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1

Macrophages express functional receptors for calcitonin-gene-related peptide.  

PubMed

The present study was designed to investigate whether non-activated macrophages express calcitonin (CT) or calcitonin-gene-related peptide (CGRP) receptors. To this end, we first analyzed whether CT and CGRP induce a cAMP accumulation in macrophages. Macrophages were treated for 2 min with increasing concentrations of either CT or CGRP in the presence or absence of IBMX. A dose-dependent cAMP accumulation was measured in response to CGRP with a half-maximal effect attained with 1 nM CGRP. CT failed at all doses to induce an accumulation of cAMP. The effects of CT and CGRP on the activation of the Na-H exchanger were next assessed by spectrofluorometry by using the pH-sensitive dye 2,7 biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). Steady-state pHi of macrophages in a 7.4, HCO3-free solution (HEPES-buffered) was 7.04 +/- 0.08 (n = 22). pHi recovery following an NH4+/NH3 acid load was inhibited by the removal of Na+ or by the addition of the amiloride analog EIPA; therefore recovery is dependent on Na-H exchange activity. CT had no effect on steady-state pHi but CGRP increased pHi in a dose-dependent fashion (10(-12) to 10(-6) M). The pHi change induced by CGRP was due to the stimulation of the Na-H exchanger as CGRP enhanced the rate of recovery (dpHi/dt) from an acid load from 45.3 to 77.2 microMs-1 (n = 8, P less than 0.002) and was completely blocked by EIPA. These data indicate that CGRP both enhances the activity of the Na-H exchanger and increases intracellular cAMP, thus demonstrating that macrophages express functional CGRP receptors. PMID:1721072

Vignery, A; Wang, F; Ganz, M B

1991-11-01

2

Identification of three related human GRO genes encoding cytokine functions  

SciTech Connect

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. The authors have identified two additional genes, GRO{beta} and GRO{gamma}, that share 90{percent} and 86{percent} identity at the deduced amino acid level with the original GRO{alpha} isolate. One amino acid substitution of proline in GRO{alpha} by leucine in GRO{beta} and GRO{gamma} leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO{alpha} cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide.

Haskill, S.; Peace, A.; Morris, J.; Sporn, S.A. (Univ. of North Carolina at Chapel Hill, (USA)); Anisowicz, A.; Lee, S.W.; Sager, R. (Dana-Farber Cancer Institute, Boston, MA (USA)); Smith, T. (Harvard School of Public Health, Boston, MA (USA)); Martin, G.; Ralph, P. (Cetus Corporation, Emeryville, CA (USA))

1990-10-01

3

Gametocidal genes in wheat and its relatives. IV. Functional relationships between six gametocidal genes.  

PubMed

Gametocidal (Gc) genes in Aegilops species are known to cause gamete abortion and chromosome breakage when they are introduced into the wheat genetic background. Interactions of five Gc genes so far identified were investigated by analysis of wheat hybrids among lines carrying different gametocidal genes. As a result, the genes were classified into three functional groups. The first group includes two Gc genes of Ae. speltoides (Gc1a and Gc1b) and one gene (Gc-Sl3) on chromosome 2S1 of Ae. sharonensis. These genes were hypostatic to the genes (Gc-Sl1, Gc-Sl2) on chromosome 4S1 of Ae. longissima and Ae. sharonensis, which constitute the second group. In addition, plants carrying Gc genes of both the first and the second group produced progeny with higher frequencies of chromosome breakage than those found in the progeny of single gene carriers. It was concluded that there were specific interactions between these genes to enhance chromosome breakage. On the other hand, there was no interaction between the Gc gene (Gc-C) of Ae. triuncialis, the third group, and Gc genes belonging to the former two groups. These functional groups might be a reflection of the mechanisms by which Gc genes induce gamete abortion and chromosome breakage. Based on functional and local relationships, the symbols of the Gc genes were systematically redesignated. PMID:18470167

Tsujimoto, H

1995-04-01

4

An unsupervised approach to predict functional relations between genes based on expression data.  

PubMed

This work presents a novel approach to predict functional relations between genes using gene expression data. Genes may have various types of relations between them, for example, regulatory relations, or they may be concerned with the same protein complex or metabolic/signaling pathways and obviously gene expression data should contain some clues to such relations. The present approach first digitizes the log-ratio type gene expression data of S. cerevisiae to a matrix consisting of 1, 0, and -1 indicating highly expressed, no major change, and highly suppressed conditions for genes, respectively. For each gene pair, a probability density mass function table is constructed indicating nine joint probabilities. Then gene pairs were selected based on linear and probabilistic relation between their profiles indicated by the sum of probability density masses in selected points. The selected gene pairs share many Gene Ontology terms. Furthermore a network is constructed by selecting a large number of gene pairs based on FDR analysis and the clustering of the network generates many modules rich with similar function genes. Also, the promoters of the gene sets in many modules are rich with binding sites of known transcription factors indicating the effectiveness of the proposed approach in predicting regulatory relations. PMID:24800208

Altaf-Ul-Amin, Md; Katsuragi, Tetsuo; Sato, Tetsuo; Ono, Naoaki; Kanaya, Shigehiko

2014-01-01

5

An Unsupervised Approach to Predict Functional Relations between Genes Based on Expression Data  

PubMed Central

This work presents a novel approach to predict functional relations between genes using gene expression data. Genes may have various types of relations between them, for example, regulatory relations, or they may be concerned with the same protein complex or metabolic/signaling pathways and obviously gene expression data should contain some clues to such relations. The present approach first digitizes the log-ratio type gene expression data of S. cerevisiae to a matrix consisting of 1, 0, and ?1 indicating highly expressed, no major change, and highly suppressed conditions for genes, respectively. For each gene pair, a probability density mass function table is constructed indicating nine joint probabilities. Then gene pairs were selected based on linear and probabilistic relation between their profiles indicated by the sum of probability density masses in selected points. The selected gene pairs share many Gene Ontology terms. Furthermore a network is constructed by selecting a large number of gene pairs based on FDR analysis and the clustering of the network generates many modules rich with similar function genes. Also, the promoters of the gene sets in many modules are rich with binding sites of known transcription factors indicating the effectiveness of the proposed approach in predicting regulatory relations. PMID:24800208

Altaf-Ul-Amin, Md.; Sato, Tetsuo; Ono, Naoaki; Kanaya, Shigehiko

2014-01-01

6

The ash-1, ash-2 and trithorax Genes of Drosophila melanogaster Are Functionally Related  

Microsoft Academic Search

Mutations in the ash-1 and ash-2 genes of Drosophila melanogaster cause a wide variety of homeotic transformations that are similar to the transformations caused by mutations in the trithorax gene. Based on this similar variety of transformations, it was hypothesized that these genes are members of a functionally related set. Three genetic tests were employed here to evaluate that hypothesis.

Allen Shearn

1989-01-01

7

Identification and functional analysis of differentially expressed genes related to obesity using DNA microarray.  

PubMed

We looked for differentially expressed genes at different stages of preadipocyte differentiation and examined their functions, based on DNA microarrays of preadipocytes obtained from healthy subjects undergoing cosmetic liposuction. We downloaded gene expression profile GSE25910 from the Gene Expression Omnibus database and identified the differentially expressed genes with packages in R language. The selected differentially expressed genes were further analyzed using bioinformatics methods. Comparing gene expression at different stages of preadipocytes differentiation, we found that expression of 668 and 1007 genes were altered in middle and late stages compared with the early stage, respectively. Function analysis revealed that the differentially expressed genes were mainly related to fatty acid metabolic processes in the former two stages. PMID:24446288

Du, J Y; Yang, H; Tian, D R; Wang, Q M; He, L

2014-01-01

8

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

PubMed Central

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

2013-01-01

9

Functional polymorphisms in dopamine-related genes: Effect on neurocognitive functioning in HIV+ adults  

Microsoft Academic Search

Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults. Method: A total of 184 HIV+ adults were

Andrew J. Levine; Janet S. Sinsheimer; Robert Bilder; Paul Shapshak; Elyse J. Singer

2012-01-01

10

Functional polymorphisms in dopamine-related genes: Effect on neurocognitive functioning in HIV+ adults  

Microsoft Academic Search

Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults. Method: A total of 184 HIV+ adults were

Andrew J. Levine; Janet S. Sinsheimer; Robert Bilder; Paul Shapshak; Elyse J. Singer

2011-01-01

11

Evidence for Related Functions of the RNA Genes of Saccharomyces cerevisiae  

PubMed Central

The yeast genes RNA2-RNA11 are necessary for splicing of nuclear intron-containing pre-mRNAs. We investigated the relationships among these genes by asking whether increased expression of one RNA gene leads to suppression of the temperature-sensitive lethality of a mutation in any other RNA gene. The presence of extra plasmid-borne copies of the RNA3 gene relieves the lethality of temperature-sensitive rna4 mutations. A region of the yeast genome (SRN2) is described that suppresses temperature-sensitive rna2 mutations when it is present on either medium or high-copy number plasmids. Neither suppression occurs via a bypass of RNA gene function since null alleles of rna2 and rna4 are not suppressed by elevated dosage of SRN2 and RNA3, respectively. These results suggest that the SRN2 and RNA2 gene products have related functions, as do the RNA3 and RNA4 gene products. PMID:3322934

Last, Robert L.; Maddock, Janine R.; Woolford, John L.

1987-01-01

12

Identification of functionally related genes using data mining and data integration: a breast cancer case study  

Microsoft Academic Search

BACKGROUND: The identification of the organisation and dynamics of molecular pathways is crucial for the understanding of cell function. In order to reconstruct the molecular pathways in which a gene of interest is involved in regulating a cell, it is important to identify the set of genes to which it interacts with to determine cell function. In this context, the

Ettore Mosca; Gloria Bertoli; Eleonora Piscitelli; Laura Vilardo; Rolland A. Reinbold; Ileana Zucchi; Luciano Milanesi

2009-01-01

13

Transcriptional interference networks coordinate the expression of functionally related genes clustered in the same genomic loci  

PubMed Central

The regulation of gene expression is essential for normal functioning of biological systems in every form of life. Gene expression is primarily controlled at the level of transcription, especially at the phase of initiation. Non-coding RNAs are one of the major players at every level of genetic regulation, including the control of chromatin organization, transcription, various post-transcriptional processes, and translation. In this study, the Transcriptional Interference Network (TIN) hypothesis was put forward in an attempt to explain the global expression of antisense RNAs and the overall occurrence of tandem gene clusters in the genomes of various biological systems ranging from viruses to mammalian cells. The TIN hypothesis suggests the existence of a novel layer of genetic regulation, based on the interactions between the transcriptional machineries of neighboring genes at their overlapping regions, which are assumed to play a fundamental role in coordinating gene expression within a cluster of functionally linked genes. It is claimed that the transcriptional overlaps between adjacent genes are much more widespread in genomes than is thought today. The Waterfall model of the TIN hypothesis postulates a unidirectional effect of upstream genes on the transcription of downstream genes within a cluster of tandemly arrayed genes, while the Seesaw model proposes a mutual interdependence of gene expression between the oppositely oriented genes. The TIN represents an auto-regulatory system with an exquisitely timed and highly synchronized cascade of gene expression in functionally linked genes located in close physical proximity to each other. In this study, we focused on herpesviruses. The reason for this lies in the compressed nature of viral genes, which allows a tight regulation and an easier investigation of the transcriptional interactions between genes. However, I believe that the same or similar principles can be applied to cellular organisms too. PMID:22783276

Boldogköi, Zsolt

2012-01-01

14

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

PubMed

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

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

2015-02-01

15

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

PubMed Central

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

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

2014-01-01

16

Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity.  

PubMed

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

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

2014-01-01

17

Role of Calcitonin Gene-Related Peptide in Functional Adaptation of the Skeleton  

PubMed Central

Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRP? and CGRP?. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRP? and CGRP? knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRP? signaling. This effect was not evident in CGRP? knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRP? deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRP?-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation. PMID:25536054

Sample, Susannah J.; Heaton, Caitlin M.; Behan, Mary; Bleedorn, Jason A.; Racette, Molly A.; Hao, Zhengling; Muir, Peter

2014-01-01

18

Expression and Functional Characterization of two Pathogenesis-Related Protein 10 Genes from Zea mays  

Technology Transfer Automated Retrieval System (TEKTRAN)

Pathogenesis-related protein 10 (PR10) is one of seventeen PR protein families and plays important roles in plant response to biotic and abiotic stresses. A novel PR10 gene (ZmPR10.1), which shares 89.8% and 85.7% identity to the previous ZmPR10 at the nucleotide and amino acid sequence level, respe...

19

[Studies on learning and memory function-related genes in the hippocampus and the relationship between the cognitive enhancing effect of liuwei dihuang decoction (LW) and gene expression].  

PubMed

Our studies showed that the expressions of the genes including glucocorticoid receptor (GR), mineralocorticoid receptor (MR), bcl-2, c-fos, neural cell adhesion molecule(NCAM), presenilin-2 (PS-2) and apoE in the hippocampus were closely related to the central learning and memory function in senescence accelerated mice (SAM), hydrocortisone(HC)-treated mice and normal mice. The differential display technique was applied to compare mRNAs expression between SAM-prone/8 (SAMP8), and SAM-resistance/1 (SAMR1). Six differentially expressed cDNA bands were identified and two of them are unknown genes. Chronic oral administration of LW (5 g/kg), a traditional Chinese medicinal prescription, significantly ameliorated the deterioration of learning and memory ability in SAMP8 and HC-treated mice and corrected the abnormal expressions of hippocampal genes. Further studies showed that corticosterone significantly affected the gene expression in primary cultured hippocampal neurons. These results suggested that central learning and memory function is closely related to the expressions of hippocampal genes. The imbalance of hypothalamic-pituitary-adrenal (HPA) axis leads to the deterioration of learning and memory function and the abnormal expressions of hippocampal genes. Therefore, one of the important ways of the cognitive enhancing effect of LW is to correct the abnormal expressions of hippocampal genes. PMID:12545709

Wei, X L

2000-07-01

20

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

21

Functional characterization of an apple apomixis-related MhFIE gene in reproduction development.  

PubMed

The products of the FIS genes play important regulatory roles in diverse developmental processes, especially in seed formation after fertilization. In this study, a FIS-class gene MhFIE was isolated from apple. It encoded a predicted protein highly similar to polycomb group (PcG) protein FERTILIZATION-INDEPENDENT ENDOSPERM (FIE). MhFIE functioned as an Arabidopsis FIE homologue, as indicated by functional complementation experiment using Arabidopsis fie mutant. In addition, BiFC assay showed that MhFIE protein interacted with AtCLF. Furthermore, transgenic Arabidopsis ectopically expressing MhFIE produced less APETALA3 (AtAP3) and AGAMOUS (AtAG) transcripts than WT control, and therefore exhibited abnormal flower, seed development. These results suggested that polycomb complex including FIE and CLF proteins played an important role in reproductive development by regulating the expression of its downstream genes. In addition, it was found that MhFIE constitutively expressed in various tissues tested. Its expression levels were lower in apomictic apple species than the sexual reproductive species, suggested it was possibly involved into apomixis in apple. Furthermore, the hybrids of tea crabapple generated MhFIE transcripts at different levels. The parthenogenesis capacity was negatively correlated with MhFIE expression level in these hybrids. These results suggested that MhFIE was involved into the regulation of flower development and apomixis in apple. PMID:22325871

Liu, Dan-Dan; Dong, Qing-Long; Sun, Chao; Wang, Qing-Lian; You, Chun-Xiang; Yao, Yu-Xin; Hao, Yu-Jin

2012-04-01

22

Discovery of Genes Related to Insecticide Resistance in Bactrocera dorsalis by Functional Genomic Analysis of a De Novo Assembled Transcriptome  

PubMed Central

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; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S.; Chen, Chien-Yu

2012-01-01

23

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

24

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

25

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

E-print Network

Microarray technology captures the rate of expression of genes under varying experimental conditions. Genes encode the information necessary to build proteins; proteins used by cellular functions exhibit higher rates of ...

Senf, Alexander J.

2011-02-04

26

Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.  

PubMed

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

27

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

28

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 eukaryotes due to the relatively simple structure of prokaryotes. That is why tissue-specific expression ways, especially in Gene Therapy [5]. Identifying gene function in prokaryotes is much easier than

Bonner, Anthony

29

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

30

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

PubMed

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 of crossvalidating findings. Topping the list of candidate genes, we have DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) located at 17q12, PENK (preproenkephalin) located at 8q12.1, and TAC1 (tachykinin 1, substance P) located at 7q21.3. These data suggest that more primitive molecular mechanisms involved in pleasure and pain may have been recruited by evolution to play a role in higher mental functions such as mood. The analysis also revealed other high-probability candidates genes (neurogenesis, neurotrophic, neurotransmitter, signal transduction, circadian, synaptic, and myelin related), pathways and mechanisms of likely importance in pathophysiology. PMID:15314610

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

2004-11-01

31

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

32

An algorithm for identifying clusters of functionally related genes in genomes  

E-print Network

to occur in Caenorhabditis elegans and share many similarities with their prokaryotic counterparts. Fungi also contain metabolic pathwayclustersthoughtheirstructuredifiersconsiderablyfromoperonsin C. elegans (Blumenthal [3], Zorio [4] and Spieth [5]). Some.... elegans, Thomas [16] showed that clusters of homologous genes tend to be formed of species speciflc gene families that play roles in detoxiflcation and immunity, and are found in chromosomal regions that undergo rapid evolution and reorganization. Further...

Yi, Gang Man

2009-05-15

33

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

SciTech Connect

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

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

2007-05-25

34

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

35

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

PubMed Central

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

2013-01-01

36

Genomic Resources for Gene Discovery, Functional Genome Annotation, and Evolutionary Studies of Maize and Its Close Relatives  

PubMed Central

Maize is one of the most important food crops and a key model for genetics and developmental biology. A genetically anchored and high-quality draft genome sequence of maize inbred B73 has been obtained to serve as a reference sequence. To facilitate evolutionary studies in maize and its close relatives, much like the Oryza Map Alignment Project (OMAP) (www.OMAP.org) bacterial artificial chromosome (BAC) resource did for the rice community, we constructed BAC libraries for maize inbred lines Zheng58, Chang7-2, and Mo17 and maize wild relatives Zea mays ssp. parviglumis and Tripsacum dactyloides. Furthermore, to extend functional genomic studies to maize and sorghum, we also constructed binary BAC (BIBAC) libraries for the maize inbred B73 and the sorghum landrace Nengsi-1. The BAC/BIBAC vectors facilitate transfer of large intact DNA inserts from BAC clones to the BIBAC vector and functional complementation of large DNA fragments. These seven Zea Map Alignment Project (ZMAP) BAC/BIBAC libraries have average insert sizes ranging from 92 to 148 kb, organellar DNA from 0.17 to 2.3%, empty vector rates between 0.35 and 5.56%, and genome equivalents of 4.7- to 8.4-fold. The usefulness of the Parviglumis and Tripsacum BAC libraries was demonstrated by mapping clones to the reference genome. Novel genes and alleles present in these ZMAP libraries can now be used for functional complementation studies and positional or homology-based cloning of genes for translational genomics. PMID:24037269

Wang, Chao; Shi, Xue; Liu, Lin; Li, Haiyan; Ammiraju, Jetty S.S.; Kudrna, David A.; Xiong, Wentao; Wang, Hao; Dai, Zhaozhao; Zheng, Yonglian; Lai, Jinsheng; Jin, Weiwei; Messing, Joachim; Bennetzen, Jeffrey L; Wing, Rod A.; Luo, Meizhong

2013-01-01

37

Genomic resources for gene discovery, functional genome annotation, and evolutionary studies of maize and its close relatives.  

PubMed

Maize is one of the most important food crops and a key model for genetics and developmental biology. A genetically anchored and high-quality draft genome sequence of maize inbred B73 has been obtained to serve as a reference sequence. To facilitate evolutionary studies in maize and its close relatives, much like the Oryza Map Alignment Project (OMAP) (www.OMAP.org) bacterial artificial chromosome (BAC) resource did for the rice community, we constructed BAC libraries for maize inbred lines Zheng58, Chang7-2, and Mo17 and maize wild relatives Zea mays ssp. parviglumis and Tripsacum dactyloides. Furthermore, to extend functional genomic studies to maize and sorghum, we also constructed binary BAC (BIBAC) libraries for the maize inbred B73 and the sorghum landrace Nengsi-1. The BAC/BIBAC vectors facilitate transfer of large intact DNA inserts from BAC clones to the BIBAC vector and functional complementation of large DNA fragments. These seven Zea Map Alignment Project (ZMAP) BAC/BIBAC libraries have average insert sizes ranging from 92 to 148 kb, organellar DNA from 0.17 to 2.3%, empty vector rates between 0.35 and 5.56%, and genome equivalents of 4.7- to 8.4-fold. The usefulness of the Parviglumis and Tripsacum BAC libraries was demonstrated by mapping clones to the reference genome. Novel genes and alleles present in these ZMAP libraries can now be used for functional complementation studies and positional or homology-based cloning of genes for translational genomics. PMID:24037269

Wang, Chao; Shi, Xue; Liu, Lin; Li, Haiyan; Ammiraju, Jetty S S; Kudrna, David A; Xiong, Wentao; Wang, Hao; Dai, Zhaozhao; Zheng, Yonglian; Lai, Jinsheng; Jin, Weiwei; Messing, Joachim; Bennetzen, Jeffrey L; Wing, Rod A; Luo, Meizhong

2013-11-01

38

The impact of mitochondrial DNA and nuclear genes related to mitochondrial functioning on the risk of Parkinson's disease.  

PubMed

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

2013-12-01

39

Functional conservation of Toxoplasma gondii virulence genes in its avirulent relative, Hammondia hammondi  

Technology Transfer Automated Retrieval System (TEKTRAN)

Toxoplasma gondii is a ubiquitous protozoan parasite capable of infecting all warm blooded animals, including humans. Its closest extant relative, Hammondia hammondi, has never been found to infect humans and in contrast to T. gondii is highly attenuated in mice. To better understand the genetic b...

40

Loss-of-function of Constitutive Expresser of Pathogenesis Related Genes5 affects potassium homeostasis in Arabidopsis thaliana.  

PubMed

Here, we demonstrate that the reduction in leaf K(+) observed in a mutant previously identified in an ionomic screen of fast neutron mutagenized Arabidopsis thaliana is caused by a loss-of-function allele of CPR5, which we name cpr5-3. This observation establishes low leaf K(+) as a new phenotype for loss-of-function alleles of CPR5. We investigate the factors affecting this low leaf K(+) in cpr5 using double mutants defective in salicylic acid (SA) and jasmonic acid (JA) signalling, and by gene expression analysis of various channels and transporters. Reciprocal grafting between cpr5 and Col-0 was used to determine the relative importance of the shoot and root in causing the low leaf K(+) phenotype of cpr5. Our data show that loss-of-function of CPR5 in shoots primarily determines the low leaf K(+) phenotype of cpr5, though the roots also contribute to a lesser degree. The low leaf K(+) phenotype of cpr5 is independent of the elevated SA and JA known to occur in cpr5. In cpr5 expression of genes encoding various Cyclic Nucleotide Gated Channels (CNGCs) are uniquely elevated in leaves. Further, expression of HAK5, encoding the high affinity K(+) uptake transporter, is reduced in roots of cpr5 grown with high or low K(+) supply. We suggest a model in which low leaf K(+) in cpr5 is driven primarily by enhanced shoot-to-root K(+) export caused by a constitutive activation of the expression of various CNGCs. This activation may enhance K(+) efflux, either indirectly via enhanced cytosolic Ca(2+) and/or directly by increased K(+) transport activity. Enhanced shoot-to-root K(+) export may also cause the reduced expression of HAK5 observed in roots of cpr5, leading to a reduction in uptake of K(+). All ionomic data presented is publically available at www.ionomicshub.org. PMID:22046278

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

2011-01-01

41

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; Moënne-Loccoz, Yvan

2014-01-01

42

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

43

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

44

Systematic Identification of Cell-Wall Related Genes in Populus Based on Analysis of Functional Modules in Co-Expression Network  

PubMed Central

The identification of novel genes relevant to plant cell wall (PCW) biosynthesis in Populus is a highly important and challenging problem. We surveyed candidate Populus cell wall genes using a non-targeted approach. First, a genome-wide Populus gene co-expression network (PGCN) was constructed using microarray data available in the public domain. Module detection was then performed, followed by gene ontology (GO) enrichment analysis, to assign the functional category to these modules. Based on GO annotation, the modules involved in PCW biosynthesis were then selected and analyzed in detail to annotate the candidate PCW genes in these modules, including gene annotation, expression of genes in different tissues, and so on. We examined the overrepresented cis-regulatory elements (CREs) in the gene promoters to understand the possible transcriptionally co-regulated relationships among the genes within the functional modules of cell wall biosynthesis. PGCN contains 6,854 nodes (genes) with 324,238 edges. The topological properties of the network indicate scale-free and modular behavior. A total of 435 modules were identified; among which, 67 modules were identified by overrepresented GO terms. Six modules involved in cell wall biosynthesis were identified. Module 9 was mainly involved in cellular polysaccharide metabolic process in the primary cell wall, whereas Module 4 comprises genes involved in secondary cell wall biogenesis. In addition, we predicted and analyzed 10 putative CREs in the promoters of the genes in Module 4 and Module 9. The non-targeted approach of gene network analysis and the data presented here can help further identify and characterize cell wall related genes in Populus. PMID:24736620

Cai, Bin; Li, Cheng-Hui; Huang, Jian

2014-01-01

45

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

46

Comparative mapping reveals similar linkage of functional genes to QTL of yield-related traits between Brassica napus and Oryza sativa.  

PubMed

Oryza sativa and Brassica napus-two important crops for food and oil, respectively-share high seed yield as a common breeding goal. As a model plant, O. sativa genomics have been intensively investigated and its agronomic traits have been advanced. In the present study, we used the available information on O. sativa to conduct comparative mapping between O. sativa and B. napus, with the aim of advancing research on seed-yield and yield-related traits in B. napus. Firstly, functional markers (from 55 differentially expressed genes between a hybrid and its parents) were used to detect B. napus genes that co-localized with yield-related traits in an F(2:3) population. Referring to publicly available sequences of 55 B. napus genes, 53 homologous O. sativa genes were subsequently detected by screening, and their chromosomal locations were determined using silico mapping. Comparative location of yield-related QTL between the two species showed that a total of 37 O. sativa and B. napus homologues were located in similar yield-related QTL between species. Our results indicate that homologous genes between O. sativa and B. napus may have consistent function and control similar traits, which may be helpful for agronomic gene characterization in B. napus based on what is known in O. sativa. PMID:22942086

Li, Fupeng; Ma, Chaozhi; Chen, Qingfang; Liu, Touming; Shen, Jinxiong; Tu, Jinxing; Xing, Yongzhong; Fu, Tingdong

2012-08-01

47

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

PubMed

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, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; 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

2012-12-15

48

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, Åsa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; 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

49

Transient expression of ?C1 protein differentially regulates host genes related to stress response, chloroplast and mitochondrial functions  

PubMed Central

Background Geminiviruses are emerging plant pathogens that infect a wide variety of crops including cotton, cassava, vegetables, ornamental plants and cereals. The geminivirus disease complex consists of monopartite begomoviruses that require betasatellites for the expression of disease symptoms. These complexes are widespread throughout the Old World and cause economically important diseases on several crops. A single protein encoded by betasatellites, termed ?C1, is a suppressor of gene silencing, inducer of disease symptoms and is possibly involved in virus movement. Studies of the interaction of ?C1 with hosts can provide useful insight into virus-host interactions and aid in the development of novel control strategies. We have used the differential display technique to isolate host genes which are differentially regulated upon transient expression of the ?C1 protein of chili leaf curl betasatellite (ChLCB) in Nicotiana tabacum. Results Through differential display analysis, eight genes were isolated from Nicotiana tabacum, at two and four days after infitration with ?C1 of ChLCB, expressed under the control of the Cauliflower mosaic virus 35S promoter. Cloning and sequence analysis of differentially amplified products suggested that these genes were involved in ATP synthesis, and acted as electron carriers for respiration and photosynthesis processes. These differentially expressed genes (DEGs) play an important role in plant growth and development, cell protection, defence processes, replication mechanisms and detoxification responses. Kegg orthology based annotation system analysis of these DEGs demonstrated that one of the genes, coding for polynucleotide nucleotidyl transferase, is involved in purine and pyrimidine metabolic pathways and is an RNA binding protein which is involved in RNA degradation. Conclusion ?C1 differentially regulated genes are mostly involved in chloroplast and mitochondrial functions. ?C1 also increases the expression of those genes which are involved in purine and pyrimidine metabolism. This information gives a new insight into the interaction of ?C1 with the host and can be used to understand host-virus interactions in follow-up studies. PMID:21192819

2010-01-01

50

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

51

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool  

PubMed Central

Motivation: Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. Implementation: The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. Contact: abutte@stanford.edu Supplementary information: Supplementary material is available at Bioinformatics online. PMID:23732275

Auerbach, Raymond K.; Chen, Bin; Butte, Atul J.

