenger in the fungal symbiont. The spatio-temporal expression pattern of putatively Ca(2+)-related genes of Glomus intraradices BEG141 encoding five proteins involved in membrane transport and one nuclear protein kinase, was investigated during the AM symbiosis. Expression profiles related to successful colonization of host roots were observed in interactions of G. intraradices with roots of wild-type Medicago truncatula (line J5) compared to the mycorrhiza-defective mutant dmi3/Mtsym13. Symbiotic fungal activity was monitored using stearoyl-CoA desaturase and phosphate transporter genes. Laser microdissection based-mapping of fungal gene expression in mycorrhizal root tissues indicated that the Ca(2+)-related genes were differentially upregulated in arbuscules and/or in intercellular hyphae. The spatio-temporal variations in gene expression suggest that the encoded proteins may have different functions in fungal development or function during symbiosis development. Full-length cDNA obtained for two genes with interesting expression profiles confirmed a close similarity with an endoplasmic reticulum P-type ATPase and a Vcx1-like vacuolar Ca(2+) ion transporter functionally characterized in other fungi and involved in the regulation of cell calcium pools. Possible mechanisms are discussed in which Ca(2+)-related proteins G. intraradices BEG141 may play a role in mobilization and perception of the intracellular messenger by the AM fungus during symbiotic interactions with host roots. PMID:23332830

Liu, Yi; Gianinazzi-Pearson, Vivienne; Arnould, Christine; Wipf, Daniel; Zhao, Bin; van Tuinen, Diederik

2013-01-01

271

Functional analysis of a melanin biosynthetic gene using RNAi-mediated gene silencing in Rosellinia necatrix.  

PubMed

Rosellinia necatrix causes white root rot in a wide range of fruit trees and persists for extended periods as pseudosclerotia on root debris. However, the pathogenesis of this disease has yet to be clarified. The functions of endogeneous target genes have not been determined because of the inefficiency in genetic transformation. In this study, the function of a melanin biosynthetic gene was determined to examine its role in morphology and virulence. A polyketide synthase gene (termed as RnPKS1) in the R. necatrix genome is homologous to the 1,8-dihydroxynaphthalene (DHN) melanin biosynthetic gene of Colletotrichum lagenarium. Melanin-deficient strains of R. necatrix were obtained by RNA interference-mediated knockdown of RnPKS1. The virulence of these strains was not significantly reduced compared with the parental melanin-producing strain. However, knockdown strains failed to develop pseudosclerotia and were degraded sooner in soil than the parental strain. Microscopic observations of albino conidiomata produced by knockdown strains revealed that melanization is involved in synnema integrity. These results suggest that melanin is not necessary for R. necatrix pathogenesis but is involved in survival through morphogenesis. This is the first report on the functional analysis of an endogenous target gene in R. necatrix. PMID:24742836

Shimizu, Takeo; Ito, Tsutae; Kanematsu, Satoko

2014-04-01

272

Functional annotation of human cytomegalovirus gene products: an update  

PubMed Central

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

Van Damme, Ellen; Van Loock, Marnix

2014-01-01

273

Comparison of lists of genes based on functional profiles  

PubMed Central

Background How to compare studies on the basis of their biological significance is a problem of central importance in high-throughput genomics. Many methods for performing such comparisons are based on the information in databases of functional annotation, such as those that form the Gene Ontology (GO). Typically, they consist of analyzing gene annotation frequencies in some pre-specified GO classes, in a class-by-class way, followed by p-value adjustment for multiple testing. Enrichment analysis, where a list of genes is compared against a wider universe of genes, is the most common example. Results A new global testing procedure and a method incorporating it are presented. Instead of testing separately for each GO class, a single global test for all classes under consideration is performed. The test is based on the distance between the functional profiles, defined as the joint frequencies of annotation in a given set of GO classes. These classes may be chosen at one or more GO levels. The new global test is more powerful and accurate with respect to type I errors than the usual class-by-class approach. When applied to some real datasets, the results suggest that the method may also provide useful information that complements the tests performed using a class-by-class approach if gene counts are sparse in some classes. An R library, goProfiles, implements these methods and is available from Bioconductor, http://bioconductor.org/packages/release/bioc/html/goProfiles.html. Conclusions The method provides an inferential basis for deciding whether two lists are functionally different. For global comparisons it is preferable to the global chi-square test of homogeneity. Furthermore, it may provide additional information if used in conjunction with class-by-class methods. PMID:21999355

2011-01-01

274

Gene-Specific Function Prediction for Non-Synonymous Mutations in Monogenic Diabetes Genes  

PubMed Central

The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY) molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose of this study is to compare the performance of different bioinformatics methods in the functional prediction of nonsynonymous mutations in each MODY gene, and provides reference matrices to assist the molecular diagnosis of MODY. Our study showed that the prediction scores by different methods of the diabetes mutations were highly correlated, but were more complimentary than replacement to each other. The available in silico methods for the prediction of diabetes mutations had varied performances across different genes. Applying gene-specific thresholds defined by this study may be able to increase the performance of in silico prediction of disease-causing mutations. PMID:25136813

Li, Quan; Liu, Xiaoming; Gibbs, Richard A.; Boerwinkle, Eric; Polychronakos, Constantin; Qu, Hui-Qi

2014-01-01

275

Gene therapy rescues cone function in congenital achromatopsia  

PubMed Central

The successful restoration of visual function with recombinant adeno-associated virus (rAAV)-mediated gene replacement therapy in animals and humans with an inherited disease of the retinal pigment epithelium has ushered in a new era of retinal therapeutics. For many retinal disorders, however, targeting of therapeutic vectors to mutant rods and/or cones will be required. In this study, the primary cone photoreceptor disorder achromatopsia served as the ideal translational model to develop gene therapy directed to cone photoreceptors. We demonstrate that rAAV-mediated gene replacement therapy with different forms of the human red cone opsin promoter led to the restoration of cone function and day vision in two canine models of CNGB3 achromatopsia, a neuronal channelopathy that is the most common form of achromatopsia in man. The robustness and stability of the observed treatment effect was mutation independent, but promoter and age dependent. Subretinal administration of rAAV5–hCNGB3 with a long version of the red cone opsin promoter in younger animals led to a stable therapeutic effect for at least 33 months. Our results hold promise for future clinical trials of cone-directed gene therapy in achromatopsia and other cone-specific disorders. PMID:20378608

Komaromy, Andras M.; Alexander, John J.; Rowlan, Jessica S.; Garcia, Monique M.; Chiodo, Vince A.; Kaya, Asli; Tanaka, Jacqueline C.; Acland, Gregory M.; Hauswirth, William W.; Aguirre, Gustavo D.

2010-01-01

276

Functional Divergence of a Syntenic Invertase Gene Family in Tomato, Potato, and Arabidopsis1  

PubMed Central

Comparative analysis of complex developmental pathways depends on our ability to resolve the function of members of gene families across taxonomic groups. LIN5, which belongs to a small gene family of apoplastic invertases in tomato (Lycopersicon esculentum), is a quantitative trait locus that modifies fruit sugar composition. We have compared the genomic organization and expression of this gene family in the two distantly related species: tomato and Arabidopsis. Invertase family members reside on segmental duplications in the near-colinear genomes of tomato and potato (Solanum tuberosum). These chromosomal segments are syntenically duplicated in the model plant Arabidopsis. On the basis of phylogenetic analysis of genes in the microsyntenic region, we conclude that these segmental duplications arose independently after the separation of the tomato/potato clade from Arabidopsis. Rapid regulatory divergence is characteristic of the invertase family. Interestingly, although the processes of gene duplication and specialization of expression occurred separately in the two species, synteny-based orthologs from both clades acquired similar organ-specific expression. This similar expression pattern of the genes is evidence of comparable evolutionary constraints (parallel evolution) rather than of functional orthology. The observation that functional orthology cannot be identified through analysis of expression similarity highlights the caution that needs to be exercised in extrapolating developmental networks from a model organism. PMID:12586884

Fridman, Eyal; Zamir, Dani

2003-01-01

277

Downregulation of Apoptosis-Related Genes in Keloid Tissues  

Microsoft Academic Search

Background. Physiologically programmed cell death or apoptosis occurs during the natural balance between cellular proliferation and demise.Materials and Methods. We compared the expression of 64 apoptosis-related genes in keloids and normal scars to investigate the potential role of apoptosis in keloid formation. Two sets of mRNA were isolated from keloids excised from four previously untreated patients and four normal scar

David N. Sayah; Chia Soo; William W. Shaw; James Watson; Diana Messadi; Michael T. Longaker; Xinli Zhang; Kang Ting

1999-01-01

278

Functional neuroimaging of dressing-related skills.  

PubMed

Restoration of motor function following stroke involves reorganization of motor output through intact pathways, with compensatory brain activity likely variable by task. One class of motor tasks, those involved in self-care, is particularly important in stroke rehabilitation. Identifying the brain areas that are engaged in self-care and how they reorganize after stroke may enable development of more effective rehabilitation strategies. We piloted a paradigm for functional MRI assessment of self-care activity. In two groups, young adults and older adults, two self-care tasks (buttoning and zipping) produce activation similar to a bimanual tapping task, with bilateral activation of primary and secondary motor cortices, primary sensory cortex, and cerebellum. Quantitative differences include more activation of sensorimotor cortex and cerebellum in buttoning than bimanual tapping. Pilot subjects with stroke showed greater superior parietal activity across tasks than controls, potentially representing an increased need for sensorimotor integration to perform motor tasks. PMID:23070748

Wittenberg, George F; Lovelace, Christopher T; Foster, Donald J; Maldjian, Joseph A

2014-09-01

279

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

PubMed

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. PMID:20376100

Reeve, Jennifer R; Schadt, Christopher W; Carpenter-Boggs, Lynne; Kang, Sanghoon; Zhou, Jizhong; Reganold, John P

2010-09-01

280

Widespread decreased expression of immune function genes in human peripheral blood following radiation exposure.  

PubMed

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

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

2013-12-01

281

Functional Analysis of the Two Brassica AP3 Genes Involved in Apetalous and Stamen Carpelloid Phenotypes  

PubMed Central

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B. napus were investigated and two types of AP3 genes, B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share high similarity in amino acid sequences except for 8 residues difference located at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI-derived motifs. Meanwhile, B.AP3.a specified petal and stamen development, whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the apetalous mutation, however, the loss-of-function in all four AP3 was related to the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3 gene probably relates to petal formation. PMID:21738595

Zhang, Yanfeng; Wang, Xuefang; Zhang, Wenxue; Yu, Fei; Tian, Jianhua; Li, Dianrong; Guo, Aiguang

2011-01-01

282

Functional role of VNTR polymorphism of human genes  

Microsoft Academic Search

A brief overview of the current views on the functional role of genetic VNTR polymorphism in humans is given. Data on the\\u000a involvement of VNTRs in the regulation of gene expression and in the formation of complex phenotypes are presented. According\\u000a to these data, the effects of VNTRs are determined by the number of repeats, the structure of their monomers

N. P. Babushkina; A. N. Kucher

2011-01-01

283

Virus-induced gene silencing is a versatile tool for unraveling the functional relevance of multiple abiotic-stress-responsive genes in crop plants.  