2013-01-01

52

Lack of influence of COMT and NET genes variants on executive functions in schizophrenic and bipolar patients, their first-degree relatives and controls.  

PubMed

Abnormal dopaminergic function in the prefrontal cortex (PFC) may be a key factor in the etiopathogeny of schizophrenia and bipolar disorder. Both schizophrenic and bipolar subjects have executive functions (EF) deficits, thought to reflect abnormal PFC function. The main inactivation pathways for dopamine in the PFC are enzymatic cleavage by the Carboxy-O-Methyl-Transferase (COMT) and reuptake by the nor-epinephrine transporter (NET). Our aim in this study was to replicate previous studies that investigated influence of the COMT genotype on EF in schizophrenic subjects, their relatives and controls and extend their scope by including bipolar patients, and their relatives and by exploring NET gene polymorphisms influence on executive performances. We investigated one functional polymorphism of the COMT gene and two polymorphisms of the NET gene. EF were assessed by means of the Trail Making Test (TMT) and the Wisconsin Card Sorting Test (WCST). We assessed the effect of each of the three genotypes on EF for the whole sample (N = 318) and separately in schizophrenic (N = 66), bipolar (N = 94) and healthy subjects (i.e., relatives and controls N = 158). Separate analyses were performed because of the presence, in patients samples, of potentially confounding factors, especially medication. Genotype had no significant effect on the cognitive measures in any of the analyses (for the two EF measures, the three polymorphisms, and the four groups). In our sample we found no evidence in favor of a major effect of COMT or NET polymorphisms on the two tests of EF. PMID:16741933

Szöke, A; Schürhoff, F; Méary, A; Mathieu, F; Chevalier, F; Trandafir, A; Alter, C; Roy, I; Bellivier, F; Leboyer, M

2006-07-01

53

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

54

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

55

Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas  

PubMed Central

The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system. PMID:23062308

NAUMOVA, OKSANA YU.; PALEJEV, DEAN; VLASOVA, NATALIA V.; LEE, MARIA; RYCHKOV, SERGEI YU.; BABICH, OLGA N.; VACCARINO, FLORA M.; GRIGORENKO, ELENA L.

2012-01-01

56

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 Sanità; Kohler, Annegret; Tisserant, Emilie; Martin, Francis; Ottonello, Simone

2011-06-01

57

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  

PubMed Central

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 in serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species; an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene; and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species. PMID:18824000

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

2009-01-01

58

Phylogenetic and In Silico Functional Analyses of Thermostable-Direct Hemolysin and tdh-Related Encoding Genes in Vibrio parahaemolyticus and Other Gram-Negative Bacteria  

PubMed Central

Emergence and spread of pandemic strains of Vibrio parahaemolyticus have drawn attention to make detailed study on their genomes. The pathogenicity of V. parahaemolyticus has been associated with thermostable-direct hemolysin (TDH) and/or TDH-related hemolysin (TRH). The present study evaluated characteristics of tdh and trh genes, considering the phylogenetic and in silico functional features of V. parahaemolyticus and other bacteria. Fifty-two tdh and trh genes submitted to the GenBank were analyzed for sequence similarity. The promoter sequences of these genes were also analyzed from transcription start point to ?35 regions and correlated with amino acid substitution within the coding regions. The phylogenetic analysis revealed that tdh and trh are highly distinct and also differ within the V. parahaemolyticus strains that were isolated from different geographical regions. Promoter sequence analysis revealed nucleotide substitutions and deletions at ?18 and ?19 positions among the pandemic, prepandemic, and nonpandemic tdh sequences. Many amino acid substitutions were also found within the signal peptide and also in the matured protein region of several TDH proteins as compared to TDH-S protein of pandemic V. parahaemolyticus. Experimental evidences are needed to recognize the importance of substitutions and deletions in the tdh and trh genes. PMID:25114910

Bhowmik, Sushanta K.; Pazhani, Gururaja P.; Ramamurthy, Thandavarayan

2014-01-01

59

Functional loss of all ndh genes in an otherwise relatively unaltered plastid genome of the holoparasitic flowering plant Cuscuta reflexa  

Microsoft Academic Search

We have cloned and sequenced an area of about 9.0 kb of the plastid DNA (ptDNA) from the holoparasitic flowering plant Cuscuta reflexa to investigate the evolutionary response of plastid genes to a reduced selective pressure. The region contains genes for the 16S rRNA, a subunit of a plastid NAD(P)H dehydrogenase (ndhB), three transfer RNAs (trnA, trnI, trnV) as well

Gerd Haberhausen; Klaus Zetsche

1994-01-01

60

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

61

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

E-print Network

applications. Identifying gene function based on gene expression data is much easier in prokaryotes than eukaryotes due to the relatively simple structure of prokaryotes. Recent studies have shown in many ways, especially in Gene Therapy [18]. Identifying gene function in prokaryotes is much easier

Bonner, Anthony

62

Loss of functional K+ channels encoded by ether-à-go-go-related genes in mouse myometrium prior to labour onset.  

PubMed

There is a growing appreciation that ion channels encoded by the ether-à-go-go-related gene family have a functional impact in smooth muscle in addition to their accepted role in cardiac myocytes and neurones. This study aimed to assess the expression of ERG1-3 (KCNH1-3) genes in the murine myometrium (smooth muscle layer of the uterus) and determine the functional impact of the ion channels encoded by these genes in pregnant and non-pregnant animals. Quantitative RT-PCR did not detect message for ERG2 and 3 in whole myometrial tissue extracts. In contrast, message for two isoforms of mERG1 were readily detected with mERG1a more abundant than mERG1b. In isometric tension studies of non-pregnant myometrium, the ERG channel blockers dofetilide (1 microM), E4031 (1 microM) and Be-KM1 (100 nM) increased spontaneous contractility and ERG activators (PD118057 and NS1643) inhibited spontaneous contractility. In contrast, neither ERG blockade nor activation had any effect on the inherent contractility in myometrium from late pregnant (19 days gestation) animals. Moreover, dofetilide-sensitive K(+) currents with distinctive 'hooked' kinetics were considerably smaller in uterine myocytes from late pregnant compared to non-pregnant animals. Expression of mERG1 isoforms did not alter throughout gestation or upon delivery, but the expression of genes encoding auxillary subunits (KCNE) were up-regulated considerably. This study provides the first evidence for a regulation of ERG-encoded K(+) channels as a precursor to late pregnancy physiological activity. PMID:19332483

Greenwood, I A; Yeung, S Y; Tribe, R M; Ohya, S

2009-05-15

63

Immunity-Related Genes and Gene Families in Anopheles gambiae  

Microsoft Academic Search

We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In

George K. Christophides; Evgeny Zdobnov; Carolina Barillas-Mury; Ewan Birney; Stephanie Blandin; Claudia Blass; Paul T. Brey; Frank H. Collins; Alberto Danielli; George Dimopoulos; Charles Hetru; Ngo T. Hoa; Jules A. Hoffmann; Stefan M. Kanzok; Ivica Letunic; Elena A. Levashina; Thanasis G. Loukeris; Gareth Lycett; Stephan Meister; Kristin Michel; Luis F. Moita; Hans-Michael Müller; Mike A. Osta; Susan M. Paskewitz; Jean-Marc Reichhart; Andrey Rzhetsky; Laurent Troxler; Kenneth D. Vernick; Dina Vlachou; Jennifer Volz; Christian von Mering; Jiannong Xu; Liangbiao Zheng; Peer Bork; Fotis C. Kafatos

2002-01-01

64

Chronic exposure to high levels of atrazine alters expression of genes that regulate immune and growth-related functions in developing Xenopus laevis tadpoles.  

PubMed

Atrazine is the most commonly detected pesticide in ground and surface waters, with seasonal spikes that often exceed the Environmental Protection Agency's "Recommended Water Quality Criterion" of 350 parts per billion (ppb). Although numerous studies have shown atrazine produces adverse effects on growth, development, immune and endocrine system functions in a wide range of species, few describe gene expression changes concurrent with atrazine-induced changes in phenotype during development. In this report, developing Xenopus laevis tadpoles were chronically exposed to 400 ppb atrazine, an environmentally relevant concentration. Affymetrix microarrays and Taqman qRT-PCR were used to define gene expression changes that underlie atrazine-induced phenotypic alterations. Atrazine significantly reduced survival and growth (weight, length and fat body size) in male and female tadpoles. Microarray analysis showed atrazine altered expression of 44 genes in male tadpoles (18 upregulated, 26 downregulated) and 77 genes in female tadpoles (23 upregulated, 54 downregulated). Classification of the genes into functional groups showed the majority of genes were associated with the following biological functions: growth and metabolism, proteolysis, fibrinogen complex formation and immune regulation. Seven genes associated with immune system function, specifically defense molecules present in the skin (e.g. magainin II, levitide A, preprocarulein, skin granule protein), were significantly downregulated in female tadpoles. These results support the idea that environmental contaminants such as atrazine compromise important gene pathways during frog development that may, ultimately, be relevant to global amphibian decline. PMID:19272595

Langerveld, Anna Jelaso; Celestine, Ronald; Zaya, Renee; Mihalko, Daniel; Ide, Charles F

2009-05-01

65

Flik, a chick follistatin-related gene, functions in gastrular dorsalisation/neural induction and in subsequent maintenance of midline Sonic hedgehog signalling.  

PubMed

We have targetted the chick gene Flik with antisense oligodeoxynucleotide treatment at gastrular stages, when it is expressed in organiser-derived structures of the midline (K. Patel et al., 1996, Dev. Biol. 178, 327-342). A specific syndrome of deficient axial patterning and holoprosencephaly is produced. Most aspects of this syndrome can be understood as due to attenuation of dorsalising and neural-inducing signals during gastrulation, followed by failure to maintain the later signals from chordamesoderm/neural midline that pattern the mesodermal and neural cross sections during subsequent stages. Anatomical effects are first apparent at early neurula stages and correspond with what might be expected from a reduced counteraction of the ventralising Bone morphogenetic protein (BMP) pathway at the earlier stages, coupled with inadequate Sonic hedgehog (Shh) signalling subsequently. Delay in the clearing of BMP-4 RNA expression from the presumptive neural region at gastrulation is indeed seen, though chordin RNA expression within organiser derivatives remains normal. Subsequently, specific attenuation of chordamesoderm and neural midline Shh expression is observed. Brief preincubation of stage 4 chick blastoderms in supernatant from Xenopus oocytes that have been injected with Flik RNA prolongs and enhances the competence of their peripheral epiblast to respond to neural inductive signals from grafted Hensen's nodes. This effect specifically mimics that recently observed using microg/ml solutions of recombinant Follistatin (D. J. Connolly et al., 1999, Int. J. Dev. Biol., in press), further suggesting that Flik protein might act in vivo by somehow modulating activity of signalling pathways through BMP or other TGFbeta-related ligands. We discuss the significance of the observations in relation to recent ideas about neural induction, about possible redundancy in gene action, and about subsequent patterning of the axial cross section, suggesting that a Flik function in autocrine/paracrine maintenance of later midline Shh signalling represents a role of the gene separate from that in primary dorsalisation/neural induction. PMID:10525336

Towers, P; Patel, K; Withington, S; Isaac, A; Cooke, J

1999-10-15

66

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

PubMed Central

Association rules mining methods have been recently applied to gene expression data analysis to reveal relationships between genes and different conditions and features. However, not much effort has focused on detecting the relation between gene expression maps and related gene functions. Here we describe such an approach to mine association rules among gene functions in clusters of similar gene expression maps on mouse brain. The experimental results show that the detected association rules make sense biologically. By inspecting the obtained clusters and the genes having the gene functions of frequent itemsets, interesting clues were discovered that provide valuable insight to biological scientists. Moreover, discovered association rules can be potentially used to predict gene functions based on similarity of gene expression maps.

An, Li; Obradovic, Zoran; Smith, Desmond; Bodenreider, Olivier; Megalooikonomou, Vasileios

2015-01-01

67

Common Functions or Only Phylogenetically Related? The Large Family of PLAC8 Motif-Containing/PCR Genes  

PubMed Central

PLAC8 motif-containing proteins form a large family and members can be found in fungi, algae, higher plants and animals. They include the PCR proteins of plants. The name giving PLAC8 domain was originally found in a protein residing in the spongiotrophoblast layer of the placenta of mammals. A further motif found in a large number of these proteins including several PCR proteins is the CCXXXXCPC or CLXXXXCPC motif. Despite their wide distribution our knowledge about the function of these proteins is very limited. For most of them two membranespanning ?-helices are predicted, indicating that they are membrane associated or membrane intrinsic proteins. In plants PLAC8 motif-containing proteins have been described to be implicated in two very different functions. On one hand, it has been shown that they are involved in the determination of fruit size and cell number. On the other hand, two members of this family, AtPCR1 and AtPCR2 play an important role in transport of heavy metals such as cadmium or zinc. Transport experiments and approaches to model the 3_D structure of these proteins indicate that they could act as transporters for these divalent cations by forming homomultimers. In this minireview we discuss the present knowledge about this protein family and try to give an outlook on how to integrate the different proposed functions into a common picture about the role of PLAC8 motif-containing proteins. PMID:21347707

Song, Won-Yong; Hörtensteiner, Stefan; Tomioka, Rie; Lee, Youngsook; Martinoia, Enrico

2011-01-01

68

Structural and functional association between substance P- and calcitonin gene-related peptide-immunoreactive nerves and accessory cells in the rat dental pulp.  

PubMed

Defense mechanisms of the dentin/pulp complex involve a variety of biological systems in which immunocompetent cells, the nervous system, and the vascular supply play important roles. In the present study, pulpal accessory cells were examined regarding (i) their structural relationship to nerves and (ii) how the functional capacities of these cells were affected by neuropeptides. Micro-anatomic association was investigated in the normal rat molar pulp with the use of double-immunofluorescence staining and dual-channel confocal laser scanning microscopy. Examinations of confocal laser scanning microscopic images from single focal planes revealed the presence of apparent contacts between thin, varicose nerve fibers and immunocompetent cells, indicating proximity between these two structures. The close associations were most frequently observed in the para-odontoblastic region of the coronal pulp, where more than 70% of class II antigen-expressing (OX6+) cells showed proximity to nerve fibers immunoreactive to calcitonin gene-related peptide. The corresponding figure for substance P was about 50%. ED2+ macrophages closely associated with nerves were less frequently observed. Functional studies conducted in vitro demonstrated that 10(-9) to 10(-7) mol/L of substance P significantly increased (p < 0.05), while 10(-7) to 10(-6) mol/L of calcitonin gene-related peptide suppressed (p < 0.01) proliferation of purified T-lymphocytes stimulated with sub-optimal concentrations of concanavalin A in the presence of rat incisor pulpal cells as accessory cells. These data suggest that pulpal sensory nerve fibers and their products may have an influence upon the immune defense of the dental pulp. PMID:9390474

Okiji, T; Jontell, M; Belichenko, P; Dahlgren, U; Bergenholtz, G; Dahlström, A

1997-12-01

69

Hammondia hammondi, an avirulent relative of Toxoplasma gondii, has functional orthologs of known T. gondii virulence genes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Toxoplasma gondii is a ubiquitous protozoan parasite capable of infecting all warm-blooded animals, including humans. Its closest extant relative, Hammondia hammondi, has never been found to infect humans and in contrast to T. gondii is highly attenuated in mice. To better understand the genetic bas...

70

A study on the functions of ubiquitin metabolic system related gene FBG2 in gastric cancer cell line  

PubMed Central

Background FBG2 (F-BOX6) gene is an important member in ubiquitin metabolic system F-BOX family, and forms E3 complex with the other members in the family. But its role in gastric cancer is still not clear. In the present study, we intended to investigate the influence of FBG2 on the growth, proliferation, apoptosis, invasion and cell cycle of the gastric cancer line MKN45 and gastric cell line HFE145. Methods As a critical component of ubiquitin-protein ligase complex, FBG2 cDNA was subcloned into a constitutive vector PCDNA3.1 followed by transfection in MKN45 and HFE145 by using liposome. Then stable transfectants were selected and appraised. The apoptosis and cell cycles of these clones were analyzed by using flow cytometry. The growth and proliferation were analyzed by cell growth curves and colony-forming assay respectively. The invasion of these clones was tested by using cancer cell migration assay. The FBG2 stable expression clones(MKN-FBG2 and HFE-FBG2) and their control groups were detected and compared respectively. Results MKN-FBG2 grew faster than MKN45 and MKN-PC(MKN45 transfected with PCDNA3.1 vector). HFE-FBG2 grew faster than HFE145 and HFE-PC(HFE145 transfected with PCDNA3.1 vector). The cell counts of MKN-FBG2 in the forth, fifth, sixth and seventh days were significantly more than those of others (P < 0.05). Cell cycle analysis showed that MKN-FBG2 and HFE-FBG2 proliferated faster, proportions of cells in G2-M and S were different significantly with control groups (P < 0.05). Results of colony-forming assay showed that the colony formation rates of MKN-FBG2 and HFE-FBG2 were higher than those of control groups (P < 0.05). The results of cell migration assay were all negative. Conclusion FBG2 can promote the growth and proliferation of gastric cancer cells and normal gastric cells. It can help tumor cell maintain malignant phenotype too. But it can have a negative influence on the apoptosis or the ability of invasion of gastric cancer cells. PMID:19515249

Zhang, Lin; Hou, Yanhong; Wang, Mengwei; Wu, Benyan; Li, Nan

2009-01-01

71

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

E-print Network

function based on gene expression data is much easier in prokaryotes than eukaryotes due to the relatively simple structure of prokaryotes. Recent studies have shown that there is a strong learnable correlation, especially in gene therapy [18]. Identifying gene function in prokaryotes is much easier than eukaryotes due

Morris, Quaid

72

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

73

Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy  

PubMed Central

Background Single-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms ? FAS ?670 A>G, FAS ligand ?844 T>C, survivin ?31 G>C, and survivin 9386 C>T – with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy. Materials and methods Polymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique. Results Patients with the CC genotype of FAS ?670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS ?670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively). Conclusion The functional FAS ?670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. PMID:25609982

Tao, Kai-Yi; Li, Xian-Xing; Xu, Wei-Zhen; Wang, Yin; Zhu, Shuang-Mei; Xie, Hua-Xia; Luo, Wen-Hua; Xu, Yan-Jun; Xu, Xiao-Ling

2015-01-01

74

Relational Descriptive Analysis of Gene Expression Data  

Microsoft Academic Search

This paper presents a method that uses gene ontologies, to- gether with the paradigm of relational subgroup discovery, to help nd description of groups of genes dieren tialy expressed in specic can- cers. The descriptions are represented by means of relational features, extracted from publicly available gene ontology information, and are straightforwardly interpretable by medical\\/biology researchers. We ap- plied the

Igor Trajkovski; Filip Zelezný; Nada Lavrac; Jakub Tolar

2006-01-01

75

Identification and Evaluation of Functional Modules in Gene Coexpression Networks  

Microsoft Academic Search

Identifying gene functional modules is an im- portant step towards elucidating gene func- tions at a global scale. In this paper, we introduce a simple method to construct gene co-expression networks from microarray data, and then propose an efficient spectral clustering algorithm to identify natural com- munities, which are relatively densely con- nected sub-graphs, in the network. To as- sess

Jianhua Ruan; Weixiong Zhang

2006-01-01

76

[The molecular evolution of rice stress-related genes].  

PubMed

In the processes of evolution, plants have formed a perfect regulation system to tolerate adverse environmental conditions. However, there has not been any report about the molecular evolution of rice stress-related genes. We derived a family of 22 stress-related genes in rice from Plant Stress Gene Database, and analyzed it by bioinformatics and comparative genome method. The results showed that these genes are relatively conservative in low organisms, and their copy numbers increase along with the environmental changes and the evolution. We also found four conserved sequence motifs and three other specific motifs. We propose that these motifs are closely associated with the function of rice stress-related genes. The analysis of selection pressure showed that about 50% rice stress-related genes have positive selection sites, although they were subject to a strong purifying selection. Positive selection sites might be very significant for plants to adapt to environmental changes. PMID:25406251

Song, Xiaojun; Xie, Kaibin; Zhang, Yanping; Jin, Ping

2014-10-01

77

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

78

Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development.  

PubMed

Drug lag, recently discussed extensively in Japan, can be divided into two phases: clinical development time and application review time. The former factor is still an important problem that might be improved by promoting multi-regional clinical trials and considering the results from other similar populations with Japanese, such as Koreans and Chinese. In this review, we compare the allelic or genotype frequencies of 30 relatively common functional alleles mainly between Eastern Asians and Europeans as well as among 3 major populations in Eastern Asian countries, Japan, Korea, and China, in 12 pharmacokinetics (PK)/pharmacodynamics (PD)-related genes; CYP2C9 (*2 and *3), CYP2C19 (*2, *3 and *17), 13 CYP2D6 haplotypes including *4, *5 and *10, CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5, *6 and *7), GSTM1 and GSTT1 null genotypes, SLCO1B1 521T>C, ABCG2 421C>A, and HLA-A*31:01 and HLA-B*58:01. In this review, differences in allele frequencies (AFs) or genotype frequencies (GFs) less than 0.1 (in the cases of highest AF (GF) ?0.1) or less than 0.05 (in the cases of lowest AF (GF) <0.1) were regarded as similar. Between Eastern Asians and Europeans, AFs (or GFs) are regarded as being different for many alleles such as CYP2C9 (*2), CYP2C19 (*2, *3 and *17), CYP2D6 (*4 and *10), CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5*7), GSTT1 null and ABCG2 421C>A. Among the 3 Eastern Asian populations, however, only AFs of CYP2C19*3, CYP2D6*10, HLA-A*31:01 and HLA-B*58:01 are regarded as dissimilar. For CYP2C19*3, the total functional impact on CYP2C19 could be small if the frequencies of the two null alleles CYP2C19*2 and *3 are combined. Regarding CYP2D6*10, frequency difference over 0.1 is observed only between Japanese and Chinese (0.147). Although environmental factors should be considered for PK/PD differences, we could propose that among Japan, Korea, and China, genetic differences are very small for the analyzed common PK-related gene polymorphisms. On the other hand, AFs of the two HLA alleles important for cutaneous adverse drug reactions are diverse even among Eastern Asians and thus should be taken into account. PMID:22123129

Kurose, Kouichi; Sugiyama, Emiko; Saito, Yoshiro

2012-01-01

79

Mapping and Functional Characterization of Candidate Genes  

E-print Network

Mapping and Functional Characterization of Candidate Genes and Mutations for Chicken Growth: GeneticAssociation) #12;Mapping and Functional Characterization of Candidate Genes and Mutations Karyotype 17! 2.4! Gene Mapping and Association Studies 19! 2.4.1! QTL Analysis 19! 2.4.2! Genome

80

Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of calcitonin gene-related peptide and adrenomedullin receptors.  

PubMed

Receptor activity-modifying proteins (RAMPs) enable calcitonin receptor-like receptor (CRLR) to function as a calcitonin gene-related peptide receptor (CRLR/RAMP1) or an adrenomedullin (AM) receptor (CRLR/RAMP2 or -3). Here we investigated the functions of the cytoplasmic C-terminal tails (C-tails) of human RAMP1, -2, and -3 (hRAMP1, -2, and -3) by cotransfecting their C-terminal deletion or progressive truncation mutants into HEK-293 cells stably expressing hCRLR. Deletion of the C-tail from hRAMP1 had little effect on the surface expression, function, or intracellular trafficking of the mutant heterodimers. By contrast, deletion of the C-tail from hRAMP2 disrupted transport of hCRLR to the cell surface, resulting in significant reductions in (125)I-hAM binding and evoked cAMP accumulation. The transfection efficiency for the hRAMP2 mutant was comparable with that for wild-type hRAMP2; moreover, immunocytochemical analysis showed that the mutant hRAMP2 remained within the endoplasmic reticulum. FACS analysis revealed that deleting the C-tail from hRAMP3 markedly enhances AM-evoked internalization of the mutant heterodimers, although there was no change in agonist affinity. Truncating the C-tails by removing the six C-terminal amino acids of hRAMP2 and -3 or exchanging their C-tails with one another had no effect on surface expression, agonist affinity, or internalization of hCRLR, which suggests that the highly conserved Ser-Lys sequence within hRAMP C-tails is involved in cellular trafficking of the two AM receptors. Notably, deleting the respective C-tails from hRAMPs had no effect on lysosomal sorting of hCRLR. Thus, the respective C-tails of hRAMP2 and -3 differentially affect hCRLR surface delivery and internalization. PMID:16410241

Kuwasako, Kenji; Cao, Yuan-Ning; Chu, Chun-Ping; Iwatsubo, Shuji; Eto, Tanenao; Kitamura, Kazuo

2006-03-17

81

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

82

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

E-print Network

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function and evolution- ary aspects of plastid chromosome architecture in land plants and their putative ancestors. We. Keywords Plastid genome Á Land plants Á Genome evolution Á Plastid gene function Á Gene retention

dePamphilis, Claude

83

Redundant Gene Functions and Natural Selection  

Microsoft Academic Search

Redundant gene functions are ubiquitous, and they are a potentially important source of evolutionary innovations on the biochemical level. It is therefore highly desirable to understand the mechanisms governing their evolution. Gene duplication is clearly a prominent mechanism generating redundant genes. However, because redundancy provides a protective effect against deleterious mutations, natural selection might be involved in generating and maintaining

Andreas Wagner

1997-01-01

84

DETECTING CANCER-RELATED GENES AND GENE-GENE INTERACTIONS BY MACHINE LEARNING METHODS  

E-print Network

..........................................................................................................1 1.1 SIGNIFICANCE OF DETECTING CANCER-RELATED GENES AND GENE-GENE INTERACTIONS ...1 1.2 MY CONTRIBUTION.................................................................................................................3 CHAPTER 2 BACKGROUND... AND RELATED WORK.................................................................8 2.1 DIFFERENTIAL GENE DETECTION...................................................................................................8 2.1.1 Statistical Methods for Detecting...

Han, Bing

2011-12-31

85

alpha7 Nicotinic receptor gene delivery into mouse hippocampal neurons leads to functional receptor expression, improved spatial memory-related performance, and tau hyperphosphorylation.  

PubMed

Brain alpha7 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 alpha7 receptor functions using a gene delivery approach based on neuron-selective recombinant adeno-associated virus (rAAV)-derived vectors. In order to determine whether alpha7 receptor-mediated cytotoxicity was dependent on receptor density, rat alpha7 nicotinic receptors were expressed at high concentrations in GH4C1 cells as measured with nicotine-displaceable [3H]methyllycaconitine (MLA) binding. The potency of GTS-21 (an alpha7 receptor agonist) to induce cell loss was similar in these cells to that seen in pheochromocytoma (PC12) cells expressing nine-times-lower receptor levels, suggesting that cytotoxicity was more dependent on agonist concentration than receptor density. Hippocampal transduction with rat alpha7 nicotinic receptors increased [3H]MLA binding in this region in wild type and alpha7 receptor-knockout (KO) mice without apparent cytotoxicity. No difference was observed in Kd values for MLA binding between endogenous and transgenic receptors. Single cell recordings demonstrated that dentate granule cells that normally have no alpha7 receptor response did so following alpha7 receptor gene delivery in wild type mice. Recovery of alpha7 function was also observed in stratum oriens and stratum radiatum neurons of KO mice following gene delivery. Wild type mice exhibited improved acquisition performance in the Morris water task 1 month after bilateral hippocampal transductions with the rat alpha7 receptor gene compared with green fluorescent protein-transduced controls. However, both groups reached similar training levels and there was no difference in subsequent probe performance. Finally, this gene delivery approach was used to test whether alpha7 receptors affect tau-phosphorylation. Chronic (i.e. 2 month but not 2 week) expression of high levels of alpha7 receptors in hippocampus increased AT8 staining characteristic of hyperphosphorylated tau in that region, indicating that endogenous agonist-mediated receptor activation may be able to modulate this process. PMID:17218065

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

2007-03-01

86

Gene Transfer Strategies for Augmenting Cardiac Function  

Microsoft Academic Search

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

Karsten Peppel; Walter J Koch; Robert J Lefkowitz

1997-01-01

87

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

88

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

89

Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.  

PubMed

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; Liu, Yu-Li

2013-10-01

90

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

91

Drug target-gene signatures that predict teratogenicity are enriched for developmentally related genes  

PubMed Central

Drugs prescribed during pregnancy affect two populations simultaneously: fetuses and their mothers. Drug-induced fetal injury (teratogenicity) has a significant impact on current and future public health. Teratogenic risk designation of many drugs relies on associating rare fetal events with rare environmental exposures. Therefore we aim to develop preclinical predictive models of clinical teratogenicity. We collated public databases for drug-target-gene relationships for 619 drugs spanning the 5 pregnancy risk classes. Genes targeted by high risk but not low risk drugs demonstrated 79% accuracy (p<0.0001 vs. random) for predicting high vs. low fetal risk on cross validation. Functional enrichment analysis revealed that target genes of drugs known to be safe in pregnancy contained no developmentally related terms, while target genes of known teratogens contained 85 developmentally related terms. Drug target gene signatures that are enriched for known developmental genes may provide valuable preclinical predictive information regarding drug pregnancy risk. PMID:21115113

Schachter, Asher D.; Kohane, Isaac S.

2010-01-01

92

Human Intellectual Disability Genes Form Conserved Functional Modules in Drosophila  

PubMed Central

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

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

2013-01-01

93

Functional identity of the gamma tropomyosin gene  

PubMed Central

The actin filament system is fundamental to cellular functions including regulation of shape, motility, cytokinesis, intracellular trafficking and tissue organization. Tropomyosins (Tm) are highly conserved components of actin filaments which differentially regulate filament stability and function. The mammalian Tm family consists of four genes; ?Tm, ?Tm, ?Tm and ?Tm. Multiple Tm isoforms (>40) are generated by alternative splicing and expression of these isoforms is highly regulated during development. In order to further identify the role of Tm isoforms during development, we tested the specificity of function of products from the ?Tm gene family in mice using a series of gene knockouts. Ablation of all ?Tm gene cytoskeletal products results in embryonic lethality. Elimination of just two cytoskeletal products from the ?Tm gene (NM1,2) resulted in a 50% reduction in embryo viability. It was also not possible to generate homozygous knockout ES cells for the targets which eliminated or reduced embryo viability in mice. In contrast, homozygous knockout ES cells were generated for a different set of isoforms (NM3,5,6,8,9,11) which were not required for embryogenesis. We also observed that males hemizygous for the knockout of all cytoskeletal products from the ?Tm gene preferentially transmitted the minus allele with 80–100% transmission. Since all four Tm genes are expressed in early embryos, ES cells and sperm, we conclude that isoforms of the ?Tm gene are functionally unique in their role in embryogenesis, ES cell viability and sperm function. PMID:21866263

Hook, Jeff; Lemckert, Frances; Schevzov, Galina; Fath, Thomas

2011-01-01

94

Evolutionary Approach for Relative Gene Expression Algorithms  

PubMed Central

A Relative Expression Analysis (RXA) uses ordering relationships in a small collection of genes and is successfully applied to classiffication using microarray data. As checking all possible subsets of genes is computationally infeasible, the RXA algorithms require feature selection and multiple restrictive assumptions. Our main contribution is a specialized evolutionary algorithm (EA) for top-scoring pairs called EvoTSP which allows finding more advanced gene relations. We managed to unify the major variants of relative expression algorithms through EA and introduce weights to the top-scoring pairs. Experimental validation of EvoTSP on public available microarray datasets showed that the proposed solution significantly outperforms in terms of accuracy other relative expression algorithms and allows exploring much larger solution space. PMID:24790574

Czajkowski, Marcin

2014-01-01

95

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

PubMed Central

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

2014-01-01

96

Functional requirements driving the gene duplication in 12 Drosophila species  

PubMed Central

Background Gene duplication supplies the raw materials for novel gene functions and many gene families arisen from duplication experience adaptive evolution. Most studies of young duplicates have focused on mammals, especially humans, whereas reports describing their genome-wide evolutionary patterns across the closely related Drosophila species are rare. The sequenced 12 Drosophila genomes provide the opportunity to address this issue. Results In our study, 3,647 young duplicate gene families were identified across the 12 Drosophila species and three types of expansions, species-specific, lineage-specific and complex expansions, were detected in these gene families. Our data showed that the species-specific young duplicate genes predominated (86.6%) over the other two types. Interestingly, many independent species-specific expansions in the same gene family have been observed in many species, even including 11 or 12 Drosophila species. Our data also showed that the functional bias observed in these young duplicate genes was mainly related to responses to environmental stimuli and biotic stresses. Conclusions This study reveals the evolutionary patterns of young duplicates across 12 Drosophila species on a genomic scale. Our results suggest that convergent evolution acts on young duplicate genes after the species differentiation and adaptive evolution may play an important role in duplicate genes for adaption to ecological factors and environmental changes in Drosophila. PMID:23945147

2013-01-01

97

Fungal avirulence genes: structure and possible functions.  

PubMed

Avirulence (Avr) genes exist in many fungi that share a gene-for-gene relationship with their host plant. They represent unique genetic determinants that prevent fungi from causing disease on plants that possess matching resistance (R) genes. Interaction between elicitors (primary or secondary products of Avr genes) and host receptors in resistant plants causes induction of various defense responses often involving a hypersensitive response. Avr genes have been successfully isolated by reverse genetics and positional cloning. Five cultivar-specific Avr genes (Avr4, Avr9, and Ecp2 from Cladosporium fulvum; nip1 from Rhynchosporium secalis; and Avr2-YAMO from Magnaporthe grisea) and three species-specific Avr genes (PWL1 and PWL2 from M. grisea and inf1 from Phytophthora infestans) have been cloned. Isolation of additional Avr genes from these fungi, but also from other fungi such as Uromyces vignae, Melampsora lini, Phytophthora sojae, and Leptosphaeria maculans, is in progress. Molecular analyses of nonfunctional Avr gene alleles show that these originate from deletions or mutations in the open reading frame or the promoter sequence of an Avr gene. Although intrinsic biological functions of most Avr gene products are still unknown, recent studies have shown that two Avr genes, nip1 and Ecp2, encode products that are important pathogenicity factors. All fungal Avr genes cloned so far have been demonstrated or predicted to encode extracellular proteins. Current studies focus on unraveling the mechanisms of perception of avirulence factors by plant receptors. The exploitation of Avr genes and the matching R genes in engineered resistance is also discussed. PMID:9756710

Laugé, R; De Wit, P J

1998-08-01

98

Rapid detection of Mycobacterium tuberculosis and pyrazinamide susceptibility related to pncA mutations in sputum specimens through an integrated gene-to-protein function approach.  

PubMed

Testing the pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis isolates is challenging. In a previous paper, we described the development of a rapid colorimetric test for the PZA susceptibility of M. tuberculosis by a PCR-based in vitro-synthesized-pyrazinamidase (PZase) assay. Here, we present an integrated approach to detect M. tuberculosis and PZA susceptibility directly from sputum specimens. M. tuberculosis was detected first, using a novel long-fragment quantitative real-time PCR (LF-qPCR), which amplified a fragment containing the whole pncA gene. Then, the positive amplicons were sequenced to find mutations in the pncA gene. For new mutations not found in the Tuberculosis Drug Resistance Mutation Database (www.tbdreamdb.com), the in vitro PZase assay was used to test the PZA resistance. This approach could detect M. tuberculosis within 3 h with a detection limit of 7.8 copies/reaction and report the PZA susceptibility within 2 days. In an initial testing of 213 sputum specimens, the LF-qPCR found 53 positive samples with 92% sensitivity and 97% specificity compared to the culture test for M. tuberculosis detection. DNA sequencing of the LF-qPCR amplicons revealed that 49 samples were PZA susceptible and 1 was PZA resistant. In the remaining 3 samples, with new pncA mutations, the in vitro PZase assay found that 1 was PZA susceptible and 2 were PZA resistant. This integrated approach provides a rapid, efficient, and relatively low-cost solution for detecting M. tuberculosis and PZA susceptibility without culture. PMID:24226918

Li, Heng; Chen, Jun; Zhou, Man; Geng, Xuelei; Yu, Junping; Wang, Weihua; Zhang, Xian-En; Wei, Hongping

2014-01-01

99

Rapid Detection of Mycobacterium tuberculosis and Pyrazinamide Susceptibility Related to pncA Mutations in Sputum Specimens through an Integrated Gene-to-Protein Function Approach  

PubMed Central

Testing the pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis isolates is challenging. In a previous paper, we described the development of a rapid colorimetric test for the PZA susceptibility of M. tuberculosis by a PCR-based in vitro-synthesized-pyrazinamidase (PZase) assay. Here, we present an integrated approach to detect M. tuberculosis and PZA susceptibility directly from sputum specimens. M. tuberculosis was detected first, using a novel long-fragment quantitative real-time PCR (LF-qPCR), which amplified a fragment containing the whole pncA gene. Then, the positive amplicons were sequenced to find mutations in the pncA gene. For new mutations not found in the Tuberculosis Drug Resistance Mutation Database (www.tbdreamdb.com), the in vitro PZase assay was used to test the PZA resistance. This approach could detect M. tuberculosis within 3 h with a detection limit of 7.8 copies/reaction and report the PZA susceptibility within 2 days. In an initial testing of 213 sputum specimens, the LF-qPCR found 53 positive samples with 92% sensitivity and 97% specificity compared to the culture test for M. tuberculosis detection. DNA sequencing of the LF-qPCR amplicons revealed that 49 samples were PZA susceptible and 1 was PZA resistant. In the remaining 3 samples, with new pncA mutations, the in vitro PZase assay found that 1 was PZA susceptible and 2 were PZA resistant. This integrated approach provides a rapid, efficient, and relatively low-cost solution for detecting M. tuberculosis and PZA susceptibility without culture. PMID:24226918

Li, Heng; Chen, Jun; Zhou, Man; Geng, Xuelei; Yu, Junping; Wang, Weihua; Zhang, Xian-En

2014-01-01

100

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

101

Gene finding using multiple related species: a classification approach. Manolis Kellis  

E-print Network

Gene finding using multiple related species: a classification approach. Manolis Kellis Special of functional human genes remains uncertain. Several expression-based analyses still argue for a hundred thousand transcribed genes, whereas more conservative estimates range between 20 and 25 thousand genes

Kellis, Manolis

102

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

103

Microarray analysis of genes and gene functions in disc degeneration  

PubMed Central

The aim of the present study was to screen differentially expressed genes (DEGs) in human degenerative intervertebral discs (IVDs), and to perform functional analysis on these DEGs. The gene expression profile was downloaded from the Gene Expression Omnibus database (GSE34095)and included six human IVD samples: three degenerative and three non-degenerative. The DEGs between the normal and disease samples were identified using R packages. The online software WebGestalt was used to perform the functional analysis of the DEGs, followed by Osprey software to search for interactions between the DEGs. The Database for Annotation, Visualization and Integrated Discovery was utilized to annotate the DEGs in the interaction network and then the DEGs were uploaded to the Connectivity Map database to search for small molecules. In addition, the active binding sites for the hub genes in the network were obtained, based on the Universal Protein database. By comparing the gene expression profiles of the non-degenerative and degenerative IVDs, the DEGs between the samples were identified. The DEGs were significantly associated with transforming growth factor ? and the extracellular matrix. Matrix metalloproteinase 2 (MMP2) was identified as the hub gene of the interaction network of DEGs. In addition, MMP2 was found to be upregulated in degenerative IVDs. The screened small molecules and the active binding sites of MMP2 may facilitate the development of methods to inhibit overexpression of MMP2. PMID:24396401

TANG, YANCHUN; WANG, SHAOKUN; LIU, YING; WANG, XUYUN

2014-01-01

104

Immune and ribosome related genes were associated with systemic vasculitis.  

PubMed

This study aimed to investigate the molecular mechanism of systemic vasculitis via bioinformatics analysis. Gene express profile of E-GEOD-16945 (13 Takayasu arteritis samples and 13 control samples) was downloaded from EBI (European Bioinformatics Institute) database. Differentially expressed genes (DEGs) were screened between Takayasu arteritis and normal controls (|log FC| >1). Basic local alignment search tool (BLASTX) was used for the COG (Clusters of Orthologous Groups) classification of DEGs. Gene ontology analysis was performed for the DEGs (p<0.05). A gene expression network was built with DEGs. Mcode in Cytoscape software was used to extract modules from the network (degree?2, K-core?2 and adjusted p-value <0.05) followed by pathway analysis using GenMAPP (false discovery rate <0.05). A total of 747 DEGs were identified. There were 16 significant GO function terms enriched with DEGs, out of which immune and defense response was the most significant GO term. Totally, 3 modules were extracted from gene expression network, including one module constituted with up-regulated genes and two modules constituted with down-regulated genes. Furthermore, human leukocyte antigen (HLA)-DRB1, HLA-DPA1, HLA-DPB1, HLA-DOA and HLA-DRA in the down-regulated modules were significantly linked to immune related pathways (Intestinal immune network for IgA production and Systemic lupus erythematosus pathways), while ribosomal protein L 31 (RPL31), RPS3A and RPL9 in the up-regulated module were enriched in ribosome pathway. The immune related pathways, ribosome pathway, immune-related genes including (HLA-DRB1, HLA-DPA1, HLA-DPB1, HLA-DOA and HLA-DRA) and ribosome related genes (RPL31, RPS3A and RPL9) might be involved in systemic vasculitis. This article is protected by copyright. All rights reserved. PMID:25410188

Gan, Shujie; Ye, Bo; Qian, Shuixian; Zhang, Ci; Mao, Jieqi; Li, Ke; Tang, Jingdong

2014-11-20

105

Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP).  

PubMed

Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (p<0.05) in mechanical behavioral and locomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2±2.3 to 1140.3±4.5pg/ml due to SCI and reached 789.1±2.7pg/ml after crocin treatment. These changes were significant at the level of p<0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain. PMID:24051216

Karami, Masoume; Bathaie, S Zahra; Tiraihi, Taqi; Habibi-Rezaei, Mehran; Arabkheradmand, Jalil; Faghihzadeh, Soghrat

2013-12-15

106

A search for growth related genes in Kalanchoë blossfeldiana.  

PubMed

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

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

2009-01-01

107

Studying Functions of All Yeast Genes Simultaneously  

NASA Technical Reports Server (NTRS)

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

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

2006-01-01

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

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

PubMed Central

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

2013-01-01

110

Fatty acid-related functions.  

PubMed

The first recommendations for specific nutrient quantities that must be obtained to support health were made by the US Department of Agriculture before 1939. Hazel Stiebeling was the leader of this effort and the scientific background was published in the Yearbook of Agriculture. The recommendations clearly stated that food must be available to provide the nutrients to support health. The science of nutrition in the United States is engaged in the most thorough review and reexamination of the recommended dietary allowances in at least a generation of nutrition scientists. There is a new awareness of nutrition complexity and the likelihood of identification of new essential nutrients. This meeting was devoted to the search for functional endpoints to reach quantitative estimates of dietary substances needed to support a function. Included in that concept is determining a range of individual needs and identifying factors that alter these needs. We give the rationale for endpoints of fatty acid metabolism related to platelets and the risk of thrombosis, give the rationale for the recommendation for a new nutrient, and show the necessity for including nutrient interaction in the determination of needs for two nutrients. PMID:8644699

Dupont, J; Holub, B J; Knapp, H R; Meydani, M

1996-06-01

111

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

PubMed Central

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

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

2014-01-01

112

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

113

Defining functional distances over Gene Ontology  

PubMed Central

Background A fundamental problem when trying to define the functional relationships between proteins is the difficulty in quantifying functional similarities, even when well-structured ontologies exist regarding the activity of proteins (i.e. 'gene ontology' -GO-). However, functional metrics can overcome the problems in the comparing and evaluating functional assignments and predictions. As a reference of proximity, previous approaches to compare GO terms considered linkage in terms of ontology weighted by a probability distribution that balances the non-uniform 'richness' of different parts of the Direct Acyclic Graph. Here, we have followed a different approach to quantify functional similarities between GO terms. Results We propose a new method to derive 'functional distances' between GO terms that is based on the simultaneous occurrence of terms in the same set of Interpro entries, instead of relying on the structure of the GO. The coincidence of GO terms reveals natural biological links between the GO functions and defines a distance model Df which fulfils the properties of a Metric Space. The distances obtained in this way can be represented as a hierarchical 'Functional Tree'. Conclusion The method proposed provides a new definition of distance that enables the similarity between GO terms to be quantified. Additionally, the 'Functional Tree' defines groups with biological meaning enhancing its utility for protein function comparison and prediction. Finally, this approach could be for function-based protein searches in databases, and for analysing the gene clusters produced by DNA array experiments. PMID:18221506

del Pozo, Angela; Pazos, Florencio; Valencia, Alfonso

2008-01-01

114

Transitive Functional Annotation by Shortest-path Analysis of Gene Expression Data  

Microsoft Academic Search

attribute to link genes of the same biological pathway. Based on large-scale yeast microarray expression data, we use the shortest-path analysis to identify transitive genes between two given genes from the same biological process. We find that not only functionally related genes with correlated expression profiles are identified but also those without. In the latter case, we compare our method

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

2002-01-01

115

Proteomics – post-genomic cartography to understand gene function  

Microsoft Academic Search

The completion of the genomic sequences of numerous organisms from human and mouse to Caenorhabditis elegans and many microorganisms, and the definition of their genes provides a database to interpret cellular protein-expression patterns and relate them to protein function. Proteomics technologies that are dependent on mass spectrometry and involve two-dimensional gel electrophoresis are providing the main window into the world

Soren Naaby-Hansen; Michael D. Waterfield; Rainer Cramer

2001-01-01

116

Functional analysis of the uropathogenic Escherichia coli R049 gene.  

PubMed

The objective of this study was to determine the function of the novel uropathogenic Escherichia coli (UPEC) gene R049 during host infection. We infected the urinary tracts of mice with E. coli UPEC132 or the R049 deletion mutant UPEC132?R049.The mouse kidneys were harvested at 4 and 8h post-infection and screened for differentially expressed genes by microarray analysis. We identified 379 and 515 differentially expressed genes at 4 and 8h post-infection, respectively. Thirty-four of these genes were associated with inflammatory and immune signaling pathways, including those related to mitogen-activated protein kinase signaling, leukocyte transendothelial migration, cytokine-cytokine receptor interaction, Toll-like receptor signaling, and apoptosis. Protein binding (GO 0005515) was the most prevalent molecular function in the Gene Ontology terms related to differentially expressed genes. In conclusion, R049 expression in UPEC132 is related to the early innate immune and inflammatory responses in UPEC-infected hosts. This work lays the foundation for further research on anti-infective immunity against UPEC. PMID:25644951

Yang, Dongjing; Dong, Jie; Su, Xu; Zhang, Wei; Zhang, Li; Li, Li; Lv, Likun; Guo, Liru

2015-02-01

117

The structure of a gene co-expression network reveals biological functions underlying eQTLs  

E-print Network

1 The structure of a gene co-expression network reveals biological functions underlying e.villa@toulouse.inra.fr Abstract 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

Paris-Sud XI, Université de

118

Norrie disease gene: Characterization of deletions and possible function  

SciTech Connect

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

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

1993-05-01

119

Rice functionality, starch structure and the genes  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

120

Functional gene diversity of oolitic sands from Great Bahama Bank.  

PubMed

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

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

2014-05-01

121

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

122

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

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

The systematic functional characterisation of Xq28 genes prioritises candidate disease genes  

PubMed Central

Background Well known for its gene density and the large number of mapped diseases, the human sub-chromosomal region Xq28 has long been a focus of genome research. Over 40 of approximately 300 X-linked diseases map to this region, and systematic mapping, transcript identification, and mutation analysis has led to the identification of causative genes for 26 of these diseases, leaving another 17 diseases mapped to Xq28, where the causative gene is still unknown. To expedite disease gene identification, we have initiated the functional characterisation of all known Xq28 genes. Results By using a systematic approach, we describe the Xq28 genes by RNA in situ hybridisation and Northern blotting of the mouse orthologs, as well as subcellular localisation and data mining of the human genes. We have developed a relational web-accessible database with comprehensive query options integrating all experimental data. Using this database, we matched gene expression patterns with affected tissues for 16 of the 17 remaining Xq28 linked diseases, where the causative gene is unknown. Conclusion By using this systematic approach, we have prioritised genes in linkage regions of Xq28-mapped diseases to an amenable number for mutational screens. Our database can be queried by any researcher performing highly specified searches including diseases not listed in OMIM or diseases that might be linked to Xq28 in the future. PMID:16503986

Kolb-Kokocinski, Anja; Mehrle, Alexander; Bechtel, Stephanie; Simpson, Jeremy C; Kioschis, Petra; Wiemann, Stefan; Wellenreuther, Ruth; Poustka, Annemarie

2006-01-01

125

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

126

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

127

Clock genes, pancreatic function, and diabetes.  

PubMed

Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic ? cells, glucose homeostasis, and diabetes. PMID:25457619

Vieira, Elaine; Burris, Thomas P; Quesada, Ivan

2014-11-01

128

Genotype and Gene Expression Associations with Immune Function in Drosophila  

PubMed Central

It is now well established that natural populations of Drosophila melanogaster harbor substantial genetic variation associated with physiological measures of immune function. In no case, however, have intermediate measures of immune function, such as transcriptional activity of immune-related genes, been tested as mediators of phenotypic variation in immunity. In this study, we measured bacterial load sustained after infection of D. melanogaster with Serratia marcescens, Providencia rettgeri, Enterococcus faecalis, and Lactococcus lactis in a panel of 94 third-chromosome substitution lines. We also measured transcriptional levels of 329 immune-related genes eight hours after infection with E. faecalis and S. marcescens in lines from the phenotypic tails of the test panel. We genotyped the substitution lines at 137 polymorphic markers distributed across 25 genes in order to test for statistical associations among genotype, bacterial load, and transcriptional dynamics. We find that genetic polymorphisms in the pathogen recognition genes (and particularly in PGRP-LC, GNBP1, and GNBP2) are most significantly associated with variation in bacterial load. We also find that overall transcriptional induction of effector proteins is a significant predictor of bacterial load after infection with E. faecalis, and that a marker upstream of the recognition gene PGRP-SD is statistically associated with variation in both bacterial load and transcriptional induction of effector proteins. These results show that polymorphism in genes near the top of the immune system signaling cascade can have a disproportionate effect on organismal phenotype due to the amplification of minor effects through the cascade. PMID:20066029

Sackton, Timothy B.; Lazzaro, Brian P.; Clark, Andrew G.

2010-01-01

129

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

130

Inferring gene transcriptional modulatory relations: a genetical genomics approach  

SciTech Connect

Bayesian network modeling is a promising approach to define and evaluate gene expression circuits in diverse tissues and cell types under different experimental conditions. The power and practicality of this approach can be improved by restricting the number of potential interactions among genes and by defining causal relations before evaluating posterior probabilities for billions of networks. A newly developed genetical genomics method that combines transcriptome profiling with complex trait analysis now provides strong constraints on network architecture. This method detects those chromosomal intervals responsible for differences in mRNA expression using quantitative trait locus (QTL) mapping. We have developed an efficient Bayesian approach that exploits the genetical genomics method to focus computational effort on the most plausible gene modulatory networks. We exploit a dense marker map for a genetic reference population (GRP) that consists of 32 BXD strains of mice made by intercrossing two progenitor strains- C57BL/6J and DBA/2J. These progenitors differ at 1.3 million known single nucleotide polymorphisms (SNPs), all of which can be exploited to estimate the probability that a gene contains functional polymorphisms that segregate within the GRP. We constructed 66 candidate networks that include all the candidate modulator genes located in the 209 statistically significant trans-acting QTL regions. SNPs that distinguish between the two progenitor strains were used to further winnow the list of candidate modulators. Bayesian network was then used to identify the genetic modulatory relations that best explain the microarray data.

Li, Hongqiang [University of Tennessee Health Science Center, Memphis; Lu, Lu [University of Tennessee Health Science Center, Memphis; Manly, Kenneth [University of Tennessee Health Science Center, Memphis; Chesler, Elissa J [ORNL; Bao, Lei [University of Tennessee Health Science Center, Memphis; Wang, Jintao [University of Tennessee Health Science Center, Memphis; Zhou, Mi [University of Tennessee Health Science Center, Memphis; Williams, Robert [University of Tennessee Health Science Center, Memphis; Cui, Yan [University of Tennessee Health Science Center, Memphis

2005-01-01

131

Identification of functional SNPs in the 5-prime flanking sequences of human genes  

Microsoft Academic Search

BACKGROUND: Over 4 million single nucleotide polymorphisms (SNPs) are currently reported to exist within the human genome. Only a small fraction of these SNPs alter gene function or expression, and therefore might be associated with a cell phenotype. These functional SNPs are consequently important in understanding human health. Information related to functional SNPs in candidate disease genes is critical for

Salim Mottagui-Tabar; Mohammad A Faghihi; Yosuke Mizuno; Pär G Engström; Boris Lenhard; Wyeth W Wasserman; Claes Wahlestedt

2005-01-01

132

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

PubMed

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

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

2012-04-01

133

Child ?-Opioid Receptor Gene Variant Influences Parent–Child Relations  

PubMed Central

Variation in the ?-opioid receptor gene has been associated with early social behavior in mice and rhesus macaques. The current study tested whether the functional OPRM1 A118G predicted various indices of social relations in children. The sample included 226 subjects of self-reported European ancestry (44% female; mean age 13.6, SD=2.2) who were part of a larger representative study of children aged 9–17 years in rural North Carolina. Multiple aspects of recent (past 3 months) parent–child relationship were assessed using the Child and Adolescent Psychiatric Assessment. Parent problems were coded based upon a lifetime history of mental health problems, substance abuse, or criminality. Child genotype interacted with parent behavior such that there were no genotype differences for those with low levels of parent problems; however, when a history of parent problems was reported, the G allele carriers had more enjoyment of parent–child interactions (mean ratio (MR)=3.5, 95% CI=1.6, 8.0) and fewer arguments (MR=3.1, 95% CI=1.1, 8.9). These findings suggest a role for the OPRM1 gene in the genetic architecture of social relations in humans. In summary, a variant in the ?-opioid receptor gene (118G) was associated with improved parent–child relations, but only in the context of a significant disruption in parental functioning. PMID:21326192

Copeland, William E; Sun, Hui; Costello, E Jane; Angold, Adrian; Heilig, Markus A; Barr, Christina S

2011-01-01

134

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

PubMed Central

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

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

2014-01-01

135

Migraine genes and the relation to gender.  