PubMed

Virus-induced gene silencing (VIGS) is an effective tool for gene function analysis in plants. Over the last decade, VIGS has been successfully used as both a forward and reverse genetics technique for gene function analysis in various model plants, as well as crop plants. With the increased identification of differentially expressed genes under various abiotic stresses through high-throughput transcript profiling, the application of VIGS is expected to be important in the future for functional characterization of a large number of genes. In the recent past, VIGS was proven to be an elegant tool for functional characterization of genes associated with abiotic stress responses. In this review, we provide an overview of how VIGS is used in different crop species to characterize genes associated with drought-, salt-, oxidative- and nutrient-deficiency-stresses. We describe the examples from studies where abiotic stress related genes are characterized using VIGS. In addition, we describe the major advantages of VIGS over other currently available functional genomics tools. We also summarize the recent improvements, limitations and future prospects of using VIGS as a tool for studying plant responses to abiotic stresses. PMID:25071806

Ramegowda, Venkategowda; Mysore, Kirankumar S; Senthil-Kumar, Muthappa

2014-01-01

284

Genomic Evidence Reveals the Extreme Diversity and Wide Distribution of the Arsenic-Related Genes in Burkholderiales  

PubMed Central

So far, numerous genes have been found to associate with various strategies to resist and transform the toxic metalloid arsenic (here, we denote these genes as “arsenic-related genes”). However, our knowledge of the distribution, redundancies and organization of these genes in bacteria is still limited. In this study, we analyzed the 188 Burkholderiales genomes and found that 95% genomes harbored arsenic-related genes, with an average of 6.6 genes per genome. The results indicated: a) compared to a low frequency of distribution for aio (arsenite oxidase) (12 strains), arr (arsenate respiratory reductase) (1 strain) and arsM (arsenite methytransferase)-like genes (4 strains), the ars (arsenic resistance system)-like genes were identified in 174 strains including 1,051 genes; b) 2/3 ars-like genes were clustered as ars operon and displayed a high diversity of gene organizations (68 forms) which may suggest the rapid movement and evolution for ars-like genes in bacterial genomes; c) the arsenite efflux system was dominant with ACR3 form rather than ArsB in Burkholderiales; d) only a few numbers of arsM and arrAB are found indicating neither As III biomethylation nor AsV respiration is the primary mechanism in Burkholderiales members; (e) the aio-like gene is mostly flanked with ars-like genes and phosphate transport system, implying the close functional relatedness between arsenic and phosphorus metabolisms. On average, the number of arsenic-related genes per genome of strains isolated from arsenic-rich environments is more than four times higher than the strains from other environments. Compared with human, plant and animal pathogens, the environmental strains possess a larger average number of arsenic-related genes, which indicates that habitat is likely a key driver for bacterial arsenic resistance. PMID:24632831

Li, Xiangyang; Zhang, Linshuang; Wang, Gejiao

2014-01-01

285

Genomic evidence reveals the extreme diversity and wide distribution of the arsenic-related genes in Burkholderiales.  

PubMed

So far, numerous genes have been found to associate with various strategies to resist and transform the toxic metalloid arsenic (here, we denote these genes as "arsenic-related genes"). However, our knowledge of the distribution, redundancies and organization of these genes in bacteria is still limited. In this study, we analyzed the 188 Burkholderiales genomes and found that 95% genomes harbored arsenic-related genes, with an average of 6.6 genes per genome. The results indicated: a) compared to a low frequency of distribution for aio (arsenite oxidase) (12 strains), arr (arsenate respiratory reductase) (1 strain) and arsM (arsenite methytransferase)-like genes (4 strains), the ars (arsenic resistance system)-like genes were identified in 174 strains including 1,051 genes; b) 2/3 ars-like genes were clustered as ars operon and displayed a high diversity of gene organizations (68 forms) which may suggest the rapid movement and evolution for ars-like genes in bacterial genomes; c) the arsenite efflux system was dominant with ACR3 form rather than ArsB in Burkholderiales; d) only a few numbers of arsM and arrAB are found indicating neither As III biomethylation nor AsV respiration is the primary mechanism in Burkholderiales members; (e) the aio-like gene is mostly flanked with ars-like genes and phosphate transport system, implying the close functional relatedness between arsenic and phosphorus metabolisms. On average, the number of arsenic-related genes per genome of strains isolated from arsenic-rich environments is more than four times higher than the strains from other environments. Compared with human, plant and animal pathogens, the environmental strains possess a larger average number of arsenic-related genes, which indicates that habitat is likely a key driver for bacterial arsenic resistance. PMID:24632831

Li, Xiangyang; Zhang, Linshuang; Wang, Gejiao

2014-01-01

286

Functional gene variants of CYP3A4.  

PubMed

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

Werk, A N; Cascorbi, I

2014-09-01

287

Functional relations for the density-functional exchange and correlation functionals connecting functionals at three densities  

NASA Astrophysics Data System (ADS)

It is shown that the density-functional-theory exchange and correlation functionals satisfy 0=?Ehx[?N]+2Ec?[?N]-?Ehx[?N-1?]-2Ec?[?N-1?]+2?d3r'[?N-10(r)-?N-1?(r)]v0([?N];r)+?d3r'[?N-10(r)-?N-1?(r)]r·?v0([?N];r)+?d3r'?N(r)r·?vc?([?N];r)-?d3r'?N-1?(r)r·?vc?([?N-1?];r)-?d3r'f?(r)r·?vhxc?([?N];r)-2?d3r'f?(r)vhxc?([?N];r). In the derivation of this equation the adiabatic connection formulation is used, where the ground-state density of an N-electron system ?N is kept constant independent of the electron-electron coupling strength ?. Here Ehx[?] is the Hartree plus exchange energy, Ec?[?] is the correlation energy, vhxc?[?] is the Hartree plus exchange-correlation potential, vc[?] is the correlation potential, and v0[?]is the Kohn-Sham potential. The charge densities ?N and ?N-1? are the N- and (N-1)-electron ground-state densities of the same Hamiltonian at electron-electron coupling strength ?. f?(r)=?N(r)-?N-1?(r) is the Fukui function. This equation can be useful in testing the internal self-consistency of approximations to the exchange and correlation functionals. As an example the identity is tested on the analytical Hooke's atom charge density for some frequently used approximate functionals.

Joubert, Daniel P.

2012-03-01

288

Learning Gene Functional Classifications From Multiple Data Types  

E-print Network

In our attempts to understand cellular function at the molecular level, we must be able to synthesize information from disparate types of genomic data. We consider the problem of inferring gene functional classifications from a heterogeneous data set consisting of DNA microarray expression measurements and phylogenetic profiles from whole-genome sequence comparisons. We demonstrate the application of the support vector machine (SVM) learning algorithm to this functional inference task. Our results suggest the importance of exploiting prior information about the heterogeneity of the data. In particular, we propose an SVM kernel function that is explicitly heterogeneous. In addition, we describe feature scaling methods for further exploiting prior knowledge of heterogeneity by giving each data type different weights.

Paul Pavlidis; Jinsong Cai; Jason Weston; William Stafford Noble

2002-01-01

289

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

PubMed

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

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

2014-05-01

290

Genome-Wide Expression Analysis of Soybean MADS Genes Showing Potential Function in the Seed Development  

PubMed Central

The MADS family is an ancient and best-studied transcription factor and plays fundamental roles in almost every developmental process in plants. In the plant evolutionary history, the whole genome duplication (WGD) events are important not only to the plant species evolution, but to expansion of members of the gene families. Soybean as a model legume crop has experience three rounds of WGD events. Members of some MIKCC subfamilies, such as SOC, AGL6, SQUA, SVP, AGL17 and DEF/GLO, were expanded after soybean three rounds of WGD events. And some MIKCC subfamilies, MIKC* and type I MADS families had experienced faster birth-and-death evolution and their traces before the Glycine WGD event were not found. Transposed duplication played important roles in tandem arrangements among the members of different subfamilies. According to the expression profiles of type I and MIKC paralog pair genes, the fates of MIKC paralog gene pairs were subfunctionalization, and the fates of type I MADS paralog gene pairs were nonfunctionalization. 137 out of 163 MADS genes were close to 186 loci within 2 Mb genomic regions associated with seed-relative QTLs, among which 115 genes expressed during the seed development. Although MIKCC genes kept the important and conserved functions of the flower development, most MIKCC genes showed potentially essential roles in the seed development as well as the type I MADS. PMID:23638026

Hu, Rui-Bo; Zhang, Xiao-Mei; Chen, Jian-Xin; Fu, Yong-Fu

2013-01-01

291

Transglutaminase regulates immune-related genes in shrimp.  

PubMed

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

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

2012-05-01

292

First survey and functional annotation of prohormone and convertase genes in the pig  

PubMed Central

Background The pig is a biomedical model to study human and livestock traits. Many of these traits are controlled by neuropeptides that result from the cleavage of prohormones by prohormone convertases. Only 45 prohormones have been confirmed in the pig. Sequence homology can be ineffective to annotate prohormone genes in sequenced species like the pig due to the multifactorial nature of the prohormone processing. The goal of this study is to undertake the first complete survey of prohormone and prohormone convertases genes in the pig genome. These genes were functionally annotated based on 35 gene expression microarray experiments. The cleavage sites of prohormone sequences into potentially active neuropeptides were predicted. Results We identified 95 unique prohormone genes, 2 alternative calcitonin-related sequences, 8 prohormone convertases and 1 cleavage facilitator in the pig genome 10.2 assembly and trace archives. Of these, 11 pig prohormone genes have not been reported in the UniProt, UniGene or Gene databases. These genes are intermedin, cortistatin, insulin-like 5, orexigenic neuropeptide QRFP, prokineticin 2, prolactin-releasing peptide, parathyroid hormone 2, urocortin, urocortin 2, urocortin 3, and urotensin 2-related peptide. In addition, a novel neuropeptide S was identified in the pig genome correcting the previously reported pig sequence that is identical to the rabbit sequence. Most differentially expressed prohormone genes were under-expressed in pigs experiencing immune challenge relative to the un-challenged controls, in non-pregnant relative to pregnant sows, in old relative to young embryos, and in non-neural relative to neural tissues. The cleavage prediction based on human sequences had the best performance with a correct classification rate of cleaved and non-cleaved sites of 92% suggesting that the processing of prohormones in pigs is similar to humans. The cleavage prediction models did not find conclusive evidence supporting the production of the bioactive neuropeptides urocortin 2, urocortin 3, torsin family 2 member A, tachykinin 4, islet amyloid polypeptide, and calcitonin receptor-stimulating peptide 2 in the pig. Conclusions The present genomic and functional characterization supports the use of the pig as an effective animal model to gain a deeper understanding of prohormones, prohormone convertases and neuropeptides in biomedical and agricultural research. PMID:23153308