PubMed

Migraine is an episodic brain disorder that is characterized by recurrent attacks of severe unilateral headache that are accompanied by various neurological symptoms. In addition, many patients have what is called an aura with visual and sensory disturbances. The majority of patients are female, suggesting that female hormones play an important role in the pathophysiology of the disorder. The molecular mechanisms, however, underlying this female preponderance are not well understood. It can be expected that the field of genetics that aims at identifying genetic factors that cause migraine by lowering the threshold for attacks will unravel some of these mechanisms. The 3 best known migraine genes encode ion transporters and were identified in families with familial hemiplegic migraine (FHM), a rare subtype of migraine with aura. FHM gene mutations cause alterations in mechanisms that control and modulate the neurotransmitter balance in the brain. Transgenic mice knock-in with human pathogenic mutations that were shown to exhibit some migraine-relevant features were very helpful in dissecting molecular mechanisms of migraine and pointed to a central role for cortical glutamate. In addition, transgenic mice that overexpress human RAMP1 exist and exhibit an increased sensitivity to calcitonin gene-related peptide. Findings from genetic and animal experiments on gender differences in migraine are discussed. Recently, a role for glutamate also came forward from a genome-wide association study in common migraine. By deciphering genetic and pathogenic migraine pathways, it can be expected that in the near future we will better understand mechanisms behind the female preponderance in migraine. PMID:21631474

Shyti, Reinald; de Vries, Boukje; van den Maagdenberg, Arn

2011-06-01

136

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

137

HDL quality and functionality: what can proteins and genes predict?  

PubMed

Epidemiological and clinical studies have over the years established that dyslipidemia constitutes the main risk factor for atherosclerosis. The inverse correlation between HDL cholesterol (HDL-C) levels and coronary heart disease morbidity and mortality identified HDL-C as an alternative pharmacological target to LDL-C and a potential anti-atherosclerosis marker. However, more recent data reinforced the principle of 'HDL quality' in atherosclerosis that refers to the functionality of HDL particle, as defined by its protein and lipid content, rather than HDL-C levels in plasma. Since HDL functionality depends on the genes and proteins of the HDL metabolic pathway, its apoprotein composition may serve as a surrogate marker of atheroprotection. In this manuscript we review the atheroprotective properties of HDL in relation to the proteins of HDL metabolic pathway and discuss what HDL-associated genes and proteins may reveal about HDL functionality in the assessment of coronary risk. PMID:24650316

Karavia, Eleni A; Zvintzou, Evangelia; Petropoulou, Peristera-Ioanna; Xepapadaki, Eva; Constantinou, Caterina; Kypreos, Kyriakos E

2014-04-01

138

Relating Phylogenetic and Functional Diversity among Denitrifiers and Quantifying their Capacity to Predict Community Functioning  

PubMed Central

Genetic diversity of phylogenetic or functional markers is widely used as a proxy of microbial diversity. However, it remains unclear to what extent functional diversity (FD), gene sequence diversity and community functioning are linked. For a range of denitrifying bacteria, we analyzed the relationships between (i) the similarity of functional traits evaluated from metabolic profiles (BIOLOG plates) or from N2O accumulation patterns on different carbon sources and (ii) the similarity of phylogenetic (16S rRNA gene) or functional (nir gene) markers. We also calculated different proxies for the diversity of denitrifier community based on taxa richness, phylogenetic (16S rRNA gene) or functional similarities (based either on metabolic profiles or N2O accumulation patterns), and evaluated their performance in inferring the functioning of assembled denitrifying communities. For individual strains, the variation in the 16S rRNA gene sequence was weakly correlated with the variation in metabolic patterns (??=?0.35) and was not related to N2O accumulation. The latter was correlated with the similarity of nitrite reductase residues. When nir genes were analyzed separately, the similarity in amino acids coded by the nirS genes was highly correlated with the observed patterns of N2O accumulation (??=?0.62), whereas nirK amino acid residues were unrelated to N2O accumulation. For bacterial assemblages, phylogenetic diversity (average similarity among species in a community) and mean community dissimilarity (average distance between species) calculated using 16S rRNA gene sequences, and FD measures associated with metabolic profiles, poorly predicted the variation in the functioning of assembled communities (?15%). In contrast, the proxies of FD based on N2O accumulation patterns performed better and explained from 23 to 42% of the variation in denitrification. Amongst those, community niche was the best metric, indicating the importance of complementarity for resources in the context of bacterial community functioning. PMID:22701450

Salles, Joana Falcão; Le Roux, Xavier; Poly, Franck

2012-01-01

139

A family of genes related to a new expression site-associated gene in Trypanosoma equiperdum.  

PubMed Central

Two genes, belonging to a new expression site-associated gene family of six to eight members in Trypanosoma equiperdum and Trypanosoma brucei, have been cloned from a T. equiperdum variant. One of them, called ESAG-9c, is contained in the 1.78-C expression site and is found just upstream of the 5' barren region. The other one, called ESAG-9u, is unique in the family, is not telomere linked, and apparently is not expression site related. A 2-kb poly(A)+ mRNA is detected with probes for this ESAG-9 family in all T. equiperdum variants examined. By using polymerase chain reaction and restriction fragment length polymorphism techniques, it has been possible to distinguish between ESAG-9c and ESAG-9u and to show that ESAG-9c is transcribed in an expression site-specific manner. However, ESAG-9u (or another gene in the family having identical characteristics) is transcribed in all variants, regardless of the expression site used by these variants. Thus, this ESAG-9 family contains at least one gene that is under expression site control but might have other genes that are not. The function of these ESAG-9 genes is unknown. Transcripts homologous to ESAG-9 were detected in T. brucei bloodstream forms but not in procyclics. Images PMID:1672441

Florent, I C; Raibaud, A; Eisen, H

1991-01-01

140

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

141

Structure, function, and evolution of mouse TL genes, nonclassical class I genes of the major histocompatibility complex.  

PubMed Central

In contrast to well-studied "classical" class I genes of the major histocompatibility complex (MHC), the biology of nonclassical class I genes remains largely unexamined. The mouse TL genes constitute one of the best defined systems among nonclassical class I genes in the T region of the MHC. To elucidate the function and the evolution of TL genes and their relationship to classical class I genes, seven TL DNA sequences, including one from a Japanese wild mouse, were examined and compared with those of several mouse and human classical class I genes. The TL genes differ from either classical class I genes or pseudogenes in the extent and pattern of nucleotide substitutions. Natural selection appears to have operated so as to preserve the function of TL, which might have been acquired in an early stage of its evolution. In a putative peptide-binding region encoded by TL genes, the rate of nonsynonymous (amino acid replacing) substitution is considerably lower than that of synonymous substitution. This conservation is completely opposite that in classical class I genes, in which the peptide-binding region has evolved to diversify amino acid sequences so as to recognize a variety of antigens. Thus, it is suggested that the function of TL antigens is distinct from that of classical class I antigens and is related to the recognition of a relatively restricted repertoire of antigens and their presentation to T-cell receptors. Images PMID:8022824

Obata, Y; Satta, Y; Moriwaki, K; Shiroishi, T; Hasegawa, H; Takahashi, T; Takahata, N

1994-01-01

142

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

143

A conserved family of doublesex-related genes from fishes.  

PubMed

The sex-determining gene Mab-3 of C. elegans and the doublesex gene of Drosophila each contain a common DM domain and share a similar role. Human doublesex-related gene DMRT1 also encodes a conserved DM-related DNA-binding domain. We present here the amplification of a broad range of DM domain sequences from three fish species using degenerate PCR. Our results reveal unexpected complexity of the DM domain gene family in vertebrates. PMID:11932949

Huang, Xiao; Cheng, Hanhua; Guo, Yiqing; Liu, Li; Gui, Jianfang; Zhou, Rongjia

2002-04-15

144

Genomic Resources and Tools for Gene Function Analysis in Potato  

PubMed Central

Potato, a highly heterozygous tetraploid, is undergoing an exciting phase of genomics resource development. The potato research community has established extensive genomic resources, such as large expressed sequence tag (EST) data collections, microarrays and other expression profiling platforms, and large-insert genomic libraries. Moreover, potato will now benefit from a global potato physical mapping effort, which is serving as the underlying resource for a full potato genome sequencing project, now well underway. These tools and resources are having a major impact on potato breeding and genetics. The genome sequence will provide an invaluable comparative genomics resource for cross-referencing to the other Solanaceae, notably tomato, whose sequence is also being determined. Most importantly perhaps, a potato genome sequence will pave the way for the functional analysis of the large numbers of potato genes that await discovery. Potato, being easily transformable, is highly amenable to the investigation of gene function by biotechnological approaches. Recent advances in the development of Virus Induced Gene Silencing (VIGS) and related methods will facilitate rapid progress in the analysis of gene function in this important crop. PMID:19107214

Bryan, Glenn J.; Hein, Ingo

2008-01-01

145

Systematically characterizing and prioritizing chemosensitivity related gene based on Gene Ontology and protein interaction network  

PubMed Central

Background The identification of genes that predict in vitro cellular chemosensitivity of cancer cells is of great importance. Chemosensitivity related genes (CRGs) have been widely utilized to guide clinical and cancer chemotherapy decisions. In addition, CRGs potentially share functional characteristics and network features in protein interaction networks (PPIN). Methods In this study, we proposed a method to identify CRGs based on Gene Ontology (GO) and PPIN. Firstly, we documented 150 pairs of drug-CCRG (curated chemosensitivity related gene) from 492 published papers. Secondly, we characterized CCRGs from the perspective of GO and PPIN. Thirdly, we prioritized CRGs based on CCRGs’ GO and network characteristics. Lastly, we evaluated the performance of the proposed method. Results We found that CCRG enriched GO terms were most often related to chemosensitivity and exhibited higher similarity scores compared to randomly selected genes. Moreover, CCRGs played key roles in maintaining the connectivity and controlling the information flow of PPINs. We then prioritized CRGs using CCRG enriched GO terms and CCRG network characteristics in order to obtain a database of predicted drug-CRGs that included 53 CRGs, 32 of which have been reported to affect susceptibility to drugs. Our proposed method identifies a greater number of drug-CCRGs, and drug-CCRGs are much more significantly enriched in predicted drug-CRGs, compared to a method based on the correlation of gene expression and drug activity. The mean area under ROC curve (AUC) for our method is 65.2%, whereas that for the traditional method is 55.2%. Conclusions Our method not only identifies CRGs with expression patterns strongly correlated with drug activity, but also identifies CRGs in which expression is weakly correlated with drug activity. This study provides the framework for the identification of signatures that predict in vitro cellular chemosensitivity and offers a valuable database for pharmacogenomics research. PMID:23031817

2012-01-01

146

Functional and evolutionary correlates of gene constellations in the Drosophila melanogaster genome that deviate from the stereotypical gene architecture  

Microsoft Academic Search

BACKGROUND: The biological dimensions of genes are manifold. These include genomic properties, (e.g., X\\/autosomal linkage, recombination) and functional properties (e.g., expression level, tissue specificity). Multiple properties, each generally of subtle influence individually, may affect the evolution of genes or merely be (auto-)correlates. Results of multidimensional analyses may reveal the relative importance of these properties on the evolution of genes, and

Shuwei Li; Ching-Hua Shih; Michael H Kohn

2010-01-01

147

A Prototype System for Retrieval of Gene Functional Information  

PubMed Central

Microarrays allow researchers to gather data about the expression patterns of thousands of genes simultaneously. Statistical analysis can reveal which genes show statistically significant results. Making biological sense of those results requires the retrieval of functional information about the genes thus identified, typically a manual gene-by-gene retrieval of information from various on-line databases. For experiments generating thousands of genes of interest, retrieval of functional information can become a significant bottleneck. To address this issue, we are currently developing a prototype system to automate the process of retrieval of functional information from multiple on-line sources. PMID:14728346

Folk, Lillian C.; Patrick, Timothy B.; Pattison, James S.; Wolfinger, Russell D.; Mitchell, Joyce A.

2003-01-01

148

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

149

Functional genomics and molecular networks Gene expression regulations  

E-print Network

ontology categorization has allowed a more functional view on the list of differentially ex- pressed genes. Gene ontology now groups 28 154 terms with 19 913 for biological_process, 2 775 for cellular gene expression studies have always the same question in mind which is: what are the genes dif

150

Drosophila Genes That Affect Meiosis Duration Are among the Meiosis Related Genes That Are More Often Found Duplicated  

PubMed Central

Using a phylogenetic approach, the examination of 33 meiosis/meiosis-related genes in 12 Drosophila species, revealed nine independent gene duplications, involving the genes cav, mre11, meiS332, polo and mtrm. Evidence is provided that at least eight out of the nine gene duplicates are functional. Therefore, the rate at which Drosophila meiosis/meiosis-related genes are duplicated and retained is estimated to be 0.0012 per gene per million years, a value that is similar to the average for all Drosophila genes. It should be noted that by using a phylogenetic approach the confounding effect of concerted evolution, that is known to lead to overestimation of the duplication and retention rate, is avoided. This is an important issue, since even in our moderate size sample, evidence for long-term concerted evolution (lasting for more than 30 million years) was found for the meiS332 gene pair in species of the Drosophila subgenus. Most striking, in contrast to theoretical expectations, is the finding that genes that encode proteins that must follow a close stoichiometric balance, such as polo, mtrm and meiS332 have been found duplicated. The duplicated genes may be examples of gene neofunctionalization. It is speculated that meiosis duration may be a trait that is under selection in Drosophila and that it has different optimal values in different species. PMID:21423746

Reis, Micael; Sousa-Guimarães, Sofia; Vieira, Cristina P.; Sunkel, Cláudio E.; Vieira, Jorge

2011-01-01

151

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

Microsoft Academic Search

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

Bi-Qing Li; Tao Huang; Lei Liu; Yu-Dong Cai; Kuo-Chen Chou

2012-01-01

152

Phylogenetic and functional analysis of Arabidopsis RCI2 genes.  

PubMed

Six new Arabidopsis thaliana genes (AtRCI2C-H) have been identified that show high homology to AtRCI2A and AtRCI2B. Sequence comparisons revealed that AtRCI2-related genes are widely spread among very different organisms, including other plant species, prokaryotes, fungi, and simply organized animals, and are also organized in gene families. Most RCI2 genes show a similar exon-intron organization, which indicates that they have been structurally conserved during evolution, and encode small, highly hydrophobic proteins containing two putative transmembrane domains. Consistently, the majority of AtRCI2 proteins localize in the plasma membrane. RCI2 proteins exhibit an elevated level of sequence similarity and seem to have evolved from a common ancestor. In spite of their high similarity, conserved subcellular localization, and common origin, experimental evidence is presented suggesting that different RCI2 proteins may have distinct functional roles. Thus, as previously demonstrated for AtRCI2A and AtRCI2B, the newly identified AtRCI2 genes (AtRCI2C-H) are differentially regulated in Arabidopsis organs and in response to abiotic stresses and ABA treatment. Furthermore, only the AtRCI2 proteins that do not contain the C-terminal hydrophilic tail (i.e. AtRCI2A-C and AtRCI2H) are able to complement for the loss of the yeast AtRCI2-related gene PMP3. On the basis of these results, different aspects on the evolution and roles of RCI2 genes are discussed. PMID:18182435

Medina, Joaquín; Ballesteros, María Luisa; Salinas, Julio

2007-01-01

153

Classification using functional data analysis for temporal gene expression data  

Microsoft Academic Search

Motivation: Temporal gene expression profiles provide an important characterization of gene function, as biological systems are pre- dominantly developmental and dynamic. We propose a method of classifying collections of temporal gene expression curves in which individual expression profiles are modeled as independent realizati- ons of a stochastic process. The method uses a recently developed functional logistic regression tool based on

Xiaoyan Leng; Hans-georg Müller

2006-01-01

154

INVESTIGATION Gene Functional Trade-Offs and the Evolution  

E-print Network

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

Otto, Sarah

155

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

156

Inference of Gene Relations from Microarray Data by Abduction  

E-print Network

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

Sergot, Marek

157

Selecting Informative Genes from Microarray Dataset Using Fuzzy Relational Clustering  

NASA Astrophysics Data System (ADS)

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

Kasiri-Bidhendi, Soudeh; Shiry Ghidary, Saeed

158

Transport of magnesium by a bacterial Nramp-related gene.  

PubMed

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

Shin, Jung-Ho; Wakeman, Catherine A; Goodson, Jonathan R; Rodionov, Dmitry A; Freedman, Benjamin G; Senger, Ryan S; Winkler, Wade C

2014-06-01

159

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

160

Gene Coexpression Network Analysis as a Source of Functional Annotation for Rice Genes  

PubMed Central

With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa) gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional annotation of those modules. Additionally, the expression patterns of genes across the treatments/conditions of an expression experiment comprise a second form of useful annotation. PMID:21799793

Childs, Kevin L.; Davidson, Rebecca M.; Buell, C. Robin

2011-01-01

161

Cancer-Related Gene Therapy Clinical Trials  

Microsoft Academic Search

Gene therapy represents a strategy using transfer of genetic information to modify a population of target cells for therapeutic\\u000a purposes. The transferred genetic material has typically included double-stranded deoxyribonucleic acid (DNA), but occasionally\\u000a single-stranded DNA and even ribonucleic acid (RNA). Gene therapy represents one of the many novel “targeted” antineoplastic\\u000a treatment approaches with the goal to inhibit the growth of

Robert J. Korst; Ronald G. Crystal

162

Isolation of tumor suppressor genes from MEN-1 related neoplasms  

SciTech Connect

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

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

1994-09-01

163

Research article The functional landscape of mouse gene expression  

E-print Network

organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom function. Hundreds of functional categories, as defined by Gene Ontology `Biological Processes

Frey, Brendan J.

164

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 Magalhães, João Pedro

2012-01-01

165

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

166

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

167

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

Microsoft Academic Search

Inactivation of the Caenorhabditis elegans APC-related gene (apr-1) has pointed at two separate functions of apr-1. First, apr-1 is required for the migration of epithelial cells during morphogenesis of the embryo. In this process, APR-1 may act in a Cadherin\\/a-Catenin\\/b-Catenin complex as a component of adherens junctions. Second, apr-1 is required for Hox gene expression, most likely by positively regulating

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

2006-01-01

168

Mining functionally relevant gene sets for analyzing physiologically novel clinical expression data.  

PubMed

Gene set analyses have become a standard approach for increasing the sensitivity of transcriptomic studies. However, analytical methods incorporating gene sets require the availability of pre-defined gene sets relevant to the underlying physiology being studied. For novel physiological problems, relevant gene sets may be unavailable or existing gene set databases may bias the results towards only the best-studied of the relevant biological processes. We describe a successful attempt to mine novel functional gene sets for translational projects where the underlying physiology is not necessarily well characterized in existing annotation databases. We choose targeted training data from public expression data repositories and define new criteria for selecting biclusters to serve as candidate gene sets. Many of the discovered gene sets show little or no enrichment for informative Gene Ontology terms or other functional annotation. However, we observe that such gene sets show coherent differential expression in new clinical test data sets, even if derived from different species, tissues, and disease states. We demonstrate the efficacy of this method on a human metabolic data set, where we discover novel, uncharacterized gene sets that are diagnostic of diabetes, and on additional data sets related to neuronal processes and human development. Our results suggest that our approach may be an efficient way to generate a collection of gene sets relevant to the analysis of data for novel clinical applications where existing functional annotation is relatively incomplete. PMID:21121032

Turcan, Sevin; Vetter, Douglas E; Maron, Jill L; Wei, Xintao; Slonim, Donna K

2011-01-01

169

MINING FUNCTIONALLY RELEVANT GENE SETS FOR ANALYZING PHYSIOLOGICALLY NOVEL CLINICAL EXPRESSION DATA  

PubMed Central

Gene set analyses have become a standard approach for increasing the sensitivity of transcriptomic studies. However, analytical methods incorporating gene sets require the availability of pre-defined gene sets relevant to the underlying physiology being studied. For novel physiological problems, relevant gene sets may be unavailable or existing gene set databases may bias the results towards only the best-studied of the relevant biological processes. We describe a successful attempt to mine novel functional gene sets for translational projects where the underlying physiology is not necessarily well characterized in existing annotation databases. We choose targeted training data from public expression data repositories and define new criteria for selecting biclusters to serve as candidate gene sets. Many of the discovered gene sets show little or no enrichment for informative Gene Ontology terms or other functional annotation. However, we observe that such gene sets show coherent differential expression in new clinical test data sets, even if derived from different species, tissues, and disease states. We demonstrate the efficacy of this method on a human metabolic data set, where we discover novel, uncharacterized gene sets that are diagnostic of diabetes, and on additional data sets related to neuronal processes and human development. Our results suggest that our approach may be an efficient way to generate a collection of gene sets relevant to the analysis of data for novel clinical applications where existing functional annotation is relatively incomplete. PMID:21121032

Turcan, Sevin; Vetter, Douglas E.; Maron, Jill L.; Wei, Xintao; Slonim, Donna K.

2011-01-01

170

Epigenetic regulation of the calcitonin gene–related peptide gene in trigeminal glia  

PubMed Central

Background The neuropeptide calcitonin gene–related peptide (CGRP) plays a key role in migraine. CGRP gene expression involves an enhancer that is active in neurons, yet inactive in glia. In this report, we analyze epigenetic modifications that allow enhancer activation in glia. Methods DNA methylation and histone acetylation states were measured in rat and human-model cell lines and primary cultures of rat trigeminal ganglia glia. The functional consequence of altering the chromatin state was determined by quantitative measurements of both calcitonin (CT) and CGRP mRNAs. Results A hypermethylated CpG island flanking the enhancer was identified in glia and non-expressing cell lines. In addition, the chromatin was hypoacetylated. Treatment with the DNA methylation inhibitor 5-aza-2?-deoxycytidine induced CT mRNA ~30-fold in glial cultures. Treatment with a histone deacetylase inhibitor alone had little effect; however, the combination of inhibitors yielded a synergistic ~80-fold increase in CT and ~threefold increase in CGRP mRNA. Treated glia contained CT precursor (pro-CT) immunoreactivity. Conclusions Epigenetic modulation is sufficient to induce the CGRP gene in glia. Because the CGRP gene is systemically activated by inflammatory conditions, this suggests that glial pro-CT may be an unexplored biomarker during migraine. PMID:21216873

Park, Ki-Youb; Fletcher, Joshua R; Raddant, Ann C; Russo, Andrew F

2012-01-01

171

Global functional proling of gene expression  

Microsoft Academic Search

The typical result of a microarray experiment is a list of tens or hundreds of genes found to be dieren tially regulated in the condition under study. Independently of the methods used to select these genes, the common task faced by any researcher is to translate these lists of genes into a better understanding of the biological phenomena involved. Currently,

Sorin Draghici; Purvesh Khatri; Rui P. Martins; G. Charles Ostermeier; Stephen A. Krawetz

172

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

173

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

PubMed Central

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

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

2015-01-01

174

Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells  

PubMed Central

AIM: The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cycle-related, cell growth-related, stress response-related and transcription-related genes. METHODS: We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated (5 mg/mL, 24 h) and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT-PCR. RESULTS: Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F, member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE11A), topoisomerase (DNA) I (TOP1), and FK506 binding protein 12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. CONCLUSION: These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug. PMID:16127745

Park, Hae-Jeong; Yoon, Seo-Hyun; Han, Long-Shan; Zheng, Long-Tai; Jung, Kyung-Hee; Uhm, Yoon-Kyung; Lee, Je-Hyun; Jeong, Ji-Seon; Joo, Woo-Sang; Yim, Sung-Vin; Chung, Joo-Ho; Hong, Seon-Pyo

2005-01-01

175

Statistical analysis of genomic protein family and domain controlled annotations for functional investigation of classified gene lists  

Microsoft Academic Search

BACKGROUND: The increasing protein family and domain based annotations constitute important information to understand protein functions and gain insight into relations among their codifying genes. To allow analyzing of gene proteomic annotations, we implemented novel modules within GFINDer, a Web system we previously developed that dynamically aggregates functional and phenotypic annotations of user-uploaded gene lists and allows performing their statistical

Marco Masseroli; Elisa Bellistri; Andrea Franceschini; Francesco Pinciroli

2007-01-01

176

The estrogen-related receptors: orphans orchestrating myriad functions.  

PubMed

Coordinated and tight regulation of gene expression in metazoans is essential for cellular homeostasis and functions. Tissue- and cell-specific regulatory factors are indispensable and a wide variety of them exist to regulate genes. A family of transcriptional factors was identified in the past two decades through gene cloning studies and was informally referred as "orphan receptors", as appropriate endogenous ligands for such receptors were unknown. One of the subclasses of such receptors is known as the estrogen-related receptors (ERRs), which include three isoforms, namely ERR?, ERR? and ERR?. Over the past one decade, unprecedented knowledge about the ERRs biology has been generated, indicating their vital roles in various metabolic and physiological activities in animals. The ERRs cellular action is largely attributed to its interaction with a wide variety of other nuclear receptors, including some orphan nuclear receptors, and thereby can modulate diverse array of genes involved in metabolism and animal physiology. Studies using genome-wide location analyses, microarray and functional genomics, including ERR-specific null mice have revealed a number of pathways controlled by the ERRs. In this context, new and recent information on the biological functions of ERRs are being reviewed. PMID:22268851

Ranhotra, Harmit S

2012-04-01

177

Tissue-specific functions based on information content of gene ontology using cap analysis gene expression  

Microsoft Academic Search

Gene expressions differ depending on tissue types and developmental stages. Analyzing how each gene is expressed is thus important.\\u000a One way of analyzing gene expression patterns is to identify tissue-specific functions. This is useful for understanding how\\u000a vital activities are performed. DNA microarray has been widely used to observe gene expressions exhaustively. However, comparing\\u000a the expression value of a gene

Sami Maekawa; Atsuko Matsumoto; Yoichi Takenaka; Hideo Matsuda

2007-01-01

178

Geochip-Based Functional Gene Analysis of Anodophilic  

E-print Network

that the functional and phylogenetic diversity of MEC microbial communities after 4 months was quite high despite microbial diversity. Multivariateanalysesshowedthatcommunitiesthatdeveloped in the MECs were well separatedGeochip-Based Functional Gene Analysis of Anodophilic Communities in Microbial Electrolysis Cells

179

Complementation of an RNase P RNA (rnpB) gene deletion in Escherichia coli by homologous genes from distantly related eubacteria.  

PubMed Central

We report the construction of a strain of Escherichia coli in which the only functional gene for the RNA moiety of RNase P (rnpB) resides on a plasmid that is temperature sensitive for replication. The chromosomal RNase P RNA gene was replaced with a chloramphenicol acetyltransferase gene. The conditionally lethal phenotype of this strain was suppressed by plasmids that carry RNase P RNA genes from some distantly related eubacteria, including Alcaligenes eutrophus, Bacillus subtilis, and Chromatium vinosum. Thus, the rnpB genes from these organisms are capable of functioning as the sole source of RNase P RNA in E. coli. The rnpB genes of some other organisms (Agrobacterium tumefaciens, Pseudomonas fluorescens, Bacillus brevis, Bacillus megaterium, and Bacillus stearothermophilus) could not replace the E. coli gene. The significance of these findings as they relate to RNase P RNA structure and function and the utility of the described strain for genetic studies are discussed. Images PMID:1699929

Waugh, D S; Pace, N R

1990-01-01

180

Range of potential functions of the Drosophila melanogaster hdc gene  

Microsoft Academic Search

The Drosophila melanogaster hdc gene controls trachea branching, which starts during embryo development. Expression in imaginal disks and reproductive organs\\u000a suggests additional functions for the hdc gene. The gene was demonstrated to have a maternal effect, which was denied previously. Analysis of cell proliferation in\\u000a imaginal disks with hdc mutations showed that the gene does not possess tumor suppressor properties

A. M. Gusachenko; E. M. Akhmamet’eva; L. V. Omel’yanchuk

2006-01-01

181

Recent achievement in gene cloning and functional genomics in soybean.  

PubMed

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

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

2013-01-01

182

Gene expression modeling through positive boolean functions  

Microsoft Academic Search

Abstract In the framework of gene expression data analysis, the selection of biologically rel- evant sets of genes and the discovery of new subclasses of diseases at bio-molecular level represent two significant problems. Unfortunately, in both cases the correct solution is usually unknown,and the evaluation of the performance of gene selection and clustering methods is dicult,and in many cases unfeasible.

Francesca Ruffino; Marco Muselli; Giorgio Valentini

2008-01-01

183

Structural, functional, and evolutionary analysis of the unusually large stilbene synthase gene family in grapevine.  

PubMed

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

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

2012-11-01

184

Generalizing the spatial relative risk function.  

PubMed

The spatial relative risk function is defined as the ratio of densities describing respectively the spatial distribution of cases and controls. It has proven to be an effective tool for visualizing spatial variation in risk in many epidemiological applications over the past 20 years. We discuss the generalization of this function to spatio-temporal case-control data, and also to situations where there are covariates available that may affect the spatial patterns of disease. We examine estimation of the generalized relative risk functions using kernel smoothing, including asymptotic theory and data-driven bandwidth selection. We also consider construction of tolerance contours. Our methods are illustrated on spatio-temporal data describing the 2001 outbreak of foot-and-mouth disease in the United Kingdom, with farm size as a covariate. PMID:24606990

Sarojinie Fernando, W T P; Hazelton, Martin L

2014-04-01

185

Relating perturbation magnitude to temporal gene expression in biological systems  

Microsoft Academic Search

BACKGROUND: Most transcriptional activity is a result of environmental variability. This cause (environment) and effect (gene expression) relationship is essential to survival in any changing environment. The specific relationship between environmental perturbation and gene expression – and stability of the response – has yet to be measured in detail. We describe a method to quantitatively relate perturbation magnitude to response

Stephen J. Callister; J Jacob Parnell; Michael E. Pfrender; Syed A Hashsham

2009-01-01

186

Genetic Regulation of Caenorhabditis elegans Lysosome Related Organelle Function  

PubMed Central

Lysosomes are membrane-bound organelles that contain acid hydrolases that degrade cellular proteins, lipids, nucleic acids, and oligosaccharides, and are important for cellular maintenance and protection against age-related decline. Lysosome related organelles (LROs) are specialized lysosomes found in organisms from humans to worms, and share many of the features of classic lysosomes. Defective LROs are associated with human immune disorders and neurological disease. Caenorhabditis elegans LROs are the site of concentration of vital dyes such as Nile red as well as age-associated autofluorescence. Even though certain short-lived mutants have high LRO Nile red and high autofluorescence, and other long-lived mutants have low LRO Nile red and low autofluorescence, these two biologies are distinct. We identified a genetic pathway that modulates aging-related LRO phenotypes via serotonin signaling and the gene kat-1, which encodes a mitochondrial ketothiolase. Regulation of LRO phenotypes by serotonin and kat-1 in turn depend on the proton-coupled, transmembrane transporter SKAT-1. skat-1 loss of function mutations strongly suppress the high LRO Nile red accumulation phenotype of kat-1 mutation. Using a systems approach, we further analyzed the role of 571 genes in LRO biology. These results highlight a gene network that modulates LRO biology in a manner dependent upon the conserved protein kinase TOR complex 2. The results implicate new genetic pathways involved in LRO biology, aging related physiology, and potentially human diseases of the LRO. PMID:24204312

Soukas, Alexander A.; Carr, Christopher E.; Ruvkun, Gary

2013-01-01

187

Predicting function: from genes to genomes and back1  

Microsoft Academic Search

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

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

1998-01-01

188

Calcitonin gene-related peptide: physiology and pathophysiology.  

PubMed

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (? and ?). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule. PMID:25287861

Russell, F A; King, R; Smillie, S-J; Kodji, X; Brain, S D

2014-10-01

189

The Complete Spectrum of Yeast Chromosome Instability Genes Identifies Candidate CIN Cancer Genes and Functional Roles for ASTRA Complex Components  

PubMed Central

Chromosome instability (CIN) is observed in most solid tumors and is linked to somatic mutations in genome integrity maintenance genes. The spectrum of mutations that cause CIN is only partly known and it is not possible to predict a priori all pathways whose disruption might lead to CIN. To address this issue, we generated a catalogue of CIN genes and pathways by screening ?2,000 reduction-of-function alleles for 90% of essential genes in Saccharomyces cerevisiae. Integrating this with published CIN phenotypes for other yeast genes generated a systematic CIN gene dataset comprised of 692 genes. Enriched gene ontology terms defined cellular CIN pathways that, together with sequence orthologs, created a list of human CIN candidate genes, which we cross-referenced to published somatic mutation databases revealing hundreds of mutated CIN candidate genes. Characterization of some poorly characterized CIN genes revealed short telomeres in mutants of the ASTRA/TTT components TTI1 and ASA1. High-throughput phenotypic profiling links ASA1 to TTT (Tel2-Tti1-Tti2) complex function and to TORC1 signaling via Tor1p stability, consistent with the role of TTT in PI3-kinase related kinase biogenesis. The comprehensive CIN gene list presented here in principle comprises all conserved eukaryotic genome integrity pathways. Deriving human CIN candidate genes from the list allows direct cross-referencing with tumor mutational data and thus candidate mutations potentially driving CIN in tumors. Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease. PMID:21552543

Stirling, Peter C.; Bloom, Michelle S.; Solanki-Patil, Tejomayee; Smith, Stephanie; Sipahimalani, Payal; Li, Zhijian; Kofoed, Megan; Ben-Aroya, Shay; Myung, Kyungjae; Hieter, Philip

2011-01-01

190

Functional Hypervariability and Gene Diversity of Cardioactive Neuropeptides*  

PubMed Central

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

2010-01-01

191

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

192

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

193

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

194

FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY  

PubMed Central

Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. PMID:22473061

Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

2010-01-01

195

Sexual Dimorphism in the Expression of Mitochondria-Related Genes in Rat Heart at Different Ages  

PubMed Central

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males. PMID:25615628

Vijay, Vikrant; Han, Tao; Moland, Carrie L.; Kwekel, Joshua C.; Fuscoe, James C.; Desai, Varsha G.

2015-01-01

196

Gene Coexpression Network Analysis as a Source of Functional Annotation for Rice Genes  

Microsoft Academic Search

With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions\\/treatments have also been used to create coexpression networks to help

Kevin L. Childs; Rebecca M. Davidson; C. Robin Buell

2011-01-01

197

Saliva Microbiota Carry Caries-Specific Functional Gene Signatures  

PubMed Central

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

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

2014-01-01

198

Saliva microbiota carry caries-specific functional gene signatures.  

PubMed

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

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

2014-01-01

199

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

200

The evolution of reproduction-related NLRP genes.  

PubMed

NLRP proteins are important components of inflammasomes with a major role in innate immunity. A subset of NLRP genes, with unknown functions, are expressed in oocytes and early embryos. Mutations of Nlrp5 in mice are associated with maternal-effect embryonic lethality and mutations of NLRP7 in women are associated with conception of biparental complete hydatidiform moles (biCHMs), suggesting perturbed processes of genomic imprinting. Recessive mutations on NLRP2/7 in humans are associated with reproductive disorders and appear to be induced by a demethylation of the maternal pronucleus. In this study, we find that radiation of NLRP genes occurred before the common ancestor of Afrotheria and Boreoeutheria, with the clade of oocyte-expressed genes originating before the divergence of marsupial and eutherian mammals. There have been multiple independent duplications of NLRP2 genes one of which produced the NLRP7 gene associated with biCHMs. PMID:24615281

Duéñez-Guzmán, Edgar A; Haig, David

2014-04-01

201

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

202

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

PubMed

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

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

2007-06-01

203

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

204

Selecting causal genes from genome-wide association studies via functionally coherent subnetworks.  

PubMed

Genome-wide association (GWA) studies have linked thousands of loci to human diseases, but the causal genes and variants at these loci generally remain unknown. Although investigators typically focus on genes closest to the associated polymorphisms, the causal gene is often more distal. Reliance on published work to prioritize candidates is biased toward well-characterized genes. We describe a 'prix fixe' strategy and software that uses genome-scale shared-function networks to identify sets of mutually functionally related genes spanning multiple GWA loci. Using associations from ?100 GWA studies covering ten cancer types, our approach outperformed the common alternative strategy in ranking known cancer genes. As more GWA loci are discovered, the strategy will have increased power to elucidate the causes of human disease. PMID:25532137

Ta?an, Murat; Musso, Gabriel; Hao, Tong; Vidal, Marc; MacRae, Calum A; Roth, Frederick P

2015-02-01

205

Functionally Enigmatic Genes: A Case Study of the Brain Ignorome  

PubMed Central

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

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

2014-01-01

206

An improved chemically inducible gene switch that functions in the monocotyledonous plant sugar cane.  

PubMed

Chemically inducible gene switches can provide precise control over gene expression, enabling more specific analyses of gene function and expanding the plant biotechnology toolkit beyond traditional constitutive expression systems. The alc gene expression system is one of the most promising chemically inducible gene switches in plants because of its potential in both fundamental research and commercial biotechnology applications. However, there are no published reports demonstrating that this versatile gene switch is functional in transgenic monocotyledonous plants, which include some of the most important agricultural crops. We found that the original alc gene switch was ineffective in the monocotyledonous plant sugar cane, and describe a modified alc system that is functional in this globally significant crop. A promoter consisting of tandem copies of the ethanol receptor inverted repeat binding site, in combination with a minimal promoter sequence, was sufficient to give enhanced sensitivity and significantly higher levels of ethanol inducible gene expression. A longer CaMV 35S minimal promoter than was used in the original alc gene switch also substantially improved ethanol inducibility. Treating the roots with ethanol effectively induced the modified alc system in sugar cane leaves and stem, while an aerial spray was relatively ineffective. The extension of this chemically inducible gene expression system to sugar cane opens the door to new opportunities for basic research and crop biotechnology. PMID:24142380

Kinkema, Mark; Geijskes, R Jason; Shand, Kylie; Coleman, Heather D; De Lucca, Paulo C; Palupe, Anthony; Harrison, Mark D; Jepson, Ian; Dale, James L; Sainz, Manuel B

2014-03-01

207

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

208

Automated Discovery of Functional Generality of Human Gene Expression Programs  

E-print Network

expression datasets measuring the responses of human cells to infectious agents or immuneAutomated Discovery of Functional Generality of Human Gene Expression Programs Georg K. Gerber1 is the identification of expression programs, sets of co- expressed genes orchestrating normal or pathological processes

Williams, Brian C.

209

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

PubMed

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

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

2014-06-01

210

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

PubMed Central

Vesicle transport occurs in the cytosol through a COPI, COPII and 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, or 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 COPII related proteins to be putatively chloroplast localized in Arabidopsis and thus function in vesicle transport in chloroplasts. Here we present gene expression profiles of these COPII related putatively chloroplast localized proteins using Genevestigator (https://www.genevestigator.com/gv/) with special emphasis on Rab related proteins since they represent several stages of vesicle transport e.g., uncoating, tethering and fusion. PMID:24577429

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

2014-01-01

211

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

E-print Network

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

Weigel, Detlef

212

The genomic and functional characteristics of disease genes.  

PubMed

Increasing evidence indicates that genes containing disease causal variation have distinct functional and genomic properties. The importance of understanding these properties is highlighted by efforts to filter lists of variants from next-generation sequencing studies, where the number of potentially deleterious variants, which are in fact unrelated to disease, may be large. Available evidence indicates that the majority of disease genes are 'non-essential' and their products occupy functionally peripheral positions in protein networks. They tend to be intermediate between genes that have core biological functions, particularly low mutation rates and low haplotype diversity, and genes for which high haplotype diversity and high mutation rates are advantageous (such as those involved in sensory perception and some immune system functions). Evidence presented here supports these conclusions through analysis of integrated data sets incorporating the latest mutational profiles, linkage disequilibrium structure and other genomic properties of individual genes. The analysis highlights the contrasting functions of genes predicted as least and most likely to contain disease variation and provides a basis for filtering gene variant lists to exclude the least plausible disease candidates. PMID:24425794

Collins, Andrew

2015-01-01

213

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

214

A Graphic Method for Identification of Novel Glioma Related Genes  

PubMed Central

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

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

2014-01-01

215

A graphic method for identification of novel glioma related genes.  

PubMed

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

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

2014-01-01

216

Functional gene-set analysis does not support a major role for synaptic function in attention deficit/hyperactivity disorder (ADHD).  

PubMed

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

217

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

218

Consequences of recurrent gene flow from crops to wild relatives.  

PubMed

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

2003-09-22

219

Genome-wide identification and functional analyses of calmodulin genes in Solanaceous species  

PubMed Central

Background Calmodulin (CaM) is a major calcium sensor in all eukaryotes. It binds calcium and modulates the activity of a wide range of downstream proteins in response to calcium signals. However, little is known about the CaM gene family in Solanaceous species, including the economically important species, tomato (Solanum lycopersicum), and the gene silencing model plant, Nicotiana benthamiana. Moreover, the potential function of CaM in plant disease resistance remains largely unclear. Results We performed genome-wide identification of CaM gene families in Solanaceous species. Employing bioinformatics approaches, multiple full-length CaM genes were identified from tomato, N. benthamiana and potato (S. tuberosum) genomes, with tomato having 6 CaM genes, N. benthamiana having 7 CaM genes, and potato having 4 CaM genes. Sequence comparison analyses showed that three tomato genes, SlCaM3/4/5, two potato genes StCaM2/3, and two sets of N. benthamiana genes, NbCaM1/2/3/4 and NbCaM5/6, encode identical CaM proteins, yet the genes contain different intron/exon organization and are located on different chromosomes. Further sequence comparisons and gene structural and phylogenetic analyses reveal that Solanaceous species gained a new group of CaM genes during evolution. These new CaM genes are unusual in that they contain three introns in contrast to only a single intron typical of known CaM genes in plants. The tomato CaM (SlCaM) genes were found to be expressed in all organs. Prediction of cis-acting elements in 5' upstream sequences and expression analyses demonstrated that SlCaM genes have potential to be highly responsive to a variety of biotic and abiotic stimuli. Additionally, silencing of SlCaM2 and SlCaM6 altered expression of a set of signaling and defense-related genes and resulted in significantly lower resistance to Tobacco rattle virus and the oomycete pathogen, Pythium aphanidermatum. Conclusions The CaM gene families in the Solanaceous species tomato, N. benthamiana and potato were identified through a genome-wide analysis. All three plant species harbor a small set of genes that encode identical CaM proteins, which may manifest a strategy of plants to retain redundancy or enhanced quantitative gene function. In addition, Solanaceous species have evolved one new group of CaM genes during evolution. CaM genes play important roles in plant disease resistance to a variety of pathogens. PMID:23621884

2013-01-01

220

Organization of Gene Function in Bacillus subtilis Bacteriophage SP82G 1  

PubMed Central

A generalized assessment of the functions of 26 genes of SP82G, a bacteriophage of Bacillus subtilis, has been made. The production of phage-specific deoxyribonucleic acid (DNA), DNA-filled phage heads, completed phage particles, phage-specific antigen, and developmental aberrations has been examined in lysates of temperature-sensitive mutants grown under selective conditions. The genes show a tendency to occur on the genome in three groups of related function: genes involved with DNA synthesis, with tail synthesis, and with head synthesis. Images PMID:4113884

Green, D. MacDonald; Laman, David

1972-01-01

221

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

222

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease  

PubMed Central

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

223

Functions of the gene products of Escherichia coli.  

PubMed Central

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

Riley, M

1993-01-01

224

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

PubMed Central

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

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

2008-01-01

225

Using PPI network autocorrelation in hierarchical multi-label classification trees for gene function prediction  

PubMed Central

Background Ontologies and catalogs of gene functions, such as the Gene Ontology (GO) and MIPS-FUN, assume that functional classes are organized hierarchically, that is, general functions include more specific ones. This has recently motivated the development of several machine learning algorithms for gene function prediction that leverages on this hierarchical organization where instances may belong to multiple classes. In addition, it is possible to exploit relationships among examples, since it is plausible that related genes tend to share functional annotations. Although these relationships have been identified and extensively studied in the area of protein-protein interaction (PPI) networks, they have not received much attention in hierarchical and multi-class gene function prediction. Relations between genes introduce autocorrelation in functional annotations and violate the assumption that instances are independently and identically distributed (i.i.d.), which underlines most machine learning algorithms. Although the explicit consideration of these relations brings additional complexity to the learning process, we expect substantial benefits in predictive accuracy of learned classifiers. Results This article demonstrates the benefits (in terms of predictive accuracy) of considering autocorrelation in multi-class gene function prediction. We develop a tree-based algorithm for considering network autocorrelation in the setting of Hierarchical Multi-label Classification (HMC). We empirically evaluate the proposed algorithm, called NHMC (Network Hierarchical Multi-label Classification), on 12 yeast datasets using each of the MIPS-FUN and GO annotation schemes and exploiting 2 different PPI networks. The results clearly show that taking autocorrelation into account improves the predictive performance of the learned models for predicting gene function. Conclusions Our newly developed method for HMC takes into account network information in the learning phase: When used for gene function prediction in the context of PPI networks, the explicit consideration of network autocorrelation increases the predictive performance of the learned models. Overall, we found that this holds for different gene features/ descriptions, functional annotation schemes, and PPI networks: Best results are achieved when the PPI network is dense and contains a large proportion of function-relevant interactions. PMID:24070402

2013-01-01

226

Structure and function of the deleted in azoospermia gene  

E-print Network

A number of genes have been associated with variation in human spermatogenesis related to fertility. One of these, the Deleted in Azoospermia (DAZ) gene, exists as copies on two chromosomes, 3 and Y. The autosomal copy, DAZ-like (DAZL), has one RNA...

Sprague, David Chase Cameron

2009-05-15

227

Identifying and prioritizing disease-related genes based on the network topological features.  

PubMed

Identifying and prioritizing disease-related genes are the most important steps for understanding the pathogenesis and discovering the therapeutic targets. The experimental examination of these genes is very expensive and laborious, and usually has a higher false positive rate. Therefore, it is highly desirable to develop computational methods for the identification and prioritization of disease-related genes. In this study, we develop a powerful method to identify and prioritize candidate disease genes. The novel network topological features with local and global information are proposed and adopted to characterize genes. The performance of these novel features is verified based on the 10-fold cross-validation test and leave-one-out cross-validation test. The proposed features are compared with the published features, and fused strategy is investigated by combining the current features with the published features. And, these combination features are also utilized to identify and prioritize Parkinson's disease-related genes. The results indicate that identified genes are highly related to some molecular process and biological function, which provides new clues for researching pathogenesis of Parkinson's disease. The source code of Matlab is freely available on request from the authors. PMID:25183318

Li, Zhan-Chao; Lai, Yan-Hua; Chen, Li-Li; Xie, Yun; Dai, Zong; Zou, Xiao-Yong

2014-08-23

228

Functional gene array-based analysis of microbial communities in heavy metals-contaminated lake sediments.  

PubMed

Lake DePue (IL, USA) has been contaminated for > 80 years by an adjacent Zn-smelting facility. Previous work indicated that sulfate reduction increased and biomass declined as pore-water metal concentrations increased, while 16S rRNA gene profiles remained relatively stable. To better understand this phenomenon, the sediment microbial community structure and functional potential were investigated using a functional gene microarray (GeoChip) targeting > 10,000 functional genes. Nonmetric multidimensional scaling and clustering analyses showed that the overall community structure was similar across all sites based on the relative abundance of all detected genes, but some individual gene categories did show differences. A subset of sulfate reduction genes (dsr) and the most relevant metal resistance genes were more abundant than other categories and were highly correlated with metal contamination. The most significant correlations were between pore-water metal concentrations and dsr, with Zn, Cd, and Mn as the most predictive for the presence of dsr. These results suggest that metal contamination influences sediment microbial community structure and function by increasing the abundance of relevant metal-resistant and sulfate-reducing populations. These populations therefore appear to contribute significantly to the resistance and stability of the microbial communities throughout the gradient of metal contamination in Lake DePue. PMID:23710534

Kang, Sanghoon; Van Nostrand, Joy D; Gough, Heidi L; He, Zhili; Hazen, Terry C; Stahl, David A; Zhou, Jizhong

2013-11-01

229

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 LESSARD sequence, we have developed bioinformatics tools that can be run on a desktop computer and save significant

Sinskey, Anthony J.

230

Age and Gender Related Differences in Human Parotid Gland Gene Expression  

PubMed Central

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

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

2008-01-01

231

Functional genomics: Gene identification via T-DNA mediated gene trap tagging in plants  

Microsoft Academic Search

The fully sequenced genomes of Arabidopsis, rice, tomato, potato, maize, wheat, and soybean offer large amounts of information\\u000a about cellular and developmental biology. It is a central challenge of genomics to use this information in discovering the\\u000a function of proteins and identifying developmentally important genes. Although classical genetic approaches to gene identification\\u000a which rely on disruption of a gene leading

Tang Wei; Vanessa Samuels; Janet Ogbon; Aquilla McCoy

2001-01-01

232

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

PubMed Central

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

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

2014-01-01

233

Capsaicin-sensitive sensory neurons regulate myocardial function and gene expression pattern of rat hearts: a DNA microarray study  

Microsoft Academic Search

We have previously shown that capsaicin-sensitive sensory nerves contribute to the regulation of normal cardiac function and to the development of cardiac adaptation to ischemic stress; however, the underlying molecular mechanisms remain unknown. Therefore, here we assessed cardiac functional alterations and relative gene expression changes by DNA microarray analysis of 6400 genes in rat hearts 7 days after the end

A. Zvara; Péter Bencsik; Gabriella Fodor; Tamás Csont; László Hackler; Mária Dux; Susanna Fürst; Gábor Jancsó; László G. Puskás; Péter Ferdinandy

2005-01-01

234

Symbiosis-related pea genes modulate fungal and plant gene expression during the arbuscule stage of mycorrhiza with Glomus intraradices  

Microsoft Academic Search

The arbuscular mycorrhiza association results from a successful interaction between genomes of the plant and fungal symbiotic\\u000a partners. In this study, we analyzed the effect of inactivation of late-stage symbiosis-related pea genes on symbiosis-associated\\u000a fungal and plant molecular responses in order to gain insight into their role in the functional mycorrhizal association. The\\u000a expression of a subset of ten fungal

Elena Kuznetsova; Pascale M. A. Seddas-Dozolme; Christine Arnould; Marie Tollot; Diederik van Tuinen; Alexey Borisov; Silvio Gianinazzi; Vivienne Gianinazzi-Pearson

2010-01-01

235

Age-related gene expression in Tourette syndrome  

PubMed Central

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

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

2009-01-01

236

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

237

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

238

Rapid Determination of Gene Function by Virus-Induced Gene Silencing in Wheat and Barley  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

239

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

240

Gene evolution and functions of extracellular matrix proteins in teeth  

PubMed Central

The extracellular matrix (ECM) not only provides physical support for tissues, but it is also critical for tissue development, homeostasis and disease. Over 300 ECM molecules have been defined as comprising the “core matrisome” in mammals through the analysis of whole genome sequences. During tooth development, the structure and functions of the ECM dynamically change. In the early stages, basement membranes (BMs) separate two cell layers of the dental epithelium and the mesenchyme. Later in the differentiation stages, the BM layer is replaced with the enamel matrix and the dentin matrix, which are secreted by ameloblasts and odontoblasts, respectively. The enamel matrix genes and the dentin matrix genes are each clustered in two closed regions located on human chromosome 4 (mouse chromosome 5), except for the gene coded for amelogenin, the major enamel matrix protein, which is located on the sex chromosomes. These genes for enamel and dentin matrix proteins are derived from a common ancestral gene, but as a result of evolution, they diverged in terms of their specific functions. These matrix proteins play important roles in cell adhesion, polarity, and differentiation and mineralization of enamel and dentin matrices. Mutations of these genes cause diseases such as odontogenesis imperfect (OI) and amelogenesis imperfect (AI). In this review, we discuss the recently defined terms matrisome and matrixome for ECMs, as well as focus on genes and functions of enamel and dentin matrix proteins. PMID:23539364

Yoshizaki, Keigo; Yamada, Yoshihiko

2013-01-01

241

Transferred interbacterial antagonism genes augment eukaryotic innate immune function.  

PubMed

Horizontal gene transfer allows organisms to rapidly acquire adaptive traits. Although documented instances of horizontal gene transfer from bacteria to eukaryotes remain rare, bacteria represent a rich source of new functions potentially available for co-option. One benefit that genes of bacterial origin could provide to eukaryotes is the capacity to produce antibacterials, which have evolved in prokaryotes as the result of eons of interbacterial competition. The type VI secretion amidase effector (Tae) proteins are potent bacteriocidal enzymes that degrade the cell wall when delivered into competing bacterial cells by the type VI secretion system. Here we show that tae genes have been transferred to eukaryotes on at least six occasions, and that the resulting domesticated amidase effector (dae) genes have been preserved for hundreds of millions of years through purifying selection. We show that the dae genes acquired eukaryotic secretion signals, are expressed within recipient organisms, and encode active antibacterial toxins that possess substrate specificity matching extant Tae proteins of the same lineage. Finally, we show that a dae gene in the deer tick Ixodes scapularis limits proliferation of Borrelia burgdorferi, the aetiologic agent of Lyme disease. Our work demonstrates that a family of horizontally acquired toxins honed to mediate interbacterial antagonism confers previously undescribed antibacterial capacity to eukaryotes. We speculate that the selective pressure imposed by competition between bacteria has produced a reservoir of genes encoding diverse antimicrobial functions that are tailored for co-option by eukaryotic innate immune systems. PMID:25470067

Chou, Seemay; Daugherty, Matthew D; Peterson, S Brook; Biboy, Jacob; Yang, Youyun; Jutras, Brandon L; Fritz-Laylin, Lillian K; Ferrin, Michael A; Harding, Brittany N; Jacobs-Wagner, Christine; Yang, X Frank; Vollmer, Waldemar; Malik, Harmit S; Mougous, Joseph D

2015-02-01

242

Identification of Genes Related to Beak Deformity of Chickens Using Digital Gene Expression Profiling  

PubMed Central

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

Sun, Yanyan; Liu, Ranran; Liu, Nian; Li, Dongli; Wen, Jie; Chen, Jilan

2014-01-01

243

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

PubMed

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

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

2015-01-28

244

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

245

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

246

Functional and regulatory interactions between Hox and extradenticle?genes  

PubMed Central

The homeobox gene extradenticle (exd) acts as a cofactor of Hox function both in Drosophila and vertebrates. It has been shown that the distribution of the Exd protein is developmentally regulated at the post-translational level; in the regions where exd is not functional Exd is present only in the cell cytoplasm, whereas it accumulates in the nuclei of cells requiring exd function. We show that the subcellular localization of Exd is regulated by the BX-C genes and that each BX-C gene can prevent or reduce nuclear translocation of Exd to different extents. In spite of this negative regulation, two BX-C genes, Ultrabithorax and abdominal-A, require exd activity for their maintenance and function. We propose that mutual interactions between Exd and BX-C proteins ensure the correct amounts of interacting molecules. As the Hoxd10 gene has the same properties as Drosophila BX-C genes, we suggest that the control mechanism of subcellular distribution of Exd found in Drosophila probably operates in other organisms as well. PMID:9436985

Azpiazu, Natalia; Morata, Ginés

1998-01-01

247

MAPPING R-GENES IN RICE WILD RELATIVES (ORYZA SPP.)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Rice sheath blight caused by Rhizoctonia solani Kühn and leaf blast caused by Magnaporthe grisea (T.T. Herbert) Yaegashi & Udagawa are major fungal diseases of cultivated rice (Oryza sativa L.). Rice wild relatives (Oryza spp.) are the source of several resistance (R-) genes including those for bla...

248

Turning a hobby into a job: How duplicated genes find new functions  

Microsoft Academic Search

Gene duplication provides raw material for functional innovation. Recent advances have shed light on two fundamental questions regarding gene duplication: which genes tend to undergo duplication? And how does natural selection subsequently act on them? Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications. We also know that functional differences between duplicate genes

Gavin C. Conant; Kenneth H. Wolfe

2008-01-01

249

On Hypergeometric Functions and Generalizations of Legendre's Relation  

Microsoft Academic Search

We prove some convexity properties for a sum of hypergeometric functions and obtain a generalization of Legendre's relation for complete elliptic integrals. We apply these results to prove some inequalities for hypergeometric functions, incomplete beta-functions, and Legendre functions.

E. A Karatsuba; M Vuorinen

2001-01-01

250

RGFinder: A System for Determining Se-mantically Related Genes using GO Graph Minimum Spanning Tree.  