2012-01-01

293

Cloning and functional characterization of carotenoid cleavage dioxygenase 4 genes  

PubMed Central

Although a number of plant carotenoid cleavage dioxygenase (CCD) genes have been functionally characterized in different plant species, little is known about the biochemical role and enzymatic activities of members of the subclass 4 (CCD4). To gain insight into their biological function, CCD4 genes were isolated from apple (Malus×domestica, MdCCD4), chrysanthemum (Chrysanthemum×morifolium, CmCCD4a), rose (Rosa×damascena, RdCCD4), and osmanthus (Osmanthus fragrans, OfCCD4), and were expressed, together with AtCCD4, in Escherichia coli. In vivo assays showed that CmCCD4a and MdCCD4 cleaved ?-carotene well to yield ?-ionone, while OfCCD4, RdCCD4, and AtCCD4 were almost inactive towards this substrate. No cleavage products were found for any of the five CCD4 genes when they were co-expressed in E. coli strains that accumulated cis-?-carotene and lycopene. In vitro assays, however, demonstrated the breakdown of 8?-apo-?-caroten-8?-al by AtCCD4 and RdCCD4 to ?-ionone, while this apocarotenal was almost not degraded by OfCCD4, CmCCD4a, and MdCCD4. Sequence analysis of genomic clones of CCD4 genes revealed that RdCCD4, like AtCCD4, contains no intron, while MdCCD, OfCCD4, and CmCCD4a contain introns. These results indicate that plants produce at least two different forms of CCD4 proteins. Although CCD4 enzymes cleave their substrates at the same position (9,10 and 9?,10?), they might have different biochemical functions as they accept different (apo)-carotenoid substrates, show various expression patterns, and are genomically differently organized. PMID:19436048

Huang, Fong-Chin; Molnar, Peter; Schwab, Wilfried

2009-01-01

294

Impact of obesity-related genes in Spanish population  

PubMed Central

Background The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Results Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). Conclusion The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population. PMID:24267414

2013-01-01

295

Nonmotor symptoms in Parkin gene-related parkinsonism.  

PubMed

The aim of the study was to explore the prevalence and differences of nonmotor symptoms (NMSs) in patients with young-onset Parkinson's disease (YOPD) with and without mutations in the Parkin gene and late-onset Parkinson's disease (LOPD). Twenty-seven patients with YOPD and 27 with LOPD, as well as 16 patients with homozygous or compound heterozygote Parkin mutations filled in the nonmotor symptoms questionnaire, a 30-item self-completed questionnaire that addresses various NMSs. Overall, NMSs were more prevalent in YOPD (12.07 +/- 3.9; P = 0.009) and LOPD (13.26 +/- 5.8; P = 0.001) compared with Parkin mutation carriers (7.38 +/- 4.2). Dribbling of saliva, vivid dreams, loss of smell, and urinary urgency were more prevalent in YOPD compared with Parkin mutation carriers. Only anxiety was more prevalent in the latter. Apart from anxiety, NMSs appear to be less prevalent in Parkin gene-related parkinsonism. Although these results need further study, the presented data might be helpful in the clinical recognition of specific phenotypes and genotypes in YOPD. The data are in keeping with a different pathological disease process in Parkin gene-related parkinsonism. PMID:20629119

Kägi, Georg; Klein, Christine; Wood, Nicholas W; Schneider, Susanne A; Pramstaller, Peter P; Tadic, Vera; Quinn, Niall P; van de Warrenburg, Bart P C; Bhatia, Kailash P

2010-07-15

296

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

PubMed Central

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

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

297

A Relative Variation-Based Method to Unraveling Gene Regulatory Networks  

PubMed Central

Gene regulatory network (GRN) reconstruction is essential in understanding the functioning and pathology of a biological system. Extensive models and algorithms have been developed to unravel a GRN. The DREAM project aims to clarify both advantages and disadvantages of these methods from an application viewpoint. An interesting yet surprising observation is that compared with complicated methods like those based on nonlinear differential equations, etc., methods based on a simple statistics, such as the so-called -score, usually perform better. A fundamental problem with the -score, however, is that direct and indirect regulations can not be easily distinguished. To overcome this drawback, a relative expression level variation (RELV) based GRN inference algorithm is suggested in this paper, which consists of three major steps. Firstly, on the basis of wild type and single gene knockout/knockdown experimental data, the magnitude of RELV of a gene is estimated. Secondly, probability for the existence of a direct regulation from a perturbed gene to a measured gene is estimated, which is further utilized to estimate whether a gene can be regulated by other genes. Finally, the normalized RELVs are modified to make genes with an estimated zero in-degree have smaller RELVs in magnitude than the other genes, which is used afterwards in queuing possibilities of the existence of direct regulations among genes and therefore leads to an estimate on the GRN topology. This method can in principle avoid the so-called cascade errors under certain situations. Computational results with the Size 100 sub-challenges of DREAM3 and DREAM4 show that, compared with the -score based method, prediction performances can be substantially improved, especially the AUPR specification. Moreover, it can even outperform the best team of both DREAM3 and DREAM4. Furthermore, the high precision of the obtained most reliable predictions shows that the suggested algorithm may be very helpful in guiding biological experiment designs. PMID:22363578

Wang, Yali; Zhou, Tong

2012-01-01

298

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

PubMed

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

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

299

A relative variation-based method to unraveling gene regulatory networks.  

PubMed

Gene regulatory network (GRN) reconstruction is essential in understanding the functioning and pathology of a biological system. Extensive models and algorithms have been developed to unravel a GRN. The DREAM project aims to clarify both advantages and disadvantages of these methods from an application viewpoint. An interesting yet surprising observation is that compared with complicated methods like those based on nonlinear differential equations, etc., methods based on a simple statistics, such as the so-called Z-score, usually perform better. A fundamental problem with the Z-score, however, is that direct and indirect regulations can not be easily distinguished. To overcome this drawback, a relative expression level variation (RELV) based GRN inference algorithm is suggested in this paper, which consists of three major steps. Firstly, on the basis of wild type and single gene knockout/knockdown experimental data, the magnitude of RELV of a gene is estimated. Secondly, probability for the existence of a direct regulation from a perturbed gene to a measured gene is estimated, which is further utilized to estimate whether a gene can be regulated by other genes. Finally, the normalized RELVs are modified to make genes with an estimated zero in-degree have smaller RELVs in magnitude than the other genes, which is used afterwards in queuing possibilities of the existence of direct regulations among genes and therefore leads to an estimate on the GRN topology. This method can in principle avoid the so-called cascade errors under certain situations. Computational results with the Size 100 sub-challenges of DREAM3 and DREAM4 show that, compared with the Z-score based method, prediction performances can be substantially improved, especially the AUPR specification. Moreover, it can even outperform the best team of both DREAM3 and DREAM4. Furthermore, the high precision of the obtained most reliable predictions shows that the suggested algorithm may be very helpful in guiding biological experiment designs. PMID:22363578

Wang, Yali; Zhou, Tong

2012-01-01

300

Inferring Hypotheses on Functional Relationships of Genes: Analysis of the Arabidopsis thaliana Subtilase Gene Family  

PubMed Central

The gene family of subtilisin-like serine proteases (subtilases) in Arabidopsis thaliana comprises 56 members, divided into six distinct subfamilies. Whereas the members of five subfamilies are similar to pyrolysins, two genes share stronger similarity to animal kexins. Mutant screens confirmed 144 T-DNA insertion lines with knockouts for 55 out of the 56 subtilases. Apart from SDD1, none of the confirmed homozygous mutants revealed any obvious visible phenotypic alteration during growth under standard conditions. Apart from this specific case, forward genetics gave us no hints about the function of the individual 54 non-characterized subtilase genes. Therefore, the main objective of our work was to overcome the shortcomings of the forward genetic approach and to infer alternative experimental approaches by using an integrative bioinformatics and biological approach. Computational analyses based on transcriptional co-expression and co-response pattern revealed at least two expression networks, suggesting that functional redundancy may exist among subtilases with limited similarity. Furthermore, two hubs were identified, which may be involved in signalling or may represent higher-order regulatory factors involved in responses to environmental cues. A particular enrichment of co-regulated genes with metabolic functions was observed for four subtilases possibly representing late responsive elements of environmental stress. The kexin homologs show stronger associations with genes of transcriptional regulation context. Based on the analyses presented here and in accordance with previously characterized subtilases, we propose three main functions of subtilases: involvement in (i) control of development, (ii) protein turnover, and (iii) action as downstream components of signalling cascades. Supplemental material is available in the Plant Subtilase Database (PSDB) (http://csbdb.mpimp-golm.mpg.de/psdb.html) , as well as from the CSB.DB (http://csbdb.mpimp-golm.mpg.de). PMID:16193095

Bussis, Dirk; Stintzi, Annick; Schaller, Andreas; Kopka, Joachim; Altmann, Thomas

2005-01-01

301

Inferring hypotheses on functional relationships of genes: Analysis of the Arabidopsis thaliana subtilase gene family.  

PubMed

The gene family of subtilisin-like serine proteases (subtilases) in Arabidopsis thaliana comprises 56 members, divided into six distinct subfamilies. Whereas the members of five subfamilies are similar to pyrolysins, two genes share stronger similarity to animal kexins. Mutant screens confirmed 144 T-DNA insertion lines with knockouts for 55 out of the 56 subtilases. Apart from SDD1, none of the confirmed homozygous mutants revealed any obvious visible phenotypic alteration during growth under standard conditions. Apart from this specific case, forward genetics gave us no hints about the function of the individual 54 non-characterized subtilase genes. Therefore, the main objective of our work was to overcome the shortcomings of the forward genetic approach and to infer alternative experimental approaches by using an integrative bioinformatics and biological approach. Computational analyses based on transcriptional co-expression and co-response pattern revealed at least two expression networks, suggesting that functional redundancy may exist among subtilases with limited similarity. Furthermore, two hubs were identified, which may be involved in signalling or may represent higher-order regulatory factors involved in responses to environmental cues. A particular enrichment of co-regulated genes with metabolic functions was observed for four subtilases possibly representing late responsive elements of environmental stress. The kexin homologs show stronger associations with genes of transcriptional regulation context. Based on the analyses presented here and in accordance with previously characterized subtilases, we propose three main functions of subtilases: involvement in (i) control of development, (ii) protein turnover, and (iii) action as downstream components of signalling cascades. Supplemental material is available in the Plant Subtilase Database (PSDB) (http://csbdb.mpimp-golm.mpg.de/psdb.html), as well as from the CSB.DB (http://csbdb.mpimp-golm.mpg.de). PMID:16193095

Rautengarten, Carsten; Steinhauser, Dirk; Büssis, Dirk; Stintzi, Annick; Schaller, Andreas; Kopka, Joachim; Altmann, Thomas

2005-09-01

302

prdl-a, a gene marker for hydra apical differentiation related to triploblastic paired-like head-specific genes.  