PubMed

Biologists often need to know the set S¿ of genes that are the most functionally and semantically related to a given set S of genes. For determining the set S¿ , most current gene similarity measures overlook the structural dependencies among the Gene Ontology (GO) terms annotating the set S , which may lead to erroneous results. We introduce in this paper a biological search engine called RGFinder that considers the structural dependencies among GO terms by employing the concept of existence dependency. RGFinder assigns a weight to each edge in GO graph to represent the degree of relatedness between the two GO terms connected by the edge. The value of the weight is determined based on the following factors: (1) type of the relation represented by the edge (e.g., an "is-a" relation is assigned a different weight than a "part-of" relation), (2) the functional relationship between the two GO terms connected by the edge, and (3) the string-substring relationship between the names of the two GO terms connected by the edge. RGFinder then constructs a minimum spanning tree of GO graph based on these weights. In the framework of RGFinder, the set S¿ is annotated to the GO terms located at the lowest convergences of the subtree of the minimum spanning tree that passes through the GO terms annotating set S . We evaluated RGFinder experimentally and compared it with four gene set enrichment systems. Results showed marked improvement. PMID:25343765

Taha, Kamal

2014-10-16

251

Database for exploration of functional context of genes implicated in ovarian cancer  

PubMed Central

Ovarian cancer (OC) is becoming the most common gynecological cancer in developed countries and the most lethal gynecological malignancy. It is also the fifth leading cause of all cancer-related deaths in women. The identification of diagnostic biomarkers and development of early detection techniques for OC largely depends on the understanding of the complex functionality and regulation of genes involved in this disease. Unfortunately, information about these OC genes is scattered throughout the literature and various databases making extraction of relevant functional information a complex task. To reduce this problem, we have developed a database dedicated to OC genes to support exploration of functional characterization and analysis of biological processes related to OC. The database contains general information about OC genes, enriched with the results of transcription regulation sequence analysis and with relevant text mining to provide insights into associations of the OC genes with other genes, metabolites, pathways and nuclear proteins. Overall, it enables exploration of relevant information for OC genes from multiple angles, making it a unique resource for OC and will serve as a useful complement to the existing public resources for those interested in OC genetics. Access is free for academic and non-profit users and database can be accessed at http://apps.sanbi.ac.za/ddoc/. PMID:18790805

Kaur, Mandeep; Radovanovic, Aleksandar; Essack, Magbubah; Schaefer, Ulf; Maqungo, Monique; Kibler, Tracey; Schmeier, Sebastian; Christoffels, Alan; Narasimhan, Kothandaraman; Choolani, Mahesh; Bajic, Vladimir B.

2009-01-01

252

Drosha regulates gene expression independently of RNA cleavage function.  

PubMed

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

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

2013-12-26

253

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

254

Functional analysis of fungal polyketide biosynthesis genes  

Microsoft Academic Search

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

Isao Fujii

2010-01-01

255

The Apolipoprotein E Gene, Attention, and Brain Function  

Microsoft Academic Search

The ?4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-?4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-?4 gene show deficits in spatial attention and working memory that are qualitatively similar

Raja Parasuraman; Pamela M. Greenwood; Trey Sunderland

2002-01-01

256

Molecular characterization of cbf? gene and identification of new transcription variants: Implications for function.  

PubMed

The CBF? gene encodes a transcription factor that, in combination with CBF? (also called Runx, runt-related transcription factor) regulates expression of several target genes. CBF? interacts with all Runx family members, such as RUNX2, a regulator of bone-related gene transcription that contains a conserved DNA-binding domain. CBF? stimulates DNA binding of the Runt domain, and is essential for most of the known functions of RUNX2. A comparative analysis of the zebrafish cbf? gene and protein, and of its orthologous identified homologous proteins in different species indicates a highly conserved function. We cloned eleven zebrafish cbf? gene transcripts, one resulting in the known Cbf? protein (with 187 aa), and three additional variants resulting from skipping exon 5a (resulting in a protein with 174 aa) or exon 5b (resulting in a protein with 201 aa), both observed for the first time in zebrafish, and a completely novel isoform containing both exon 5a and 5b (resulting in a protein with 188 aa). Functional analysis of these isoforms provides insight into their role in regulating gene transcription. From the other variants two are premature termination Cbf? forms, while the others show in-frame exon-skipping causing changes in the Cbf? domain that may affect its function. PMID:25575784

Simões, B; Conceição, N; Matias, A C; Bragança, J; Kelsh, R N; Cancela, M L

2015-02-01

257

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

258

Comprehensive analysis of gene expression patterns of hedgehog-related genes  

Microsoft Academic Search

BACKGROUND: The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity with the Hedgehog signaling molecule through their C-terminal autoprocessing Hint\\/Hog domain. These proteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteins containing only these N-terminal domains. These gene families are called warthog, groundhog, ground-like and quahog, collectively called hedgehog (hh)-related genes. Previously, the expression

Limin Hao; Robert Johnsen; Gilbert Lauter; David Baillie; Thomas R Bürglin

2006-01-01

259

Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration.  

PubMed

Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)-related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

2014-05-14

260

Function of the Evx-2 gene in the morphogenesis of vertebrate limbs.  

PubMed Central

Vertebrate gene members of the HoxD complex are essential for proper development of the appendicular skeletons. Inactivation of these genes induces severe alterations in the size and number of bony elements. Evx-2, a gene related to the Drosophila even-skipped (eve) gene, is located close to Hoxd-13 and is expressed in limbs like the neighbouring Hoxd genes. To investigate whether this tight linkage reflects a functional similarity, we produced a null allele of Evx-2. Furthermore, and because Hoxd-13 function is prevalent over that of nearby Hoxd genes, we generated two different double mutant loci wherein both Evx-2 and Hoxd-13 were inactivated in cis. The analysis of these various genetic configurations revealed the important function of Evx-2 during the development of the autopod as well as its genetic interaction with Hoxd-13. These results show that, in limbs, Evx-2 functions like a Hoxd gene. A potential evolutionary scenario is discussed, in which Evx-2 was recruited by the HoxD complex in conjunction with the emergence of digits in an ancestral tetrapod. Images PMID:8978698

Hérault, Y; Hraba-Renevey, S; van der Hoeven, F; Duboule, D

1996-01-01

261

Function and expression pattern of nonsyndromic deafness genes  

PubMed Central

Hearing loss is the most common sensory disorder, present in 1 of every 500 newborns. To date, 46 genes have been identified that cause nonsyndromic hearing loss, making it an extremely heterogeneous trait. This review provides a comprehensive overview of the inner ear function and expression pattern of these genes. In general, they are involved in hair bundle morphogenesis, form constituents of the extracellular matrix, play a role in cochlear ion homeostasis or serve as transcription factors. During the past few years, our knowledge of genes involved in hair bundle morphogenesis has increased substantially. We give an up-to-date overview of both the nonsyndromic and Usher syndrome genes involved in this process, highlighting proteins that interact to form macromolecular complexes. For every gene, we also summarize its expression pattern and impact on hearing at the functional level. Gene-specific cochlear expression is summarized in a unique table by structure/cell type and is illustrated on a cochlear cross-section, which is available online via the Hereditary Hearing Loss Homepage. This review should provide auditory scientists the most relevant information for all identified nonsyndromic deafness genes. PMID:19601806

Hilgert, Nele; Smith, Richard J.H.; Van Camp, Guy

2010-01-01

262

Functional interactions between NURF and Ctcf regulate gene expression.  

PubMed

Gene expression frequently requires chromatin-remodeling complexes, and it is assumed that these complexes have common gene targets across cell types. Contrary to this belief, we show by genome-wide expression profiling that Bptf, an essential and unique subunit of the nucleosome-remodeling factor (NURF), predominantly regulates the expression of a unique set of genes between diverse cell types. Coincident with its functions in gene expression, we observed that Bptf is also important for regulating nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin. NURF function at Ctcf binding sites could be direct, because Bptf occupies Ctcf binding sites in vivo and has physical interactions with CTCF and the cohesin subunit SA2. Assays of several Ctcf binding sites using reporter assays showed that their regulatory activity requires Bptf in two different cell types. Focused studies at H2-K1 showed that Bptf regulates the ability of Klf4 to bind near an upstream Ctcf site, possibly influencing gene expression. In combination, these studies demonstrate that gene expression as regulated by NURF occurs partly through physical and functional interactions with the ubiquitous and multivalent factors Ctcf and cohesin. PMID:25348714

Qiu, Zhijun; Song, Carolyn; Malakouti, Navid; Murray, Daniel; Hariz, Aymen; Zimmerman, Mark; Gygax, Derek; Alhazmi, Aiman; Landry, Joseph W

2015-01-01

263

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

264

The evolution of cancer-related genes in hominoids.  

PubMed

The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans. PMID:25249249

Kang, Lin; Michalak, Pawel

2015-01-01

265

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

266

Function of androgen receptor in gene regulations.  

PubMed

Most of the androgen actions are considered to be mediated by the androgen receptor (AR) of the target genes. The AR is composed of a fairly large molecule because of the long A/B domains of its N-terminal. However, the independent roles of the AR as well as those of the estrogen receptors largely remained unknown mainly due to the lack of the AR knockout (ARKO) mice line. We have succeeded in generating the ARKO mouse by means of a conditional targeting using the Cre/loxP system. The ARKO males grew healthily although they showed a typical feature of the testicular feminization mutation (Tfm) and the hormonal assay revealed significantly lower serum androgen and higher LH levels in comparison with those of the wild type (WT) males. The serum estrogen levels were, however, comparable between both the ARKO and the WT. Another hallmark of the ARKO males was a state of high bone turnover osteopenia, in which the acceleration in the bone resorption clearly exceeded the bone formation. Male-typical behaviors were disrupted in male ARKO mice. Aiming at a quick differentiation of an androgen-dependent polyQ disease such as Kennedy's disease, the authors also developed the Drosophila fly-eye model in which the wild type and the polyQ-expanded human AR (hAR) was induced in the eyes of Drosophila. When androgen was administered to the flies induced with the polyQ-expanded hAR, their optical nerves were devastated. PMID:15225853

Kato, Shigeaki; Matsumoto, Takahiro; Kawano, Hirotaka; Sato, Takashi; Takeyama, Ken-ichi

2004-05-01

267

Bach2 maintains T cells in a naive state by suppressing effector memory-related genes.  

PubMed

The transcriptional repressor BTB and CNC homology 2 (Bach2) is thought to be mainly expressed in B cells with specific functions such as class switch recombination and somatic hypermutation, but its function in T cells is not known. We found equal Bach2 expression in T cells and analyzed its function using Bach2-deficient (-/-) mice. Although T-cell development was normal, numbers of peripheral naive T cells were decreased, which rapidly produced Th2 cytokines after TCR stimulation. Bach2(-/-) naive T cells highly expressed genes related to effector-memory T cells such as CCR4, ST-2 and Blimp-1. Enhanced expression of these genes induced Bach2(-/-) naive T cells to migrate toward CCR4-ligand and respond to IL33. Forced expression of Bach2 restored the expression of these genes. Using Chromatin Immunoprecipitation (ChIP)-seq analysis, we identified S100 calcium binding protein a, Heme oxigenase 1, and prolyl hydroxylase 3 as Bach2 direct target genes, which are highly expressed in effector-memory T cells. These findings indicate that Bach2 suppresses effector memory-related genes to maintain the naive T-cell state and regulates generation of effector-memory T cells. PMID:23754397

Tsukumo, Shin-ichi; Unno, Midori; Muto, Akihiko; Takeuchi, Arata; Kometani, Kohei; Kurosaki, Tomohiro; Igarashi, Kazuhiko; Saito, Takashi

2013-06-25

268

Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism  

PubMed Central

Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene’s function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput “next-generation sequencing” technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism. PMID:23134044

Reilly, Matthew T.; Harris, R. Adron; Noronha, Antonio

2012-01-01

269

PHYLOGENOMICS - GUIDED VALIDATION OF FUNCTION FOR CONSERVED UNKNOWN GENES  

SciTech Connect

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

V, DE CRECY-LAGARD; D, HANSON A

2012-01-03

270

Tandem riboswitch architectures exhibit complex gene control functions.  

PubMed

Riboswitches are structured RNAs typically located in the 5' untranslated regions of bacterial mRNAs that bind metabolites and control gene expression. Most riboswitches sense one metabolite and function as simple genetic switches. However, we found that the 5' region of the Bacillus clausii metE messenger RNA includes two riboswitches that respond to S-adenosylmethionine and coenzyme B12. This tandem arrangement yields a composite gene control system that functions as a two-input Boolean NOR logic gate. These findings and the discovery of additional tandem riboswitch architectures reveal how simple RNA elements can be assembled to make sophisticated genetic decisions without involving protein factors. PMID:17038623

Sudarsan, Narasimhan; Hammond, Ming C; Block, Kirsten F; Welz, Rüdiger; Barrick, Jeffrey E; Roth, Adam; Breaker, Ronald R

2006-10-13

271

Presence and Functionality of Mating Type Genes in the Supposedly Asexual Filamentous Fungus Aspergillus oryzae  

PubMed Central

The potential for sexual reproduction in Aspergillus oryzae was assessed by investigating the presence and functionality of MAT genes. Previous genome studies had identified a MAT1-1 gene in the reference strain RIB40. We now report the existence of a complementary MAT1-2 gene and the sequencing of an idiomorphic region from A. oryzae strain AO6. This allowed the development of a PCR diagnostic assay, which detected isolates of the MAT1-1 and MAT1-2 genotypes among 180 strains assayed, including industrial tane-koji isolates. Strains used for sake and miso production showed a near-1:1 ratio of the MAT1-1 and MAT1-2 mating types, whereas strains used for soy sauce production showed a significant bias toward the MAT1-2 mating type. MAT1-1 and MAT1-2 isogenic strains were then created by genetic manipulation of the resident idiomorph, and gene expression was compared by DNA microarray and quantitative real-time PCR (qRT-PCR) methodologies under conditions in which MAT genes were expressed. Thirty-three genes were found to be upregulated more than 10-fold in either the MAT1-1 host strain or the MAT1-2 gene replacement strain relative to each other, showing that both the MAT1-1 and MAT1-2 genes functionally regulate gene expression in A. oryzae in a mating type-dependent manner, the first such report for a supposedly asexual fungus. MAT1-1 expression specifically upregulated an ?-pheromone precursor gene, but the functions of most of the genes affected were unknown. The results are consistent with a heterothallic breeding system in A. oryzae, and prospects for the discovery of a sexual cycle are discussed. PMID:22327593

Wada, Ryuta; Maruyama, Jun-ichi; Yamaguchi, Haruka; Yamamoto, Nanase; Wagu, Yutaka; Paoletti, Mathieu; Archer, David B.; Dyer, Paul S.

2012-01-01

272

Gene Network Analysis in a Pediatric Cohort Identifies Novel Lung Function Genes  

PubMed Central

Lung function is a heritable trait and serves as an important clinical predictor of morbidity and mortality for pulmonary conditions in adults, however, despite its importance, no studies have focused on uncovering pediatric-specific loci influencing lung function. To identify novel genetic determinants of pediatric lung function, we conducted a genome-wide association study (GWAS) of four pulmonary function traits, including FVC, FEV1, FEV1/FVC and FEF25–75% in 1556 children. Further, we carried out gene network analyses for each trait including all SNPs with a P-value of <1.0×10?3 from the individual GWAS. The GWAS identified SNPs with notable trends towards association with the pulmonary function measures, including the previously described INTS12 locus association with FEV1 (pmeta?=?1.41×10?7). The gene network analyses identified 34 networks of genes associated with pulmonary function variables in Caucasians. Of those, the glycoprotein gene network reached genome-wide significance for all four variables. P-value range pmeta?=?6.29×10?4 - 2.80×10?8 on meta-analysis. In this study, we report on specific pathways that are significantly associated with pediatric lung function at genome-wide significance. In addition, we report the first loci associated with lung function in both pediatric Caucasian and African American populations. PMID:24023788

McDonough, Joseph M.; Wei, Zhi; Kim, Cecilia; Chiavacci, Rosetta; Mentch, Frank; Caboot, Jason B.; Spergel, Jonathan; Allen, Julian L.; Sleiman, Patrick M. A.; Hakonarson, Hakon

2013-01-01

273

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

274

Calcitonin gene-related peptide: key regulator of cutaneous immunity.  

PubMed

Calcitonin gene-related peptide (CGRP) has been viewed as a neuropeptide and vasodilator. However, CGRP is more appropriately thought of as a pleiotropic signalling molecule. Indeed, CGRP has key regulatory functions on immune and inflammatory processes within the skin. CGRP-containing nerves are intimately associated with epidermal Langerhans cells (LCs), and CGRP has profound regulatory effects on Langerhans cell antigen-presenting capability. When LCs are exposed to CGRP in vitro, their ability to present antigen for in vivo priming of naïve mice or elicitation of delayed-type hypersensitivity is inhibited in at least some situations. Administration of CGRP intradermally inhibits acquisition of immunity to Th1-dominant haptens applied to the injected site while augmenting immunity to Th2-dominant haptens, although the cellular targets of activity in these experiments remain unclear. Although CGRP can be a pro-inflammatory agent, several studies have demonstrated that administration of CGRP can inhibit the elicitation of inflammation by inflammatory stimuli in vivo. In this regard, CGRP inhibits the release of certain chemokines by stimulated endothelial cells. This is likely to be physiologically relevant as cutaneous blood vessels are innervated by sensory nerves. Exciting new studies suggest a significant role for CGRP in the pathogenesis of psoriasis and, most strikingly, that CGRP inhibits the ability of LCs to transmit the human immunodeficiency virus 1 to T lymphocytes. A more complete understanding of the role of CGRP in the skin immune system may lead to new and novel approaches for the therapy of immune-mediated skin disorders. PMID:25534428

Granstein, R D; Wagner, J A; Stohl, L L; Ding, W

2015-03-01

275

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

276

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

PubMed Central

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

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

2012-01-01

277

Gene co-expression network and function modules in three types of glioma.  

PubMed

The aim of the present study was to identify the disease?associated genes and their functions involved in the development of three types of glioma (astrocytoma, glioblastoma and oligodendroglioma) with DNA microarray technology, and to analyze their differences and correlations. First, the gene expression profile GSE4290 was downloaded from the Gene Expression Omnibus database, then the probe?level data were pre?processed and the differentially expressed genes (DEGs) were identified with limma package in R language. Gene functions of the selected DEGs were further analyzed with the Database for Annotation, Visualization and Integrated Discovery. After the co?expression network of DEGs was constructed by Cytoscape, the functional modules were mined and enrichment analysis was performed, and then the similarities and differences between any two types of glioma were compared. A total of 1151 genes between normal and astrocytoma tissues, 684 genes between normal and malignant glioma tissues, and 551 genes between normal and oligodendroglioma tissues were filtered as DEGs, respectively. By constructing co?expression networks of DEGs, a total of 77232, 455 and 987 interactions were involved in the differentially co?expressed networks of astrocytoma, oligodendroglioma and glioblastoma, respectively. The functions of DEGs were consistent with the modules in astrocytoma, glioblastoma and oligodendroglioma, which were mainly enriched in neuron signal transmission, immune responses and synthesis of organic acids, respectively. Model functions of astrocytoma and glioblastoma were similar (mainly related with immune response), while the model functions of oligodendroglioma differed markedly from that of the other two types. The identification of the associations among these three types of glioma has potential clinical utility for improving the diagnosis of different types of glioma in the future. In addition, these results have marked significance in studying the underlying mechanisms, distinguishing between normal and cancer tissues, and examining novel therapeutic strategies for patients with glioma. PMID:25435164

Li, Gang; Pan, Weiran; Yang, Xiaoxiao; Miao, Jinming

2015-04-01

278

New gene functions in megakaryopoiesis and platelet formation.  

PubMed

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; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O'Reilly, Paul F; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; Ellen van der Schoot, C; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C; Cucca, Francesco; D'Adamo, Pio; Davies, Gail; de Boer, Rudolf A; de Geus, Eco J C; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M; Falchi, Mario; Feng, Wei; Folsom, Aaron R; Frazer, Ian H; Gibson, Quince D; Glazer, Nicole L; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J F; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Mateo Leach, Irene; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D; Montgomery, Grant W; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M; Porteous, David J; Pouta, Anneli; Pramstaller, Peter P; Pullat, Janne; Ring, Susan M; Rotter, Jerome I; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L; Snieder, Harold; Starr, John M; Stumvoll, Michael; Takahashi, Atsushi; Tang, W H Wilson; Taylor, Kent; Tenesa, Albert; Lay Thein, Swee; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J; Visscher, Peter M; Völker, Uwe; Wichmann, H-Erich; Wiggins, Kerri L; Willemsen, Gonneke; Yang, Tsun-Po; Hua Zhao, Jing; Zitting, Paavo; Bradley, John R; Dedoussis, George V; Gasparini, Paolo; Hazen, Stanley L; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R; Joost van Pelt, L; 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

2011-12-01

279

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

2012-01-01

280

The ergot alkaloid gene cluster: functional analyses and evolutionary aspects.  

PubMed

Ergot alkaloids and their derivatives have been traditionally used as therapeutic agents in migraine, blood pressure regulation and help in childbirth and abortion. Their production in submerse culture is a long established biotechnological process. Ergot alkaloids are produced mainly by members of the genus Claviceps, with Claviceps purpurea as best investigated species concerning the biochemistry of ergot alkaloid synthesis (EAS). Genes encoding enzymes involved in EAS have been shown to be clustered; functional analyses of EAS cluster genes have allowed to assign specific functions to several gene products. Various Claviceps species differ with respect to their host specificity and their alkaloid content; comparison of the ergot alkaloid clusters in these species (and of clavine alkaloid clusters in other genera) yields interesting insights into the evolution of cluster structure. This review focuses on recently published and also yet unpublished data on the structure and evolution of the EAS gene cluster and on the function and regulation of cluster genes. These analyses have also significant biotechnological implications: the characterization of non-ribosomal peptide synthetases (NRPS) involved in the synthesis of the peptide moiety of ergopeptines opened interesting perspectives for the synthesis of ergot alkaloids; on the other hand, defined mutants could be generated producing interesting intermediates or only single peptide alkaloids (instead of the alkaloid mixtures usually produced by industrial strains). PMID:19695648

Lorenz, Nicole; Haarmann, Thomas; Pazoutová, Sylvie; Jung, Manfred; Tudzynski, Paul

2009-01-01

281

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

282

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

283

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

PubMed

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

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

2015-02-01

284

[Range of potential functions of the Drosophila melanogaster hdc gene].  

PubMed

The Drosophila melanogaster hdc gene controls trachea branching, which starts during embryo development. Expression in imaginal disks and reproductive organs suggests additional functions for the hdc gene. The gene was demonstrated to have a maternal effect, which was denied previously. Analysis of cell proliferation in imaginal disks with hdc mutations showed that the gene does not possess tumor suppressor properties at the levels of mosaic cuticle clones of adults and transplanted imaginal disks. Transplanted imaginal disks homozygous, but not heterozygous, for an hdc mutation were found to affect oogenesis in the recipient females, implicating the hdc activity in exchanging signals between different organs. Amino acid sequence analysis of the Hdc protein revealed a region homologous to the human HRS proteins, which directly interact with the NF2 tumor suppressor on experimental evidence. PMID:16523666

Gusachenko, A M; Akhmamet'eva, E M; Omel'ianchuk, L V

2006-01-01

285

A functional polymorphism in the monoamine oxidase A gene promoter.  

PubMed

We describe a new polymorphism upstream of the gene for monoamine oxidase A (MAOA), an important enzyme in human physiology and behavior. The polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies. The polymorphism is in linkage disequilibrium with other MAOA and MAOB gene markers and displays significant variations in allele frequencies across ethnic groups. The polymorphism has been shown to affect the transcriptional activity of the MAOA gene promoter by gene fusion and transfection experiments involving three different cell types. Alleles with 3.5 or 4 copies of the repeat sequence are transcribed 2-10 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. This promoter region polymorphism may be useful as both a functional and an anonymous genetic marker for MAOA. PMID:9799080

Sabol, S Z; Hu, S; Hamer, D

1998-09-01

286

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

287

29 CFR 1208.4 - Material relating to representation function.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Material relating to representation function. 1208.4 Section 1208... § 1208.4 Material relating to representation function. (a) The documents...evidence submitted in connection with a representation dispute and the investigatory...

2011-07-01

288

29 CFR 1208.4 - Material relating to representation function.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Material relating to representation function. 1208.4 Section 1208... § 1208.4 Material relating to representation function. (a) The documents...evidence submitted in connection with a representation dispute and the investigatory...

2010-07-01

289

29 CFR 1208.4 - Material relating to representation function.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Material relating to representation function. 1208.4 Section 1208... § 1208.4 Material relating to representation function. (a) The documents...evidence submitted in connection with a representation dispute and the investigatory...

2012-07-01

290

Functional association networks as priors for gene regulatory network inference  

PubMed Central

Motivation: Gene regulatory network (GRN) inference reveals the influences genes have on one another in cellular regulatory systems. If the experimental data are inadequate for reliable inference of the network, informative priors have been shown to improve the accuracy of inferences. Results: This study explores the potential of undirected, confidence-weighted networks, such as those in functional association databases, as a prior source for GRN inference. Such networks often erroneously indicate symmetric interaction between genes and may contain mostly correlation-based interaction information. Despite these drawbacks, our testing on synthetic datasets indicates that even noisy priors reflect some causal information that can improve GRN inference accuracy. Our analysis on yeast data indicates that using the functional association databases FunCoup and STRING as priors can give a small improvement in GRN inference accuracy with biological data. Contact: matthew.studham@scilifelab.se Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24931976

Studham, Matthew E.; Nordling, Torbjörn E.M.; Nelander, Sven; Sonnhammer, Erik L. L.

2014-01-01

291

New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas.  

PubMed

Human epithelial tumors need to accumulate multiple genetic alterations to form invasive carcinomas. These genetic alterations are related with growth factor receptors, cell signalling, the cell cycle and cell invasiveness. Importantly, cells need to avoid senescence and become immortalized for this process. Recently, five genes: RPS6KA6, HDAC4, KIAA0828, TCP1 and Tip60, which modulate p53-dependent function and avoid senescence were identified in a large-scale RNA interference screen. Twenty colon, 20 prostate and 20 lung carcinomas were studied to investigate whether these genes might be related with human tumors. RNA was extracted from both normal and tumor tissue from each patient. Real-time RT-PCR was performed using TaqMan probes corresponding to the RPS6KA6, HDAC4, KIAA0828, TCP1, Tip60 and p53 genes. In colon carcinomas, the RPS6KA6, HDAC4, KIAA0828 and Tip60 genes were downregulated in tumor tissue as compared with normal tissue (P < 0.001 for all genes). In lung carcinomas, HDAC4, KIAA0820 and Tip60 were downregulated (P < 0.01, P < 0.001 and P < 0.001 respectively). Whereas no significant differences were observed in prostate carcinomas, striking downregulation of the RPS6KA6 and KIAA0828 genes was observed in colon carcinomas and KIAA0828 in a subset of lung carcinomas. mRNA expression of these genes may control p53 function as well as the ras-MAPK pathway, methylation and transcriptional cellular programs. These results could unravel a novel set of regulatory suppressor genes involved in human colon and lung tumors. PMID:16865262

LLeonart, M E; Vidal, F; Gallardo, D; Diaz-Fuertes, M; Rojo, F; Cuatrecasas, M; López-Vicente, L; Kondoh, H; Blanco, C; Carnero, A; Ramón y Cajal, S

2006-09-01

292

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

293

Gene Fusion Technology NEW METHODS FOR ENHANCING FUNCTIONAL PROTEIN  

E-print Network

SUMOpro-3® Gene Fusion Technology NEW METHODS FOR ENHANCING FUNCTIONAL PROTEIN EXPRESSION packed globular fold with -sheets wrapped around an -helix. SUMO3 Fusions Human SUMO3 fused (ubiquitin or SUMO) at the N-terminus of a partner protein increases the recombinant fusion protein yield

Lebendiker, Mario

294

Cancer Genes: Discovery and Function - Michael Dean, Ph.D.  