PubMed

Two homeobox genes, prdl-a and prdl-b, which were isolated from a Hydra vulgaris cDNA library, encode paired-like class homeodomains highly related to that of the aristaless-related genes. In adult polyps, prdl-b is a marker for synchronously dividing nematoblasts while prdl-a displays an expression restricted to the the nerve cell lineage of the head region. During budding and apical regeneration, an early and transient prdl-a expression was observed in endodermal cells of the stump at a time when the head organizer is established. When apical regeneration was delayed upon concomittant budding, prdl-a expression was found to be altered in the stump. Furthermore, a specific anti-prdl-a protein immunoserum revealed that prdl-a was overexpressed in adult polyps of the Chlorohydra viridissima multiheaded mutant, with an expression domain extending below the tentacle ring towards the body column. Accordingly, prdl-a DNA-binding activity was enhanced in nuclear extracts from this mutant. These results suggest that prdl-a responds to apical forming signals and might thus be involved in apical specification. When a marine hydrozoan (Podocorynae carnea) was used, the anti-prdl-a antibody showed cross-reactivity with cells located around the oral region, indicating that prdl-a function is shared by other cnidaria. The ancestral role for prdl-a-related genes in the molecular definition of the head (or oral-surrounding region) is discussed. PMID:9521902

Gauchat, D; Kreger, S; Holstein, T; Galliot, B

1998-05-01

303

NK cell-based approach for screening novel functional immune genes  

Microsoft Academic Search

The human genome project provides extensive opportunities for the discovery of novel functional immune genes. In order to find innate immune genes that might regulate the function of NK cells from a cDNA library, we used an NK cell line, NK-92, as a platform to screen candidate genes. After comparing with other gene transfer methods, electroporation was selected as the

Longyan Wu; Cai Zhang; Zhigang Tian; Jian Zhang

2011-01-01

304

Meaning of relative gene expression in multilayered cultures of epidermal keratinocytes.  

PubMed

Reconstructed human epidermis (RHE) has become an in vitro model of choice for studying cell and tissue functions. Analysis of gene expression over the course of reconstruction must take into account the heterogeneous differentiation states of keratinocytes reconstituting the typical epidermal layers. In monolayer cultures, relative mRNA expression levels of differentiation markers are usually expressed as a ratio versus a classical reference gene (also named house-keeping gene) tested to be expressed equally in certain experimental conditions. Applied to complex tissues in which the cell number increases over time together with differentiation, calculation of relative gene expression does not take enough into account a crucial phenomenon: epidermal morphogenesis results in progressive restriction of differentiation markers, such as involucrin, to a specific layer, or in the delayed onset of mRNA expression of filaggrin or TMEM45A for instance following stratification. Our study illustrates that comparing the relative expression level of mRNAs to that of a basal layer-specific gene (e.g. ITGA6) better illustrates the contribution of specific differentiation markers to the process of epidermal morphogenesis. PMID:25049045

Malaisse, Jérémy; Hermant, Maryse; Hayez, Aurélie; Poumay, Yves; Lambert de Rouvroit, Catherine

2014-10-01

305

Brain region-specific altered expression and association of mitochondria-related genes in autism  

PubMed Central

Background Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. Methods For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (??Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Results Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients. Conclusions Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. PMID:23116158

2012-01-01

306

Diversity of laccase-like multicopper oxidase genes in Morchellaceae: identification of genes potentially involved in extracellular activities related to plant litter decay.  

PubMed

Despite the important role played by soil-inhabiting ascomycetes in plant litter decay processes, studies on the diversity and function of their laccase-like multicopper oxidase (LMCO) genes are scarce. In the present work, the LMCO gene diversity in 15 strains representing nine Morchellaceae and one Discinaceae species was evaluated by PCR. One to six different genes were found within the species, representing 26 different sequence types. Cluster analysis revealed LMCO genes belonging to four main gene families encoding different protein classes (Class I-IV). To identify the genes related to extracellular activities and potentially involved in litter decay processes, liquid cultures were induced by different aromatic compounds. Morchella conica and Verpa conica showed the strongest LMCO activity enhancement in the presence of the naturally occurring phenolic compound guaiacol, and their expressed LMCO genes were identified by sequencing. Only genes belonging to the gene families encoding the Class II and III proteins were expressed. Both genes (Class II and III) of the mycorrhizal-like strain M. conica were exclusively expressed in the presence of guaiacol. In contrast to the saprotrophic strain V. conica, the gene encoding the Class III protein was constitutively expressed as it was also found in control cultures without guaiacol. PMID:17466024

Kellner, Harald; Luis, Patricia; Buscot, François

2007-07-01

307

Nucleotide Diversity and Linkage Disequilibrium in Cold-Hardiness- and Wood Quality-Related Candidate Genes in Douglas Fir  

Microsoft Academic Search

Nuclear sequence variation and linkage disequilibrium (LD) were studied in 15 cold-hardiness- and 3 wood quality-related candidate genes in Douglas fir (Pseudotsuga menziesii (Mirb.) Franco). This set of genes was selected on the basis of its function in other plants and collocation with cold-hardiness-related quantitative trait loci (QTL). The single-nucleotide polymorphism (SNP) discovery panel represented 24 different trees from six

Konstantin V. Krutovsky; David B. Neale

2005-01-01

308

Gene-environment interaction and male reproductive function  

Microsoft Academic Search

As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or

Jonatan Axelsson; Jens Peter Bonde; Yvonne L. Giwercman; Lars Rylander; Aleksander Giwercman

2010-01-01

309

Evolution and functional diversification of fructose bisphosphate aldolase genes in photosynthetic marine diatoms.  

PubMed

Diatoms and other chlorophyll-c containing, or chromalveolate, algae are among the most productive and diverse phytoplankton in the ocean. Evolutionarily, chlorophyll-c algae are linked through common, although not necessarily monophyletic, acquisition of plastid endosymbionts of red as well as most likely green algal origin. There is also strong evidence for a relatively high level of lineage-specific bacterial gene acquisition within chromalveolates. Therefore, analyses of gene content and derivation in chromalveolate taxa have indicated particularly diverse origins of their overall gene repertoire. As a single group of functionally related enzymes spanning two distinct gene families, fructose 1,6-bisphosphate aldolases (FBAs) illustrate the influence on core biochemical pathways of specific evolutionary associations among diatoms and other chromalveolates with various plastid-bearing and bacterial endosymbionts. Protein localization and activity, gene expression, and phylogenetic analyses indicate that the pennate diatom Phaeodactylum tricornutum contains five FBA genes with very little overall functional overlap. Three P. tricornutum FBAs, one class I and two class II, are plastid localized, and each appears to have a distinct evolutionary origin as well as function. Class I plastid FBA appears to have been acquired by chromalveolates from a red algal endosymbiont, whereas one copy of class II plastid FBA is likely to have originated from an ancient green algal endosymbiont. The other copy appears to be the result of a chromalveolate-specific gene duplication. Plastid FBA I and chromalveolate-specific class II plastid FBA are localized in the pyrenoid region of the chloroplast where they are associated with ?-carbonic anhydrase, which is known to play a significant role in regulation of the diatom carbon concentrating mechanism. The two pyrenoid-associated FBAs are distinguished by contrasting gene expression profiles under nutrient limiting compared with optimal CO2 fixation conditions, suggestive of a distinct specialized function for each. Cytosolically localized FBAs in P. tricornutum likely play a role in glycolysis and cytoskeleton function and seem to have originated from the stramenopile host cell and from diatom-specific bacterial gene transfer, respectively. PMID:21903677

Allen, Andrew E; Moustafa, Ahmed; Montsant, Anton; Eckert, Angelika; Kroth, Peter G; Bowler, Chris

2012-01-01

310

Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.  

PubMed

BRCA2 mutations are significantly associated with early-onset breast cancer, and the tumour-suppressing function of BRCA2 has been attributed to its involvement in homologous recombination (HR)-mediated DNA repair. In order to identify additional functions of BRCA2, we generated BRCA2-knockout HCT116 human colorectal carcinoma cells. Using genome-wide microarray analyses, we have discovered a link between the loss of BRCA2 and the up-regulation of a subset of interferon (IFN)-related genes, including APOBEC3F and APOBEC3G. The over-expression of IFN-related genes was confirmed in different human BRCA2(-/-) and mouse Brca2(-/-) tumour cell lines, and was independent of senescence and apoptosis. In isogenic wild-type BRCA2 cells, we observed over-expression of IFN-related genes after treatment with DNA-damaging agents, and following ionizing radiation. Cells with endogenous DNA damage because of defective BRCA1 or RAD51 also exhibited over-expression of IFN-related genes. Transcriptional activity of the IFN-stimulated response element (ISRE) was increased in BRCA2 knockout cells, and the expression of BRCA2 greatly decreased IFN?-stimulated ISRE reporter activity, suggesting that BRCA2 directly represses the expression of IFN-related genes through the ISRE. Finally, the colony-forming capacity of BRCA2 knockout cells was significantly reduced in the presence of either IFN? or IFN?, suggesting that IFNs may have potential as therapeutic agents in cancer cells with BRCA2 mutations. The GEO Accession No. for microarray analysis is GSE54830. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:25043256

Xu, Hong; Xian, Jian; Vire, Emmanuelle; McKinney, Steven; Wei, Vivien; Wong, Jason; Tong, Rebecca; Kouzarides, Tony; Caldas, Carlos; Aparicio, Samuel

2014-11-01

311

Major histocompatibility complex gene organization in the mole rat Spalax ehrenbergi: evidence for transfer of function between class II genes.  

PubMed Central

A genomic DNA library prepared from the kidney of the mole rat Spalax ehrenbergi was screened with mouse probes representing major histocompatibility complex genes that encode alpha and beta polypeptide chains of class II molecules (alpha and beta genes). Restriction maps were constructed for the cross-hybridizing clones, and the class II genes borne by these clones were identified. By this procedure, five main regions containing class II genes were established. One region contained four genes and two gene fragments, the second region contained two genes, the third region contained one gene and one gene fragment, and the remaining two regions contained one gene each. Altogether, six beta genes, two alpha genes, and three alpha-gene fragments were identified. Two of the genes (one alpha and one beta) were established as belonging to the DQ subclass, and all other genes were found to be members of the DP subclass. (Subclass designations are based on the human HLA class II genes). No genes belonging to the DR and DO (DZ) subclasses were found in the library. The absence of DR genes in S. ehrenbergi was also indicated when other experimental methods were used. At least some of the DP loci are polymorphic and most likely also functional. Thus, in the evolution of the mole rat, the DR (and probably also the DO) loci have been deleted and their function(s) has been taken over by the DP loci, which have expanded to a great extent. These findings argue for functional interchangeability of the individual subclasses of class II loci. Images PMID:3039509

Nizetic, D; Figueroa, F; Dembic, Z; Nevo, E; Klein, J

1987-01-01

312

Functional imaging: monitoring heme oxygenase-1 gene expression in vivo  

NASA Astrophysics Data System (ADS)

The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

1999-07-01

313

A large and functionally diverse family of Fad2 genes in safflower (Carthamus tinctorius L.)  

PubMed Central

Background The application and nutritional value of vegetable oil is highly dependent on its fatty acid composition, especially the relative proportion of its two major fatty acids, i.e oleic acid and linoleic acid. Microsomal oleoyl phosphatidylcholine desaturase encoded by FAD2 gene is known to introduce a double bond at the ?12 position of an oleic acid on phosphatidylcholine and convert it to linoleic acid. The known plant FAD2 enzymes are encoded by small gene families consisting of 1-4 members. In addition to the classic oleate ?12-desaturation activity, functional variants of FAD2 that are capable of undertaking additional or alternative acyl modifications have also been reported in a limited number of plant species. In this study, our objective was to identify FAD2 genes from safflower and analyse their differential expression profile and potentially diversified functionality. Results We report here the characterization and functional expression of an exceptionally large FAD2 gene family from safflower, and the temporal and spatial expression profiles of these genes as revealed through Real-Time quantitative PCR. The diversified functionalities of some of the safflower FAD2 gene family members were demonstrated by ectopic expression in yeast and transient expression in Nicotiana benthamiana leaves. CtFAD2-1 and CtFAD2-10 were demonstrated to be oleate desaturases specifically expressed in developing seeds and flower head, respectively, while CtFAD2-2 appears to have relatively low oleate desaturation activity throughout the plant. CtFAD2-5 and CtFAD2-8 are specifically expressed in root tissues, while CtFAD2-3, 4, 6, 7 are mostly expressed in the cotyledons and hypocotyls in young safflower seedlings. CtFAD2-9 was found to encode a novel desaturase operating on C16:1 substrate. CtFAD2-11 is a tri-functional enzyme able to introduce a carbon double bond in either cis or trans configuration, or a carbon triple (acetylenic) bond at the ?12 position. Conclusions In this study, we isolated an unusually large FAD2 gene family with 11 members from safflower. The seed expressed FAD2 oleate ?12 desaturase genes identified in this study will provide candidate targets to manipulate the oleic acid level in safflower seed oil. Further, the divergent FAD2 enzymes with novel functionality could be used to produce rare fatty acids, such as crepenynic acid, in genetically engineered crop plants that are precursors for economically important phytoalexins and oleochemical products. PMID:23289946

2013-01-01

314

Molecular evolution of the duplicated TFIIA? genes in Oryzeae and its relatives  

PubMed Central

Background Gene duplication provides raw genetic materials for evolutionary novelty and adaptation. The evolutionary fate of duplicated transcription factor genes is less studied although transcription factor gene plays important roles in many biological processes. TFIIA? is a small subunit of TFIIA that is one of general transcription factors required by RNA polymerase II. Previous studies identified two TFIIA?-like genes in rice genome and found that these genes either conferred resistance to rice bacterial blight or could be induced by pathogen invasion, raising the question as to their functional divergence and evolutionary fates after gene duplication. Results We reconstructed the evolutionary history of the TFIIA? genes from main lineages of angiosperms and demonstrated that two TFIIA? genes (TFIIA?1 and TFIIA?5) arose from a whole genome duplication that happened in the common ancestor of grasses. Likelihood-based analyses with branch, codon, and branch-site models showed no evidence of positive selection but a signature of relaxed selective constraint after the TFIIA? duplication. In particular, we found that the nonsynonymous/synonymous rate ratio (? = dN/dS) of the TFIIA?1 sequences was two times higher than that of TFIIA?5 sequences, indicating highly asymmetric rates of protein evolution in rice tribe and its relatives, with an accelerated rate of TFIIA?1 gene. Our expression data and EST database search further indicated that after whole genome duplication, the expression of TFIIA?1 gene was significantly reduced while TFIIA?5 remained constitutively expressed and maintained the ancestral role as a subunit of the TFIIA complex. Conclusion The evolutionary fate of TFIIA? duplicates is not consistent with the neofunctionalization model that predicts that one of the duplicated genes acquires a new function because of positive Darwinian selection. Instead, we suggest that subfunctionalization might be involved in TFIIA? evolution in grasses. The fact that both TFIIA?1 and TFIIA?5 genes were effectively involved in response to biotic or abiotic factors might be explained by either Dykhuizen-Hartl effect or buffering hypothesis. PMID:20438643

2010-01-01

315

Induction of Protective Genes Leads to Islet Survival and Function  

PubMed Central

Islet transplantation is the most valid approach to the treatment of type 1 diabetes. However, the function of transplanted islets is often compromised since a large number of ? cells undergo apoptosis induced by stress and the immune rejection response elicited by the recipient after transplantation. Conventional treatment for islet transplantation is to administer immunosuppressive drugs to the recipient to suppress the immune rejection response mounted against transplanted islets. Induction of protective genes in the recipient (e.g., heme oxygenase-1 (HO-1), A20/tumor necrosis factor alpha inducible protein3 (tnfaip3), biliverdin reductase (BVR), Bcl2, and others) or administration of one or more of the products of HO-1 to the donor, the islets themselves, and/or the recipient offers an alternative or synergistic approach to improve islet graft survival and function. In this perspective, we summarize studies describing the protective effects of these genes on islet survival and function in rodent allogeneic and xenogeneic transplantation models and the prevention of onset of diabetes, with emphasis on HO-1, A20, and BVR. Such approaches are also appealing to islet autotransplantation in patients with chronic pancreatitis after total pancreatectomy, a procedure that currently only leads to 1/3 of transplanted patients being diabetes-free. PMID:22220267

Wang, Hongjun; Ferran, Christiane; Attanasio, Chiara; Calise, Fulvio; Otterbein, Leo E.

2011-01-01

316

Rapid cloning of genes and promoters for functional analyses.  

PubMed

Next-generation sequencing has resulted in a massive flow of new information predicting the existence of many new genes, their putative promoters, as well as long and small noncoding RNA. However, this is currently largely unmatched by functional studies. A cost-effective and high-throughput cloning system for PCR products and synthetic sequences was therefore developed to allow the rapid evaluation of coding and noncoding sequences in functional expression and reporter assays. Unlike traditional cloning approaches that involve subcloning or a special recipient vector and special flanking sequences, this protocol describes a rapid and cost-effective method for the direct insertion into the vector of choice. Restriction enzymes are only needed once to prepare the vector, which is blunt ended and dephosphorylated, and can then serve as the recipient vector for many hundreds of sequences to be tested. Examples are provided of how this method can be used to rapidly reveal functionality of regulatory genes, promoters, and microRNAs. PMID:24243200

Schenk, Peer M

2014-01-01

317

Genome-wide SNP genotyping to infer the effects on gene functions in tomato.  

PubMed

The genotype data of 7054 single nucleotide polymorphism (SNP) loci in 40 tomato lines, including inbred lines, F1 hybrids, and wild relatives, were collected using Illumina's Infinium and GoldenGate assay platforms, the latter of which was utilized in our previous study. The dendrogram based on the genotype data corresponded well to the breeding types of tomato and wild relatives. The SNPs were classified into six categories according to their positions in the genes predicted on the tomato genome sequence. The genes with SNPs were annotated by homology searches against the nucleotide and protein databases, as well as by domain searches, and they were classified into the functional categories defined by the NCBI's eukaryotic orthologous groups (KOG). To infer the SNPs' effects on the gene functions, the three-dimensional structures of the 843 proteins that were encoded by the genes with SNPs causing missense mutations were constructed by homology modelling, and 200 of these proteins were considered to carry non-synonymous amino acid substitutions in the predicted functional sites. The SNP information obtained in this study is available at the Kazusa Tomato Genomics Database (http://plant1.kazusa.or.jp/tomato/). PMID:23482505

Hirakawa, Hideki; Shirasawa, Kenta; Ohyama, Akio; Fukuoka, Hiroyuki; Aoki, Koh; Rothan, Christophe; Sato, Shusei; Isobe, Sachiko; Tabata, Satoshi

2013-06-01

318

The Drosophila alcohol dehydrogenase gene may have evolved independently of the functionally homologous medfly, olive fly, and flesh fly genes.  

PubMed

cDNAs for alcohol dehydrogenase (ADH) isozymes were cloned and sequenced from two tephritid fruit flies, the medfly Ceratitis capitata and the olive fly Bactrocera oleae. Because of the high sequence divergence compared with the Drosophila sequences, the medfly cDNAs were cloned using sequence information from the purified proteins, and the olive fly cDNAs were cloned by functional complementation in yeast. The medfly peptide sequences are about 83% identical to each other, and the corresponding mRNAs have the tissue distribution shown by the corresponding isozymes, ADH-1 and ADH-2. The olive fly peptide sequence is more closely related to medfly ADH-2. The tephritid ADHs share less than 40% sequence identity with Drosophila ADH and ADH-related genes but are >57% identical to the ADH of the flesh fly Sarcophaga peregrina, a more distantly related species. To explain this unexpected finding, it is proposed that the ADH: genes of the family Drosophilidae may not be orthologous to the ADH: genes of the other two families, Tephritidae and Sarcophagidae. PMID:11230533

Brogna, S; Benos, P V; Gasperi, G; Savakis, C

2001-03-01

319

Functional genes to assess nitrogen cycling and aromatic hydrocarbon degradation: primers and processing matter  

PubMed Central

Targeting sequencing to genes involved in key environmental processes, i.e., ecofunctional genes, provides an opportunity to sample nature's gene guilds to greater depth and help link community structure to process-level outcomes. Vastly different approaches have been implemented for sequence processing and, ultimately, for taxonomic placement of these gene reads. The overall quality of next generation sequence analysis of functional genes is dependent on multiple steps and assumptions of unknown diversity. To illustrate current issues surrounding amplicon read processing we provide examples for three ecofunctional gene groups. A combination of in silico, environmental and cultured strain sequences was used to test new primers targeting the dioxin and dibenzofuran degrading genes dxnA1, dbfA1, and carAa. The majority of obtained environmental sequences were classified into novel sequence clusters, illustrating the discovery value of the approach. For the nitrite reductase step in denitrification, the well-known nirK primers exhibited deficiencies in reference database coverage, illustrating the need to refine primer-binding sites and/or to design multiple primers, while nirS primers exhibited bias against five phyla. Amino acid-based OTU clustering of these two N-cycle genes from soil samples yielded only 114 unique nirK and 45 unique nirS genus-level groupings, likely a reflection of constricted primer coverage. Finally, supervised and non-supervised OTU analysis methods were compared using the nifH gene of nitrogen fixation, with generally similar outcomes, but the clustering (non-supervised) method yielded higher diversity estimates and stronger site-based differences. High throughput amplicon sequencing can provide inexpensive and rapid access to nature's related sequences by circumventing the culturing barrier, but each unique gene requires individual considerations in terms of primer design and sequence processing and classification. PMID:24062736

Penton, C. Ryan; Johnson, Timothy A.; Quensen, John F.; Iwai, Shoko; Cole, James R.; Tiedje, James M.