Cancer.gov

April 29, 2014 1:00 PM - 2:00 PM Shady Grove, Room TE408/410 + Add to Outlook Calendar Speaker: Michael Dean, Ph.D. Chief, Human Genetics Section Laboratory of Experimental Immunology, CCR, NCI Print This Page Cancer Genes: Discovery and Function

295

UNDERSTANDING GENE AND ALLELE FUNCTION WITH TWO-HYBRID METHODS  

Microsoft Academic Search

Two-hybrid schemes for detecting protein-protein interactions have deepened our understanding of biology by allowing scientists to identify individual important proteins. Recent developments will allow biologists to chart regulatory networks and to rapidly generate hypotheses for the function of genes, allelic variants, and the connections between proteins that make up these networks. Future devel- opments will allow biologists to test inferences

Roger Brent; Russell L. Finley Jr

1997-01-01

296

Automated Discovery of Functional Generality of Human Gene Expression Programs  

Microsoft Academic Search

An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in

Georg K. Gerber; Robin D. Dowell; Tommi S. Jaakkola; David K. Gifford

2007-01-01

297

Multiple Functions of a Feed-Forward-Loop Gene Circuit  

E-print Network

Multiple Functions of a Feed-Forward-Loop Gene Circuit Michael E. Wall1,2 *, Mary J. Dunlop3 of this class of circuits, examining a comprehensive array of subclasses that differ in the way a signal interactions in a circuit. We find that circuits can exhibit any of 13 qualitatively distinct steady-state I

Dunlop, Mary

298

Evolutionary Conservation of Ceratitis capitata transformer Gene Function  

Microsoft Academic Search

Transformer functions as a binary switch gene in the sex determination and sexual differentiation of Drosophila melanogaster and Ceratitis capitata, two insect species that separated nearly 100 million years ago. The TRA protein is required for female differentiation of XX individuals, while XY individuals express smaller, presumably nonfunctional TRA peptides and consequently develop into adult males. In both species, tra

Attilio Pane; Annamaria De Simone; Giuseppe Saccone; Catello Polito

2005-01-01

299

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

SciTech Connect

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

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

2010-05-17

300

Transcriptional Analysis of Essential Genes of the Escherichia coli Fatty Acid Biosynthesis Gene Cluster by Functional Replacement with the Analogous Salmonella typhimurium Gene Cluster  

PubMed Central

The genes encoding several key fatty acid biosynthetic enzymes (called the fab cluster) are clustered in the order plsX-fabH-fabD-fabG-acpP-fabF at min 24 of the Escherichia coli chromosome. A difficulty in analysis of the fab cluster by the polar allele duplication approach (Y. Zhang and J. E. Cronan, Jr., J. Bacteriol. 178:3614–3620, 1996) is that several of these genes are essential for the growth of E. coli. We overcame this complication by use of the fab gene cluster of Salmonella typhimurium, a close relative of E. coli, to provide functions necessary for growth. The S. typhimurium fab cluster was isolated by complementation of an E. coli fabD mutant and was found to encode proteins with >94% homology to those of E. coli. However, the S. typhimurium sequences cannot recombine with the E. coli sequences required to direct polar allele duplication via homologous recombination. Using this approach, we found that although approximately 60% of the plsX transcripts initiate at promoters located far upstream and include the upstream rpmF ribosomal protein gene, a promoter located upstream of the plsX coding sequence (probably within the upstream gene, rpmF) is sufficient for normal growth. We have also found that the fabG gene is obligatorily cotranscribed with upstream genes. Insertion of a transcription terminator cassette (?-Cm cassette) between the fabD and fabG genes of the E. coli chromosome abolished fabG transcription and blocked cell growth, thus providing the first indication that fabG is an essential gene. Insertion of the ?-Cm cassette between fabH and fabD caused greatly decreased transcription of the fabD and fabG genes and slower cellular growth, indicating that fabD has only a weak promoter(s). PMID:9642179

Zhang, Yan; Cronan, John E.

1998-01-01

301

Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia  

PubMed Central

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

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

2012-01-01

302

Atelocollagen-based gene transfer in cells allows high-throughput screening of gene functions.  

PubMed

We have previously demonstrated that Atelocollagen, used clinically for wound healing, is a reliable safe carrier for gene delivery. To obtain phenotypic changes by gene expression of cDNA, we developed an efficient technique for high-throughput gene transfer and expression screening in mammalian cells in microarrays by precoating a microplate with an Atelocollagen complexed with cDNA to which cells are then seeded. The complexes with a nanoparticle form were efficiently transduced into cells without use of any additional transfection reagent, and they allowed for long-term gene expression without apparent chromosomal integration. The complex spotted onto the well of a microplate was stable for a long period and allowed the cells to transduce and express reporter genes in a dose-dependent manner. We also showed that the present method using Atelocollagen-based gene transfer is applicable to gene medicines such as antisense ODNs and adenovirus vectors. These results suggest that Atelocollagen may be appropriate for general use in high-throughput screening of large sets of gene medicines for functional analyses in mammalian cells. PMID:11741301

Honma, K; Ochiya, T; Nagahara, S; Sano, A; Yamamoto, H; Hirai, K; Aso, Y; Terada, M

2001-12-21

303

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

SciTech Connect

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

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

2010-10-25

304

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

305

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

306

Expression and interaction analysis of Arabidopsis Skp1-related genes.  

PubMed

Specific protein degradation has been observed in several aspects of development and differentiation in many organisms. One example of such proteolysis is regulated by protein polyubiquitination that is promoted by the SCF complex consisting of Skp1, cullin, and an F-box protein. We examined the activities of the Arabidopsis Skp1-related proteins (ASKs). Among 19 annotated ASK genes, we isolated 16 of the corresponding cDNAs (ASK1, 2, 3, 4, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19), and examined their gene products for interactions with 24 representatives of F-box proteins carrying various classes of the C-terminal domains using the yeast two-hybrid system. As a result, we found diverse binding specificities: ASK1, ASK2, ASK11 and ASK12 interacted well with COI1, FKF1, UFO-like protein, LRR-containing F-box proteins, and other F-box proteins with unknown C-terminal motifs. We also observed specific interaction between F-box proteins and ASK3, ASK9, ASK13, ASK14, ASK16 and ASK18. In contrast, we detected no interaction between any of the 12 ASK proteins and F-box proteins containing CRFA, CRFB or CRFC domains. Both histochemical and RT-PCR analysis of eight ASK genes expression revealed unique expression patterns for the respective genes. PMID:14749489

Takahashi, Naoki; Kuroda, Hirofumi; Kuromori, Takashi; Hirayama, Takashi; Seki, Motoaki; Shinozaki, Kazuo; Shimada, Hiroaki; Matsui, Minami

2004-01-01

307

Genomic Organization and Expression of the Doublesex-Related Gene Cluster in Vertebrates and Detection of Putative Regulatory Regions for DMRT1  

Microsoft Academic Search

Genes related to the Drosophila melanogaster doublesex and Caenorhabditis elegans mab-3 genes are conserved in human. They are identified by a DNA-binding homology motif, the DM domain, and constitute a gene family (DMRTs). Unlike the invertebrate genes, whose role in the sex-determination process is essentially understood, the function of the different vertebrate DMRT genes is not as clear. Evidence has

Bodo Brunner; Ute Hornung; Zihong Shan; Indrajit Nanda; Mariko Kondo; Enchshargal Zend-Ajusch; Thomas Haaf; Hans-Hilger Ropers; Akihiro Shima; Michael Schmid; Vera M. Kalscheuer; Manfred Schartl

2001-01-01

308

Analysis of gene expression data using functional principal components.  

PubMed

The large amount of data involved in DNA microarrays implies the development of efficient computer algorithms to analyze the gene expressions, and thus to study the transcriptome. Numerous techniques already exist and we propose a new method based on the key idea that gene profiles may be considered as continuous curves. The analysis of the set of curves stemming from the DNA microarray may be then performed using a functional analysis which can exhibit the main modes of variations in this set, gather genes with similar variations and extract characteristic parameters of gene profiles. We aim here at introducing this method, called the Functional Principal Component Analysis. A prospective study has been performed on two available datasets, concerning on the one hand the sporulation data of the Saccharomyces cerevisiae, and on the other hand data of tumor cell lines. Results are very promising: the method is able to extract characteristic parameters from the datasets, to extract significant modes of variations in the set of gene profiles, and to link these variations to biological processes already studied in literature. PMID:15158042

Barra, Vincent

2004-07-01

309

Altered Expression of Immune-Related Genes in Children with Down Syndrome  

PubMed Central

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, Érika Cristina

2014-01-01

310

An adaptive radiation model for the origin of new gene functions  

Microsoft Academic Search

Current models for the evolution of new gene functions after gene duplication presume that the duplication events themselves have no effect on fitness. But those duplications that result in new gene functions are likely to be positively selected from their inception. The evolution of new function may start with the amplification of an existing gene with some level of preadaptation

M Pilar Francino

2005-01-01

311

Promyelocytic leukemia gene functions and roles in tumorigenesis.  

PubMed

The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha (RAR?). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors. PMID:25338978

Imani-Saber, Zeinab; Ghafouri-Fard, Soudeh

2014-01-01

312

Structure and function of pseudoknots involved in gene expression control.  

PubMed

Natural RNA molecules can have a high degree of structural complexity but even the most complexly folded RNAs are assembled from simple structural building blocks. Among the simplest RNA elements are double-stranded helices that participate in the formation of different folding topologies and constitute the major fraction of RNA structures. One common folding motif of RNA is a pseudoknot, defined as a bipartite helical structure formed by base-pairing of the apical loop in the stem-loop structure with an outside sequence. Pseudoknots constitute integral parts of the RNA structures essential for various cellular activities. Among many functions of pseudoknotted RNAs is feedback regulation of gene expression, carried out through specific recognition of various molecules. Pseudoknotted RNAs autoregulate ribosomal and phage protein genes in response to downstream encoded proteins, while many metabolic and transport genes are controlled by cellular metabolites interacting with pseudoknotted RNA elements from the riboswitch family. Modulation of some genes also depends on metabolite-induced messenger RNA (mRNA) cleavage performed by pseudoknotted ribozymes. Several regulatory pseudoknots have been characterized biochemically and structurally in great detail. These studies have demonstrated a plethora of pseudoknot-based folds and have begun uncovering diverse molecular principles of the ligand-dependent gene expression control. The pseudoknot-mediated mechanisms of gene control and many unexpected and interesting features of the regulatory pseudoknots have significantly advanced our understanding of the genetic circuits and laid the foundation for modulation of their outcomes. PMID:25044223

Peselis, Alla; Serganov, Alexander

2014-01-01

313

Conditional control of gene function by an invertible gene trap in zebrafish  

PubMed Central

Conditional mutations are essential for determining the stage- and tissue-specific functions of genes. Here we achieve conditional mutagenesis in zebrafish using FT1, a gene-trap cassette that can be stably inverted by both Cre and Flp recombinases. We demonstrate that intronic insertions in the gene-trapping orientation severely disrupt the expression of the host gene, whereas intronic insertions in the neutral orientation do not significantly affect host gene expression. Cre- and Flp-mediated recombination switches the orientation of the gene-trap cassette, permitting conditional rescue in one orientation and conditional knockout in the other. To illustrate the utility of this system we analyzed the functional consequence of intronic FT1 insertion in supv3l1, a gene encoding a mitochondrial RNA helicase. Global supv311 mutants have impaired mitochondrial function, embryonic lethality, and agenesis of the liver. Conditional rescue of supv311 expression in hepatocytes specifically corrected the liver defects. To test whether the liver function of supv311 is required for viability we used Flp-mediated recombination in the germline to generate a neutral allele at the locus. Subsequently, tissue-specific expression of Cre conditionally inactivated the targeted locus. Hepatocyte-specific inactivation of supv311 caused liver degeneration, growth retardation, and juvenile lethality, a phenotype that was less severe than the global disruption of supv311. Thus, supv311 is required in multiple tissues for organismal viability. Our mutagenesis approach is very efficient and could be used to generate conditional alleles throughout the zebrafish genome. Furthermore, because FT1 is based on the promiscuous Tol2 transposon, it should be applicable to many organisms. PMID:22908272

Ni, Terri T.; Lu, Jianjun; Zhu, Meiying; Maddison, Lisette A.; Boyd, Kelli L.; Huskey, Lindsey; Ju, Bensheng; Hesselson, Daniel; Zhong, Tao P.; Page-McCaw, Patrick S.; Stainier, Didier Y.; Chen, Wenbiao

2012-01-01

314

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

315

EST sequencing and gene expression profiling of defence-related genes from Persea americana infected with Phytophthora cinnamomi  

PubMed Central

Background Avocado (Persea americana) belongs to the Lauraceae family and is an important commercial fruit crop in over 50 countries. The most serious pathogen affecting avocado production is Phytophthora cinnamomi which causes Phytophthora root rot (PRR). Root pathogens such as P. cinnamomi and their interactions with hosts are poorly understood and despite the importance of both the avocado crop and the effect Phytophthora has on its cultivation, there is a lack of molecular knowledge underpinning our understanding of defence strategies against the pathogen. In order to initiate a better understanding of host-specific defence we have generated EST data using 454 pyrosequencing and profiled nine defence-related genes from Pc-infected avocado roots. Results 2.0 Mb of data was generated consisting of ~10,000 reads on a single lane of the GS FLX platform. Using the Newbler assembler 371 contigs were assembled, of which 367 are novel for Persea americana. Genes were classified according to Gene Ontology terms. In addition to identifying root-specific ESTs we were also able to identify and quantify the expression of nine defence-related genes that were differentially regulated in response to P. cinnamomi. Genes such as metallothionein, thaumatin and the pathogenesis related PsemI, mlo and profilin were found to be differentially regulated. Conclusions This is the first study in elucidating the avocado root transcriptome as well as identifying defence responses of avocado roots to the root pathogen P. cinnamomi. Our data is currently the only EST data that has been generated for avocado rootstocks, and the ESTs identified in this study have already been useful in identifying defence-related genes as well as providing gene information for other studies looking at processes such as ROS regulation as well as hypoxia in avocado roots. Our EST data will aid in the elucidation of the avocado transcriptome and identification of markers for improved rootstock breeding and screening. The characterization of the avocado transcriptome will furthermore form a basis for functional genomics of basal angiosperms. PMID:22108245

2011-01-01

316

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

317

Isolation of Oligotrophic Denitrifiers Carrying Previously Uncharacterized Functional Gene Sequences? †  

PubMed Central

Oligotrophic denitrifying bacteria, including those belonging to the genera Herbaspirillum, Azospirillum, and Bradyrhizobium, were obtained using a single-cell isolation technique. The taxonomic composition of the denitrifier population was similar to those assessed by previous culture-independent studies. The sequencing of nitrite reductase and N2O reductase genes of these strains revealed previously unknown links between 16S rRNA and the denitrification-functional gene phylogenies. In particular, we identified Bradyrhizobium strains that harbor nirS sequences previously detected only in culture-independent studies. PMID:21075882

Ishii, Satoshi; Ashida, Naoaki; Otsuka, Shigeto; Senoo, Keishi

2011-01-01

318

The lysis genes of bacteriophage 21: structure and function  

E-print Network

THE LYSIS GENES OF BACTERIOPHAGE 21: STRUCTURE AND FUNCTION A Thesis by MARIA TERESA BONOVICH Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE... December 1991 Major Subject: Biology THE LYSIS GENES OP BACTERIOPHAGE 2l: STRUCTURE AND PUNCTION A Thesis by MARIA TERESA BONOVICH Approved as to style and content by: Ryland Young (Co-Chair of Co 'ttee) Ni enedik (Co-Chair of Committee) Susan...

Bonovich, Maria Teresa

1991-01-01

319

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

320

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

PubMed

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

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

2013-12-01

321

Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia  

PubMed Central

Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of ?1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P=7.6 × 10?11) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P<0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P=2.0 × 10?4), excitability (P=9.0 × 10?4) and cell adhesion and trans-synaptic signaling (P=2.4 × 10?3). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia. PMID:21931320

Lips, E S; Cornelisse, L N; Toonen, R F; Min, J L; Hultman, C M; Holmans, P A; O'Donovan, M C; Purcell, S M; Smit, A B; Verhage, M; Sullivan, P F; Visscher, P M; Posthuma, D

2012-01-01

322

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. 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

323

Fungal Genes in Context: Genome Architecture Reflects Regulatory Complexity and Function  

PubMed Central

Gene context determines gene expression, with local chromosomal environment most influential. Comparative genomic analysis is often limited in scope to conserved or divergent gene and protein families, and fungi are well suited to this approach with low functional redundancy and relatively streamlined genomes. We show here that one aspect of gene context, the amount of potential upstream regulatory sequence maintained through evolution, is highly predictive of both molecular function and biological process in diverse fungi. Orthologs with large upstream intergenic regions (UIRs) are strongly enriched in information processing functions, such as signal transduction and sequence-specific DNA binding, and, in the genus Aspergillus, include the majority of experimentally studied, high-level developmental and metabolic transcriptional regulators. Many uncharacterized genes are also present in this class and, by implication, may be of similar importance. Large intergenic regions also share two novel sequence characteristics, currently of unknown significance: they are enriched for plus-strand polypyrimidine tracts and an information-rich, putative regulatory motif that was present in the last common ancestor of the Pezizomycotina. Systematic consideration of gene UIR in comparative genomics, particularly for poorly characterized species, could help reveal organisms’ regulatory priorities. PMID:23699226

Noble, Luke M.; Andrianopoulos, Alex

2013-01-01

324

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

PubMed Central

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.

2014-01-01

325

A novel growth-related nuclear protein binds and inhibits rat aldolase B gene promoter.  

PubMed

The promoter of the rat aldolase B (AldB) gene that confers liver-specific transcription has an additional role. It functions in vivo as an origin region of DNA replication in the cells in which the gene is repressed (Zhao, Y., Tsutsumi, R., Yamaki, M., Nagatsuka, N., Ejiri, S., Tsutsumi, K., 1994. Initiation zone of DNA replication at the rat aldolase B locus encompasses transcription promoter region. Nucleic Acids Res. 22, 5385-5390). This promoter/origin region has multiple protein-binding sites and, thus, binding of a particular set of protein factors in AldB-expressing or non-expressing cells seems to correlate with functional switch of this promoter/origin region. In the present study, we characterized two closely related proteins, termed AlF-C1 and AlF-C2, which are assumed to be involved in repression of the AldB gene. These two proteins share an identical amino acid sequence except for a 47-residue-insertion in AlF-C1, and are members of a gene family including heterogeneous nuclear ribonucleoprotein (hnRNP) and CCAAT-binding factor subunit A (CBF-A) genes. Bacterially expressed AlF-C1 can bind sequence-specifically to the AldB gene promoter, whereas AlF-C2 can only weakly. Transfection experiments using mammalian expression vectors showed that AlF-C1 down-regulates the AldB gene promoter in rat hepatoma cells, while AlF-C2 had no or little effect. Expressions of mRNAs encoding these two proteins are enriched in fetal livers and in regenerating livers. These results implied that AlF-C1 and/or C2 is involved in growth-regulated repression of the AldB gene. PMID:11245986

Yabuki, T; Miyagi, S; Ueda, H; Saitoh, Y; Tsutsumi, K

2001-02-01

326

QKI-7 Regulates Expression of Interferon-Related Genes in Human Astrocyte Glioma Cells  

PubMed Central

Background The human QKI gene, called quaking homolog, KH domain RNA binding (mouse), is a candidate gene for schizophrenia encoding an RNA-binding protein. This gene was shown to be essential for myelination in oligodendrocytes. QKI is also highly expressed in astrocytes, but its function in these cells is not known. Methods/Principal Findings We studied the effect of small interference RNA (siRNA)-mediated QKI depletion on global gene expression in human astrocyte glioma cells. Microarray measurements were confirmed with real-time quantitative polymerase chain reaction (qPCR). The presence of QKI binding sites (QRE) was assessed by a bioinformatic approach. Viability and cell morphology were also studied. The most significant alteration after QKI silencing was the decreased expression of genes involved in interferon (IFN) induction (P?=?6.3E-10), including IFIT1, IFIT2, MX1, MX2, G1P2, G1P3, GBP1 and IFIH1. All eight genes were down-regulated after silencing of the splice variant QKI-7, but were not affected by QKI-5 silencing. Interestingly, four of them were up-regulated after treatment with the antipsychotic agent haloperidol that also resulted in increased QKI-7 mRNA levels. Conclusions/Significance The coordinated expression of QKI-7 splice variant and IFN-related genes supports the idea that this particular splice variant has specific functions in astrocytes. Furthermore, a role of QKI-7 as a regulator of an inflammatory gene pathway in astrocytes is suggested. This hypothesis is well in line with growing experimental evidence on the role of inflammatory components in schizophrenia. PMID:20927331

Jiang, Lin; Saetre, Peter; Radomska, Katarzyna J.; Jazin, Elena; Lindholm Carlström, Eva

2010-01-01

327

Functional analysis of a relA/spoT gene homolog from Streptococcus equisimilis.  

PubMed Central

We examined the functional attributes of a gene encountered by sequencing the streptokinase gene region of Streptococcus equisimilis H46A. This gene, originally called rel, here termed relS. equisimilis, is homologous to two related Escherichia coli genes, spoT and relA, that function in the metabolism of guanosine 5',3'-polyphosphates [(p)ppGpp]. Studies with a variety of E. coli mutants led us to deduce that the highly expressed rel S. equisimilis gene encodes a strong (p)ppGppase and a weaker (p)ppGpp synthetic activity, much like the spoT gene, with a net effect favoring degradation and no complementation of the absence of the relA gene. We verified that the Rel S. equisimilis protein, purified from an E. coli relA spoT double mutant, catalyzed a manganese-activated (p)ppGpp 3'-pyrophosphohydrolase reaction similar to that of the SpoT enzyme. This Rel S. equisimilis protein preparation also weakly catalyzed a ribosome-independent synthesis of (p)ppGpp by an ATP to GTP 3'-pyrophosphoryltransferase reaction when degradation was restricted by the absence of manganese ions. An analogous activity has been deduced for the SpoT protein from genetic evidence. In addition, the Rel S. equisimilis protein displays immunological cross-reactivity with polyclonal antibodies specific for SpoT but not for RelA. Despite assignment of rel S. equisimilis gene function in E. coli as being similar to that of the native spoT gene, disruptions of rel S. equisimilis in S. equisimilis abolish the parental (p)ppGpp accumulation response to amino acid starvation in a manner expected for relA mutants rather than spoT mutants. PMID:8631718

Mechold, U; Cashel, M; Steiner, K; Gentry, D; Malke, H

1996-01-01

328

Functionally relevant diversity of closely related Nitrospira in activated sludge.  

PubMed

Nitrospira are chemolithoautotrophic nitrite-oxidizing bacteria that catalyze the second step of nitrification in most oxic habitats and are important for excess nitrogen removal from sewage in wastewater treatment plants (WWTPs). To date, little is known about their diversity and ecological niche partitioning within complex communities. In this study, the fine-scale community structure and function of Nitrospira was analyzed in two full-scale WWTPs as model ecosystems. In Nitrospira-specific 16S rRNA clone libraries retrieved from each plant, closely related phylogenetic clusters (16S rRNA identities between clusters ranged from 95.8% to 99.6%) within Nitrospira lineages I and II were found. Newly designed probes for fluorescence in situ hybridization (FISH) allowed the specific detection of several of these clusters, whose coexistence in the WWTPs was shown for prolonged periods of several years. In situ ecophysiological analyses based on FISH, relative abundance and spatial arrangement quantification, as well as microautoradiography revealed functional differences of these Nitrospira clusters regarding the preferred nitrite concentration, the utilization of formate as substrate and the spatial coaggregation with ammonia-oxidizing bacteria as symbiotic partners. Amplicon pyrosequencing of the nxrB gene, which encodes subunit beta of nitrite oxidoreductase of Nitrospira, revealed in one of the WWTPs as many as 121 species-level nxrB operational taxonomic units with highly uneven relative abundances in the amplicon library. These results show a previously unrecognized high diversity of Nitrospira in engineered systems, which is at least partially linked to niche differentiation and may have important implications for process stability. PMID:25148481

Gruber-Dorninger, Christiane; Pester, Michael; Kitzinger, Katharina; Savio, Domenico F; Loy, Alexander; Rattei, Thomas; Wagner, Michael; Daims, Holger

2015-03-01

329

Fermionic representation for basic hypergeometric functions related to Schur polynomials  

Microsoft Academic Search

We present the fermionic representation for the q-deformed hypergeometric functions related to Schur polynomials considered by S.Milne \\\\cite{Milne}. For $q=1$ these functions are also known as hypergeometric functions of matrix argument which are related to zonal spherical polynomials for $GL(N,C)\\/U(N)$ symmetric space. We show that these multivariable hypergeometric functions are tau-functions of the KP hierarchy. At the same time they

A. Yu. Orlov; D. M. Scherbin

2000-01-01

330

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

SciTech Connect

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.

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

2010-01-01

331

Early steps in the evolution of multicellularity: deep structural and functional homologies among homeobox genes in sponges and higher metazoans  

Microsoft Academic Search

The sponge homeobox gene EmH-3 had not been attributed to any homeobox family. Comparative promoter and homeodomain sequence analyses suggest that it is related to the Hox11 gene, which belongs to the Tlx homeobox family. Hox11 is highly expressed in proliferating progenitor cells, but expression is downregulated during cell differentiation. Using reporter gene methodology, we monitored function of the sponge

Cristiano C. Coutinho; Rodrigo N. Fonseca; José João C. Mansure; Radovan Borojevic

2003-01-01

332

Relations among Functional Systems in Behavior Analysis  

PubMed Central

This paper proposes that an organism's integrated repertoire of operant behavior has the status of a biological system, similar to other biological systems, like the nervous, cardiovascular, or immune systems. Evidence from a number of sources indicates that the distinctions between biological and behavioral events is often misleading, engendering counterproductive explanatory controversy. A good deal of what is viewed as biological (often thought to be inaccessible or hypothetical) can become publicly measurable variables using currently available and developing technologies. Moreover, such endogenous variables can serve as establishing operations, discriminative stimuli, conjoint mediating events, and maintaining consequences within a functional analysis of behavior and need not lead to reductionistic explanation. I suggest that explanatory misunderstandings often arise from conflating different levels of analysis and that behavior analysis can extend its reach by identifying variables operating within a functional analysis that also serve functions in other biological systems. PMID:17575907

Thompson, Travis

2007-01-01

333

Two orthodenticle -related genes in the short-germ beetle Tribolium castaneum  

Microsoft Academic Search

To investigate the molecular basis of head evolution, we searched for genes related to the Drosophila orthodenticle (otd) homeobox gene in the short-germ beetle Tribolium castaneum. Unexpectedly, we found that there are two otd-related genes in Tribolium, with predicted homeodomains highly similar to that of the single Drosophila gene. One of the two genes (Tc otd-1) is more related in

Yuebing Li; Susan J. Brown; Bernhard Hausdorf; Diethard Tautz; Robin E. Denell; R. Finkelstein

1996-01-01

334

Relatively Recursive Reals and Real Functions  

Microsoft Academic Search

Intuitively, a real number is recursive if we can get as accurate an approximation as we like, using a mechanical procedure such as a Turing machine. A real function is recursive if its value at a point x in its domain can be approximated effectively given an approximation to x. However, since there are only countably many Turing machines, there

Chun-kuen Ho

1999-01-01

335

Integrable pseudopotentials related to generalized hypergeometric functions  

E-print Network

We construct integrable pseudopotentials with an arbitrary number of fields in terms of generalized hypergeometric functions. These pseudopotentials yield some integrable (2+1)-dimensional hydrodynamic type systems. An interesting class of integrable (1+1)-dimensional hydrodynamic type systems is also generated by our pseudopotentials.