2013-01-01

320

Functional gene groups are concentrated within chromosomes, among chromosomes and in the nuclear space  

E-print Network

1 Functional gene groups are concentrated within chromosomes, among chromosomes and in the nuclear:+972-3-6405384 Keywords: chromosomes organization, gene function, chromosome conformation, spatial;2 Functional gene groups are concentrated within chromosomes, among chromosomes and in the nuclear space

Shamir, Ron

321

Characterization of the rainbow trout spleen transcriptome and identification of immune-related genes  

PubMed Central

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

Ali, Ali; Rexroad, Caird E.; Thorgaard, Gary H.; Yao, Jianbo; Salem, Mohamed

2014-01-01

322

Characterization of the rainbow trout spleen transcriptome and identification of immune-related genes.  

PubMed

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

Ali, Ali; Rexroad, Caird E; Thorgaard, Gary H; Yao, Jianbo; Salem, Mohamed

2014-01-01

323

Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway.  

PubMed

Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two genome-wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. PMID:24186849

Paré-Brunet, Laia; Glubb, Dylan; Evans, Patrick; Berenguer-Llergo, Antoni; Etheridge, Amy S; Skol, Andrew D; Di Rienzo, Anna; Duan, Shiwei; Gamazon, Eric R; Innocenti, Federico

2014-02-01

324

Brain galanin system genes interact with life stresses in depression-related phenotypes.  

PubMed

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

Juhasz, Gabriella; Hullam, Gabor; Eszlari, Nora; Gonda, Xenia; Antal, Peter; Anderson, Ian Muir; Hökfelt, Tomas G M; Deakin, J F William; Bagdy, Gyorgy

2014-04-22

325

Brain galanin system genes interact with life stresses in depression-related phenotypes  

PubMed Central

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

Juhasz, Gabriella; Hullam, Gabor; Eszlari, Nora; Gonda, Xenia; Antal, Peter; Anderson, Ian Muir; Hokfelt, Tomas G. M.; Deakin, J. F. William; Bagdy, Gyorgy

2014-01-01

326

Integrative approaches for predicting protein function and prioritizing genes for complex phenotypes using protein interaction networks.  

PubMed

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

Ma, Xiaotu; Chen, Ting; Sun, Fengzhu

2014-09-01

327

Identification of Genes to Differentiate Closely Related Salmonella Lineages  

PubMed Central

Background Salmonella are important human and animal pathogens. Though highly related, the Salmonella lineages may be strictly adapted to different hosts or cause different diseases, from mild local illness like gastroenteritis to fatal systemic infections like typhoid. Therefore, rapid and accurate identification of Salmonella is essential for timely and correct diagnosis of Salmonella infections. The current identification methods such as 16S rRNA sequencing and multilocus sequence typing are expensive and time consuming. Additionally, these methods often do not have sufficient distinguishing resolution among the Salmonella lineages. Methodologies/Principal Findings We compared 27 completely sequenced Salmonella genomes to identify possible genomic features that could be used for differentiation of individual lineages. We concatenated 2372 core genes in each of the 27 genomes and constructed a neighbor-joining tree. On the tree, strains of each serotype were clustered tightly together and different serotypes were unambiguously separated with clear genetic distances, demonstrating systematic genomic divergence among the Salmonella lineages. We made detailed comparisons among the 27 genomes and identified distinct sets of genomic differences, including nucleotide variations and genomic islands (GIs), among the Salmonella lineages. Two core genes STM4261 and entF together could unambiguously distinguish all Salmonella lineages compared in this study. Additionally, strains of a lineage have a common set of GIs and closely related lineages have similar sets of GIs. Conclusions Salmonella lineages have accumulated distinct sets of mutations and laterally acquired DNA (e.g., GIs) in evolution. Two genes entF and STM4261 have diverged sufficiently among the Salmonella lineages to be used for their differentiation. Further investigation of the distinct sets of mutations and GIs will lead to novel insights into genomic evolution of Salmonella and greatly facilitate the elucidation of pathogeneses of Salmonella infections. PMID:23441160

Zou, Qing-Hua; Li, Ren-Qing; Wang, Ye-Jun; Liu, Shu-Lin

2013-01-01

328

Functional genomic analysis of the AUXIN RESPONSE FACTOR gene family members in Arabidopsis thaliana: unique and overlapping functions of ARF7 and ARF19.  

PubMed

The AUXIN RESPONSE FACTOR (ARF) gene family products, together with the AUXIN/INDOLE-3-ACETIC ACID proteins, regulate auxin-mediated transcriptional activation/repression. The biological function(s) of most ARFs is poorly understood. Here, we report the identification and characterization of T-DNA insertion lines for 18 of the 23 ARF gene family members in Arabidopsis thaliana. Most of the lines fail to show an obvious growth phenotype except of the previously identified arf2/hss, arf3/ett, arf5/mp, and arf7/nph4 mutants, suggesting that there are functional redundancies among the ARF proteins. Subsequently, we generated double mutants. arf7 arf19 has a strong auxin-related phenotype not observed in the arf7 and arf19 single mutants, including severely impaired lateral root formation and abnormal gravitropism in both hypocotyl and root. Global gene expression analysis revealed that auxin-induced gene expression is severely impaired in the arf7 single and arf7 arf19 double mutants. For example, the expression of several genes, such as those encoding members of LATERAL ORGAN BOUNDARIES domain proteins and AUXIN-REGULATED GENE INVOLVED IN ORGAN SIZE, are disrupted in the double mutant. The data suggest that the ARF7 and ARF19 proteins play essential roles in auxin-mediated plant development by regulating both unique and partially overlapping sets of target genes. These observations provide molecular insight into the unique and overlapping functions of ARF gene family members in Arabidopsis. PMID:15659631

Okushima, Yoko; Overvoorde, Paul J; Arima, Kazunari; Alonso, Jose M; Chan, April; Chang, Charlie; Ecker, Joseph R; Hughes, Beth; Lui, Amy; Nguyen, Diana; Onodera, Courtney; Quach, Hong; Smith, Alison; Yu, Guixia; Theologis, Athanasios

2005-02-01

329

INVERTED-U FUNCTION RELATING CORTICAL PLASTICITY AND TASK DIFFICULTY  

E-print Network

INVERTED-U FUNCTION RELATING CORTICAL PLASTICITY AND TASK DIFFICULTY N. D. ENGINEER,a * C. T an inverted-U function relating neural plasticity and task difficulty. © 2012 IBRO. Published by Elsevier Ltd; but see Brown et al., 2004; Ghose, 2004). Motivation is believed to regulate learning and plasticity (Bao

Kilgard, Michael P.

330

Functional expression of plant acetolactate synthase genes in Escherichia coli  

PubMed Central

Acetolactate synthase (ALS; EC 4.1.3.18) is the first common enzyme in the biosynthetic pathways leading to leucine, isoleucine, and valine. It is the target enzyme for three classes of structurally unrelated herbicides, the sulfonylureas, the imidazolinones, and the triazolopyrimidines. A cloned ALS gene from the small cruciferous plant Arabidopsis thaliana has been fused to bacterial transcription/translation signals and the resulting plasmid has been used to transform Escherichia coli. The cloned plant gene, which includes sequences encoding the chloroplast transit peptide, is functionally expressed in the bacteria. It is able to complement genetically a strain of E. coli that lacks endogenous ALS activity. An ALS gene cloned from a line of Arabidopsis previously shown to be resistant to sulfonylurea herbicides has been similarly expressed in E. coli. The herbicide-resistance phenotype is expressed in the bacteria, as assayed by both enzyme activity and the ability to grow in the presence of herbicides. This system has been useful for purifying substantial amounts of the plant enzyme, for studying the sequence parameters involved in subcellular protein localization, and for characterizing the interactions that occur between ALS and its various inhibitors. Images PMID:16594052

Smith, Julie K.; Schloss, John V.; Mazur, Barbara J.

1989-01-01

331

Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga Nannochloropsis oceanica CCMP1779  

PubMed Central

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

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; Zauner, 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

332

Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population  

PubMed Central

Objective: To investigate the contribution of polymorphic variation in genes involved in the folate-dependent homocysteine pathway in the aetiology of neural tube defects (NTD). Design: Case-control association study. Subjects: A total of 530 individuals from families affected by NTD, 645 maternal controls, and 602 healthy newborn controls from the northern UK. Main outcome measures: Seven polymorphisms in six genes coding for proteins in the folate-dependent homocysteine pathway (MTHFR 677C?T, MTHFR 1298A?C, MTRR 66A?G, SHMT 1420C?T, CßS 844ins68, GCPII 1561C?T, RFC-1 80G?A). The impact of each polymorphism and the effect of gene–gene interactions (epistasis) upon risk of NTD were assessed using logistic regression analysis. Results: The MTHFR 677C?T polymorphism was shown to represent a risk factor in NTD cases (CC v CT+TT odds ratio (OR) 2.03 [95% confidence interval (CI) 1.09, 3.79] p = 0.025) and the MTRR 66A?G polymorphism was shown to exert a protective effect in NTD cases (AA v AG+GG OR 0.31 [95% CI 0.10, 0.94] p = 0.04). When statistical tests for interaction were conducted, three genotype combinations in cases (MTRR/GCPII; MTHFR 677/CßS; MTHFR 677/MTRR) and one combination in case mothers (CßS/RFC-1) were shown to elevate NTD risk. Maternal–fetal interaction was also detected when offspring carried the MTHFR 677C?T variant and mothers carried the MTRR 66A?G variant, resulting in a significantly elevated risk of NTD. Conclusion: Both independent genetic effects and gene–gene interaction were observed in relation to NTD risk. Multi-locus rather than single locus analysis might be preferable to gain an accurate assessment of genetic susceptibility to NTD. PMID:15060097

Relton, C; Wilding, C; Pearce, M; Laffling, A; Jonas, P; Lynch, S; Tawn, E; Burn, J

2004-01-01

333

Molecular Evolution of Candidate Genes for Crop-Related Traits in Sunflower (Helianthus annuus L.)  

E-print Network

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

Burke, John M.

334

Plastic Changes of Calcitonin Gene-Related Peptide in Morphine Tolerance: Behavioral  

E-print Network

Plastic Changes of Calcitonin Gene-Related Peptide in Morphine Tolerance: Behavioral Biotechnology, Peking University, Beijing, People's Republic of China The present study was undertaken to investigate the plasticity of calcitonin gene-related peptide (CGRP) in antinociception after morphine

Stephens, Matthew

335

Comparative analysis of grapevine whole-genome gene predictions, functional annotation, categorization and integration of the predicted gene sequences  

PubMed Central

Background The first draft assembly and gene prediction of the grapevine genome (8X base coverage) was made available to the scientific community in 2007, and functional annotation was developed on this gene prediction. Since then additional Sanger sequences were added to the 8X sequences pool and a new version of the genomic sequence with superior base coverage (12X) was produced. Results In order to more efficiently annotate the function of the genes predicted in the new assembly, it is important to build on as much of the previous work as possible, by transferring 8X annotation of the genome to the 12X version. The 8X and 12X assemblies and gene predictions of the grapevine genome were compared to answer the question, “Can we uniquely map 8X predicted genes to 12X predicted genes?” The results show that while the assemblies and gene structure predictions are too different to make a complete mapping between them, most genes (18,725) showed a one-to-one relationship between 8X predicted genes and the last version of 12X predicted genes. In addition, reshuffled genomic sequence structures appeared. These highlight regions of the genome where the gene predictions need to be taken with caution. Based on the new grapevine gene functional annotation and in-depth functional categorization, twenty eight new molecular networks have been created for VitisNet while the existing networks were updated. Conclusions The outcomes of this study provide a functional annotation of the 12X genes, an update of VitisNet, the system of the grapevine molecular networks, and a new functional categorization of genes. Data are available at the VitisNet website (http://www.sdstate.edu/ps/research/vitis/pathways.cfm). PMID:22554261

2012-01-01

336

Human tRNA genes function as chromatin insulators  

PubMed Central

Insulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs are repetitive sequences dispersed throughout the human genome and we now show that some of these tDNAs can function as insulators in human cells. Using computational methods, we identified putative human tDNA insulators. Using silencer blocking, transgene protection and repressor blocking assays we show that some of these tDNA-containing fragments can function as barrier insulators in human cells. We find that these elements also have the ability to block enhancers from activating RNA pol II transcribed promoters. Characterization of a putative tDNA insulator in human cells reveals that the site possesses chromatin signatures similar to those observed at other better-characterized eukaryotic insulators. Enhanced 4C analysis demonstrates that the tDNA insulator makes long-range chromatin contacts with other tDNAs and ETC sites but not with intervening or flanking RNA pol II transcribed genes. PMID:22085927

Raab, Jesse R; Chiu, Jonathan; Zhu, Jingchun; Katzman, Sol; Kurukuti, Sreenivasulu; Wade, Paul A; Haussler, David; Kamakaka, Rohinton T

2012-01-01

337

Genes implicated in serotonergic and dopaminergic functioning predict BMI categories  

PubMed Central

Objective This study addressed the hypothesis that variation in genes associated with dopamine function (SLC6A3, DRD2, DRD4), serotonin function (SLC6A4), and regulation of monoamine levels (MAOA) may be predictive of BMI categories (obese and overweight + obese) in young adulthood and of changes in BMI as adolescents transition into young adulthood. Interactions with gender and race/ethnicity were also examined. Research Methods and Procedures Participants were a subsample of individuals from The National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset of 1584 unrelated individuals with genotype data. Multiple logistic regressions were conducted to evaluate associations between genotypes and obesity (BMI > 29.9) or overweight + obese combined (BMI > 25) with normal weight (BMI = 18.5–24.9) as a referent. Linear regression models were used examine change in BMI from adolescence to young adulthood. Results Significant associations were found between SLC6A4 5HTTLPR and categories of BMI, and between MAOA promoter VNTR among males and categories of BMI. Stratified analyses revealed that the association between these two genes and excess BMI was significant for males overall, and for White and Hispanic males specifically. Linear regression models indicated a significant effect of SLC6A4 5HTTLPR on change in BMI from adolescence to young adulthood. Discussion Our findings lend further support to the involvement of genes implicated in dopamine and serotonin regulation on energy balance. PMID:18239643

Fuemmeler, Bernard F.; Agurs-Collins, Tanya; McClernon, F. Joseph; Kollins, Scott H.; Kail, Melanie; Bergen, Andrew W.; Ashley-Koch, Allison E.

2010-01-01

338

Genome-wide identification and divergent transcriptional expression of StAR-related lipid transfer (START) genes in teleosts.  

PubMed

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

Teng, Huajing; Cai, Wanshi; Zeng, Kun; Mao, Fengbiao; You, Mingcong; Wang, Tao; Zhao, Fangqing; Sun, Zhongsheng

2013-04-25

339

Tumor suppressor function of Betaig-H3 gene in radiation carcinogenesis  

NASA Astrophysics Data System (ADS)

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.

Zhao, Y. L.; Piao, C. Q.; Hei, T. K.

340

The Ghost of Selection Past: Rates of Evolution and Functional Divergence of Anciently Duplicated Genes  

Microsoft Academic Search

.   The duplication of genes and even complete genomes may be a prerequisite for major evolutionary transitions and the origin\\u000a of evolutionary novelties. However, the evolutionary mechanisms of gene evolution and the origin of novel gene functions after\\u000a gene duplication have been a subject of many debates. Recently, we compiled 26 groups of orthologous genes, which included\\u000a one gene from

Yves Van de Peer; John S. Taylor; Ingo Braasch; Axel Meyer

2001-01-01

341

Systematic Learning of Gene Functional Classes From DNA Array Expression Data by Using Multilayer Perceptrons  

PubMed Central

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

Mateos, Alvaro; Dopazo, Joaquin; Jansen, Ronald; Tu, Yuhai; Gerstein, Mark; Stolovitzky, Gustavo

2002-01-01

342

GENOME-WIDE ANALYSIS OF AGING AND LEARNING-RELATED GENES IN THE HIPPOCAMPAL DENTATE GYRUS  

PubMed Central

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

Burger, Corinna; Lopez, M. Cecilia; Baker, Henry V.; Mandel, Ronald J.; Muzyczka, Nick

2008-01-01

343

What's that gene (or protein)? Online resources for exploring functions of genes, transcripts, and proteins  

PubMed Central

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

Hutchins, James R. A.

2014-01-01

344

Evolution of xyloglucan-related genes in green plants  

PubMed Central

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

2010-01-01

345

PaGenBase: a pattern gene database for the global and dynamic understanding of gene function.  

PubMed

Pattern genes are a group of genes that have a modularized expression behavior under serial physiological conditions. The identification of pattern genes will provide a path toward a global and dynamic understanding of gene functions and their roles in particular biological processes or events, such as development and pathogenesis. In this study, we present PaGenBase, a novel repository for the collection of tissue- and time-specific pattern genes, including specific genes, selective genes, housekeeping genes and repressed genes. The PaGenBase database is now freely accessible at http://bioinf.xmu.edu.cn/PaGenBase/. In the current version (PaGenBase 1.0), the database contains 906,599 pattern genes derived from the literature or from data mining of more than 1,145,277 gene expression profiles in 1,062 distinct samples collected from 11 model organisms. Four statistical parameters were used to quantitatively evaluate the pattern genes. Moreover, three methods (quick search, advanced search and browse) were designed for rapid and customized data retrieval. The potential applications of PaGenBase are also briefly described. In summary, PaGenBase will serve as a resource for the global and dynamic understanding of gene function and will facilitate high-level investigations in a variety of fields, including the study of development, pathogenesis and novel drug discovery. PMID:24312499

Pan, Jian-Bo; Hu, Shi-Chang; Shi, Dan; Cai, Mei-Chun; Li, Yin-Bo; Zou, Quan; Ji, Zhi-Liang

2013-01-01

346

Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament.  

PubMed

A common variant (rs53576) of the OXTR gene has been implicated in a number of socio-emotional phenotypes, such as anxiety-related behavior. Previous studies have demonstrated that A-allele carriers have higher levels of physiological and dispositional stress reactivity and depressive symptomatology compared to those with the GG genotype, but the mediating neural mechanisms remain poorly understood. We combined voxel-based morphometry and resting-state functional connectivity analyses in a large cohort of healthy young Chinese Han individuals to test the hypothesis that the OXTR gene polymorphism influences an anxiety-related temperamental trait, as assessed by the harm avoidance subscale from the Tridimensional Personality Questionnaire via modulating the gray matter volume and resting-state functional connectivity of the brain, especially the limbic system. We revealed that female subjects with the AA genotype showed increased harm avoidance scores relative to G-carrier females. We also found that, compared to female individuals with the GG/GA genotype, female individuals with the AA genotype exhibited significantly smaller amygdala volumes bilaterally (especially the centromedial subregion), with a trend of allele-load-dependence. Compared to female individuals with the GG/GA genotype, female subjects with the AA genotype demonstrated reduced resting-state functional coupling between the prefrontal cortex and amygdala bilaterally, also with an allele-load-dependent trend. Furthermore, the magnitude of prefrontal-amygdala coupling in the left hemisphere was positively correlated with harm avoidance scores in female subjects. Our findings highlight a possible neural pathway by which a naturally occurring variation of the OXTR gene may affect an anxiety-related temperamental trait in female subjects by modulating prefrontal-amygdala functional connectivity. PMID:23708061

Wang, Junping; Qin, Wen; Liu, Bing; Zhou, Yuan; Wang, Dawei; Zhang, Yunting; Jiang, Tianzi; Yu, Chunshui

2014-09-01

347

Development and validation of a species-independent functional gene microarray that targets lactic acid bacteria.  