Alexander Odesskii; Vladimir Sokolov

2008-05-12

336

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

337

Differential Expression of Granulopoiesis Related Genes in Neutrophil Subsets Distinguished by Membrane Expression of CD177  

PubMed Central

Objective Differential gene expression in CD177+ and CD177? neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). Methods Neutrophils were isolated from healthy controls (HC) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177? subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177? subsets in microarray analysis were re-assessed using quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. Results The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177? neutrophils resulted in 14 genes with fold change (fc) >3 difference in expression. Interestingly, 10 of these genes have been reported to change significantly in expression during neutrophil maturation, and most of these genes were granule protein (GP) coding genes. mRNA expression levels measured by RT-PCR of a number of these GP, and of PR3 and MPO were higher in the CD177? neutrophil subset in HC, however, particular granule protein amounts were comparable between CD177+ and CD177? neutrophil subsets. AAV patients had higher amounts of CD177+ neutrophils, but contrary to neutrophils from HC expression of GP-genes was increased, possibly due to activation. Conclusion The neutrophil population can be distinguished by membrane expression of CD177 into subsets that are different in expression of GP mRNA but not in GP protein production. GP gene expression is also elevated in AAV patients, which is not explained by skewed distribution of CD177+ and CD177? subsets but may be associated with neutrophil activation during on-going inflammation. PMID:24926686

Hu, Nan; Mora-Jensen, Helena; Theilgaard-Mönch, Kim; Doornbos-van der Meer, Berber; Huitema, Minke G.; Stegeman, Coen A.; Heeringa, Peter; Kallenberg, Cees G. M.; Westra, Johanna

2014-01-01

338

Some recurrence relations for the generalized basic hypergeometric functions  

Microsoft Academic Search

In the present paper, we express the generalized basic hypergeometric function r s(·) (for r = s+1) in terms of an iterated q-integrals involving the basic analogue of the Gauss's hypergeometric function. Further, using the relations between q-contiguous hypergeometric series, we obtain some recurrence relations for the generalized basic hypergeometric functions of one variable.

S. D. Purohit

339

KMD: Korean Mutation Database for genes related to diseases.  

PubMed

The number of known disease-causing mutations has increased dramatically. However, there have been few organized mutation databases developed that are available to the public or not-for-profit entities. Thus, clinicians and diagnostic laboratories had to spend time searching many publications and databases to determine whether a mutation has been previously reported. To assist in genetic diagnoses, the systematic collection and curation of mutations are necessary. The Korean Mutation Database (KMD; http://kmd.cdc.go.kr) is a country-specific database of human gene mutations that was established in September 2009. The KMD is a database consolidating mutations of genes related to diseases in Korea; it now contains more than 1,600 mutations from 245 genes. We collected mutation data from diagnostic laboratories and published journals over recent decades in Korea. KMD has been open to the public for searches and registration of mutation data without charge. Our aim is to provide organized information for clinicians and researchers who are interested in genetic diseases. It will be useful not only for researchers in Korea but also for researchers in countries with similar ethnic backgrounds. Ultimately, KMD will be an essential base to improve researches in genetic diseases, developments of diagnostics, and therapeutic optimization. PMID:22323337

Park, Mi-Hyun; Koo, Soo Kyung; Lee, Jin-Sung; Yoo, Han-Wook; Kim, Jong-Won; Cheong, Hae Il; Park, Hyun-Young

2012-04-01

340

First evidence for functional vomeronasal 2 receptor genes in primates.  

PubMed

Two classes of vomeronasal receptor genes, V1R and V2R, occur in vertebrates. Whereas, V1R loci are found in a wide variety of mammals, including primates, intact V2R genes have thus far only been described in rodents and marsupials. In primates, the V2R repertoire has been considered degenerate. Here, we identify for the first time two intact V2R loci in a strepsirrhine primate, the grey mouse lemur (Microcebus murinus), and demonstrate their expression in the vomeronasal organ. Putatively functional orthologues are present in two other strepsirrhines, whereas, both loci are pseudogenes in a range of anthropoid species. The functional significance of the loci is unknown, but positive selection on one of them is consistent with an adaptive role in pheromone detection. Finally, conservation of V2R loci in strepsirrhines is notable, given their high diversity and role in MUP and MHC detection in rodents. PMID:23269843

Hohenbrink, Philipp; Mundy, Nicholas I; Zimmermann, Elke; Radespiel, Ute

2013-02-23

341

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

342

Relationship between operon preference and functional properties of persistent genes in bacterial genomes  

PubMed Central

Background Genes in bacteria may be organised into operons, leading to strict co-expression of the genes that participate in the same operon. However, comparisons between different bacterial genomes have shown that much of the operon structure is dynamic on an evolutionary time scale. This indicates that there are opposing effects influencing the tendency for operon formation, and these effects may be reflected in properties like evolutionary rate, complex formation, metabolic pathways and gene fusion. Results We have used multi-species protein-protein comparisons to generate a high-quality set of genes that are persistent in bacterial genomes (i.e. they have close to universal distribution). We have analysed these genes with respect to operon participation and important functional properties, including evolutionary rate and protein-protein interactions. Conclusions Genes for ribosomal proteins show a very slow rate of evolution. This is consistent with a strong tendency for the genes to participate in operons and for their proteins to be involved in essential and well defined complexes. Persistent genes for non-ribosomal proteins can be separated into two classes according to tendency to participate in operons. Those with a strong tendency for operon participation make proteins with fewer interaction partners that seem to participate in relatively static complexes and possibly linear pathways. Genes with a weak tendency for operon participation tend to produce proteins with more interaction partners, but possibly in more dynamic complexes and convergent pathways. Genes that are not regulated through operons are therefore more evolutionary constrained than the corresponding operon-associated genes and will on average evolve more slowly. PMID:20109203

2010-01-01

343

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

344

Functional and evolutionary inference in gene networks: does topology matter?  

Microsoft Academic Search

The relationship between the topology of a biological network and its functional or evolutionary properties has attracted\\u000a much recent interest. It has been suggested that most, if not all, biological networks are ‘scale free.’ That is, their connections\\u000a follow power-law distributions, such that there are very few nodes with very many connections and vice versa. The number of\\u000a target genes

Mark L. Siegal; Daniel E. L. Promislow; Aviv Bergman

2007-01-01

345

Glycan-related gene expression signatures in human metastatic hepatocellular carcinoma cells  

PubMed Central

Human hepatocellular carcinoma (HCC) ranks second in cancer mortality in China; recurrence and metastasis have been the cause of the high mortality. Glycans on the cell surface play a pivotal role in tumor metastasis. The global alteration in the structure and composition of N-glycans during HCC metastasis remains unknown. To understand glycan alterations of glycoproteins by correlating the glycosyltransferase expression profile with glycan structure, we systematically used glycan profiling tools: glycogene microarray analyses of 115 genes, including glycotransferases, glycosidases and nuclear sugar transporters and lectin chips to investigate the glycan-related gene expression signatures in the high metastatic potential HCC cell line, HCCLM3, in comparison to the HCC cell line, Hep3B, with low metastatic potential. Of the 115 genes, 18 genes were up-regulated in high metastatic potential HCCLM3 cells in comparison to Hep3B cells, while 11 genes were down-regulated. The differentially expressed genes, such as ST3GalI, FUT8, ?3GalT5, MGAT3 and MGAT5, were mainly involved in the synthesis of N-glycan and glycolipids, particularly the sialyl Lewis antigen. The results of the glycogene microarray analysis were further validated by quantitative real-time PCR analysis and lectin-based analysis. The differentially expressed glycogenes identified in this study may provide new insights and represent novel factors for investigating the functional role of cell surface carbohydrate-mediated HCC metastasis. PMID:22969905

KANG, XIAONAN; WANG, NIAN; PEI, CHEN; SUN, LU; SUN, RUIXIA; CHEN, JIE; LIU, YINKUN

2012-01-01

346

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; Hökfelt, Tomas G. M.; Deakin, J. F. William; Bagdy, Gyorgy

2014-01-01

347

ROS production during symbiotic infection suppresses pathogenesis-related gene expression.  

PubMed

Leguminous plants have exclusive ability to form symbiotic relationship with soil bacteria of the genus Rhizobium. Symbiosis is a complex process that involves multiple molecular signaling activities, such as calcium fluxes, production of reactive oxygen species (ROS) and synthesis of nodulation genes. We analyzed the role of ROS in defense gene expression in Medicago truncatula during symbiosis and pathogenesis. Studies in Arabidopsis thaliana showed that the induction of pathogenesis-related (PR) genes during systemic acquired resistance (SAR) is regulated by NPR1 protein, which resides in the cytoplasm as an oligomer. After oxidative burst and return of reducing conditions, the NPR1 undergoes monomerization and becomes translocated to the nucleus, where it functions in PR genes induction. We show that ROS production is both stronger and longer during symbiotic interactions than during interactions with pathogenic, nonhost or common nonpathogenic soil bacteria. Moreover, root cells inoculated with Sinorhizobium meliloti accumulated ROS in the cytosol but not in vacuoles, as opposed to Pseudomonas putida inoculation or salt stress treatment. Furthermore, increased ROS accumulation by addition of H?O? reduced the PR gene expression, while catalase had an opposite effect, establishing that the PR gene expression is opposite to the level of cytoplasmic ROS. In addition, we show that salicylic acid pretreatment significantly reduced ROS production in root cells during symbiotic interaction. PMID:22499208

Peleg-Grossman, Smadar; Melamed-Book, Naomi; Levine, Alex

2012-03-01

348

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.

349

Implementation of genomics and bioinformatics approaches for identification and characterization of tomato ripening-related genes  

E-print Network

Initial activities were focused on isolation and characterization of fruit ripening-related genes from tomato. Screening of four tomato cDNA libraries at low stringency with 10 fruit development and ripening-related genes yielded ~3000 positives...

Fei, Zhangjun

2004-09-30

350

Biological interpretation of genome-wide association studies using predicted gene functions.  

PubMed

The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes. PMID:25597830

Pers, Tune H; Karjalainen, Juha M; Chan, Yingleong; Westra, Harm-Jan; Wood, Andrew R; Yang, Jian; Lui, Julian C; Vedantam, Sailaja; Gustafsson, Stefan; Esko, Tonu; Frayling, Tim; Speliotes, Elizabeth K; Boehnke, Michael; Raychaudhuri, Soumya; Fehrmann, Rudolf S N; Hirschhorn, Joel N; Franke, Lude

2015-01-01

351

Remote Control of Gene Function by Local Translation  

PubMed Central

The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function. PMID:24679524

Jung, Hosung; Gkogkas, Christos G.; Sonenberg, Nahum; Holt, Christine E.

2014-01-01

352

A functional gene array for detection of bacterial virulence elements  

SciTech Connect

We report our development of the first of a series of microarrays designed to detect pathogens with known mechanisms of virulence and antibiotic resistance. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples. To validate our approach, we developed a first generation array targeting genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for microorganism detection and discrimination, measured the required target concentration, and assessed tolerance for mismatches between probe and target sequences. Mismatch tolerance is a priority for this application, due to DNA sequence variability among members of gene families. Arrays were created using the NimbleGen Maskless Array Synthesizer at Lawrence Livermore National Laboratory. Purified genomic DNA from combinations of one or more of the four target organisms, pure cultures of four related organisms, and environmental aerosol samples with spiked-in genomic DNA were hybridized to the arrays. Based on the success of this prototype, we plan to design further arrays in this series, with the goal of detecting all known virulence and antibiotic resistance gene families in a greatly expanded set of organisms.

Jaing, C

2007-11-01

353

OncodriveROLE classifies cancer driver genes in loss of function and activating mode of action  

PubMed Central

Motivation: Several computational methods have been developed to identify cancer drivers genes—genes responsible for cancer development upon specific alterations. These alterations can cause the loss of function (LoF) of the gene product, for instance, in tumor suppressors, or increase or change its activity or function, if it is an oncogene. Distinguishing between these two classes is important to understand tumorigenesis in patients and has implications for therapy decision making. Here, we assess the capacity of multiple gene features related to the pattern of genomic alterations across tumors to distinguish between activating and LoF cancer genes, and we present an automated approach to aid the classification of novel cancer drivers according to their role. Result: OncodriveROLE is a machine learning-based approach that classifies driver genes according to their role, using several properties related to the pattern of alterations across tumors. The method shows an accuracy of 0.93 and Matthew's correlation coefficient of 0.84 classifying genes in the Cancer Gene Census. The OncodriveROLE classifier, its results when applied to two lists of predicted cancer drivers and TCGA-derived mutation and copy number features used by the classifier are available at http://bg.upf.edu/oncodrive-role. Availability and implementation: The R implementation of the OncodriveROLE classifier is available at http://bg.upf.edu/oncodrive-role. Contact: abel.gonzalez@upf.edu or nuria.lopez@upf.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25161246

Schroeder, Michael P.; Rubio-Perez, Carlota; Tamborero, David; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria

2014-01-01

354

[Construction of nervous system relative protein and gene secondary database].  

PubMed

Along with the rapid research of neural molecular biology, abundant data are produced so that the collection and coordination of high-throughout data about nervous system relative proteins and genes are imperative. Through analyzing the biological primary databases maintained by NCBI and RCSB as the main data source and designing a new data model, a local specialized secondary database is constructed, which mainly includes nucleotide sequences, protein sequences and protein structures, and is established on Sun Blade 2000 System and Oracle 9i. All programs are developed by Java technology. A method of web information automatic retrieval with XML is proposed for sequence data collection and submission to the database. JSP + JavaBean technology is used to support data promulgation on Internet. The establishment of this database provides an excellent platform for the research of neural molecular biology and the pathogenesis of related diseases. PMID:18027688

Wang, Pan; Chen, Xinhao; Liu, Xiangming

2007-10-01

355

Angiotensin-related genes in patients with panic disorder.  

PubMed

Enhanced respiratory variability and decreased heart rate variability have repeatedly been observed in patients with panic disorder. Prompted by the notion that angiotensin may be involved in the control of respiration, heart rate variability, and anxiety-like behavior, we investigated the putative association between polymorphisms in three angiotensin-related genes and panic disorder-angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II (ANG II) receptor type 1 (ATr1) in 72 patients with panic disorder and 504 controls. Allele and genotype distribution of the ATr1 A1166C allele and the AGT M235T did not differ between patients and controls. With respect to the ACE I/D polymorphism, the I allele was found to be more frequent in male (chi(2) = 8.042, df = 1, P = 0.005), but not female, panic disorder patients than in controls. The results of this investigation provide preliminary evidence for the suggestion that angiotensin-related genes may be associated with panic disorder in men. PMID:15108186

Olsson, Marie; Annerbrink, Kristina; Westberg, Lars; Melke, Jonas; Baghaei, Fariba; Rosmond, Roland; Holm, Göran; Andersch, Sven; Allgulander, Christer; Eriksson, Elias

2004-05-15

356

Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects  

PubMed Central

Major depressive disorder (MDD) has been linked to changes in function and activity of the hippocampus, one of the central limbic regions involved in regulation of emotions and mood. The exact cellular and molecular mechanisms underlying hippocampal plasticity in response to stress are yet to be fully characterized. In this study, we examined the genetic profile of micro-dissected subfields of post-mortem hippocampus from subjects diagnosed with MDD and comparison subjects matched for sex, race and age. Gene expression profiles of the dentate gyrus and CA1 were assessed by 48K human HEEBO whole genome microarrays and a subgroup of identified genes was confirmed by real-time polymerase chain reaction (qPCR). Pathway analysis revealed altered expression of several gene families, including cytoskeletal proteins involved in rearrangement of neuronal processes. Based on this and evidence of hippocampal neuronal atrophy in MDD, we focused on the expression of cytoskeletal, synaptic and glutamate receptor genes. Our findings demonstrate significant dysregulation of synaptic function/structure related genes SNAP25, DLG2 (SAP93), and MAP1A, and 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor subunit genes GLUR1 and GLUR3. Several of these human target genes were similarly dysregulated in a rat model of chronic unpredictable stress and the effects reversed by antidepressant treatment. Together, these studies provide new evidence that disruption of synaptic and glutamatergic signalling pathways contribute to the pathophysiology underlying MDD and provide interesting targets for novel therapeutic interventions. PMID:22339950

Duric, Vanja; Banasr, Mounira; Stockmeier, Craig A.; Simen, Arthur A.; Newton, Samuel S.; Overholser, James C.; Jurjus, George J.; Dieter, Lesa; Duman, Ronald S.

2012-01-01

357

Expression of fourteen novel obesity-related genes in zucker diabetic fatty rats  

PubMed Central

Background Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes. Methods We performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22?weeks. Results All of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats. Conclusion The expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant. PMID:22553958

2012-01-01

358

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

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

2005-01-01

359

Inferring biological functions and associated transcriptional regulators using gene set expression coherence analysis  

Microsoft Academic Search

Background: Gene clustering has been widely used to group genes with similar expression pattern in microarray data analysis. Subsequent enrichment analysis using predefined gene sets can provide clues on which functional themes or regulatory sequence motifs are associated with individual gene clusters. In spite of the potential utility, gene clustering and enrichment analysis have been used in separate platforms, thus,

Tae-min Kim; Yeun-jun Chung; Mun-gan Rhyu; Myeong Ho Jung

2007-01-01

360

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

361

Evolution and Functional Diversification of Fructose Bisphosphate Aldolase Genes in Photosynthetic Marine Diatoms  

PubMed Central

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

362

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; Molnár, Péter; Schwab, Wilfried

2009-01-01

363

Plant responses to environmental stress: regulation and functions of the Arabidopsis TCH genes  

NASA Technical Reports Server (NTRS)

Expression of the Arabidopsis TCH genes is markedly upregulated in response to a variety of environmental stimuli including the seemingly innocuous stimulus of touch. Understanding the mechanism(s) and factors that control TCH gene regulation will shed light on the signaling pathways that enable plants to respond to environmental conditions. The TCH proteins include calmodulin, calmodulin-related proteins and a xyloglucan endotransglycosylase. Expression analyses and localization of protein accumulation indicates that the potential sites of TCH protein function include expanding cells and tissues under mechanical strain. We hypothesize that at least a subset of the TCH proteins may collaborate in cell wall biogenesis.

Braam, J.; Sistrunk, M. L.; Polisensky, D. H.; Xu, W.; Purugganan, M. M.; Antosiewicz, D. M.; Campbell, P.; Johnson, K. A.; McIntire, L. V. (Principal Investigator)

1997-01-01

364

New type IV pili-related genes involved in early stages of Ralstonia solanacearum potato infection.  

PubMed

This study provides insights into the pathogenesis of Ralstonia solanacearum, in particular with regards to strains belonging to phylotype IIB, sequevar 1 (IIB-1) and their interaction with potato, its natural host. We performed a comparative genomic analysis among IIB-1 R. solanacearum strains with different levels of virulence in order to identify candidate virulence genes. With this approach, we identified a 33.7-kb deletion in a strain showing reduced virulence on potato. This region contains a cluster of six genes putatively involved in type IV pili (Tfp) biogenesis. Functional analysis suggests that these proteins contribute to several Tfp-related functions such as twitching motility and biofilm formation. In addition, this genetic cluster was found to contribute to early bacterial wilt pathogenesis and colonization fitness of potato roots. PMID:24625029

Siri, María Inés; Sanabria, Analía; Boucher, Christian; Pianzzola, María Julia

2014-07-01

365

Arabidopsis thaliana ICE2 gene: Phylogeny, structural evolution and functional diversification from ICE1.  

PubMed

The ability to tolerate environmental stresses is crucial for all living organisms, and gene duplication is one of the sources for evolutionary novelties. Arabidopsis thaliana INDUCER OF CBF EXPRESSION1 and 2 (ICE1 and ICE2) encode MYC-type bHLH (basic helix-loop-helix) transcription factors. They confer cold stress tolerance by induction of the CBF/DREB1 regulon and regulate stomata formation. Although ICE2 is closely related to ICE1, its origin and role in cold response remains uncertain. Here, we used a bioinformatics/phylogenetic approach to uncover the ICE2 evolutionary history, structural evolution and functional divergence from the putative ancestral gene. Sequence diversification from ICE1 included the gain of cis-acting elements in ICE2 promoter sequence that may provide meristem-specific and defense-related gene expression. By analyzing transgenic Arabidopsis lines with ICE2 over-expression we showed that it contributes to stomata formation, flowering time regulation and cold response. Constitutive ICE2 expression led to induced meristem freezing tolerance, resulting from activation of CBF1 and CBF3 genes and ABA biosynthesis by NCED3 induction. We presume that ICE2 gene has originated from a duplication event about 17.9MYA followed by sub- and neofunctionalization of the ancestral ICE1 gene. Moreover, we predict its role in pathogen resistance and flowering time regulation. PMID:25443829

Kurbidaeva, Amina; Ezhova, Tatiana; Novokreshchenova, Maria

2014-12-01

366

Inverse regulation of plasticity-related immediate early genes by calcineurin in hippocampal neurons.  

PubMed

In the mammalian hippocampus, changes in the expression of immediate early genes (IEGs) is thought to contribute to long term plastic changes in neurons brought about by learning tasks and high frequency stimulation of synapses. The phosphatase calcineurin has emerged as an important negative regulator of hippocampus-dependent learning and long term potentiation. Here we investigated the possibility that the constraining action of calcineurin on hippocampal plasticity is mediated in part by regulation of gene expression through negative control of transcription factors, such as cAMP-response element (CRE)-binding protein (CREB). We assessed the effect of calcineurin inhibitors on CREB activation by neuronal activity and show that calcineurin activity is in fact required for CREB-mediated gene expression. However, inhibition of calcineurin had disparate effects on the transcriptional induction of CREB-dependent IEGs. We find that the IEG c-fos is unaffected by suppression of calcineurin activity, the plasticity-related genes Egr1/Zif268 and Egr2/Krox-20 are up-regulated, and genes encoding the orphan nuclear hormone receptors Nor1 and Nur77 are down-regulated. We further show that the up-regulation of particular IEGs is probably due to the presence of serum response elements (SREs) in their promoters, because SRE-mediated gene expression is enhanced by calcineurin blockers. Moreover, expression of the c-fos gene, which is unaffected by calcineurin inhibitors, could be down-regulated by mutating the SRE. Conversely, SRE-mediated c-fos induction in the absence of a functional CRE was enhanced by calcineurin inhibitors. Our experiments thus implicate calcineurin as a negative regulator of SRE-dependent neuronal genes. PMID:19270309

Lam, Brian Yee Hong; Zhang, Wenting; Enticknap, Nicola; Haggis, Eleanor; Cader, M Zaeem; Chawla, Sangeeta

2009-05-01

367

Inverse Regulation of Plasticity-related Immediate Early Genes by Calcineurin in Hippocampal Neurons*S?  

PubMed Central

In the mammalian hippocampus, changes in the expression of immediate early genes (IEGs) is thought to contribute to long term plastic changes in neurons brought about by learning tasks and high frequency stimulation of synapses. The phosphatase calcineurin has emerged as an important negative regulator of hippocampus-dependent learning and long term potentiation. Here we investigated the possibility that the constraining action of calcineurin on hippocampal plasticity is mediated in part by regulation of gene expression through negative control of transcription factors, such as cAMP-response element (CRE)-binding protein (CREB). We assessed the effect of calcineurin inhibitors on CREB activation by neuronal activity and show that calcineurin activity is in fact required for CREB-mediated gene expression. However, inhibition of calcineurin had disparate effects on the transcriptional induction of CREB-dependent IEGs. We find that the IEG c-fos is unaffected by suppression of calcineurin activity, the plasticity-related genes Egr1/Zif268 and Egr2/Krox-20 are up-regulated, and genes encoding the orphan nuclear hormone receptors Nor1 and Nur77 are down-regulated. We further show that the up-regulation of particular IEGs is probably due to the presence of serum response elements (SREs) in their promoters, because SRE-mediated gene expression is enhanced by calcineurin blockers. Moreover, expression of the c-fos gene, which is unaffected by calcineurin inhibitors, could be down-regulated by mutating the SRE. Conversely, SRE-mediated c-fos induction in the absence of a functional CRE was enhanced by calcineurin inhibitors. Our experiments thus implicate calcineurin as a negative regulator of SRE-dependent neuronal genes. PMID:19270309

Lam, Brian Yee Hong; Zhang, Wenting; Enticknap, Nicola; Haggis, Eleanor; Cader, M. Zaeem; Chawla, Sangeeta

2009-01-01

368

Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease  

PubMed Central

Background Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. Methods One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case–control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. Results For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG?+?GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG?+?GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Conclusions Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism. PMID:24192154

2013-01-01

369

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

370

Comparative sequence analysis of nitrogen fixation-related genes in six legumes  

PubMed Central

Legumes play an important role as food and forage crops in international agriculture especially in developing countries. Legumes have a unique biological process called nitrogen fixation (NF) by which they convert atmospheric nitrogen to ammonia. Although legume genomes have undergone polyploidization, duplication and divergence, NF-related genes, because of their essential functional role for legumes, might have remained conserved. To understand the relationship of divergence and evolutionary processes in legumes, this study analyzes orthologs and paralogs for selected 20 NF-related genes by using comparative genomic approaches in six legumes i.e., Medicago truncatula (Mt), Cicer arietinum, Lotus japonicus, Cajanus cajan (Cc), Phaseolus vulgaris (Pv), and Glycine max (Gm). Subsequently, sequence distances, numbers of synonymous substitutions per synonymous site (Ks) and non-synonymous substitutions per non-synonymous site (Ka) between orthologs and paralogs were calculated and compared across legumes. These analyses suggest the closest relationship between Gm and Cc and the highest distance between Mt and Pv in six legumes. Ks proportional plots clearly showed ancient genome duplication in all legumes, whole genome duplication event in Gm and also speciation pattern in different legumes. This study also reports some interesting observations e.g., no peak at Ks 0.4 in Gm-Gm, location of two independent genes next to each other in Mt and low Ks values for outparalogs for three genes as compared to other 12 genes. In summary, this study underlines the importance of NF-related genes and provides important insights in genome organization and evolutionary aspects of six legume species analyzed. PMID:23986765

Kim, Dong Hyun; Parupalli, Swathi; Azam, Sarwar; Lee, Suk-Ha; Varshney, Rajeev K.

2013-01-01

371

Sugarcane Functional Genomics: Gene Discovery for Agronomic Trait Development  

PubMed Central

Sugarcane is a highly productive crop used for centuries as the main source of sugar and recently to produce ethanol, a renewable bio-fuel energy source. There is increased interest in this crop due to the impending need to decrease fossil fuel usage. Sugarcane has a highly polyploid genome. Expressed sequence tag (EST) sequencing has significantly contributed to gene discovery and expression studies used to associate function with sugarcane genes. A significant amount of data exists on regulatory events controlling responses to herbivory, drought, and phosphate deficiency, which cause important constraints on yield and on endophytic bacteria, which are highly beneficial. The means to reduce drought, phosphate deficiency, and herbivory by the sugarcane borer have a negative impact on the environment. Improved tolerance for these constraints is being sought. Sugarcane's ability to accumulate sucrose up to 16% of its culm dry weight is a challenge for genetic manipulation. Genome-based technology such as cDNA microarray data indicates genes associated with sugar content that may be used to develop new varieties improved for sucrose content or for traits that restrict the expansion of the cultivated land. The genes can also be used as molecular markers of agronomic traits in traditional breeding programs. PMID:18273390

Menossi, M.; Silva-Filho, M. C.; Vincentz, M.; Van-Sluys, M.-A.; Souza, G. M.

2008-01-01

372

Sugarcane functional genomics: gene discovery for agronomic trait development.  

PubMed

Sugarcane is a highly productive crop used for centuries as the main source of sugar and recently to produce ethanol, a renewable bio-fuel energy source. There is increased interest in this crop due to the impending need to decrease fossil fuel usage. Sugarcane has a highly polyploid genome. Expressed sequence tag (EST) sequencing has significantly contributed to gene discovery and expression studies used to associate function with sugarcane genes. A significant amount of data exists on regulatory events controlling responses to herbivory, drought, and phosphate deficiency, which cause important constraints on yield and on endophytic bacteria, which are highly beneficial. The means to reduce drought, phosphate deficiency, and herbivory by the sugarcane borer have a negative impact on the environment. Improved tolerance for these constraints is being sought. Sugarcane's ability to accumulate sucrose up to 16% of its culm dry weight is a challenge for genetic manipulation. Genome-based technology such as cDNA microarray data indicates genes associated with sugar content that may be used to develop new varieties improved for sucrose content or for traits that restrict the expansion of the cultivated land. The genes can also be used as molecular markers of agronomic traits in traditional breeding programs. PMID:18273390

Menossi, M; Silva-Filho, M C; Vincentz, M; Van-Sluys, M-A; Souza, G M

2008-01-01

373

Genome-Wide SNP Genotyping to Infer the Effects on Gene Functions in Tomato  

PubMed Central

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