PubMed

During the last few years, genome-related information has become available for many microorganisms, including important food-related bacteria. Lactic acid bacteria (LAB) are important industrially in the production of fermented foods such as dairy products, sausages, sourdoughs, and vegetables. Despite their limited metabolic capacity, LAB contribute considerably to important characteristics of fermented foods, such as flavor and texture. In the present study, a species-independent functional gene microarray was developed that targets 406 genes that play key roles in the production of sugar catabolites, bacteriocins, exopolysaccharides, and aromas, in probiotic and biosafety characteristics, and in the stress response. Also, genes linked to negative traits, such as antibiotic resistance and virulence, are represented. As LAB ecosystems contain a variety of species, there was a more global focus on these specific functional properties. Thus, an algorithm was used to design gene-specific oligonucleotides that preferably hybridize with multiple LAB species, thereby allowing controlled cross-hybridization. For proof of concept, the microarray composed of 2,269 30-mer oligonucleotides focused on LAB species that are prevalent in sourdough ecosystems. Validation hybridizations using DNA and RNA from 18 LAB strains, covering 86% of all the oligonucleotides, showed that there were wide ranges in intensity and high reproducibility between microarrays. PMID:19684161

Weckx, Stefan; Allemeersch, Joke; Van der Meulen, Roel; Vrancken, Gino; Huys, Geert; Vandamme, Peter; Van Hummelen, Paul; De Vuyst, Luc

2009-10-01

348

Identification of Genes Required for Neural-Specific Glycosylation Using Functional Genomics  

PubMed Central

Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, ?1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific ?1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating ?1,3-fucosylation. Further analyses revealed that an RNA–binding protein, second mitotic wave missing (Swm), upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells. PMID:21203496

Yamamoto-Hino, Miki; Kanie, Yoshimi; Awano, Wakae; Aoki-Kinoshita, Kiyoko F.; Yano, Hiroyuki; Nishihara, Shoko; Okano, Hideyuki; Ueda, Ryu; Kanie, Osamu; Goto, Satoshi

2010-01-01

349

Esrrb Is a Direct Nanog Target Gene that Can Substitute for Nanog Function in Pluripotent Cells  

PubMed Central

Summary Embryonic stem cell (ESC) self-renewal efficiency is determined by the level of Nanog expression. However, the mechanisms by which Nanog functions remain unclear, and in particular, direct Nanog target genes are uncharacterized. Here we investigate ESCs expressing different Nanog levels and Nanog?/? cells with distinct functionally inducible Nanog proteins to identify Nanog-responsive genes. Surprisingly, these constitute a minor fraction of genes that Nanog binds. Prominent among Nanog-reponsive genes is Estrogen-related receptor b (Esrrb). Nanog binds directly to Esrrb, enhances binding of RNAPolII, and stimulates Esrrb transcription. Overexpression of Esrrb in ESCs maintains cytokine-independent self-renewal and pluripotency. Remarkably, this activity is retained in Nanog?/? ESCs. Moreover, Esrrb can reprogram Nanog?/? EpiSCs and can rescue stalled reprogramming in Nanog?/? pre-iPSCs. Finally, Esrrb deletion abolishes the defining ability of Nanog to confer LIF-independent ESC self-renewal. These findings are consistent with the functional placement of Esrrb downstream of Nanog. PMID:23040477

Festuccia, Nicola; Osorno, Rodrigo; Halbritter, Florian; Karwacki-Neisius, Violetta; Navarro, Pablo; Colby, Douglas; Wong, Frederick; Yates, Adam; Tomlinson, Simon R.; Chambers, Ian

2012-01-01

350

A coding-independent function of gene and pseudogene mRNAs regulates tumour biology  

PubMed Central

The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs. PMID:20577206

Poliseno, Laura; Salmena, Leonardo; Zhang, Jiangwen; Carver, Brett; Haveman, William J.; Pandolfi, Pier Paolo

2011-01-01

351

Progress and challenges in the computational prediction of gene function using networks: 2012-2013 update  

PubMed Central

In an opinion published in 2012, we reviewed and discussed our studies of how gene network-based guilt-by-association (GBA) is impacted by confounds related to gene multifunctionality. We found such confounds account for a significant part of the GBA signal, and as a result meaningfully evaluating and applying computationally-guided GBA is more challenging than generally appreciated. We proposed that effort currently spent on incrementally improving algorithms would be better spent in identifying the features of data that do yield novel functional insights. We also suggested that part of the problem is the reliance by computational biologists on gold standard annotations such as the Gene Ontology. In the year since, there has been continued heavy activity in GBA-based research, including work that contributes to our understanding of the issues we raised. Here we provide a review of some of the most relevant recent work, or which point to new areas of progress and challenges. PMID:24715959

Pavlidis, Paul; Gillis, Jesse

2013-01-01

352

Drug2Gene: an exhaustive resource to explore effectively the drug-target relation network  

PubMed Central

Background Information about drug-target relations is at the heart of drug discovery. There are now dozens of databases providing drug-target interaction data with varying scope, and focus. Therefore, and due to the large chemical space, the overlap of the different data sets is surprisingly small. As searching through these sources manually is cumbersome, time-consuming and error-prone, integrating all the data is highly desirable. Despite a few attempts, integration has been hampered by the diversity of descriptions of compounds, and by the fact that the reported activity values, coming from different data sets, are not always directly comparable due to usage of different metrics or data formats. Description We have built Drug2Gene, a knowledge base, which combines the compound/drug-gene/protein information from 19 publicly available databases. A key feature is our rigorous unification and standardization process which makes the data truly comparable on a large scale, allowing for the first time effective data mining in such a large knowledge corpus. As of version 3.2, Drug2Gene contains 4,372,290 unified relations between compounds and their targets most of which include reported bioactivity data. We extend this set with putative (i.e. homology-inferred) relations where sufficient sequence homology between proteins suggests they may bind to similar compounds. Drug2Gene provides powerful search functionalities, very flexible export procedures, and a user-friendly web interface. Conclusions Drug2Gene v3.2 has become a mature and comprehensive knowledge base providing unified, standardized drug-target related information gathered from publicly available data sources. It can be used to integrate proprietary data sets with publicly available data sets. Its main goal is to be a ‘one-stop shop’ to identify tool compounds targeting a given gene product or for finding all known targets of a drug. Drug2Gene with its integrated data set of public compound-target relations is freely accessible without restrictions at http://www.drug2gene.com. PMID:24618344

2014-01-01

353

Genetic Variants in Hormone-Related Genes and Risk of Breast Cancer  

PubMed Central

Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk. PMID:23935996

Clendenen, Tess; Zeleniuch-Jacquotte, Anne; Wirgin, Isaac; Koenig, Karen L.; Afanasyeva, Yelena; Lundin, Eva; Arslan, Alan A.; Axelsson, Tomas; Forsti, Asta; Hallmans, Goran; Hemminki, Kari; Lenner, Per; Roy, Nirmal; Shore, Roy E.; Chen, Yu

2013-01-01

354

Genetic variants in hormone-related genes and risk of breast cancer.  

PubMed

Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk. PMID:23935996

Clendenen, Tess; Zeleniuch-Jacquotte, Anne; Wirgin, Isaac; Koenig, Karen L; Afanasyeva, Yelena; Lundin, Eva; Arslan, Alan A; Axelsson, Tomas; Försti, Asta; Hallmans, Göran; Hemminki, Kari; Lenner, Per; Roy, Nirmal; Shore, Roy E; Chen, Yu

2013-01-01

355

Gene expression profile of AIDS-related Kaposi's sarcoma  

PubMed Central

Background Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. Methods In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. Results The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. Conclusion The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages. PMID:12697073

Cornelissen, Marion; van der Kuyl, Antoinette C; van den Burg, Remco; Zorgdrager, Fokla; van Noesel, Carel JM; Goudsmit, Jaap

2003-01-01

356

Charge transport in cancer-related genes and early carcinogenesis  

NASA Astrophysics Data System (ADS)

The electronic transmission properties of DNA molecules are believed to play a significant role in many physical phenomena taking place in living organisms (Chakraborty, 2007) [1]. Here we study the charge transport (CT) properties of cancer-related genes, including some of the most important tumor suppressors. We find that the changes in averaged CT around the sites of pathogenic and cancerous mutations are statistically smaller than those on sites where pathogenic mutations have not been observed. The results suggest that CT might be an indicator to discriminate between pathogenic and non-pathogenic mutations at an early stage. Mutations which cause little change in CT may be more likely to occur, or more likely to be missed by damage-repair enzymes which probe CT, and are therefore more likely to persist and cause disease.

Shih, Chi-Tin; Cheng, Yun-Yin; Wells, Stephen A.; Hsu, Ching-Ling; Römer, Rudolf A.

2011-01-01

357

The incoherent feed-forward loop can generate non-monotonic input functions for genes  

Microsoft Academic Search

Gene regulation networks contain recurring circuit patterns called network motifs. One of the most common network motif is the incoherent type 1 feed-forward loop (I1-FFL), in which an activator controls both gene and repressor of that gene. This motif was shown to act as a pulse generator and response accelerator of gene expression. Here we consider an additional function of

Shai Kaplan; Anat Bren; Erez Dekel; Uri Alon

2008-01-01

358

Natural Selection and the Origin of jingwei, a Chimeric Processed Functional Gene in Drosophila  

Microsoft Academic Search

The origin of new genes includes both the initial molecular events and subsequent population dynamics. A processed Drosophila alcohol dehydrogenase (Adh) gene, previously thought to be a pseudogene, provided an opportunity to examine the two phases of the origin of a new gene. The sequence of the processed Adh messenger RNA became part of a new functional gene by capturing

Manyuan Long; Charles H. Langley

1993-01-01

359

Origin of plant glycerol transporters by horizontal gene transfer and functional recruitment  

Microsoft Academic Search

Gene-family evolution mostly relies on gene duplication coupled with functional diversification of gene products. However, other evolutionary mechanisms may also be important in generating protein diversity. The ubiquitous membrane intrinsic protein (MIP) gene family is an excellent model system to search for such alternative evolutionary mechanisms. MIPs are proteins that transport water, glycerol, and small solutes across cell membranes in

Rafael Zardoya; Xiaodong Ding; Yoshichika Kitagawa; Maarten J. Chrispeels

2002-01-01

360

Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis  

PubMed Central

Hox genes encode transcription factors governing complex developmental processes in several organs. A subset of Hox genes are expressed in the developing lung. Except for Hoxa5, the lack of overt lung phenotype in single mutants suggests that Hox genes may not play a predominant role in lung ontogeny or that functional redundancy may mask anomalies. In the Hox5 paralog group, both Hoxa5 and Hoxb5 genes are expressed in the lung mesenchyme whereas Hoxa5 is also expressed in the tracheal mesenchyme. Herein, we generated Hoxa5;Hoxb5 compound mutant mice to evaluate the relative contribution of each gene to lung development. Hoxa5;Hoxb5 mutants carrying the four mutated alleles displayed an aggravated lung phenotype, resulting in the death of the mutant pups at birth. Characterization of the phenotype highlighted the role of Hoxb5 in lung formation, the latter being involved in branching morphogenesis, goblet cell specification, and postnatal air space structure, revealing partial functional redundancy with Hoxa5. However, the Hoxb5 lung phenotypes were less severe than those seen in Hoxa5 mutants, likely because of Hoxa5 compensation. New specific roles for Hoxa5 were also unveiled, demonstrating the extensive contribution of Hoxa5 to the developing respiratory system. The exclusive expression of Hoxa5 in the trachea and the phrenic motor column likely underlies the Hoxa5-specific trachea and diaphragm phenotypes. Altogether, our observations establish that the Hoxa5 and Hoxb5 paralog